O94972 (TRI37_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 ubiquitin-protein ligase TRIM37
EC=6.3.2.-

Alternative name(s):
Mulibrey nanism protein
Tripartite motif-containing protein 37

Gene names

Name:	TRIM37
Synonyms:	KIAA0898, MUL, POB1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	964 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	E3 ubiquitin-protein ligase. Ref.8
Pathway	Protein modification; protein ubiquitination.
Subcellular location	Cytoplasm › perinuclear region. Peroxisome. Note: Found in vesicles of the peroxisome. Aggregates as aggresomes, a perinuclear region where certain misfolded or aggregated proteins are sequestered for proteasomal degradation. Ref.6 Ref.8
Tissue specificity	Ubiquitous. Ref.5
Post-translational modification	Auto-ubiquitinated.
Involvement in disease	Defects in TRIM37 are the cause of mulibrey nanism (MUL) [MIM:253250]; also known as muscle-liver-brain-eye nanism. MUL is an autosomal recessive disorder that involves several tissues of mesodermal origin, implying a defect in a highly pleiotropic gene. Characteristic features include severe growth failure of prenatal onset and constrictive pericardium with consequent hepatomegaly. In addition, muscle hypotonia, J-shaped sella turcica, yellowish dots in the ocular fundi, typical dysmorphic features and hypoplasia of various endocrine glands causing hormonal deficiency are common. Ref.5 Ref.7 Ref.8 Ref.10 Ref.11
Sequence similarities	Belongs to the TRIM/RBCC family. Contains 1 B box-type zinc finger. Contains 1 MATH domain. Contains 1 RING-type zinc finger.
Sequence caution	The sequence BAA74921.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm Peroxisome
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Cellular component	perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell peroxisome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ligase activity Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PRC1	O43663	3	EBI-741602,EBI-741137

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O94972-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O94972-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-122: Missing.
     899-937: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 964

964

E3 ubiquitin-protein ligase TRIM37

PRO_0000056254

Regions

Domain

276 – 403

128

MATH

Zinc finger

15 – 55

41

RING-type; degenerate

Zinc finger

90 – 132

43

B box-type

Coiled coil

132 – 234

103

Potential

Coiled coil

419 – 450

32

Potential

Coiled coil

673 – 700

28

Potential

Compositional bias

534 – 540

7

Poly-Ser

Compositional bias

578 – 581

4

Poly-Ala

Amino acid modifications

Modified residue

771

1

Phosphoserine Ref.9

Modified residue

773

1

Phosphoserine Ref.9

Natural variations

Alternative sequence

1 – 122

122

Missing in isoform 2.

VSP_011919

Alternative sequence

899 – 937

39

Missing in isoform 2.

VSP_011920

Natural variant

76

1

L → P in MUL; decreased ubiquitination and abolishes the formation of perinuclear aggregates. Ref.8

VAR_060217

Natural variant

108

1

T → A. Ref.4
Corresponds to variant rs17853504 [ dbSNP | Ensembl ].

VAR_060218

Natural variant

109

1

C → S in MUL; no effect on E3 ubiquitin-protein ligase activity. Ref.11

VAR_060219

Natural variant

322

1

G → V in MUL; no effect on ubiquitination but affects subcellular localization. Ref.8 Ref.10

VAR_060220

Natural variant

838

1

V → I.
Corresponds to variant rs7222388 [ dbSNP | Ensembl ].

VAR_052142

Experimental info

Mutagenesis

35 – 36

2

CC → SS: Reduces ubiquitination and abolishes the formation of perinuclear aggregates. Ref.8

Sequence conflict

624

1

D → A in AAL36460. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

964

Helix Strand Turn

Details...

Helix

1 – 12

12

Turn

16 – 18

3

Beta strand

23 – 27

5

Turn

29 – 31

3

Beta strand

34 – 36

3

Helix

37 – 46

10

Turn

52 – 54

3

Helix

60 – 62

3

Helix

69 – 79

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 23, 2004. Version 2. Checksum: C0F08D5A5DC3B5AC	FASTA	964	107,906
	10 20 30 40 50 60 MDEQSVESIA EVFRCFICME KLRDARLCPH CSKLCCFSCI RRWLTEQRAQ CPHCRAPLQL 70 80 90 100 110 120 RELVNCRWAE EVTQQLDTLQ LCSLTKHEEN EKDKCENHHE KLSVFCWTCK KCICHQCALW 130 140 150 160 170 180 GGMHGGHTFK PLAEIYEQHV TKVNEEVAKL RRRLMELISL VQEVERNVEA VRNAKDERVR 190 200 210 220 230 240 EIRNAVEMMI ARLDTQLKNK LITLMGQKTS LTQETELLES LLQEVEHQLR SCSKSELISK 250 260 270 280 290 300 SSEILMMFQQ VHRKPMASFV TTPVPPDFTS ELVPSYDSAT FVLENFSTLR QRADPVYSPP 310 320 330 340 350 360 LQVSGLCWRL KVYPDGNGVV RGYYLSVFLE LSAGLPETSK YEYRVEMVHQ SCNDPTKNII 370 380 390 400 410 420 REFASDFEVG ECWGYNRFFR LDLLANEGYL NPQNDTVILR FQVRSPTFFQ KSRDQHWYIT 430 440 450 460 470 480 QLEAAQTSYI QQINNLKERL TIELSRTQKS RDLSPPDNHL SPQNDDALET RAKKSACSDM 490 500 510 520 530 540 LLEGGPTTAS VREAKEDEED EEKIQNEDYH HELSDGDLDL DLVYEDEVNQ LDGSSSSASS 550 560 570 580 590 600 TATSNTEEND IDEETMSGEN DVEYNNMELE EGELMEDAAA AGPAGSSHGY VGSSSRISRR 610 620 630 640 650 660 THLCSAATSS LLDIDPLILI HLLDLKDRSS IENLWGLQPR PPASLLQPTA SYSRKDKDQR 670 680 690 700 710 720 KQQAMWRVPS DLKMLKRLKT QMAEVRCMKT DVKNTLSEIK SSSAASGDMQ TSLFSADQAA 730 740 750 760 770 780 LAACGTENSG RLQDLGMELL AKSSVANCYI RNSTNKKSNS PKPARSSVAG SLSLRRAVDP 790 800 810 820 830 840 GENSRSKGDC QTLSEGSPGS SQSGSRHSSP RALIHGSIGD ILPKTEDRQC KALDSDAVVV 850 860 870 880 890 900 AVFSGLPAVE KRRKMVTLGA NAKGGHLEGL QMTDLENNSE TGELQPVLPE GASAAPEEGM 910 920 930 940 950 960 SSDSDIECDT ENEEQEEHTS VGGFHDSFMV MTQPPDEDTH SSFPDGEQIG PEDLSFNTDE NSGR
	Isoform 2 [UniParc]. Checksum: 43486E1064478477	FASTA	803	89,186
	10 20 30 40 50 60 MHGGHTFKPL AEIYEQHVTK VNEEVAKLRR RLMELISLVQ EVERNVEAVR NAKDERVREI 70 80 90 100 110 120 RNAVEMMIAR LDTQLKNKLI TLMGQKTSLT QETELLESLL QEVEHQLRSC SKSELISKSS 130 140 150 160 170 180 EILMMFQQVH RKPMASFVTT PVPPDFTSEL VPSYDSATFV LENFSTLRQR ADPVYSPPLQ 190 200 210 220 230 240 VSGLCWRLKV YPDGNGVVRG YYLSVFLELS AGLPETSKYE YRVEMVHQSC NDPTKNIIRE 250 260 270 280 290 300 FASDFEVGEC WGYNRFFRLD LLANEGYLNP QNDTVILRFQ VRSPTFFQKS RDQHWYITQL 310 320 330 340 350 360 EAAQTSYIQQ INNLKERLTI ELSRTQKSRD LSPPDNHLSP QNDDALETRA KKSACSDMLL 370 380 390 400 410 420 EGGPTTASVR EAKEDEEDEE KIQNEDYHHE LSDGDLDLDL VYEDEVNQLD GSSSSASSTA 430 440 450 460 470 480 TSNTEENDID EETMSGENDV EYNNMELEEG ELMEDAAAAG PAGSSHGYVG SSSRISRRTH 490 500 510 520 530 540 LCSAATSSLL DIDPLILIHL LDLKDRSSIE NLWGLQPRPP ASLLQPTASY SRKDKDQRKQ 550 560 570 580 590 600 QAMWRVPSDL KMLKRLKTQM AEVRCMKTDV KNTLSEIKSS SAASGDMQTS LFSADQAALA 610 620 630 640 650 660 ACGTENSGRL QDLGMELLAK SSVANCYIRN STNKKSNSPK PARSSVAGSL SLRRAVDPGE 670 680 690 700 710 720 NSRSKGDCQT LSEGSPGSSQ SGSRHSSPRA LIHGSIGDIL PKTEDRQCKA LDSDAVVVAV 730 740 750 760 770 780 FSGLPAVEKR RKMVTLGANA KGGHLEGLQM TDLENNSETG ELQPVLPEGA SAAPEEDTHS 790 800 SFPDGEQIGP EDLSFNTDEN SGR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Gene POB1 is amplified and overexpressed in human breast cancer." Wu G., Couch F.J. Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:355-364(1998) [PubMed: 10048485] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[3]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Testis.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ALA-108. Tissue: Testis.
[5]	"Gene encoding a new RING-B-box-coiled-coil protein is mutated in mulibrey nanism." Avela K., Lipsanen-Nyman M., Idanheimo N., Seemanova E., Rosengren S., Makela T.P., Perheentupa J., Chapelle A.D., Lehesjoki A.E. Nat. Genet. 25:298-301(2000) [PubMed: 10888877] [Abstract] Cited for: DISEASE, TISSUE SPECIFICITY.
[6]	"The TRIM37 gene encodes a peroxisomal RING-B-box-coiled-coil protein: classification of mulibrey nanism as a new peroxisomal disorder." Kallijarvi J., Avela K., Lipsanen-Nyman M., Ulmanen I., Lehesjoki A.E. Am. J. Hum. Genet. 70:1215-1228(2002) [PubMed: 11938494] [Abstract] Cited for: SUBCELLULAR LOCATION.
[7]	"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 J.T., Gencik M. Hum. Mutat. 21:630-635(2003) [PubMed: 12754710] [Abstract] Cited for: DISEASE.
[8]	"TRIM37 defective in mulibrey nanism is a novel RING finger ubiquitin E3 ligase." Kallijaervi J., Lahtinen U., Haemaelaeinen R., Lipsanen-Nyman M., Palvimo J.J., Lehesjoki A.-E. Exp. Cell Res. 308:146-155(2005) [PubMed: 15885686] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, AUTOUBIQUITINATION, MUTAGENESIS OF 35-CYS-CYS-36, VARIANT MUL PRO-76, CHARACTERIZATION OF VARIANTS MUL PRO-76 AND MUL VAL-322.
[9]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-771 AND SER-773, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"Novel mutations in the TRIM37 gene in Mulibrey Nanism." Haemaelaeinen R.H., Avela K., Lambert J.A., Kallijaervi J., Eyaid W., Gronau J., Ignaszewski A.P., McFadden D., Sorge G., Lipsanen-Nyman M., Lehesjoki A.E. Hum. Mutat. 23:522-522(2004) [PubMed: 15108285] [Abstract] Cited for: VARIANT MUL VAL-322, CHARACTERIZATION OF VARIANT MUL VAR-322.
[11]	"Wilms' tumor and novel TRIM37 mutations in an Australian patient with mulibrey nanism." Haemaelaeinen R.H., Mowat D., Gabbett M.T., O'brien T.A., Kallijaervi J., Lehesjoki A.-E. Clin. Genet. 70:473-479(2006) [PubMed: 17100991] [Abstract] Cited for: VARIANT MUL SER-109, CHARACTERIZATION OF VARIANT MUL SER-109.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF213365 mRNA. Translation: AAL36460.1.
AB020705 mRNA. Translation: BAA74921.1. Different initiation.
BX537955 mRNA. Translation: CAD97922.1.
BC036012 mRNA. Translation: AAH36012.1.

IPI

IPI00016619.
IPI00479325.

RefSeq

NP_001005207.1. NM_001005207.2.
NP_056109.1. NM_015294.3.

UniGene

Hs.579079.
Hs.605697.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3LRQ	X-ray	2.29	A/B/C/D	1-90	[»]

ProteinModelPortal

O94972.

SMR

O94972. Positions 1-84, 91-136, 278-404.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-34437N.

IntAct

O94972. 27 interactions.

MINT

MINT-1433848.

STRING

O94972.

PTM databases

PhosphoSite

O94972.

Proteomic databases

PRIDE

O94972.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000262294; ENSP00000262294; ENSG00000108395.
ENST00000393066; ENSP00000376785; ENSG00000108395.

GeneID

4591.

KEGG

hsa:4591.

UCSC

uc002iwy.2. human.
uc002ixa.2. human.

Organism-specific databases

CTD

4591.

GeneCards

GC17M057059.

HGNC

HGNC:7523. TRIM37.

HPA

HPA021911.

MIM

253250. phenotype.
605073. gene.

neXtProt

NX_O94972.

Orphanet

2576. MULIBREY nanism.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG06996.

GeneTree

ENSGT00410000025800.

HOGENOM

HBG443598.

HOVERGEN

HBG057591.

InParanoid

O94972.

OMA

QNEDYHH.

OrthoDB

EOG42NHZP.

PhylomeDB

O94972.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

O94972.

Bgee

O94972.

CleanEx

HS_TRIM37.

Genevestigator

O94972.

GermOnline

ENSG00000108395. Homo sapiens.

Family and domain databases

InterPro

IPR003649. Bbox_C.
IPR002083. MATH.
IPR008974. TRAF-like.
IPR013322. TRAF-type.
IPR000315. Znf_B-box.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]

Gene3D

G3DSA:2.60.210.10. TRAF-type. 1 hit.
G3DSA:3.30.40.10. Znf_RING/FYVE/PHD. 1 hit.

KO

K10608.

Pfam

PF00917. MATH. 1 hit.
PF00643. zf-B_box. 1 hit.
[Graphical view]

SMART

SM00502. BBC. 1 hit.
SM00336. BBOX. 1 hit.
SM00061. MATH. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]

SUPFAM

SSF49599. Traf_like. 1 hit.

PROSITE

PS50144. MATH. 1 hit.
PS50119. ZF_BBOX. 1 hit.
PS00518. ZF_RING_1. False negative.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

17650.

SOURCE

Search...

Entry information

Entry name

TRI37_HUMAN

Accession

Primary (citable) accession number: O94972
Secondary accession number(s): Q7Z3E6, Q8IYF7, Q8WYF7

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 23, 2004
Last sequence update:	November 23, 2004
Last modified:	January 25, 2012
This is version 104 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.