|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:
|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.|
|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.
|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.
|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.
|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|
|HGNC (Hugo)||TRIM37 7523|
|Entrez_Gene (NCBI)||TRIM37 4591 tripartite motif containing 37|
|Ensembl (Hinxton)||ENSG00000108395 [Gene_View] chr17:57060000-57184266 [Contig_View] TRIM37 [Vega]|
|SOURCE (Princeton)||NM_001005207 NM_015294|
|Genomic and cartography|
|GoldenPath (UCSC)||TRIM37 - 17q22 chr17:57060000-57184266 - 17q [Description] (hg19-Feb_2009)|
|Ensembl||TRIM37 - 17q [CytoView]|
|Mapping of homologs : NCBI||TRIM37 [Mapview]|
|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 : Unigene||Hs.579079 [ NCBI ]|
|Alternative Splicing : Fast-db (Paris)||GSHG0013611|
|Alternative Splicing Gallery||ENSG00000108395|
|Gene Expression||TRIM37 [ NCBI-GEO ] TRIM37 [ SEEK ] TRIM37 [ MEM ]|
|Protein : pattern, domain, 3D structure|
|With graphics : InterPro||O94972|
|Splice isoforms : SwissVar||O94972 (Swissvar)|
|Catalytic activity : Enzyme||6.3.2.- [ 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 MATH TRAF-like Znf_B-box Znf_RING Znf_RING/FYVE/PHD|
|Related proteins : CluSTr||O94972|
|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 mutations||4591|
|Human Protein Atlas||ENSG00000108395|
|IPI||IPI00016619 IPI00479325 IPI00872140|
|Protein Interaction databases|
|Ontologies - Pathways|
|Ontology : AmiGO||ubiquitin-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-EBI||ubiquitin-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 : KEGG||Ubiquitin mediated proteolysis|
|REACTOME Pathways||REACT_6900 Immune System [pathway]|
|Protein Interaction Database||TRIM37|
|Gene fusion - rearrangments|
|Polymorphisms : SNP, mutations, diseases|
|SNP Single Nucleotide Polymorphism (NCBI)||TRIM37|
|SNP (GeneSNP Utah)||TRIM37|
|SNP : HGBase||TRIM37|
|Genetic variants : HAPMAP||TRIM37|
|CONAN: Copy Number Analysis||TRIM37|
|Somatic Mutations in Cancer : COSMIC||TRIM37|
|LOVD (Leiden Open Variation Database)||Whole genome datasets|
|LOVD (Leiden Open Variation Database)||LOVD - Leiden Open Variation Database|
|LOVD (Leiden Open Variation Database)||LOVD 3.0 shared installation|
|Mutations and Diseases : HGMD||TRIM37|
|Disease Genetic Association||TRIM37|
|Huge Navigator||TRIM37 [HugePedia] TRIM37 [HugeCancerGEM]|
|Genomic Variants||TRIM37 TRIM37 [DGVbeta]|
|snp3D : Map Gene to Disease||4591|
|Homologs : HomoloGene||TRIM37|
|Homology/Alignments : Family Browser (UCSC)||TRIM37|
|Phylogenetic Trees/Animal Genes : TreeFam||TRIM37|
|Chemical/Protein Interactions : CTD||4591|
|Chemical/Pharm GKB Gene||PA35497|
|Cancer Resource (Charite)||ENSG00000108395|
|PubMed||36 Pubmed reference(s) in Entrez|
|BLAST 2 Sequences, a new tool for comparing protein and nucleotide sequences.|
|Tatusova TA, Madden TL|
|FEMS microbiology letters. 1999 ; 174 (2) : 247-250.|
|Gene encoding a new RING-B-box-Coiled-coil protein is mutated in mulibrey nanism.|
|Avela K, Lipsanen-Nyman M, Idˆ§nheimo N, Seemanovˆ° E, Rosengren S, Mˆ§kelˆ§ TP, Perheentupa J, Chapelle AD, Lehesjoki AE|
|Nature genetics. 2000 ; 25 (3) : 298-301.|
|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.|
|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.|
|PML protein isoforms and the RBCC/TRIM motif.|
|Jensen K, Shiels C, Freemont PS|
|Oncogene. 2001 ; 20 (49) : 7223-7233.|
|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.|
|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.|
|The TRIM37 gene encodes a peroxisomal RING-B-box-coiled-coil protein: classification of mulibrey nanism as a new peroxisomal disorder.|
|Kallijˆ§rvi J, Avela K, Lipsanen-Nyman M, Ulmanen I, Lehesjoki AE|
|American journal of human genetics. 2002 ; 70 (5) : 1215-1228.|
|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.|
|Novel mutations in the TRIM37 gene in Mulibrey Nanism.|
|Hˆ§mˆ§lˆ§inen RH, Avela K, Lambert JA, Kallijˆ§rvi J, Eyaid W, Gronau J, Ignaszewski AP, McFadden D, Sorge G, Lipsanen-Nyman M, Lehesjoki AE|
|Human mutation. 2004 ; 23 (5) : page 522.|
|Mulibrey nanism: clinical features and diagnostic criteria.|
|Karlberg N, Jalanko H, Perheentupa J, Lipsanen-Nyman M|
|Journal of medical genetics. 2004 ; 41 (2) : 92-98.|
|TRIM37 defective in mulibrey nanism is a novel RING finger ubiquitin E3 ligase.|
|Kallijˆ§rvi J, Lahtinen U, Hˆ§mˆ§lˆ§inen R, Lipsanen-Nyman M, Palvimo JJ, Lehesjoki AE|
|Experimental cell research. 2005 ; 308 (1) : 146-155.|
|Insulin resistance syndrome in subjects with mutated RING finger protein TRIM37.|
|Karlberg N, Jalanko H, Kallijˆ§rvi J, Lehesjoki AE, Lipsanen-Nyman M|
|Diabetes. 2005 ; 54 (12) : 3577-3581.|
|Characterisation of the mulibrey nanism-associated TRIM37 gene: transcription initiation, promoter region and alternative splicing.|
|Hˆ§mˆ§lˆ§inen RH, Joensuu T, Kallijˆ§rvi J, Lehesjoki AE|
|Gene. 2006 ; 366 (1) : 180-188.|
|Tissue expression of the mulibrey nanism-associated Trim37 protein in embryonic and adult mouse tissues.|
|Kallijˆ§rvi J, Hˆ§mˆ§lˆ§inen RH, Karlberg N, Sainio K, Lehesjoki AE|
|Histochemistry and cell biology. 2006 ; 126 (3) : 325-334.|
|REVIEW articles||automatic search in PubMed|
|Last year publications||automatic search in PubMed|
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|Written||06-2006||Elif Ayse Erson,.M Elizabeth Petty|
|Biology Department, Room: 141, Middle East Technical University, Ankara 06531, TURKEY|
|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|
|© Atlas of Genetics and Cytogenetics in Oncology and Haematology||indexed on : Sat Nov 8 16:54:42 CET 2014|
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