HCLSIG BioRDF Subgroup/Data/OMIM

From W3C Wiki
Jump to: navigation, search

<?xml version="1.0" encoding="UTF-8"?> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdfs="http://www.w3.org/2000/01/rdf-schema#" xmlns:xxx="urn:lsid:uniprot.org:ontology:"> <rdf:Description rdf:about="urn:lsid:uniprot.org:omim:106195"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>SOLUTE CARRIER FAMILY 4 (ANION EXCHANGER), MEMBER 3; SLC4A3</dc:title> <dc:alternative>SLC2C</dc:alternative> <dc:alternative>ANION EXCHANGER 3; AE3</dc:alternative> <dc:alternative>ANION EXCHANGER, NEURONAL</dc:alternative> <dc:description>{1:Kopito et al. (1989)} isolated AE3, a novel gene expressed primarily in brain neurons and in heart. The predicted AE3 polypeptide shares a high degree of identity with the anion exchange and cytoskeletal-binding domains of the erythrocyte band 3 protein (EPB3; {109270}), also known as AE1, or the erythrocyte anion exchanger. Expression of AE3 cDNA in COS cells led to chronic cytoplasmic acidification and to chloride- and bicarbonate-dependent changes in intracellular pH, confirming that this gene product is an anion exchanger. Characterization of an AE3 mutant lacking the N-terminal 645 amino acids demonstrated that the C-terminal half of the polypeptide is both necessary and sufficient for correct insertion into the plasma membrane and for anion exchange activity. The N-terminal domain may play a role in regulating the activity of the exchanger and may be involved in the structural organization of the cytoskeleton in neurons.</dc:description> <dc:description>The cardiac anion exchanger (AE3) cDNA was cloned from a human heart-specific cDNA library and the gene was mapped to 2q35-q37.2 by in situ hybridization ({2:Raney, 1993}). {3:Su et al. (1994)} isolated and partially sequenced the AE3 gene (also symbolized SLC4A3). Oligonucleotide primers based on this sequence were used in a PCR to specifically amplify a segment of the human gene from a panel of human/rodent somatic cell hybrids, allowing the assignment of the gene to chromosome 2. By fluorescence in situ hybridization, the gene was mapped to 2q36. A polymorphic dinucleotide (GT/CA)n repeat marker was typed on a subset of the CEPH families; multipoint linkage analysis placed the SLC2C gene between D2S128 and D2S126. The homologous gene in the mouse, Ae3, was mapped to chromosome 1 by analysis of recombinant inbred strains ({4:White et al., 1994}).</dc:description> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:107920"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>AROMATIC ALPHA-KETO ACID REDUCTASE</dc:title> <dc:alternative>ALPHA-KETO ACID REDUCTASE; KAR</dc:alternative> <dc:description>Aromatic alpha-keto acid reductase catalyzes the reduction of phenylpyruvic and p-OH-phenylpyruvic acids to their corresponding lactate derivatives in the presence of NADH2. By study of human-Chinese hamster somatic cell hybrids, {1:Donald (1982)} concluded that the gene for KAR is on chromosome 12. Interestingly, KAR's substrate specificity overlaps that of lactate dehydrogenase which, in one of its isozymic forms, is also determined by a gene on chromosome 12. However, the enzymes are distinctly different in electrophoretic mobility and subunit composition. In a single person, {1:Donald (1982)} found an unusual phenotype of KAR following electrophoresis in starch gel and interpreted this to represent a genetic variant. {3:Friedrich and Ferrell (1985)} found no variants in a starch gel electrophoresis of 509 persons from many different racial groups and none in a survey by thin-layer isoelectric focusing in polyacrylamide gel involving 232 persons. {5,4:Friedrich et al. (1987, 1988)} presented evidence from several nonhuman species and from humans that alpha-ketoacid reductase and cytoplasmic malate dehydrogenase (MDH1; {154200}) are identical. In starch-gel electrophoresis the 2 enzyme functions comigrated in all species studied except some marine species. Inhibition with malate, the end-product of the MDH reaction, substantially reduced or totally eliminated KAR activity. Genetically determined electrophoretic variants of MDH1 seen in fresh water bony fish and in the amphibian Rana pipiens exhibited identical variation of KAR, and the 2 traits cosegregated in the offspring from 1 R. pipiens heterozygote studied. Both enzymes comigrated with no electrophoretic variation among several inbred strains of mice. Antisera raised against purified chicken MDH1 totally inhibited both MDH1 and KAR activity in chicken liver homogenates. In all species examined, KAR activity was associated only with cytoplasmic MDH, not with mitochondrial MDH (MDH2; {154100}). MDH1 in man maps to 2p23. {4:Friedrich et al. (1988)} called into question the assignment of KAR to chromosome 12 in somatic cell hybrids because interspecific hybrid bands of both MDH1 and LDH appeared with slightly different mobility approximately midway between the human and hamster controls in somatic cell hybrid studies. {4:Friedrich et al. (1988)} concluded that the bulk of KAR activity in human blood is due to MDH1, with a minor fraction catalyzed by LDH, as is the case in most other species studied.</dc:description> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:131330"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>PROENKEPHALIN; PENK</dc:title> <dc:alternative>ENKEPHALIN A</dc:alternative> <dc:alternative>PREPROENKEPHALIN A</dc:alternative> <dc:description>Met-enkephalin (tyr-gly-gly-phe-met) and leu-enkephalin (tyr-gly-gly-phe-leu) are pentapeptides which compete with and mimic the effects of opiate drugs. Although interest in enkephalins stems largely from their possible role in the brain, the richest source of these peptides is the adrenal gland. Pheochromocytomas have been used to prepare cDNA clones of the preproenkephalin gene ({3:Legon et al., 1982}). {1:Comb et al. (1982)} determined the complete nucleotide sequence of a cDNA copy of enkephalin precursor mRNA from human pheochromocytoma. The corresponding amino acid sequence shows that the precursor is 267 amino acids long and contains 6 interspersed Met-enkephalin sequences and 1 Leu-enkephalin sequence. The precursor does not contain the sequences of dynorphin, alpha-neo-endorphin or beta-endorphin. (Because of structural similarities it had been postulated that beta-endorphin is precursor of Met-enkephalin, and that dynorphin or alpha-neo-endorphin is precursor of Leu-enkephalin.) See {131340}. {6:Noda et al. (1982)} cloned a human genomic DNA segment containing the entire gene. They found that the general organization of the preproenkephalin gene is strikingly similar to that of the gene encoding preproopiomelanocortin ({176830}), another multihormone precursor. The complete mRNA and amino acid sequence of human preproenkephalin were deduced from the gene sequence. Preproenkephalin has 267 amino acids, as does proopiomelanocortin. Both genes contain 2 introns. In both, all the repeated enkephalin or melanotropin sequences are encoded by a single large exon (exon 3). Preproenkephalin mRNA encodes 4 copies of met-enkephalin, 2 copies of met-enkephalin extended sequences, and 1 copy of leu-enkephalin. Each copy is flanked by paired basic amino acids which are presumably recognized by the processing protease. {5,4:Litt et al. (1987, 1988)} used probes derived from rat and human proenkephalin to study DNA from rodent-human somatic cell hybrids and map PENK to chromosome 8. In situ hybridization confirmed this assignment and indicated the regional localization of 8q23-q24.</dc:description> <dc:description>{2:Konig et al. (1996)} adopted a genetic approach to study the role of the mammalian opioid system in many physiologic functions, including pain perception and analgesia, responses to stress, aggression, and dominance. Using homologous recombination in ES cells, they disrupted the preproenkephalin gene to generate enkephalin-deficient mice. Homozygous mutant mice were healthy, fertile, and cared for their offspring but displayed significant behavioral abnormalities. Abnormal behaviors in homozygous-deficient pups and adolescent mice included hiding under the bedding, frantic running or jumping, and prolonged freezing in response to moderate noise. They were more anxious, and males displayed increased offensive aggressiveness. Mutant animals showed marked differences from controls in supraspinal, but not in spinal, responses to painful stimuli. Unexpectedly, homozygous-deficient mice exhibited normal stress-induced analgesia. The results showed that enkephalins modulate responses to painful stimuli. Thus, {2:Konig et al. (1996)} concluded that genetic factors may contribute significantly to the experience of pain. Studies in humans showed that opiates do not change nociceptive thresholds, but rather reduce the subjective feeling of pain.</dc:description> <dc:description>{7:Ragnauth et al. (2001)} studied ovariectomized female transgenic preproenkephalin-knockout mice and their wildtype and heterozygous controls. They presented transgenic data strongly suggesting that opioids, and particularly enkephalin gene products, are acting naturally to inhibit fear and anxiety.</dc:description> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:164785"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>MOUSE DOUBLE MINUTE 2 HOMOLOG; MDM2</dc:title> <dc:alternative>p53-BINDING PROTEIN MDM2</dc:alternative> <dc:alternative>ONCOPROTEIN MDM2</dc:alternative> <dc:alternative>HDM2</dc:alternative> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:173410"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>PLATELET-DERIVED GROWTH FACTOR RECEPTOR, BETA; PDGFRB</dc:title> <dc:alternative>PDGFR</dc:alternative> <dc:alternative>PDGFR1</dc:alternative> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:176910"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>PROTEIN KINASE, cAMP-DEPENDENT, REGULATORY, TYPE II, ALPHA; PRKAR2A</dc:title> <dc:alternative>PROTEIN KINASE A, RII-ALPHA SUBUNIT</dc:alternative> <dc:description>See {188830}. Phosphorylation by cAMP-dependent protein kinases is essential for sperm motility. A cAMP-dependent protein kinase is bound to sperm flagella by a regulatory subunit (RII). {1:Oyen et al. (1989)} observed high testis-specific expression of a human homolog to the rat RII-alpha mRNA induced in haploid germ cells. They cloned a human cDNA that encodes a 404-amino acid polypeptide with a region (amino acids 45-75) divergent from that of the previously published mouse and rat sequences.</dc:description> <dc:description>By PCR and Southern blot analysis of somatic cell hybrid mapping panels and by radiation hybrid analysis, {2:Tasken et al. (1998)} mapped the PRKAR2A gene to chromosome 3p21.3-p21.2.</dc:description> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:176915"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>PROTEIN PHOSPHATASE 2A, CATALYTIC SUBUNIT, ALPHA ISOFORM; PPP2CA</dc:title> <dc:alternative>PP2CA</dc:alternative> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:186880"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>T-CELL ANTIGEN RECEPTOR, ALPHA SUBUNIT; TCRA</dc:title> <dc:description>T lymphocytes, like B lymphocytes, can recognize a wide range of different antigens. As with B cells, the capability to recognize a given antigen is fixed in any particular clonal line of T cells. However, unlike B cells, T cells recognize antigen in combination with self major histocompatibility complex (MHC) determinants, i.e., the function is 'MHC restricted.' Many authors commented that 'the chemical nature of the T-cell receptors has been elusive' (e.g., {39:Saito et al., 1984}). The development of monoclonal antibodies that recognize and precipitate clone-specific proteins on the surface of T cells has provided information on these receptor molecules. {17:Hedrick et al. (1984)} approached the molecular genetic study of the previously elusive T-cell antigen receptor with 4 assumptions: that they are expressed in T cells but not in B cells; that the mRNAs for the T-cell receptor proteins should be found on membrane-bound polysomes, the nascent receptor polypeptides being attached to the endoplasmic reticulum by a leader peptide (signal sequence); that like immunoglobulin genes, those that encode the T-cell receptor proteins are rearranged in T cells as a mechanism of generating diversity; and that like immunoglobulin genes, they have constant regions that share some functions and variable regions that confer antigen-binding specificity. They found that a cloned T-cell-specific cDNA showed variable, constant and joining regions remarkably similar in size and sequence to those encoding immunoglobulin proteins. {39:Saito et al. (1984)} presented the complete deduced primary structure of the T-cell receptor. {42:Siu et al. (1984)} stated that the 'T-cell antigen receptor appears to be assembled from 3 gene segments, V, D, and J, and accordingly most closely resembles immunoglobulin heavy chain V genes.' {14:Hannum et al. (1984)} presented the sequence of an alpha chain and pointed to its homology to the immunoglobulin polypeptide chains. The antigen-specific receptors of B lymphocytes and T lymphocytes share many similarities. The receptors of the B cells have long been known to be the immunoglobulins. The receptors on T cells consist of immunoglobulin-like integral membrane glycoproteins containing 2 polypeptide subunits, alpha and beta, of similar molecular weight, 40 to 55 kD in the human. Like the immunoglobulins (Ig) of the B cells, each T-cell receptor subunit has, external to the cell membrane, an N-terminal variable (V) domain and a C-terminal constant (C) domain. Like the Ig genes, the genes for the T-cell receptor subunits are assembled from gene segments which are of at least 3 types for alpha, V, joining (J) and C, and at least 4 for beta, V, diversity (D), J and C. {15:Harvey and Showe (1993)} pointed out that nearly 60 unique J regions had been identified in TCR-alpha chains, yet fewer than one-third of these had been localized within the TCRA gene. They reported a rapid method for mapping productively rearranged J-alpha regions.</dc:description> <dc:description>In the rat, {6:Binz et al. (1976)} showed linkage between heavy chain immunoglobulin genes and idiotypic T-cell receptors with specificity for MHC antigens but lack of linkage with MHC genes and with kappa light chain genes. If homology exists in man, a likely situation, then a T-cell receptor locus is linked to the Gm loci ({147100}-{147130}), which have been mapped to 14q34. In the mouse the alpha subunit is coded by chromosome 14 ({24:Kranz et al., 1985}). {5:Barker et al. (1985)} assigned the TCRA locus to human chromosome 14, proximal to 14q21. Human chromosome 14 appears to contain 2 regions of syntenic homology to mouse chromosomes: a proximal segment with TCRA and NP ({164050}) which are on mouse 14 and a distal segment with oncogene FOS ({164810}) and IGH ({147100}) which are on mouse 12. By somatic cell hybridization, {9:Croce et al. (1985)} assigned the TCRA gene to chromosome 14 and by in situ hybridization further narrowed the assignment to 14q11-14q12. This site is consistently involved in translocations and inversions detectable in human T-cell leukemias and lymphomas. Specifically, an inversion of the segment 14q11.2-q32.2 occurs in T-cell chronic lymphatic leukemia and a t(14;14)(q11;q32) translocation occurs in T-cell malignancies of patients with ataxia-telangiectasia ({208900}) ({30:McCaw et al., 1975}). These observations led {9:Croce et al. (1985)} to suggest that the oncogene for which they proposed the designation tcl-1 ({186960}) is located on band 14q32.3 and becomes activated when it is in proximity to the TCRA gene.</dc:description> <dc:description>Like the beta chain ({186930}) of the T-cell antigen receptor, the alpha chain is encoded in separate noncontiguous gene segments, V, J, and C. Using an alpha chain cDNA probe of DNA from somatic cell hybrids, {20:Jones et al. (1985)} assigned the gene to chromosome 14. From study of a deletion segregant containing only the distal half of chromosome 14 (14q22-qter), they concluded that the alpha locus is situated proximal to 14q22. They pointed out the high frequency of breaks in the 14q11-q13 segment, possibly involving the alpha locus in T-cell malignancies, and leading {16:Hecht et al. (1984)} to suggest the existence of genes relating to T-cell function in this region. {13:Erikson et al. (1985)} showed that the TCRA gene was split by chromosome translocation t(11;14)(p13;q11) in 2 cases of T-cell leukemia. The constant segment was translocated to chromosome 11 whereas the variable region remained on chromosome 14. Thus, the V segments are proximal to the C segment within band 14q11.2. {26:Lewis et al. (1985)} reported identical findings. In cases of adult T-cell leukemia in Nagasaki Prefecture of Japan, an area of high frequency, {38:Sadamori et al. (1985)} found abnormalities at band 14q11. This form of leukemia is associated with HTLV/ATLV viruses. Thus, 14q32 is associated with B-cell lymphoma/leukemia and 14q11 with T-cell lymphoma/leukemia including Sezary syndrome and mycosis fungoides. In an inversion of chromosome 14, inv(14)(q11;q32), in a T cell lymphoma, {3:Baer et al. (1985)} showed that on the normal chromosome 14, a V(alpha) segment had rearranged with a J(alpha) segment. In contrast, the inverted chromosome featured an unprecedented rearrangement in which a V-heavy chain segment from 14q32 ({147070}) had joined with a J(alpha) segment from 14q11. The V(H)-J(alpha)C(alpha) rearrangement was productive at the genomic level and presumably encodes a hybrid immunoglobulin/T cell receptor polypeptide. The MOLT-16 cell line, which was established from the malignant cells of a patient with T-cell acute lymphoblastic leukemia, carries a translocation t(8;14)(q24;q11). By molecular approaches, {31:McKeithan et al. (1986)} showed that the breakpoint on 14 occurred close to a joining sequence (J) of the TCRA gene and that the constant region and part of the J region of TCRA are translocated to the 3-prime side of the MYC gene. {25:Le Beau et al. (1986)} demonstrated that the TCRA gene was split in a cell line from a child with T-cell acute lymphoblastic leukemia and a t(11;14)(p15;q11). With in situ chromosomal hybridization and with Southern blot analysis, they showed that the break at 14q11 occurred within the variable region of TCRA; the break at 11p15 occurred between the HRAS1 gene ({190020}) and the genes for insulin and IGF2. By studies of cells from a person with T-cell acute lymphocytic leukemia and a t(10;14) translocation, {21:Kagan et al. (1987)} demonstrated that the break in chromosome 14 had occurred in the TCRA locus in a region between the variable and constant genes. The break in chromosome 10 was at 10q24. The derivative 10q+ chromosome had the human gene for terminal deoxynucleotidyltransferase (TDT; {187410}), which has been mapped to 10q23-25. These results suggested to {21:Kagan et al. (1987)} that the translocation of the TCRA constant locus to a putative cellular protooncogene located proximal to the breakpoint at 10q24, for which they proposed the name TCL3 ({186770}), had resulted in deregulation of said oncogene, leading to T-cell leukemia. Evidence suggested also that the TDT gene is located proximal to TCL3 at band 10q23-q24. {22:Klein et al. (1987)} found considerable variability in the V region and J sequences of the TCRA gene.</dc:description> <dc:description>{36:Posnett et al. (1986)} used 3 different murine monoclonal antibodies to human clonotypic T-cell antigen receptor to demonstrate inherited polymorphism comparable to the allotypic polymorphism of immunoglobulins. Restriction fragment length polymorphisms had previously been identified in human alpha and beta chain genes. These RFLPs mapped to introns; obviously, the polymorphism demonstrated with monoclonal antibodies involved exons. The authors suspected that the polymorphism represented an allotypic system of a variable or joining region. Their results indicated that allelic exclusion governs the expression of the clonotypic receptor by human T-cells and thus is a phenomenon not limited to immunoglobulin-producing cells. {37:Robinson and Kindt (1987)} identified 'hotspots' of recombination in the TCRA complex by studying the segregation of 3 RFLPs associated with the C region and 3 RFLPs associated with the V region in 8 families. {34:Oksenberg et al. (1989)} found an association between polymorphic markers in the variable and constant regions of the TCR-alpha gene and both multiple sclerosis ({126200}) and myasthenia gravis ({254200}).</dc:description> <dc:description>See review of the TCR genes by {43:Toyonaga and Mak (1987)}. {28:Marrack and Kappler (1987)} reviewed the T-cell receptor from the point of view of structure and particularly of function. {44:Weiss (1990)} reviewed the structure and function of the 6-part T-cell antigen receptor complex. Useful diagrams of the structural domains of the receptor proteins (his Figure 1) and of the organization and rearrangement of the T-cell receptor genes (his Figure 2) were presented.</dc:description> <dc:description>Studies in both mouse and man show that the TCR-delta gene (TCRD; {186810}) lies within the TCRA locus, upstream from the estimated 50 to 100 J(alpha) segments and between V(alpha) and J(alpha). Whereas TCRD genes rearrange early in thymic ontogeny, TCRA genes rearrange much later. Further, the utilization of V segments appears to be selective. {40:Satyanarayana et al. (1988)} analyzed the germline organization of the TCR-alpha/delta locus. {23:Koop et al. (1994)} sequenced and analyzed 97.6 kb of DNA containing the TCRA constant gene and the TCRD constant gene as well as the TCRDV3 and 61 different TCRAJ gene segments and compared the organization and structure to the same, previously described region in the mouse. They concluded that this region of the human and mouse genomes is remarkably conserved.</dc:description> <dc:description>Although the TCR-alpha and TCR-gamma glycoprotein chains are encoded by discrete variable (V), junctional (J), and constant (C) genes, these genes are not represented by separate entries here. (The TCR-beta and TCR-delta chains have additional diversity (D) segments.) The precise number of V-alpha segments in the germline is unknown, but sequence analyses of cDNA clones from a number of individuals have identified 100 different sequences, which can be grouped into 32 subgroups containing sequences sharing greater than, or equal to, 75% homology. During T-cell development the TCR genes rearrange to produce a contiguous VDJ exon. Subsequent splicing of the transcript joins the J and C genes, and the mature mRNA is translated into a complete polypeptide chain. The multiplicity of V, (D), and J segments and the random nature of the VDJ recombination, in addition to junctional variation produced by the enzyme N-terminal transferase (termed N-region diversity), enable the germline repertoire to generate an estimated 10(15) different alpha/beta TCRs ({10:Davis and Bjorkman, 1988}).</dc:description> <dc:description>{35:Pestano et al. (1999)} identified a differentiative pathway taken by CD8 cells bearing receptors that cannot engage class I MHC (see {142800}) self-peptide molecules because of incorrect thymic selection, defects in peripheral MHC class I expression, or antigen presentation. In any of these cases, failed CD8 T-cell receptor coengagement results in downregulation of genes that account for specialized cytolytic T-lymphocyte function and resistance to cell death (CD8-alpha/beta, see {186730}; granzyme B, {123910}; and LKLF, {602016}), and upregulation of Fas ({134637}) and FasL ({134638}) death genes. Thus, MHC engagement is required to inhibit expression and delivery of a death program rather than to supply a putative trophic factor for T cell survival. {35:Pestano et al. (1999)} hypothesized that defects in delivery of the death signal to these cells underlie the explosive growth and accumulation of double-negative T cells in animals bearing Fas and FasL mutations, in patients that carry inherited mutations of these genes, and in about 25% of systemic lupus erythematosus patients that display the cellular signature of defects in this mechanism of quality control of CD8 cells.</dc:description> <dc:description>{33:Moffatt et al. (2000)} examined linkage disequilibrium (LD) within an 850-kb section of the TCR-alpha/delta locus by genotyping 159 families at 24 V-gene segment single-nucleotide polymorphisms (SNPs) and 2 microsatellites. Significant LD was relatively common at 250 kb and was detectable beyond 500 kb, a much greater distance than suggested by simulations. The mean extent of LD was twice as far between alleles of low frequency than between common alleles, and distribution was highly irregular and concentrated in 3 distinct islands. The authors suggested that, if these data are typical of other genomic regions, the minimum number of markers necessary for comprehensive LD mapping of the genome may be reduced by at least an order of magnitude.</dc:description> <dc:description>In the thymus, immature thymocytes recognizing self MHC are selected to survive and differentiate through positive selection. Conversely, overtly self-reactive thymocytes are removed through negative selection. Positive selection is mediated in part by the connecting peptide domain (CPM) of TCRA. {2:Backstrom et al. (1998)} showed that thymocytes from mice with mutant CPMs were unable to immunoprecipitate CD3D ({186790}). {45:Werlen et al. (2000)} showed that thymocytes from mice with mutant CPMs were unable to activate ERK (MAPK3; {601795}) after stimulation with a positively selecting peptide, although other MAPKs that regulate negative selection (e.g., p38, or MAPK14; {600289}) and JNK1 (MAPK8; {601158}) cascades remained intact. The defect in ERK activation was associated with impaired recruitment of the activated tyrosine kinases LCK ({153390}) and ZAP70 ({176947}) and the phosphorylated forms of CD3Z ({186780}) and the adaptor protein LAT ({602354}) into detergent-insoluble glycolipid-enriched microdomains (DIGs).</dc:description> <dc:description>{46:Wu et al. (2002)} showed that the TCR interaction with peptide-MHC is initially with the MHC portion, but that subsequently the peptide contacts dominate stabilization, imparting specificity and influencing T cell activation by modulating the duration of TCR binding to peptide-MHC. {46:Wu et al. (2002)} concluded that the interaction is functionally subdivided into a 2-step process, such that TCRs efficiently scan diverse peptide-MHC complexes on cell surfaces and that the TCRs are inherently crossreactive toward different peptides bound by the same MHC.</dc:description> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:193245"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>VOLTAGE-DEPENDENT ANION CHANNEL 2; VDAC2</dc:title> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:202010"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>ADRENAL HYPERPLASIA, CONGENITAL, DUE TO 11-BETA-HYDROXYLASE DEFICIENCY</dc:title> <dc:alternative>ADRENAL HYPERPLASIA IV</dc:alternative> <dc:alternative>11-@BETA-HYDROXYLASE DEFICIENCY</dc:alternative> <dc:alternative>HYPERTENSIVE FORM OF ADRENAL HYPERPLASIA</dc:alternative> <dc:alternative>STEROID 11-BETA-HYDROXYLASE</dc:alternative> <dc:alternative>P450C11B1 DEFICIENCY</dc:alternative> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:300060"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>DXS9879E</dc:title> <dc:alternative>ITBA2 GENE</dc:alternative> <dc:description>By searching EST databases with genomic sequences obtained from CpG islands located in the Xq28 region, {2:Faranda et al. (1996)} detected a gene, which they called ITBA2, that mapped close to GDX ({312070}) in the interval between the color vision genes ({303800}; {303900}) and G6PD ({305900}). The gene is relatively short, contains a 105-amino acid open reading frame, and is ubiquitously expressed. {2:Faranda et al. (1996)} showed that ITBA2 is centromeric to GDX and is transcribed in the same orientation.</dc:description> <dc:description>Nomenclature: {1:Faranda (1996)} indicated that the title of the ITBA2 gene was arbitrarily chosen from the acronym of the institute where she works, Istituto di Tecnologie Biomediche Avanzate, in Milan, Italy.</dc:description> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:313500"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>OLIGODONTIA 1; ODT1</dc:title> <dc:alternative>TEETH, REDUCED NUMBER OF</dc:alternative> <dc:description>{2:Erpenstein and Pfeiffer (1967)} described transmission of oligodontia or hypodontia through 4 generations of a family. Males had oligodontia; females had hypodontia. No male-to-male transmission was observed. However, only 2 affected males had children (4 unaffected sons, 1 daughter with hypodontia). X-linkage is likely. In at least 18 persons in 4 generations {1:Dahlberg (1937)} noted absence of at least 6 anterior teeth in both dentitions. He suggested X-linked dominant inheritance, but against this is 1 unaffected daughter of the 1 affected male with children in the kindred.</dc:description> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:400006"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>RNA-BINDING MOTIF PROTEIN, Y CHROMOSOME, FAMILY 1, MEMBER A1; RBMY1A1</dc:title> <dc:alternative>RBMY</dc:alternative> <dc:alternative>RNA-BINDING MOTIF PROTEIN 1; RBM1</dc:alternative> <dc:alternative>RNA-BINDING MOTIF PROTEIN 2; RBM2</dc:alternative> <dc:alternative>Y CHROMOSOME RNA RECOGNITION MOTIF 1; YRRM1</dc:alternative> <dc:alternative>Y CHROMOSOME RNA RECOGNITION MOTIF 2; YRRM2</dc:alternative> <dc:description>{4:Ma et al. (1993)} reported the isolation and characterization of a gene family located within interval 6 (subinterval XII-XIV) of Yq11.23, a region of approximately 200 kb that, when deleted, is associated with azoospermia or severe oligospermia (see {415000} for a discussion of this so-called 'azoospermia factor' (AZF) region). Analysis of the predicted protein products suggested a possible role in RNA processing or translational control during early spermatogenesis. The expression of the genes appeared to be testis-specific, and the genes showed a male-specific conservation of expression in DNA from several other mammals. The Y chromosome RNA recognition motif (YRRM) family comprises at least 15 copies clustered at Yq11.23, of which many are pseudogenes but at least 2 are transcribed. {4:Ma et al. (1993)} detected deletions of YRRM sequences in 2 oligospermic patients with no previously detected mutation.</dc:description> <dc:description>{2:Delbridge et al. (1997)} reviewed the literature on the RBM1 gene family. Expression of the human RBM1 gene family is confined to the spermatogonia and early primary spermatocytes in the lining of the seminiferous tubules in adults, but expression of the RBM1 gene family has also been demonstrated in the testis of 2-year-old and prepubertal boys, indicating that the RBM1 gene family may have an additional role in germ cell development. RBM1 is present as multiple copies in all eutherian species examined, including primates, rabbit, pig, cattle, sheep, and mouse. The RBM1 genes encode RNA-binding proteins containing a single N-terminal RNA-binding motif and a C-terminal auxiliary domain with 4 repeated segments with a high proportion of glycine, serine, and arginine residues, typical of many RNA-binding proteins. Two other genes that map to the same small region of the long arm of the human Y chromosome and are often deleted in azoospermic men are DAZ ({400003}) and TSPY ({480100}).</dc:description> <dc:description>{2:Delbridge et al. (1997)} demonstrated that RBM1, but not DAZ or TSPY, has a Y-linked homolog in marsupials that is transcribed in the testis. This suggests that RBM1 has been retained on the Y chromosome because of a critical male-specific function. Marsupial RBM1 is closely related to human RBM1, but lacks the amplification of an exon.</dc:description> <dc:description>An active X-borne homolog of the Y-borne RBMY gene (RBMX; {300199}) was demonstrated in humans and marsupials by {3:Delbridge et al. (1999)} and in the mouse by {5:Mazeyrat et al. (1999)}. {3:Delbridge et al. (1999)} and {5:Mazeyrat et al. (1999)} found that the HNRPG gene on 6p12, known only as a cDNA with 60% sequence similarity to RBMY, is a processed pseudogene of RBMX. {3:Delbridge et al. (1999)} suggested that RBMY and RBMX evolved from a gene on the mammalian proto-X and -Y pair at least 130 million years ago, before the divergence of eutherian and metatherian mammals.</dc:description> <dc:description>To investigate the number of functional RBM genes on the Y chromosome, {1:Chai et al. (1997)} studied RBM expression by use of RT-PCR of RBM transcripts and by characterizing numerous RBM cDNA clones. A total of 27 RT-PCR and 19 cDNA clones were sequenced. Whereas the RT-PCR clones pointed to the existence of at least 6 RBM subfamilies (RBM-I to RBM-VI), the cDNA clones indicated that only RBM-I is actively transcribed and encodes functional proteins. A total of 6 RBM-I genes were identified, which produced 4 polypeptides due to some silent base substitutions. Transcripts of each gene are alternatively spliced to generate protein isoforms with 3 or 4 SRGY boxes, thus greatly increasing the complexity of the products of the RBM gene family.</dc:description> <dc:description>{7:Venables et al. (2000)} used a yeast 2-hybrid system to show that RBM, the RBMX gene product hnRNPG ({300191}), and a novel testis-specific relative (termed hnRNPG-T) interact with Tra2-beta ({602719}), an activator of pre-mRNA splicing that is ubiquitous but highly expressed in testis. RBM and Tra2-beta colocalize in 2 major domains in human spermatocyte nuclei. Incubation with the protein interaction domain of RBM inhibited splicing in vitro of a specific pre-mRNA substrate containing an essential enhancer bound by Tra2-beta. The RNA-binding domain of RBM affected 5-prime splice site selection. The authors concluded that the hnRNPG family of proteins is involved in pre-mRNA splicing and hypothesized that RBM may be involved in Tra2-beta-dependent splicing in spermatocytes.</dc:description> <dc:description>{6:Repping et al. (2004)} identified the b2/b3 deletion within the AZFc region ({415000}) of the Y chromosome, in which all 6 copies of the RBMY gene are deleted. The b2/b3 deletion has no obvious effect on fitness.</dc:description> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:403000"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>ADENINE NUCLEOTIDE TRANSLOCATOR 3, Y-CHROMOSOMAL; ANT3Y</dc:title> <dc:description>The ADP/ATP translocase gene (ANT3) is located on the pseudoautosomal region of the X and Y chromosomes, escapes X inactivation, and is transcribed from the Y chromosome and from both the active and the inactive X chromosome. See {300151} and {1:Slim et al. (1993)}.</dc:description> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:600061"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>RAD23, YEAST, HOMOLOG OF, A; RAD23A</dc:title> <dc:alternative>HHR23A</dc:alternative> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:600563"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>PROSTAGLANDIN F RECEPTOR; PTGFR</dc:title> <dc:alternative>PROSTAGLANDIN RECEPTOR F(2-ALPHA)</dc:alternative> <dc:description>Prostaglandin F(2-alpha) is involved in a number of physiologic processes. It serves as a potent luteolytic agent in many species, has been implicated as a modulator of intraocular pressure, and may be important in smooth muscle contraction in the uterus and elsewhere. Its effects on cells are mediated through specific interaction with prostaglandin receptors. {1:Abramovitz et al. (1994)} cloned a cDNA encoding the human prostanoid FP receptor from a uterus cDNA library. The 359-amino acid protein has 7 putative transmembrane domains characteristic of the G protein-coupled receptors. As expected, expression studies of the cDNA in Xenopus oocytes and COS cells showed strongest binding to PGF(2-alpha). Subsequently, {3:Duncan et al. (1995)} mapped the gene to 1p31.1 by in situ hybridization. Using a panel of interspecific backcross mice, {4:Ishikawa et al. (1996)} mapped the Ptgfr gene to distal mouse chromosome 3.</dc:description> <dc:description>{2:Betz et al. (1999)} showed that the human gene consists of 3 exons spanning approximately 10 kb of genomic DNA. The first exon is noncoding.</dc:description> <dc:description>{5:Sugimoto et al. (1997)} showed that knockout mice lacking the receptor for prostaglandin F(2-alpha) are unable to deliver normal fetuses at term due to a lack of response to oxytocin. The mice also failed to show the decline in serum progesterone expected to precede parturition. However, if the mice had their ovaries removed at day 19 of pregnancy, normal delivery occurred. The authors concluded that parturition is initiated when prostaglandin F(2-alpha) interacts with its receptor in ovarian luteal cells to induce luteolysis. {5:Sugimoto et al. (1997)} also suggested that this mechanism may explain why aspirin-like drugs delay parturition.</dc:description> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:600756"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>PROTEIN PHOSPHATASE 2A, REGULATORY SUBUNIT B-PRIME; PPP2R4</dc:title> <dc:alternative>PHOSPHOTYROSYL PHOSPHATASE ACTIVATOR; PTPA</dc:alternative> <dc:alternative>PR53</dc:alternative> <dc:description>Protein phosphorylation is a regulatory mechanism commonly employed in cellular processes such as cell cycle progression, growth factor signaling, and cell transformation. The involvement of protein phosphatase-2A (PP2A), 1 of the 4 major serine/threonine phosphatases, in these events is important. This protein phosphatase is implicated predominantly in the negative control of cell growth and division.</dc:description> <dc:description>{1:McCright et al. (1996)} stated that PP2A contains a 36-kD catalytic C subunit ({176915}) and a 65-kD structural/regulatory A subunit. Association of this dimeric core of PP2A with a third regulatory subunit (PR54, PR55, PR72, PR74, PR130, etc.) results in the formation of a specific trimeric holoenzyme.</dc:description> <dc:description>The PPP2R4 gene (which the authors symbolized PTPA) encodes a specific phosphotyrosyl phosphatase activator of the dimeric form of protein phosphatase 2A. {2:Van Hoof et al. (1995)} demonstrated that human PTPA is encoded by a single-copy gene composed of 10 exons and 9 introns with a total length of about 60 kb. The 5-prime flanking sequence of the transcription start site was analyzed for its potential as a promoter. This region lacks a TATA sequence in the appropriate position relative to the transcription start. However, this region is very GC-rich and contains four Sp1 sites (SP1; {189906}) upstream of the transcription start site, a feature common to many TATA-less promoters. Based on homology with DNA-binding consensus sequences of transcription factors, {2:Van Hoof et al. (1995)} identified several additional putative transcription factor binding sites in the promoter region. Transfection experiments with a construct containing the PTPA promoter region inserted 5-prime of a luciferase reporter gene demonstrated that the 5-prime flanking sequence of the PTPA gene indeed has promoter activity that seems to be cell-line dependent. By fluorescence in situ hybridization, {2:Van Hoof et al. (1995)} mapped the PTPA gene to 9q34. Fluorescence in situ analysis of metaphase chromosomes of patients bearing the Philadelphia chromosome indicated that PTPA is positioned centromeric of ABL1 ({189980}) and probably is not involved in chronic myeloid leukemia.</dc:description> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:601197"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>TUBBY, MOUSE, HOMOLOG OF; TUB</dc:title> <dc:description>A mutation in the mouse 'tubby' gene (tub) causes maturity-onset obesity, insulin resistance, retinal degeneration, and neurosensory hearing loss ({2:Coleman and Eicher, 1990}; {3:Heckenlively et al., 1995}). The tub gene was found to lie 2.4 cM from the mouse Hbb gene on chromosome 7. For that reason {6:Jones et al. (1992)} suggested that the human homolog of tubby resides in 11p15 and that the HBB locus in the human could be used as a linkage marker for the study of familial obesity in humans.</dc:description> <dc:description>The human obesity syndromes described by Bardet, Biedl, and Alstrom have certain features in common with the tubby phenotype. Bardet-Biedl syndrome (BBS; see {209900}), which is characterized by pigmentary retinopathy, obesity, mental retardation, hypogenitalism, and polysyndactyly, is genetically heterogeneous. Alstrom syndrome ({203800}), which is characterized by retinitis pigmentosa, deafness, obesity, and diabetes mellitus, maps to 2p13.</dc:description> <dc:description>{8:Noben-Trauth et al. (1996)} identified a candidate gene for mouse tubby on the basis of positional cloning. The candidate gene in tubby mice differed consistently from that in normal mice with respect to transcript size. Sequence analysis of the candidate gene revealed a G-to-T transversion that abolished the donor splice site in the 3-prime coding region, leading to a larger transcript in tubby. The transcript was 6.6 kb in tubby versus 6.3 kb in B6 mice. Sequence analysis of the candidate gene revealed that the 200 amino acids at the C terminus show 62% identity to a mouse phosphodiesterase. Because mutations in the cGMP phosphodiesterase genes (e.g., {180071}) are known to cause retinal degeneration through photoreceptor cell apoptosis, and because the retinal degeneration in tubby has hallmarks of apoptosis, {8:Noben-Trauth et al. (1996)} postulated that mutations in the phosphodiesterase-like candidate tubby gene lead to phenotypic effects through apoptotic events.</dc:description> <dc:description>{7:Kleyn et al. (1996)} also used positional cloning to identify a gene responsible for the tubby phenotype in mice. Tubby mutants were found to produce a larger transcript for this candidate gene (approximately 7.5 kb) than that produced by normal mice (7 kb). The RNA transcript in tubby was also 4-fold more abundant than the transcript in normal mice. The larger transcript in the mutant mice was due to a G-to-T transversion in a single splice donor site, leading to the substitution of 44 C-terminal amino acids, with 24 intron-encoded amino acids. The mutation identified by {7:Kleyn et al. (1996)} is apparently the same as that described by {8:Noben-Trauth et al. (1996)}. Northern blot analysis revealed that the candidate gene was expressed primarily in brain, particularly in the paraventricular, ventromedial, and arcuate nuclei of the hypothalamus. {7:Kleyn et al. (1996)} showed that strain-specific differences occurred in the relative abundance of alternate splice products. Alternate splice products differed with respect to the presence or absence of exon 5. {7:Kleyn et al. (1996)} demonstrated that this splice variation correlates with an intron length polymorphism and proposed this tub allele as a candidate for the obesity quantitative trait locus on mouse chromosome 7. {7:Kleyn et al. (1996)} isolated the human homolog of the mouse tub gene and determined that there is 94% identity between the human and the mouse sequence at the protein level and that the C-terminal half of the molecule is particularly highly conserved. See also UCP2 ({601693}).</dc:description> <dc:description>{9:Sahly et al. (1998)} undertook expression mapping studies in an effort to elucidate the biologic role of the TUB protein. They reported the tub gene expression pattern in embryonic, fetal, and adult mouse tissues as determined by Northern blots and in situ hybridization, using antisense oligonucleotide probes. In mouse embryos, tub was expressed selectively in differentiating neurons of the central and peripheral nervous systems, starting at 9.5 days after conception. In adult mice, tub is transcribed in several major brain areas, including cerebral cortex, hippocampus, several nuclei of the hypothalamus controlling feeding behavior, in the spiral ganglion of the inner ear, and in photoreceptor cells of the retina. These structures contain potential cellular targets of tubby mutation-induced pathogenesis. Spatial and temporal coincidences of gene expression patterns, although not a direct proof, suggested a similarity of function for TUB with carboxypeptidase E (CPE; {114855}), which is the site of a null mutation in the fat/fat mouse, prohormone convertase (PCSK1; {162150}), which is involved in the pathogenesis of one form of gross obesity, and other pro-proteases. The findings were also considered compatible with the alternative hypothesis that TUB is a neuropeptide involved in numerous neurophysiologic and endocrine functions regulating feeding behavior and sensory perception.</dc:description> <dc:description>{4:Ikeda et al. (1999)} performed a quantitative trait locus (QTL) analysis for auditory brainstem response (ABR) thresholds, which indicate hearing ability, in tubby mice from several F2 intercrosses. They identified a major QTL, which they designated 'modifier of tubby hearing-1' (moth1), that mapped to chromosome 2 with a lod score of 33.4 in the AKR intercross and of 6.0 in the CAST intercross. This QTL was responsible for 57% and 43% of ABR threshold variance, respectively, in each strain combination. In addition, a C57BL/6J congenic line carrying a segment encompassing the described QTL region also exhibited normal hearing ability when made homozygous for tubby. {4:Ikeda et al. (1999)} hypothesized that C57BL/6J mice carry a recessive mutation of the moth1 gene that interacts with the tub mutation to cause hearing loss in tub/tub mice. One allele from either AKR/J, CAST/Ei, or 129/Ola was sufficient to protect C57BL/6J tub/tub mice from hearing loss. It remained to be determined how the moth1 gene affects the other tubby phenotypes, such as retinal degeneration and obesity. {5:Ikeda et al. (2002)} reported the positional cloning of the auditory QTL modifying TUB1 as the MAP1A gene ({600178}). Through a transgenic rescue experiment, {5:Ikeda et al. (2002)} verified that sequence polymorphisms in the neuron-specific MAP1A gene observed in the susceptible strain C57BL/6J are crucial for the hearing loss phenotype. {5:Ikeda et al. (2002)} also showed that these polymorphisms changed the binding efficiency of MAP1A to postsynaptic density molecule PSD95 ({602887}), a core component in the cytoarchitecture of synapses. {5:Ikeda et al. (2002)} concluded that at least some of the observed polymorphisms are functionally important and that the hearing loss in C57BL/6J-tub/tub mice may be caused by impaired protein interactions involving MAP1A. They proposed that TUB may be associated with synaptic function in neuronal cells.</dc:description> <dc:description>{1:Boggon et al. (1999)} determined the crystal structure of the core domain of mouse tubby at a resolution of 1.9 angstroms. From primarily structural clues, {1:Boggon et al. (1999)} devised experiments, the results of which suggested that tubby-like proteins are a unique family of bipartite transcription factors. The tubby C-terminal is able to bind double-stranded DNA, while the N-terminal regions of tubby and TULP1 potently activate transcription.</dc:description> <dc:description>{10:Santagata et al. (2001)} demonstrated that tubby functions in signal transduction from heterotrimeric G protein-coupled receptors. Tubby localizes to the plasma membrane by binding phosphatidylinositol 4,5-bisphosphate through its carboxy-terminal 'tubby domain.' X-ray crystallography revealed the atomic-level basis of this interaction and implicates tubby domains as phosphorylated-phosphatidylinositol-binding factors. Receptor-mediated activation of G protein alpha-q (G-alpha-q; {600998}) releases tubby from the plasma membrane through the action of phospholipase C-beta (see {604114}), triggering translocation of tubby to the cell nucleus. The localization of tubby-like protein-3 ({604730}) is similarly regulated. {10:Santagata et al. (2001)} concluded that tubby proteins function as membrane-bound transcription regulators that translocate to the nucleus in response to phosphoinositide hydrolysis, providing a direct link between G protein signaling and the regulation of gene expression.</dc:description> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:601260"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>ZINC FINGER PROTEIN 36; ZNF36</dc:title> <dc:alternative>ZINC FINGER PROTEIN, KRUPPEL TYPE, 18; KOX18</dc:alternative> <dc:alternative>ZINC FINGER PROTEIN 139, FORMERLY; ZNF139, FORMERLY</dc:alternative> <dc:description>Transcriptional regulatory proteins containing tandemly repeated zinc finger domains are thought to be involved in both normal and abnormal cellular proliferation and differentiation. One abundant class of such transcriptional regulators resembles the Drosophila Kruppel segmentation gene product due to the presence of repeated Cys2-His2 (C2H2) zinc finger domains that are connected by conserved sequences, called H/C links. See ZNF91 ({603971}) for general information on zinc finger proteins.</dc:description> <dc:description>By screening a human insulinoma cDNA library with a degenerate oligonucleotide corresponding to the H/C linker sequence, {2:Tommerup et al. (1993)} isolated cDNAs potentially encoding zinc finger proteins. {3:Tommerup and Vissing (1995)} performed sequence analysis on a number of these cDNAs and identified several novel zinc finger protein genes, including ZNF36, which they called ZNF139. The ZNF139 cDNA predicts a protein belonging to the Kruppel family of zinc finger proteins.</dc:description> <dc:description>By isotopic in situ hybridization, {1:Rousseau-Merck et al. (1995)} mapped the ZNF36 gene, which they called KOX18, to 7q21-q22. From pulsed field gel electrophoresis studies, they showed that KOX18 is within less than 250 kb of KOX25 (ZNF38; {601261}). {1:Rousseau-Merck et al. (1995)} tabulated 18 different KOX genes that had been located in pairs within 9 DNA fragments of 200 to 580 kb on 7 different chromosomes. By FISH, {3:Tommerup and Vissing (1995)} mapped the ZNF36 gene to 7q21.3-q22.1.</dc:description> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:601395"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>CHEMOKINE, CC MOTIF, LIGAND 3-LIKE PROTEIN 1; CCL3L1</dc:title> <dc:alternative>LD78-BETA</dc:alternative> <dc:alternative>MACROPHAGE INFLAMMATORY PROTEIN 1-ALPHA-P</dc:alternative> <dc:alternative>MIP1-ALPHA-P; MIP1AP</dc:alternative> <dc:alternative>SMALL INDUCIBLE CYTOKINE A3-LIKE 1, FORMERLY: SCYA3L1, FORMERLY</dc:alternative> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:601895"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>TNF RECEPTOR-ASSOCIATED FACTOR 2; TRAF2</dc:title> <dc:alternative>TNF RECEPTOR-ASSOCIATED PROTEIN; TRAP</dc:alternative> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:602015"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>OUTER DENSE FIBER OF SPERM TAILS 2; ODF2</dc:title> <dc:alternative>OUTER DENSE FIBER OF SPERM TAILS, 84-KD; ODF84</dc:alternative> <dc:description>See ODF1 ({182878}). {1:Brohmann et al. (1997)} used antibodies against Odf proteins to screen a rat testis expression library and isolated the rat Odf2 gene. Sequence analysis revealed that the protein has an overall alpha-helical structure with 2 regions identical to the dimerization region of a leucine zipper motif. {1:Brohmann et al. (1997)} documented Odf2 cDNAs with 3 different 5-prime end sequences, presumed to be the result of alternative splicing. They found expression of the rat gene only in testis.</dc:description> <dc:description>The EST database contains several human cDNA sequences which are closely related to rat Odf2, suggesting that a human homolog exists ({2:Scott, 1997}). These human cDNA sequences were derived from testis, epididymis, and fetal brain libraries.</dc:description> <dc:description>{4:Shao et al. (1997)} used a yeast 2-hybrid screening with the leucine zipper region of ODF1 (ODF27; {5:Shao and van der Hoorn, 1996}) as bait to isolate rat testis-specific proteins that could interact with ODF27. They demonstrated that one of the novel genes isolated encoded the 84-kD ODF protein ODF2.</dc:description> <dc:description>By FISH, {3:Shao et al. (1998)} mapped the human ODF2 gene to chromosome 9q34.</dc:description> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:602133"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>PHOSPHORIBOSYLFORMYLGLYCINAMIDINE SYNTHASE; PFAS</dc:title> <dc:alternative>PHOSPHORIBOSYLFORMYLGLYCINAMIDE AMIDOTRANSFERASE; FGARAT</dc:alternative> <dc:description>The human GARS-AIRS-GART locus ({138440}), located on chromosome 21, encodes 3 of the 10 enzymatic steps necessary for the conversion of phosphoribosyl pyrophosphate to inosine monophosphate by the de novo purine pathway. The 3 enzyme activities are encoded in a linear, nonoverlapping fashion on the GARS-AIRS-GART mRNA, starting at the 5-prime end of the cDNA. These enzymatic activities catalyze the second, fifth, and third step of the de novo purine pathway, respectively. {1:Barnes et al. (1994)} purified and characterized the fourth enzyme in the pathway, phosphoribosylformylglycinamide amidotransferase (FGARAT; {EC 6.3.5.3}), which is encoded by a separate gene on chromosome 17. {2:Brodsky et al. (1997)} reported that, unlike the developmentally regulated expression of the GARS-AIRS-GART locus, expression of the FGARAT gene appears to be constitutive.</dc:description> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:602356"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>TNF RECEPTOR-ASSOCIATED FACTOR 5; TRAF5</dc:title> <dc:description>Tumor necrosis factor (TNF; {191160}) receptor-associated factors (TRAFs) are signal transducers for members of the TNF receptor superfamily (see {191190}). TRAF proteins are composed of an N-terminal cysteine/histidine-rich region containing zinc RING and/or zinc finger motifs, a coiled coil (leucine zipper) motif, and a homologous region in the C terminus that defines the TRAF family, the TRAF domain. The TRAF domain is involved in self-association and receptor binding. By degenerative oligonucleotide PCR amplification, {2:Nakano et al. (1996)} identified TRAF5 in the mouse and showed that its specifically interacts with the lymphotoxin-beta receptor ({600979}) and activates the transcription factor NF-kappa-B (see {164011}). {4:Nakano et al. (1997)} cloned the human TRAF homolog by cross hybridization with mouse TRAF5 cDNA. Their human cDNA of 2,894 bp has a 557-amino acid open reading frame that exhibits 77.5 and 80% identity to mouse TRAF5 at the nucleotide and amino acid levels, respectively. Northern blot analysis revealed that human TRAF5 mRNA is expressed in all visceral organs. Western blotting revealed that the human protein is abundantly expressed in a human follicular dendritic cell line, and to a lesser degree in several tumor cell lines.</dc:description> <dc:description>By in vitro binding, immunoprecipitation, immunoblot, and yeast 2-hybrid analyses, {1:Aizawa et al. (1997)} showed that TRAF2 ({601895}) and TRAF5 interact with overlapping but distinct sequences in the C-terminal region of CD30 ({153243}) and mediate the activation of NFKB.</dc:description> <dc:description>By interspecific backcross mapping, {4:Nakano et al. (1997)} showed that Traf5 is located in the distal region of mouse chromosome 1, which shares homology with human 1q. Fluorescence in situ hybridization confirmed the regional localization of human TRAF5 to chromosome 1q32.</dc:description> <dc:description>To investigate the functional role of Traf5 in vivo, {3:Nakano et al. (1999)} generated Traf5-deficient mice by gene targeting. They found that Traf5 -/- B lymphocytes show defects in proliferation and upregulation of various surface molecules, including CD23 ({151445}), CD54 ({147840}), CD80 ({112203}), CD86 ({601020}), and FAS ({134637}) in response to CD40 ({109535}) stimulation. Moreover, in vitro Ig production by Traf5 -/- T lymphocytes stimulated with anti-CD40 plus IL4 ({147780}) was reduced substantially. CD27-mediated costimulatory signal also was impaired in Traf5 -/- T lymphocytes. Collectively, these results demonstrated that Traf5 is involved in CD40- and CD27-mediated signaling.</dc:description> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:602505"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>PAXILLIN; PXN</dc:title> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:602704"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>MOUSE DOUBLE MINUTE 4 HOMOLOG; MDM4</dc:title> <dc:alternative>p53-BINDING PROTEIN MDM4</dc:alternative> <dc:alternative>MDMX</dc:alternative> <dc:alternative>HDMX</dc:alternative> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:603120"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>QUIESCIN Q6; QSCN6</dc:title> <dc:alternative>Q6</dc:alternative> <dc:description>Control of growth is mediated in part at the level of the transition by cells into and out of quiescence (G0). To identify genes that might play a role in the transition into quiescence and for its maintenance, {1:Coppock et al. (1993)} isolated human embryo lung fibroblast cDNAs that were expressed at a higher level in quiescent cells than in logarithmically growing cells. Several partial cDNAs corresponded to a gene that was designated Q6. Northern blot analysis revealed that Q6 is expressed as 3- and 4-kb mRNAs in embryo lung fibroblasts.</dc:description> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:603326"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>PROTEIN PHOSPHATASE 1, REGULATORY SUBUNIT 3D; PPP1R3D</dc:title> <dc:alternative>PROTEIN PHOSPHATASE 1, REGULATORY SUBUNIT 6; PPP1R6</dc:alternative> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:603833"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>NADH-UBIQUINONE OXIDOREDUCTASE 1 ALPHA SUBCOMPLEX, 4; NDUFA4</dc:title> <dc:description>The multisubunit NADH:ubiquinone oxidoreductase (complex I) is the first enzyme complex in the electron transport chain of mitochondria. See NDUFA2 ({602137}). {1:Kim et al. (1997)} isolated a human fetal liver cDNA encoding the human homolog of the bovine MLRQ subunit of complex I. The deduced 81-amino acid human MLRQ protein has a calculated molecular weight of approximately 9 kD. Human MLRQ shares 88% amino acid identity with bovine and mouse MLRQ. The hydrophobicity profile indicates the presence of a potential membrane-spanning sequence, suggesting that MLRQ is anchored into the inner mitochondrial membrane. Northern blot analysis revealed that the 0.7-kb MLRQ mRNA was expressed in all human tissues and cell lines tested. The highest expression levels were observed in heart, skeletal muscle, and brain.</dc:description> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:604275"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>CATENIN, DELTA-2; CTNND2</dc:title> <dc:alternative>NEURAL PLAKOPHILIN-RELATED ARMADILLO-REPEAT PROTEIN; NPRAP</dc:alternative> <dc:description>Armadillo-like proteins are characterized by a series of armadillo repeats, first defined in the Drosophila 'armadillo' gene product, that are typically 42 to 45 amino acids long. These proteins can be divided into subfamilies based on the number of repeats, their overall sequence similarity, and the dispersion of the repeats throughout their sequences. Members of the p120(ctn)/plakophilin subfamily of Armadillo-like proteins, including CTNND1 ({601045}), CTNND2, PKP1 ({601975}), PKP2 ({602861}), PKP4 ({604276}), and ARVCF ({602269}), have 10 armadillo repeats each.</dc:description> <dc:description>In a search for proteins with sequence homology to PKP1, {3:Paffenholz and Franke (1997)} identified a human cDNA with 45% amino acid identity to PKP1 in a segment within the armadillo (arm) repeat units. Antibodies raised against the arm repeat region recognized 2 polypeptide bands of approximately 150 and 160 kD in immunoblots of mouse brain and a weak band of approximately 160 kD in mouse skeletal muscle and pancreas. The authors, therefore, named the protein NPRAP for 'neural plakophilin-related arm-repeat protein.' {3:Paffenholz and Franke (1997)} isolated 2 partial human cDNA clones from a human fetal brain cDNA library. The longer displays 91% identity to the complete mouse cDNA. Northern blot analysis of a number of human and bovine cell lines and tissues detected CTNND2 expression as 5- and 6-kb transcripts only in human fetal brain RNA.</dc:description> <dc:description>In a yeast 2-hybrid screen to identify proteins interacting with PS1 ({104311}), a gene commonly mutated in 1 form of early-onset Alzheimer disease (AD3; {607822}), {4:Zhou et al. (1997)} identified the CTNND2 protein in an adult human brain expression library. The assembled protein sequence is 69.3% identical to that of PKP4.</dc:description> <dc:description>By FISH and analysis of a somatic cell hybrid mapping panel, {1:Bonne et al. (1998)} mapped the CTNND2 gene to 5p15.</dc:description> <dc:description>{2:Medina et al. (2000)} studied the location of the CTNND2 gene within the critical region for cri-du-chat syndrome ({123450}). By determining its presence or absence in hemizygous form in deletions of various sizes, they established its location in 5p15.2 and found a strong correlation between the hemizygous loss of delta-catenin and severe mental retardation. These findings and the property of delta-catenin as a neuronal-specific protein, expressed early in development and involved in cell motility, supported its role in the mental retardation of cri-du-chat syndrome when present in only one copy.</dc:description> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:607100"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>NEPHROCYSTIN; NPHP1</dc:title> </rdf:Description>

<rdf:Description rdf:about="urn:lsid:uniprot.org:omim:608071"> <rdf:Type rdf:resource="urn:lsid:uniprot.org:ontology:Omim"/> <dc:title>SHFM3 GENE; SHFM3</dc:title> <dc:alternative>DACTYLIN</dc:alternative> <dc:alternative>DACTYLAPLASIA, MOUSE, HOMOLOG OF</dc:alternative> <dc:alternative>DAC, MOUSE, HOMOLOG OF</dc:alternative> <dc:alternative>F-BOX AND WD40 DOMAIN PROTEIN 4; FBXW4; FBW4; FBWD4</dc:alternative> </rdf:Description> </rdf:RDF>