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TRIM37 (tripartite motif-containing 37)

Identity

Other namesMUL
KIAA0898
POB1
TEF3
HGNC (Hugo) TRIM37
LocusID (NCBI) 4591
Location 17q22
Location_base_pair Starts at 57060000 and ends at 57184266 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order Genes flanking TRIM37 oriented from centromere to telomere on 17q23 are:
  • RAD51C, 17q22-q23, D51 homolog C (S. Cerevisiae)
  • PPM1E, 17q23.2, protein phosphatase 1E (PP2C domain containing)
  • TRIM37, 17q22-q23, tripartite motif-containing 37
  • FAM33A 17q23.2, family with sequence similarity 33, member A
  • PRR11(FLJ11029) 17q23.2, proline rich 11
  • DNA/RNA

    Description The TRIM37 gene spans 106.9 kb. Promoter prediction and reporter constructs suggest the presence of elements sufficient for strong basal activity between -591 and -246 relative to the translation initiation site. This region is GC rich (70%) and TATA-less.
    Transcription RIM37 has two major well-described transcript variants: TRIM37a (4488 bp, 24 exons) and TRIM37b (3588 bp, 25 exons). The cDNA and genomic DNA alignments and boundaries of exons are determined by the mRNA-to-genomic alignment tool Spidey.
    Both of these variants encode an identical protein product but they use different termination codons and have different 3¹ untranslated sequences. In the first transcript, all of the exon 24 sequence is included, whereas in the second one, only the first 79 nucleotides of exon 24 are included followed by nucleotides of exon 25, resulting in a shorter transcript.
    A third ³TRIM37adel23² transcript is detected as an alternatively spliced transcript of TRIM37a. This transcript lacks exon 23 (only 117 bp) with an in frame deletion of 39 amino acids that span the evolutionarily conserved DES (aspartate-glutamate-serine) rich motif at the C-terminus.
    A 4.4 kb band representing the full-length transcript of TRIM37 is detected in RNA representing brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, ovary, small intestine, colon and leukocyte samples by hybridization of several PCR-generated TRIM37 cDNA probes on a multi-tissue Northern blot. In addition, a strong signal of 3.9 kb is detected in the testis sample and a 2.6 kb band is noted in the heart sample.

    In situ hybridization suggests TRIM37 expression patterns in multiple tissues during mouse and human embryogenesis. No Trim37 expression is detected up to E9.5. At E11.5, Trim37 expression is detected in cells lining the esophagus and bronchias well as the innermost cells of the optic cup adjacent to the lens. Between E12.5 and E14.5, TRIM37 is detected in different parts of ganglia and throughout liver. Intense expression is seen in gut epithelium of the midgut, stomach, esophagus and in the primitive seminiferous tubules of the developing testis at E14.5. Expression is also evident in the olfactory epithelium, epithelial lining of the bronchioles, surface ectoderm and in the developing eye lens epithelium, neural layer of the retina (but not in the optic nerve), epithelium of developing nephron, mesonephric duct, and epithelial pancreas cells. Similar to the E14.5 mouse, in 7 week old human embryos, TRIM37 expression can be detected in similar tissues including dorsal root ganglia, liver, submandibular gland and epithelial lining of the gut lumen. At 10 weeks, intense TRIM37 expression can be detected in dorsal root and trigeminal ganglia, epithelia in multiple tissues and liver. However, no TRIM37 transcript can be detected in migrating neural crest cells.

    In another study, TaqMan PCR results suggest expression of TRIM37a and TRIM37b to be the highest in testis. In the brain, TRIM37a expression is 15-fold higher in adult and 20-fold higher in fetal tissue compared to the expression in heart as a reference. The lowest TRIM37a expression is detected in skeletal muscle with 0.3 and 0.8 times the expression of heart in adult and in fetal tissues.

    Pseudogene There are no reported pseudogenes of TRIM37.

    Protein

     
     
  • RING (14th-58th aa) : RING-finger (Really Interesting New Gene) domain that has the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48) C-X2-C. This domain is believed to be involved in mediating protein-protein interactions and also found in ubiquitin ligases. Ubiquitin ligases attach ubiquitin to target proteins during a cascade of enzymatic reactions. RING finger domains are present in a variety of proteins (e.g. Anaphase promoting complex, APC, Cbl family proteins, MDM2) implicated in cancer.
  • Zf-B Box (90th-132th aa) : B-box zinc finger. Function is largely unknown.
  • BBC (132th-254th aa) : B-Box C-terminal domain; Coiled coil region C-terminal to (some) B-Box domains.
  • MATH (278th-403th aa) : Meprin and TRAF-C homology domains. Meprins are extracellular membrane metalloproteases that can cleave biologically active peptides, growth factors, extracellular matrix proteins, etc. Math domains can form hetero- and homo-oligomeric enzymes formed from dimers of disulfide-linked dimers. TRAFs are adapter proteins that link cell surface receptors (Tumor Necrosis Factor like) to downstream kinases during activation of transcription factors and regulation of cell survival, growth and stress response in the immune and inflammatory systems.
  • In addition, a nuclear coil localization signal (NLS) and two aspartate-glutamate serine (DES) rich sequences at the C terminus are found.
  • Description TRIM37 has 964 amino acids with a predicted molecular weight of 108kDa. TRIM37 antibodies (against an internal (490-513) region and a C terminal (942-964) region) recognize a 130 kDa band in TRIM37 transfected COS-1 cells. TRIM37 has the following domains 5. See above.
    Expression In mouse embryonic tissues, Trim37 protein is detected in epithelia of ducts of developing pancreas, of the midgut and in nasal epithelium. In adult mice, Trim37 immunoreactivity is detected in central and peripheral nervous systems, including retina, enteric ganglia and the adrenal medulla and in subset of cells in the adenohypophysis (endocrine part of the pituitary gland).

    In post-pubertal testis, a stage-specific cytoplasmic Trim37 staining of germ cells can be detected. Developing sperm from type B spermatogonia to early round spermatids show immunoreactivity. In post-pubertal ovary, intense Trim37 staining is observed in maturing oocytes as well as in the granulosa cells, luteal gland, and in the epithelium of the fallopian tubes.

    Localisation peroxisome
    Function Evidence suggest that TRIM37 can auto ubiquitinate itself and therefore is believed to function as an E3 ubiquitin ligase due to its RING domain that is found in ubiquitin ligases.
    Homology H.sapiens , TRIM37 tripartite motif-containing 37, 964 aa.
    P.troglodytes , LOC455163 similar to POB1, 705 aa.
    C.familiaris , LOC480575 similar to tripartite motif protein 37, 962 aa.
    M.musculus , Trim37 tripartite motif protein 37, 961 aa.
    R.norvegicus , Trim37_predicted, 1075 aa.
    G.gallus , TRIM37, 983 aa.
    A.gambiae , ENSANGG00000009789, 153 aa.

    Mutations

    Germinal 1. c.493-497 : This ³Finmajor² mutation co-segregates with the Finnish ancestral MUL haplotype. Finmajor mutation is found in 98 of 100 Finnish MUL chromosomes. This mutation is a 5-bp deletion at nucleotides 493-497 of the TRIM37 cDNA. Sequencing of genomic DNA suggets an A-to-G transition altering the consensus dinucleotide sequence of the 3' splice site (AG) at position c.493_2 and this results in aberrant splicing at the next AG site. The cDNA deletion causes a frameshift and predicts a stop codon ten codons downstream. This mutation is predicted to generate a truncated 174 aa protein.

    2. c.2212delG : This ³Finminor² mutation is a 1-bp deletion of a G at nucleotide c.2212 and results in a frameshift that predicts a stop codon 30 codons downstream. Finminor is found to be associated with a distinct haplotype that is found in 2 of 100 Finnish MUL chromosomes. This mutation is predicted to generate a truncated 767 aa protein. Two patients were found to be compound heterozygotes for the Finmajor and Finminor mutations.

    3. c.838delACTTT : This homozygous ³Czech² mutation found in a Czech patient is a 5-bp deletion of ACTTT at nucleotides c.838_842 leading to a frameshift that results in a stop codon 55 codons downstream. This mutation is predicted to generate a truncated 334 aa protein.

    4. c.134insA : this ³American² mutation is a homozygous 1-bp insertion of an A nucleotide after c.1346 in an American patient. The mutation disrupts the reading frame and results in a stop codon eight codons downstream. This mutation is predicted to generate a truncated 334 aa protein.

    5. c.855_862delTGAATTAG : This mutation detected in a Turkish family is an 8-bp deletion. On the genomic level, aberrant splicing was implicated due to a transition at the splice acceptor (AG) at position c.855­1G>A. A cryptic splice site (AG, c.860) 8-bp downstream is activated, which leads to disruption of the open reading frame (ORF) through a premature stop codon (PTC, TGA) at position c.1045­1047 that translates into a truncated protein.

    6. c.745C>T : This mutation detected in a Canadian patient is predicted to generate a truncated 249 aa protein.

    7. c.965G>T : This mutation detected in a Canadian patient is predicted to generate a missense amino acid at the 322th position (Gly322Val).

    8. c.1037_1040dupAGAT : This mutation detected in a Canadian patient is a four base-pair duplication in exon 13. It is predicted to generate a frame-shift at amino acid position 347, and truncation of the protein product after seven code-shifted amino acids.

    9. c.1411C>T : This mutation detected in Tunusian-German and Canadian patients is predicted to generate a truncated 471 aa protein.

    10. c.1314+507_1668-207del : This mutation detected in a Sicilian patient is predicted to generate a genomic deletion of 8603 bp with break points in introns 14 and 16 (c.1314+507_1668-207del), thus deleting exons 15 and 16. At the protein level this mutation leads to a frame-shift at 439th aa and truncation of the protein product after four code-shifted amino acids.

    11. c.2056C>T : This mutation detected in a Saudi-Arabian patient is predicted to generate a truncated 686 aa protein.

    Implicated in

    Entity Mulibrey nanism(MUL)
    Disease Mutations of TRIM37 have been linked to Mulibrey nanism (MUL): muscle-liver-brain-eye nanism. MUL is a rare autosomal recessively inherited disorder that is characterized by severe growth failure with prenatal onset, constrictive pericardium, hepatomegaly and characteristic dysmorphic features. Four percent of MUL patients develop Wilm¹s tumors.
    Oncogenesis The role(s) of TRIM37 has not been established for oncogenesis. Evidence suggests amplification and overexpression of TRIM37 in breast cancer cells as part of the 17q23 amplicon. The fact that 4% of the MUL patients develop Wilm¹s tumor also suggests that this gene is involved in oncogeneisis
      

    External links

    Nomenclature
    HGNC (Hugo)TRIM37   7523
    Cards
    AtlasTRIM37ID42703ch17q23
    Entrez_Gene (NCBI)TRIM37  4591  tripartite motif containing 37
    GeneCards (Weizmann)TRIM37
    Ensembl (Hinxton)ENSG00000108395 [Gene_View]  chr17:57060000-57184266 [Contig_View]  TRIM37 [Vega]
    ICGC DataPortalENSG00000108395
    cBioPortalTRIM37
    AceView (NCBI)TRIM37
    Genatlas (Paris)TRIM37
    WikiGenes4591
    SOURCE (Princeton)NM_001005207 NM_015294
    Genomic and cartography
    GoldenPath (UCSC)TRIM37  -  17q22   chr17:57060000-57184266 -  17q   [Description]    (hg19-Feb_2009)
    EnsemblTRIM37 - 17q [CytoView]
    Mapping of homologs : NCBITRIM37 [Mapview]
    OMIM253250   605073   
    Gene and transcription
    Genbank (Entrez)AB020705 AF213365 AI307801 AK022701 AK025648
    RefSeq transcript (Entrez)NM_001005207 NM_015294
    RefSeq genomic (Entrez)AC_000149 NC_000017 NC_018928 NG_009298 NT_010783 NW_001838448 NW_004929407
    Consensus coding sequences : CCDS (NCBI)TRIM37
    Cluster EST : UnigeneHs.579079 [ NCBI ]
    CGAP (NCI)Hs.579079
    Alternative Splicing : Fast-db (Paris)GSHG0013611
    Alternative Splicing GalleryENSG00000108395
    Gene ExpressionTRIM37 [ NCBI-GEO ]     TRIM37 [ SEEK ]   TRIM37 [ MEM ]
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtO94972 (Uniprot)
    NextProtO94972  [Medical]
    With graphics : InterProO94972
    Splice isoforms : SwissVarO94972 (Swissvar)
    Catalytic activity : Enzyme6.3.2.- [ Enzyme-Expasy ]   6.3.2.-6.3.2.- [ IntEnz-EBI ]   6.3.2.- [ BRENDA ]   6.3.2.- [ KEGG ]   
    Domaine pattern : Prosite (Expaxy)MATH (PS50144)    ZF_BBOX (PS50119)    ZF_RING_2 (PS50089)   
    Domains : Interpro (EBI)Bbox_C [organisation]   MATH [organisation]   TRAF-like [organisation]   Znf_B-box [organisation]   Znf_RING [organisation]   Znf_RING/FYVE/PHD [organisation]  
    Related proteins : CluSTrO94972
    Domain families : Pfam (Sanger)MATH (PF00917)    zf-B_box (PF00643)   
    Domain families : Pfam (NCBI)pfam00917    pfam00643   
    Domain families : Smart (EMBL)BBC (SM00502)  BBOX (SM00336)  MATH (SM00061)  RING (SM00184)  
    DMDM Disease mutations4591
    Blocks (Seattle)O94972
    PDB (SRS)3LRQ   
    PDB (PDBSum)3LRQ   
    PDB (IMB)3LRQ   
    PDB (RSDB)3LRQ   
    Human Protein AtlasENSG00000108395 [gene] [tissue] [antibody] [cell] [cancer]
    Peptide AtlasO94972
    HPRD05463
    IPIIPI00016619   IPI00479325   IPI00872140   
    Protein Interaction databases
    DIP (DOE-UCLA)O94972
    IntAct (EBI)O94972
    FunCoupENSG00000108395
    BioGRIDTRIM37
    InParanoidO94972
    Interologous Interaction database O94972
    IntegromeDBTRIM37
    STRING (EMBL)TRIM37
    Ontologies - Pathways
    Ontology : AmiGOubiquitin-protein transferase activity  tumor necrosis factor receptor binding  protein binding  cytoplasm  peroxisome  cytosol  zinc ion binding  aggresome  ligase activity  ubiquitin protein ligase binding  negative regulation of NF-kappaB transcription factor activity  protein homodimerization activity  negative regulation of centriole replication  perinuclear region of cytoplasm  positive regulation of sequence-specific DNA binding transcription factor activity  positive regulation of NF-kappaB transcription factor activity  protein autoubiquitination  aggresome assembly  
    Ontology : EGO-EBIubiquitin-protein transferase activity  tumor necrosis factor receptor binding  protein binding  cytoplasm  peroxisome  cytosol  zinc ion binding  aggresome  ligase activity  ubiquitin protein ligase binding  negative regulation of NF-kappaB transcription factor activity  protein homodimerization activity  negative regulation of centriole replication  perinuclear region of cytoplasm  positive regulation of sequence-specific DNA binding transcription factor activity  positive regulation of NF-kappaB transcription factor activity  protein autoubiquitination  aggresome assembly  
    Pathways : KEGGUbiquitin mediated proteolysis   
    Protein Interaction DatabaseTRIM37
    Wikipedia pathwaysTRIM37
    Gene fusion - rearrangments
    Polymorphisms : SNP, mutations, diseases
    SNP Single Nucleotide Polymorphism (NCBI)TRIM37
    snp3D : Map Gene to Disease4591
    SNP (GeneSNP Utah)TRIM37
    SNP : HGBaseTRIM37
    Genetic variants : HAPMAPTRIM37
    Exome VariantTRIM37
    1000_GenomesTRIM37 
    ICGC programENSG00000108395 
    Somatic Mutations in Cancer : COSMICTRIM37 
    CONAN: Copy Number AnalysisTRIM37 
    Mutations and Diseases : HGMDTRIM37
    Mutations and Diseases : intOGenTRIM37
    Genomic VariantsTRIM37  TRIM37 [DGVbeta]
    dbVarTRIM37
    ClinVarTRIM37
    Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
    Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
    Diseases
    OMIM253250    605073   
    MedgenTRIM37
    GENETestsTRIM37
    Disease Genetic AssociationTRIM37
    Huge Navigator TRIM37 [HugePedia]  TRIM37 [HugeCancerGEM]
    General knowledge
    Homologs : HomoloGeneTRIM37
    Homology/Alignments : Family Browser (UCSC)TRIM37
    Phylogenetic Trees/Animal Genes : TreeFamTRIM37
    Chemical/Protein Interactions : CTD4591
    Chemical/Pharm GKB GenePA35497
    Clinical trialTRIM37
    Cancer Resource (Charite)ENSG00000108395
    Other databases
    Probes
    Litterature
    PubMed36 Pubmed reference(s) in Entrez
    CoreMineTRIM37
    iHOPTRIM37
    OncoSearchTRIM37

    Bibliography

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    PMID 14757854
     
    TRIM37 defective in mulibrey nanism is a novel RING finger ubiquitin E3 ligase.
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    Contributor(s)

    Written06-2006Elif Ayse Erson,.M Elizabeth Petty
    Biology Department, Room: 141, Middle East Technical University, Ankara 06531, TURKEY

    Citation

    This paper should be referenced as such :
    Erson, AE ; Petty, EM
    TRIM37 (tripartite motif-containing 37)
    Atlas Genet Cytogenet Oncol Haematol. 2006;10(4):239-242.
    Free online version   Free pdf version   [Bibliographic record ]
    URL : http://AtlasGeneticsOncology.org/Genes/TRIM37ID42703ch17q23.html

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    indexed on : Mon Sep 22 18:25:09 CEST 2014

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