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Gene Section
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TRIM37 (tripartite motif-containing 37)
Ayse Elif Erson, Elizabeth M Petty
Biology Department, Room: 141, Middle East Technical University, Ankara 06531, Turkey (AEE);
Departments of Human Genetics and Internal Medicine, University of Michigan Medical School, Ann Arbor,
MI 48109, USA (EMP)
Published in Atlas Database: June 2006
Online updated version: http://AtlasGeneticsOncology.org/Genes/TRIM37ID42703ch17q23.html
DOI: 10.4267/2042/38349
This work is licensed under a Creative Commons Attribution-Non-commercial-No Derivative Works 2.0 France Licence.
© 2006 Atlas of Genetics and Cytogenetics in Oncology and Haematology
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 multitissue 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,
Identity
Hugo: TRIM37
Other names: MUL; KIAA0898; POB1; TEF3
Location: 17q23.2
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 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.
Atlas Genet Cytogenet Oncol Haematol. 2006;10(4)
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TRIM37 (tripartite motif-containing 37)
Erson AE, Petty EM
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.
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 postpubertal 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.
Pseudogene
Localisation
There are no reported pseudogenes of TRIM37.
Peroxisome.
Protein
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.
Description
TRIM37 has 964 amino acids with a predicted
molecular weight of 108 kDa. 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 below.
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.
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
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)- HX(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.
Atlas Genet Cytogenet Oncol Haematol. 2006;10(4)
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TRIM37 (tripartite motif-containing 37)
Erson AE, Petty EM
9. c.1411C>T: This mutation detected in TunusianGerman 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 SaudiArabian patient is predicted to generate a truncated 686
aa protein.
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.
Atlas Genet Cytogenet Oncol Haematol. 2006;10(4)
Implicated in
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
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