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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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.7
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with DTNBP1. It self-associates. Ref.7
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.10
Post-translational modification	Ubiquitinated. Ref.7
Involvement in disease	Defects in TRIM32 are the cause of limb-girdle muscular dystrophy type 2H (LGMD2H) [MIM:254110]; also known as muscular dystrophy Hutterite type. LGMD2H is 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. Ref.10 Ref.12 Defects in TRIM32 are the cause of Bardet-Biedl syndrome type 11 (BBS11) [MIM:209900]. Bardet-Biedl syndrome (BBS) is a genetically heterogeneous, autosomal recessive disorder 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. A relatively high incidence of BBS is found in the mixed Arab populations of Kuwait and in Bedouin tribes throughout the Middle East, most likely due to the high rate of consaguinity in these populations and a founder effect. Ref.11
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 Phosphoprotein 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. Source: BHF-UCL negative regulation of apoptotic process Inferred from direct assay. 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. Source: BHF-UCL positive regulation of cell growth Inferred from direct assay. Source: BHF-UCL positive regulation of cell migration Inferred from direct assay. 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. Source: BHF-UCL protein polyubiquitination Inferred from direct assay. Source: BHF-UCL protein ubiquitination involved in ubiquitin-dependent protein catabolic process Inferred from mutant phenotype Ref.7. 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	nucleus Inferred from sequence or structural similarity. Source: BHF-UCL
Molecular function	RNA binding Inferred from sequence or structural similarity. Source: BHF-UCL Tat protein binding Traceable author statement. Source: BHF-UCL myosin binding Inferred from sequence or structural similarity. Source: BHF-UCL protein self-association Inferred from direct assay Ref.7. Source: UniProtKB transcription coactivator activity Traceable author statement. Source: ProtInc translation initiation factor binding Inferred from sequence or structural similarity. Source: BHF-UCL ubiquitin binding Inferred from direct assay Ref.7. Source: UniProtKB ubiquitin-protein ligase activity Inferred from direct assay Ref.7. 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
PDE9A	O76083	3	EBI-742790,EBI-742764
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 Ref.6

Modified residue

328

1

Phosphoserine Ref.5

Modified residue

335

1

Phosphoserine Ref.5 Ref.8

Modified residue

339

1

Phosphoserine Ref.5 Ref.8

Natural variations

Natural variant

130

1

P → S in BBS11. Ref.11

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.13

VAR_066295

Natural variant

394

1

R → H in LGMD2H. Ref.12

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.10

VAR_018725

Natural variant

588

1

Missing in LGMD2H.

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: 7778269] [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: 15164053] [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: 15489334] [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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-328; SER-335 AND SER-339, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[6]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[7]	"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: 19349376] [Abstract] Cited for: FUNCTION AS A E3 UBIQUITIN-PROTEIN LIGASE, UBIQUITINATION, SELF-ASSOCIATION, INTERACTION WITH DTNBP1.
[8]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-335 AND SER-339, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[9]	"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.
[10]	"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: 11822024] [Abstract] Cited for: VARIANT LGMD2H ASN-487, TISSUE SPECIFICITY.
[11]	"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: 16606853] [Abstract] Cited for: VARIANT BBS11 SER-130.
[12]	"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: 17994549] [Abstract] Cited for: VARIANTS LGMD2H HIS-394 AND ASP-588 DEL.
[13]	"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: 21344540] [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.

SMR

Q13049. Positions 3-90, 357-541.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q13049. 7 interactions.

MINT

MINT-2854880.

STRING

Q13049.

PTM databases

PhosphoSite

Q13049.

Polymorphism databases

DMDM

20178303.

Proteomic databases

PRIDE

Q13049.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000373983; ENSP00000363095; ENSG00000119401.
ENST00000394497; ENSP00000378006; ENSG00000119401.
ENST00000450136; ENSP00000408292; ENSG00000119401.

GeneID

22954.

KEGG

hsa:22954.

UCSC

uc004bjw.2. human.

Organism-specific databases

CTD

22954.

GeneCards

GC09P119449.

H-InvDB

HIX0008331.

HGNC

HGNC:16380. TRIM32.

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

prNOG09747.

HOGENOM

HBG447330.

HOVERGEN

HBG060344.

InParanoid

Q13049.

OMA

EHHLEGG.

OrthoDB

EOG4QZ7KF.

PhylomeDB

Q13049.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q13049.

Bgee

Q13049.

CleanEx

HS_TRIM32.

Genevestigator

Q13049.

GermOnline

ENSG00000119401. Homo sapiens.

Family and domain databases

InterPro

IPR011042. 6-blade_b-propeller_TolB-like.
IPR001258. NHL_repeat.
IPR013017. NHL_repeat_subgr.
IPR000315. Znf_B-box.
IPR018957. Znf_C3HC4_RING-type.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]

Gene3D

G3DSA:2.120.10.30. 6-blade_b-propeller_TolB-like. 1 hit.
G3DSA:3.30.40.10. Znf_RING/FYVE/PHD. 1 hit.

KO

K10607.

Pfam

PF01436. NHL. 3 hits.
PF00097. zf-C3HC4. 1 hit.
[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

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:	January 25, 2012
This is version 129 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.