Q13049 (TRI32_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 ubiquitin-protein ligase TRIM32
EC=6.3.2.-

Alternative name(s):
72 kDa Tat-interacting protein
Tripartite motif-containing protein 32
Zinc finger protein HT2A

Gene names

Name:	TRIM32
Synonyms:	HT2A

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	653 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Has an E3 ubiquitin ligase activity. Ubiquitinates DTNBP1 (dysbindin) and promotes its degradation. May play a significant role in mediating the biological activity of the HIV-1 Tat protein in vivo. Binds specifically to the activation domain of HIV-1 Tat and can also interact with the HIV-2 and EIAV Tat proteins in vivo. Ref.6
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with DTNBP1. It self-associates. Ref.6
Subcellular location	Cytoplasm. Note: Localized in cytoplasmic bodies, often located around the nucleus.
Tissue specificity	Spleen, thymus, prostate, testis, ovary, intestine, colon and skeletal muscle. Ref.8
Post-translational modification	Ubiquitinated. Ref.6
Involvement in disease	Limb-girdle muscular dystrophy 2H (LGMD2H) [MIM:254110]: An autosomal recessive degenerative myopathy characterized by pelvic girdle, shoulder girdle and quadriceps muscle weakness. Clinical phenotype and severity are highly variable. Disease progression is slow and most patients remain ambulatory into the sixth decade of life. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.10 Bardet-Biedl syndrome 11 (BBS11) [MIM:209900]: A syndrome characterized by usually severe pigmentary retinopathy, early-onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease. Bardet-Biedl syndrome inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for clinical manifestation of some forms of the disease. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9
Sequence similarities	Belongs to the TRIM/RBCC family. Contains 1 B box-type zinc finger. Contains 5 NHL repeats. Contains 1 RING-type zinc finger.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Bardet-Biedl syndrome Ciliopathy Disease mutation Limb-girdle muscular dystrophy Mental retardation Obesity
Domain	Coiled coil Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	Acetylation Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	fat cell differentiation Inferred from sequence or structural similarity. Source: BHF-UCL innate immune response Traceable author statement PubMed 16175175. Source: BHF-UCL negative regulation of apoptotic process Inferred from direct assay PubMed 18632609. Source: BHF-UCL negative regulation of fibroblast proliferation Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of NF-kappaB transcription factor activity Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of cell cycle Inferred from direct assay PubMed 18632609. Source: BHF-UCL positive regulation of cell growth Inferred from direct assay PubMed 18632609. Source: BHF-UCL positive regulation of cell migration Inferred from direct assay PubMed 18632609. Source: BHF-UCL positive regulation of neurogenesis Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of neuron differentiation Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of protein catabolic process Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of proteolysis Inferred from direct assay PubMed 18632609. Source: BHF-UCL protein polyubiquitination Inferred from direct assay PubMed 18632609. Source: BHF-UCL protein ubiquitination involved in ubiquitin-dependent protein catabolic process Inferred from mutant phenotype Ref.6. Source: UniProtKB response to UV Inferred from sequence or structural similarity. Source: BHF-UCL response to tumor necrosis factor Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular_component	cytoplasm Inferred from direct assay Ref.6. Source: UniProtKB nucleus Inferred from sequence or structural similarity. Source: BHF-UCL striated muscle myosin thick filament Inferred from electronic annotation. Source: Compara
Molecular_function	RNA binding Inferred from sequence or structural similarity. Source: BHF-UCL Tat protein binding Traceable author statement PubMed 16175175. Source: BHF-UCL myosin binding Inferred from sequence or structural similarity. Source: BHF-UCL protein self-association Inferred from direct assay Ref.6. Source: UniProtKB transcription coactivator activity Traceable author statement Ref.1. Source: ProtInc translation initiation factor binding Inferred from sequence or structural similarity. Source: BHF-UCL ubiquitin binding Inferred from direct assay Ref.6. Source: UniProtKB ubiquitin-protein ligase activity Inferred from direct assay Ref.6. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ATXN1	P54253	2	EBI-742790,EBI-930964
Irak1	Q99J34	2	EBI-742790,EBI-6117042	From a different organism.
PDE9A	O76083	3	EBI-742790,EBI-742764
TRIM5	Q9C035	2	EBI-742790,EBI-924214
UBQLN4	Q9NRR5	3	EBI-742790,EBI-711226

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.4

Chain

2 – 653

652

E3 ubiquitin-protein ligase TRIM32

PRO_0000056246

Regions

Repeat

358 – 401

44

NHL 1

Repeat

415 – 458

44

NHL 2

Repeat

459 – 499

41

NHL 3

Repeat

562 – 605

44

NHL 4

Repeat

606 – 646

41

NHL 5

Zinc finger

20 – 65

46

RING-type

Zinc finger

103 – 133

31

B box-type

Coiled coil

138 – 197

60

Potential

Compositional bias

2 – 6

5

Poly-Ala

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.4

Natural variations

Natural variant

130

1

P → S in BBS11. Ref.9

VAR_038807

Natural variant

257

1

T → R.
Corresponds to variant rs3747834 [ dbSNP | Ensembl ].

VAR_038808

Natural variant

299

1

R → Q in a patient with Bardet-Biedl syndrome; unknown pathological significance. Ref.11

VAR_066295

Natural variant

394

1

R → H in LGMD2H. Ref.10

VAR_042939

Natural variant

408

1

R → C.
Corresponds to variant rs3747835 [ dbSNP | Ensembl ].

VAR_038809

Natural variant

487

1

D → N in LGMD2H. Ref.8

VAR_018725

Natural variant

588

1

Missing in LGMD2H. Ref.10

VAR_042940

Experimental info

Sequence conflict

27

1

F → I in AAA86474. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

653

Helix Strand Turn

Details...

Turn

21 – 23

3

Beta strand

34 – 36

3

Beta strand

38 – 40

3

Beta strand

42 – 44

3

Helix

45 – 54

10

Turn

62 – 64

3

Turn

73 – 75

3

Beta strand

76 – 78

3

Turn

80 – 83

4

Sequences

	Sequence		Length	Mass (Da)
	Q13049 [UniParc]. Last modified April 16, 2002. Version 2. Checksum: D83B1595CA8378FD	FASTA	653	71,989
	10 20 30 40 50 60 MAAAAASHLN LDALREVLEC PICMESFTEE QLRPKLLHCG HTICRQCLEK LLASSINGVR 70 80 90 100 110 120 CPFCSKITRI TSLTQLTDNL TVLKIIDTAG LSEAVGLLMC RSCGRRLPRQ FCRSCGLVLC 130 140 150 160 170 180 EPCREADHQP PGHCTLPVKE AAEERRRDFG EKLTRLRELM GELQRRKAAL EGVSKDLQAR 190 200 210 220 230 240 YKAVLQEYGH EERRVQDELA RSRKFFTGSL AEVEKSNSQV VEEQSYLLNI AEVQAVSRCD 250 260 270 280 290 300 YFLAKIKQAD VALLEETADE EEPELTASLP RELTLQDVEL LKVGHVGPLQ IGQAVKKPRT 310 320 330 340 350 360 VNVEDSWAME ATASAASTSV TFREMDMSPE EVVASPRASP AKQRGPEAAS NIQQCLFLKK 370 380 390 400 410 420 MGAKGSTPGM FNLPVSLYVT SQGEVLVADR GNYRIQVFTR KGFLKEIRRS PSGIDSFVLS 430 440 450 460 470 480 FLGADLPNLT PLSVAMNCQG LIGVTDSYDN SLKVYTLDGH CVACHRSQLS KPWGITALPS 490 500 510 520 530 540 GQFVVTDVEG GKLWCFTVDR GSGVVKYSCL CSAVRPKFVT CDAEGTVYFT QGLGLNLENR 550 560 570 580 590 600 QNEHHLEGGF SIGSVGPDGQ LGRQISHFFS ENEDFRCIAG MCVDARGDLI VADSSRKEIL 610 620 630 640 650 HFPKGGGYSV LIREGLTCPV GIALTPKGQL LVLDCWDHCI KIYSYHLRRY STP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of a novel human zinc finger protein that specifically interacts with the activation domain of lentiviral Tat proteins." Fridell R.A., Harding L.S., Bogerd H.P., Cullen B.R. Virology 209:347-357(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skin.
[4]	Bienvenut W.V., Waridel P., Quadroni M. Submitted (MAR-2009) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-15; 51-60; 70-101; 205-238; 248-282; 345-359; 467-500; 587-596 AND 605-613, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[5]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[6]	"TRIM32 is an E3 ubiquitin ligase for dysbindin." Locke M., Tinsley C.L., Benson M.A., Blake D.J. Hum. Mol. Genet. 18:2344-2358(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE, UBIQUITINATION, SELF-ASSOCIATION, INTERACTION WITH DTNBP1.
[7]	"Solution structure of the RING domain of the tripartite motif protein 32." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 10-84.
[8]	"Limb-girdle muscular dystrophy type 2H associated with mutation in TRIM32, a putative E3-ubiquitin-ligase gene." Frosk P., Weiler T., Nylen E., Sudha T., Greenberg C.R., Morgan K., Fujiwara T.M., Wrogemann K. Am. J. Hum. Genet. 70:663-672(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LGMD2H ASN-487, TISSUE SPECIFICITY.
[9]	"Homozygosity mapping with SNP arrays identifies TRIM32, an E3 ubiquitin ligase, as a Bardet-Biedl syndrome gene (BBS11)." Chiang A.P., Beck J.S., Yen H.-J., Tayeh M.K., Scheetz T.E., Swiderski R.E., Nishimura D.Y., Braun T.A., Kim K.-Y.A., Huang J., Elbedour K., Carmi R., Slusarski D.C., Casavant T.L., Stone E.M., Sheffield V.C. Proc. Natl. Acad. Sci. U.S.A. 103:6287-6292(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BBS11 SER-130.
[10]	"Mutations that impair interaction properties of TRIM32 associated with limb-girdle muscular dystrophy 2H." Saccone V., Palmieri M., Passamano L., Piluso G., Meroni G., Politano L., Nigro V. Hum. Mutat. 29:240-247(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LGMD2H HIS-394 AND ASP-588 DEL.
[11]	"BBS genotype-phenotype assessment of a multiethnic patient cohort calls for a revision of the disease definition." Deveault C., Billingsley G., Duncan J.L., Bin J., Theal R., Vincent A., Fieggen K.J., Gerth C., Noordeh N., Traboulsi E.I., Fishman G.A., Chitayat D., Knueppel T., Millan J.M., Munier F.L., Kennedy D., Jacobson S.G., Innes A.M. , Mitchell G.A., Boycott K., Heon E. Hum. Mutat. 32:610-619(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GLN-299.
+	Additional computationally mapped references.

Web resources

Leiden Muscular Dystrophy pages

TRIM32

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U18543 mRNA. Translation: AAA86474.1.
AL133284 Genomic DNA. Translation: CAB92723.1.
BC003154 mRNA. Translation: AAH03154.1.

IPI

IPI00297113.

RefSeq

NP_001093149.1. NM_001099679.1.
NP_036342.2. NM_012210.3.

UniGene

Hs.591910.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2CT2	NMR	-	A	10-84	[»]

ProteinModelPortal

Q13049.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q13049. 15 interactions.

MINT

MINT-2854880.

STRING

9606.ENSP00000363095.

PTM databases

PhosphoSite

Q13049.

Polymorphism databases

DMDM

20178303.

Proteomic databases

PaxDb

Q13049.

PRIDE

Q13049.

Protocols and materials databases

DNASU

22954.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000373983; ENSP00000363095; ENSG00000119401.
ENST00000450136; ENSP00000408292; ENSG00000119401.

GeneID

22954.

KEGG

hsa:22954.

UCSC

uc004bjw.2. human.

Organism-specific databases

CTD

22954.

GeneCards

GC09P119449.

HGNC

HGNC:16380. TRIM32.

HPA

HPA050060.

MIM

209900. phenotype.
254110. phenotype.
602290. gene.

neXtProt

NX_Q13049.

Orphanet

1878. Autosomal recessive limb-girdle muscular dystrophy type 2H.
110. Bardet-Biedl syndrome.

PharmGKB

PA38130.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG269289.

HOGENOM

HOG000120114.

HOVERGEN

HBG060344.

InParanoid

Q13049.

KO

K10607.

OMA

RLPRQFC.

OrthoDB

EOG4QZ7KF.

PhylomeDB

Q13049.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

UniPathway

UPA00143.

Gene expression databases

ArrayExpress

Q13049.

Bgee

Q13049.

CleanEx

HS_TRIM32.

Genevestigator

Q13049.

GermOnline

ENSG00000119401. Homo sapiens.

Family and domain databases

Gene3D

2.120.10.30. 1 hit.
3.30.40.10. 1 hit.

InterPro

IPR011042. 6-blade_b-propeller_TolB-like.
IPR001258. NHL_repeat.
IPR013017. NHL_repeat_subgr.
IPR000315. Znf_B-box.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]

Pfam

PF01436. NHL. 3 hits.
[Graphical view]

SMART

SM00336. BBOX. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]

PROSITE

PS51125. NHL. 5 hits.
PS50119. ZF_BBOX. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q13049.

GenomeRNAi

22954.

NextBio

43741.

SOURCE

Search...

Entry information

Entry name

TRI32_HUMAN

Accession

Primary (citable) accession number: Q13049
Secondary accession number(s): Q9NQP8

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	April 16, 2002
Last modified:	May 1, 2013
This is version 143 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.