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TRIM37 (tripartite motif-containing 37)

Written2006-06Elif Ayse Erson,.M Elizabeth Petty
Biology Department, Room: 141, Middle East Technical University, Ankara 06531, TURKEY

(Note : for Links provided by Atlas : click)

Identity

Alias_namesMUL
tripartite motif-containing 37
Alias_symbol (synonym)KIAA0898
POB1
TEF3
Other alias
HGNC (Hugo) TRIM37
LocusID (NCBI) 4591
Atlas_Id 42703
Location 17q22  [Link to chromosome band 17q22]
Location_base_pair Starts at 58998200 and ends at 59106964 bp from pter ( according to hg19-Feb_2009)  [Mapping TRIM37.png]
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
  • Fusion genes
    (updated 2017)
    Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
    ERBB3 (12q13.2) / TRIM37 (17q22)PPM1D (17q23.2) / TRIM37 (17q22)RNF121 (11q13.4) / TRIM37 (17q22)
    TRIM37 (17q22) / MYO19 (17q12)TRIM37 (17q22) / PCTP (17q22)TRIM37 (17q22) / RNFT1 (17q23.1)
    TRIM37 (17q22) / SKA2 (17q22)TRIM37 (17q22) / TUBD1 (17q23.1)TRIM37 (17q22) / VMP1 (17q23.1)

    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 3' 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 "TRIM37adel23" 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 "Finmajor" 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 "Finminor" 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 "Czech" 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 "American" 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.855 1G>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.1045 1047 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

    Note
      
    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 Wilm's 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 Wilm's tumor also suggests that this gene is involved in oncogeneisis
      

    Bibliography

    Gene encoding a new RING-B-box-Coiled-coil protein is mutated in mulibrey nanism.
    Avela K, Lipsanen-Nyman M, Idänheimo N, Seemanov´ E, Rosengren S, Mäkelä TP, Perheentupa J, Chapelle AD, Lehesjoki AE
    Nature genetics. 2000 ; 25 (3) : 298-301.
    PMID 10888877
     
    Overexpressed genes/ESTs and characterization of distinct amplicons on 17q23 in breast cancer cells.
    Erson AE, Niell BL, DeMers SK, Rouillard JM, Hanash SM, Petty EM
    Neoplasia (New York, N.Y.). 2001 ; 3 (6) : 521-526.
    PMID 11774034
     
    Characterisation of the mulibrey nanism-associated TRIM37 gene: transcription initiation, promoter region and alternative splicing.
    Hämä RH, Joensuu T, Kallijärvi J, Lehesjoki AE
    Gene. 2006 ; 366 (1) : 180-188.
    PMID 16310976
     
    A novel splice site mutation in the TRIM37 gene causes mulibrey nanism in a Turkish family with phenotypic heterogeneity.
    Jagiello P, Hammans C, Wieczorek S, Arning L, Stefanski A, Strehl H, Epplen JT, Gencik M
    Human mutation. 2003 ; 21 (6) : 630-635.
    PMID 12754710
     
    PML protein isoforms and the RBCC/TRIM motif.
    Jensen K, Shiels C, Freemont PS
    Oncogene. 2001 ; 20 (49) : 7223-7233.
    PMID 11704850
     
    Tissue expression of the mulibrey nanism-associated Trim37 protein in embryonic and adult mouse tissues.
    Kallijärvi J, Hämälä RH, Karlberg N, Sainio K, Lehesjoki AE
    Histochemistry and cell biology. 2006 ; 126 (3) : 325-334.
    PMID 16514549
     
    Insulin resistance syndrome in subjects with mutated RING finger protein TRIM37.
    Karlberg N, Jalanko H, Kallijärvi J, Lehesjoki AE, Lipsanen-Nyman M
    Diabetes. 2005 ; 54 (12) : 3577-3581.
    PMID 16306379
     
    Expression of MUL, a gene encoding a novel RBCC family ring-finger protein, in human and mouse embryogenesis.
    Lehesjoki AE, Reed VA, Mark Gardiner R, Greene ND
    Mechanisms of development. 2001 ; 108 (1-2) : 221-225.
    PMID 11578880
     
    Comprehensive copy number and gene expression profiling of the 17q23 amplicon in human breast cancer.
    Monni O, Barlund M, Mousses S, Kononen J, Sauter G, Heiskanen M, Paavola P, Avela K, Chen Y, Bittner ML, Kallioniemi A
    Proceedings of the National Academy of Sciences of the United States of America. 2001 ; 98 (10) : 5711-5716.
    PMID 11331760
     
    BLAST 2 Sequences, a new tool for comparing protein and nucleotide sequences.
    Tatusova TA, Madden TL
    FEMS microbiology letters. 1999 ; 174 (2) : 247-250.
    PMID 10339815
     
    A diverse family of proteins containing tumor necrosis factor receptor-associated factor domains.
    Zapata JM, Pawlowski K, Haas E, Ware CF, Godzik A, Reed JC
    The Journal of biological chemistry. 2001 ; 276 (26) : 24242-24252.
    PMID 11279055
     

    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 journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Genes/TRIM37ID42703ch17q23.html


    Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 5 ]

    Solid Tumors TT_t1117q13q22ID100984 TT_t1717q22q23ID102684 TT_t1717q22q23ID102692 TT_t1717q22q23ID102693 TT_t1717q22q23ID102694


    Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 1 ]
      Mulibrey nanism


    External links

    Nomenclature
    HGNC (Hugo)TRIM37   7523
    Cards
    AtlasTRIM37ID42703ch17q23
    Entrez_Gene (NCBI)TRIM37  4591  tripartite motif containing 37
    AliasesMUL; POB1; TEF3
    GeneCards (Weizmann)TRIM37
    Ensembl hg19 (Hinxton)ENSG00000108395 [Gene_View]
    Ensembl hg38 (Hinxton)ENSG00000108395 [Gene_View]  ENSG00000108395 [Sequence]  chr17:58998200-59106964 [Contig_View]  TRIM37 [Vega]
    ICGC DataPortalENSG00000108395
    TCGA cBioPortalTRIM37
    AceView (NCBI)TRIM37
    Genatlas (Paris)TRIM37
    WikiGenes4591
    SOURCE (Princeton)TRIM37
    Genetics Home Reference (NIH)TRIM37
    Genomic and cartography
    GoldenPath hg38 (UCSC)TRIM37  -     chr17:58998200-59106964 -  17q22   [Description]    (hg38-Dec_2013)
    GoldenPath hg19 (UCSC)TRIM37  -     17q22   [Description]    (hg19-Feb_2009)
    GoldenPathTRIM37 - 17q22 [CytoView hg19]  TRIM37 - 17q22 [CytoView hg38]
    ImmunoBaseENSG00000108395
    Mapping of homologs : NCBITRIM37 [Mapview hg19]  TRIM37 [Mapview hg38]
    OMIM253250   605073   
    Gene and transcription
    Genbank (Entrez)AB020705 AF213365 AI307801 AI610736 AK022701
    RefSeq transcript (Entrez)NM_001005207 NM_001320987 NM_001320988 NM_001320989 NM_001320990 NM_001353082 NM_001353083 NM_001353084 NM_001353085 NM_001353086 NM_015294
    RefSeq genomic (Entrez)
    Consensus coding sequences : CCDS (NCBI)TRIM37
    Alternative Splicing GalleryENSG00000108395
    Gene ExpressionTRIM37 [ NCBI-GEO ]   TRIM37 [ EBI - ARRAY_EXPRESS ]   TRIM37 [ SEEK ]   TRIM37 [ MEM ]
    Gene Expression Viewer (FireBrowse)TRIM37 [ Firebrowse - Broad ]
    SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
    BioGPS (Tissue expression)4591
    GTEX Portal (Tissue expression)TRIM37
    Human Protein AtlasENSG00000108395-TRIM37 [pathology]   [cell]   [tissue]
    Protein : pattern, domain, 3D structure
    Domain families : Pfam (Sanger)
    Domain families : Pfam (NCBI)
    Conserved Domain (NCBI)TRIM37
    DMDM Disease mutations4591
    Blocks (Seattle)TRIM37
    Human Protein Atlas [tissue]ENSG00000108395-TRIM37 [tissue]
    HPRD05463
    IPIIPI00016619   IPI00479325   IPI00872140   
    Protein Interaction databases
    FunCoupENSG00000108395
    BioGRIDTRIM37
    STRING (EMBL)TRIM37
    ZODIACTRIM37
    Ontologies - Pathways
    Huge Navigator TRIM37 [HugePedia]
    snp3D : Map Gene to Disease4591
    BioCentury BCIQTRIM37
    ClinGenTRIM37
    Clinical trials, drugs, therapy
    Chemical/Protein Interactions : CTD4591
    Chemical/Pharm GKB GenePA35497
    Clinical trialTRIM37
    Miscellaneous
    canSAR (ICR)TRIM37 (select the gene name)
    DataMed IndexTRIM37
    Probes
    Litterature
    PubMed63 Pubmed reference(s) in Entrez
    GeneRIFsGene References Into Functions (Entrez)
    CoreMineTRIM37
    EVEXTRIM37
    GoPubMedTRIM37
    iHOPTRIM37
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

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    indexed on : Wed Feb 19 16:26:28 CET 2020

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