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Protein

Tripartite motif-containing protein 5

Gene

TRIM5

Organism
Macaca mulatta (Rhesus macaque)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses. Blocks viral replication early in the life cycle, after viral entry but before reverse transcription. In addition to acting as a capsid-specific restriction factor, also acts as a pattern recognition receptor that activates innate immune signaling in response to the retroviral capsid lattice. Binding to the viral capsid triggers its E3 ubiquitin ligase activity, and in concert with the heterodimeric ubiquitin conjugating enzyme complex UBE2V1-UBE2N (also known as UBC13-UEV1A complex) generates 'Lys-63'-linked polyubiquitin chains, which in turn are catalysts in the autophosphorylation of the MAP3K7/TAK1 complex (includes TAK1, TAB2, and TAB3). Activation of the MAP3K7/TAK1 complex by autophosphorylation results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes, thereby leading to an innate immune response in the infected cell. Restricts infection by human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV-agm). Plays a role in regulating autophagy through activation of autophagy regulator BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2 (PubMed:25127057). Also plays a role in autophagy by acting as a selective autophagy receptor which recognizes and targets HIV-1 capsid protein p24 for autophagic destruction (PubMed:25127057).4 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri15 – 60RING-typePROSITE-ProRule annotationAdd BLAST46
Zinc fingeri92 – 133B box-typePROSITE-ProRule annotationAdd BLAST42

GO - Molecular functioni

GO - Biological processi

  • activation of innate immune response Source: UniProtKB
  • autophagy Source: UniProtKB
  • defense response to virus Source: UniProtKB
  • innate immune response Source: UniProtKB
  • negative regulation of viral entry into host cell Source: UniProtKB
  • negative regulation of viral genome replication Source: UniProtKB
  • negative regulation of viral release from host cell Source: UniProtKB
  • negative regulation of viral transcription Source: UniProtKB
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • positive regulation of MAPK cascade Source: UniProtKB
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • positive regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
  • protein K63-linked ubiquitination Source: UniProtKB
  • regulation of lipopolysaccharide-mediated signaling pathway Source: UniProtKB
  • regulation of protein localization Source: UniProtKB

Keywordsi

Molecular functionTransferase
Biological processAntiviral defense, Autophagy, Immunity, Innate immunity, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Tripartite motif-containing protein 5 (EC:2.3.2.27)
Alternative name(s):
RING-type E3 ubiquitin transferase TRIM5Curated
TRIM5alpha
Gene namesi
Name:TRIM5
OrganismiMacaca mulatta (Rhesus macaque)
Taxonomic identifieri9544 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniCercopithecidaeCercopithecinaeMacaca
Proteomesi
  • UP000006718 Componenti: Chromosome 14

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nucleus Source: UniProtKB-SubCell
  • omegasome Source: Ensembl
  • P-body Source: UniProtKB

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi165I → K: No effect on dimerization or higher order self-association. 1 Publication1
Mutagenesisi172W → K: No effect on dimerization or higher order self-association; when associated with K-176. 1 Publication1
Mutagenesisi176I → K: No effect on dimerization or higher order self-association; when associated with K-172. 1 Publication1
Mutagenesisi194L → K: Fails to dimerise and exhibits reduced higher order self association. 1 Publication1
Mutagenesisi202L → K: No effect on dimerization or higher order self-association. 1 Publication1
Mutagenesisi205L → K: No effect on dimerization or higher order self-association. 1 Publication1
Mutagenesisi216L → K: No effect on dimerization or higher order self-association. 1 Publication1
Mutagenesisi219S → K: No effect on dimerization or higher order self-association. 1 Publication1
Mutagenesisi230M → K: No effect on dimerization or higher order self-association. 1 Publication1
Mutagenesisi234I → K: No effect on dimerization or higher order self-association. 1 Publication1
Mutagenesisi237L → K: No effect on dimerization or higher order self-association. 1 Publication1
Mutagenesisi247 – 249DLL → KDD: No effect on dimerization but exhibits a 3-fold decrease in the efficiency of higher order association. 1 Publication3

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00002734652 – 497Tripartite motif-containing protein 5Add BLAST496

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei87PhosphoserineBy similarity1

Post-translational modificationi

Degraded in a proteasome-independent fashion in the absence of viral infection but in a proteasome-dependent fashion following exposure to restriction sensitive virus.By similarity
Autoubiquitinated in a RING finger- and UBE2D2-dependent manner. Monoubiquitinated by TRIM21. Deubiquitinated by Yersinia YopJ. Ubiquitination may not lead to proteasomal degradation.2 Publications

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Expressioni

Gene expression databases

BgeeiENSMMUG00000000335.
ExpressionAtlasiQ0PF16. baseline and differential.

Interactioni

Subunit structurei

Can form homodimers and homotrimers. In addition to lower-order dimerization, also exhibits a higher-order multimerization and both low- and high-order multimerizations are essential for its restriction activity. Interacts with MAP3K7/TAK1, TAB2 and TAB3 (By similarity). Interacts with HSPA8/HSC70, PSMC2, PSMC4, PSMC5 and PSMD7 (PubMed:20053985, PubMed:22078707). Interacts with SQSTM1 (PubMed:20357094, PubMed:25127057). Interacts (via B30.2/SPRY domain) with HSPA1A/B. Interacts with TRIM6 and TRIM34 (PubMed:21680743). Interacts with BECN1; GABARAP (PubMed:25127057). Interacts with ULK1 (phosphorylated form), GABARAPL1, GABARAPL2, MAP1LC3A and MAP1LC3C (By similarity).By similarity8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-923856,EBI-923856

GO - Molecular functioni

Protein-protein interaction databases

BioGridi695095. 11 interactors.
IntActiQ0PF16. 1 interactor.
STRINGi9544.ENSMMUP00000000454.

Structurei

Secondary structure

1497
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi6 – 12Combined sources7
Turni16 – 18Combined sources3
Beta strandi23 – 27Combined sources5
Beta strandi33 – 35Combined sources3
Helixi36 – 38Combined sources3
Turni57 – 59Combined sources3
Helixi72 – 79Combined sources8
Turni98 – 100Combined sources3
Beta strandi106 – 108Combined sources3
Turni109 – 112Combined sources4
Beta strandi113 – 115Combined sources3
Helixi117 – 121Combined sources5
Helixi123 – 125Combined sources3
Beta strandi130 – 132Combined sources3
Helixi133 – 159Combined sources27
Helixi226 – 242Combined sources17
Helixi245 – 249Combined sources5
Helixi252 – 261Combined sources10
Helixi292 – 296Combined sources5
Helixi297 – 299Combined sources3
Beta strandi319 – 323Combined sources5
Beta strandi327 – 329Combined sources3
Turni330 – 332Combined sources3
Beta strandi334 – 336Combined sources3
Beta strandi352 – 356Combined sources5
Beta strandi360 – 368Combined sources9
Beta strandi375 – 381Combined sources7
Turni384 – 390Combined sources7
Helixi391 – 394Combined sources4
Helixi399 – 401Combined sources3
Beta strandi403 – 409Combined sources7
Turni410 – 412Combined sources3
Beta strandi413 – 418Combined sources6
Beta strandi429 – 432Combined sources4
Beta strandi440 – 447Combined sources8
Turni448 – 451Combined sources4
Beta strandi452 – 457Combined sources6
Turni458 – 462Combined sources5
Beta strandi463 – 468Combined sources6
Beta strandi477 – 482Combined sources6
Beta strandi490 – 492Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2LM3NMR-A292-497[»]
3UV9X-ray1.55A292-325[»]
A350-497[»]
4B3NX-ray3.30A/B275-493[»]
4TKPX-ray2.08B2-92[»]
5EIUX-ray1.91A/D89-159[»]
A/D226-265[»]
5F7TX-ray2.29E/F/H/L89-159[»]
E/F/H/L226-265[»]
5IEAX-ray3.26A/B/C/D/F/K89-159[»]
A/B/C/D/F/K226-265[»]
5K3QX-ray1.80A/B/C/D94-154[»]
A/B/C/D229-261[»]
ProteinModelPortaliQ0PF16.
SMRiQ0PF16.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini283 – 497B30.2/SPRYPROSITE-ProRule annotationAdd BLAST215

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni187 – 200Required for interaction with GABARAP and for autophagy1 PublicationAdd BLAST14

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili137 – 225Sequence analysisAdd BLAST89

Domaini

The B box-type zinc finger domain and the coiled-coil domain contribute to the higher and low order multimerization respectively which is essential for restriction activity (By similarity). The coiled coil domain is important for higher order multimerization by promoting the initial dimerization (PubMed:21680743).By similarity1 Publication
The B30.2/SPRY domain acts as a capsid recognition domain. Polymorphisms in this domain explain the observed species-specific differences among orthologs.1 Publication
The RING-type zinc finger domain confers E3 ubiquitin ligase activity and is essential for retrovirus restriction activity, autoubiquitination and higher-order multimerization.2 Publications

Sequence similaritiesi

Belongs to the TRIM/RBCC family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri15 – 60RING-typePROSITE-ProRule annotationAdd BLAST46
Zinc fingeri92 – 133B box-typePROSITE-ProRule annotationAdd BLAST42

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

eggNOGiENOG410ITG7. Eukaryota.
ENOG410XWDC. LUCA.
GeneTreeiENSGT00760000118893.
HOGENOMiHOG000234134.
HOVERGENiHBG001357.
InParanoidiQ0PF16.
KOiK10648.
OMAiICPDRVG.
OrthoDBiEOG091G04O8.
TreeFamiTF338674.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiView protein in InterPro
IPR001870. B30.2/SPRY.
IPR003879. Butyrophylin_SPRY.
IPR013320. ConA-like_dom.
IPR003877. SPRY_dom.
IPR032917. TRIM5.
IPR027370. Znf-RING_LisH.
IPR000315. Znf_B-box.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
PANTHERiPTHR24103:SF426. PTHR24103:SF426. 1 hit.
PfamiView protein in Pfam
PF00622. SPRY. 1 hit.
PF00643. zf-B_box. 1 hit.
PF13445. zf-RING_UBOX. 1 hit.
PRINTSiPR01407. BUTYPHLNCDUF.
SMARTiView protein in SMART
SM00336. BBOX. 1 hit.
SM00184. RING. 1 hit.
SM00449. SPRY. 1 hit.
SUPFAMiSSF49899. SSF49899. 1 hit.
PROSITEiView protein in PROSITE
PS50188. B302_SPRY. 1 hit.
PS50119. ZF_BBOX. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q0PF16-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MASGILLNVK EEVTCPICLE LLTEPLSLHC GHSFCQACIT ANHKKSMLYK
60 70 80 90 100
EGERSCPVCR ISYQPENIQP NRHVANIVEK LREVKLSPEE GQKVDHCARH
110 120 130 140 150
GEKLLLFCQE DSKVICWLCE RSQEHRGHHT FLMEEVAQEY HVKLQTALEM
160 170 180 190 200
LRQKQQEAEK LEADIREEKA SWKIQIDYDK TNVSADFEQL REILDWEESN
210 220 230 240 250
ELQNLEKEEE DILKSLTKSE TEMVQQTQYM RELISELEHR LQGSMMDLLQ
260 270 280 290 300
GVDGIIKRIE NMTLKKPKTF HKNQRRVFRA PDLKGMLDMF RELTDARRYW
310 320 330 340 350
VDVTLAPNNI SHAVIAEDKR QVSSRNPQIM YQAPGTLFTF PSLTNFNYCT
360 370 380 390 400
GVLGSQSITS GKHYWEVDVS KKSAWILGVC AGFQSDAMYN IEQNENYQPK
410 420 430 440 450
YGYWVIGLQE GVKYSVFQDG SSHTPFAPFI VPLSVIICPD RVGVFVDYEA
460 470 480 490
CTVSFFNITN HGFLIYKFSQ CSFSKPVFPY LNPRKCTVPM TLCSPSS
Length:497
Mass (Da):57,299
Last modified:January 23, 2007 - v2
Checksum:i950166879B2E1A6F
GO
Isoform 2 (identifier: Q0PF16-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     301-333: VDVTLAPNNISHAVIAEDKRQVSSRNPQIMYQA → GKEKSHYHQPPCGLSLLLSLSFRILYSLLGLVF
     334-497: Missing.

Note: No experimental confirmation available.
Show »
Length:333
Mass (Da):39,027
Checksum:i33D4B364F2DCB7EC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti7L → V in AAT48102 (PubMed:15249690).Curated1
Sequence conflicti174I → T in AAX86682 (PubMed:16226405).Curated1
Sequence conflicti177D → Q in AAX86682 (PubMed:16226405).Curated1
Sequence conflicti184S → L in AAX86682 (PubMed:16226405).Curated1
Sequence conflicti192E → D in AAX86682 (PubMed:16226405).Curated1
Sequence conflicti218K → N in AAX86682 (PubMed:16226405).Curated1
Sequence conflicti221T → M in ABG67967 (Ref. 5) Curated1
Sequence conflicti229 – 230YM → SL in AAX86682 (PubMed:16226405).Curated2
Sequence conflicti236E → D in AAX86682 (PubMed:16226405).Curated1
Sequence conflicti236E → D in ABG67966 (Ref. 5) Curated1
Sequence conflicti307P → T in AAT48102 (PubMed:15249690).Curated1
Sequence conflicti307P → T in ABL14041 (PubMed:17142324).Curated1
Sequence conflicti307P → T in AAS48505 (Ref. 4) Curated1
Sequence conflicti333A → S in ABG67966 (Ref. 5) Curated1
Sequence conflicti339 – 341TFP → Q in ABG67966 (Ref. 5) Curated3

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_022569301 – 333VDVTL…IMYQA → GKEKSHYHQPPCGLSLLLSL SFRILYSLLGLVF in isoform 2. 1 PublicationAdd BLAST33
Alternative sequenceiVSP_022570334 – 497Missing in isoform 2. 1 PublicationAdd BLAST164

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY625001 mRNA. Translation: AAT48102.1.
AY899886
, AY899880, AY899881, AY899882, AY899883, AY899884, AY899885 Genomic DNA. Translation: AAX86682.1.
EF113914 mRNA. Translation: ABL14041.1.
AY523632 mRNA. Translation: AAS48505.1.
AY523633 mRNA. Translation: AAS48506.1.
DQ842020 mRNA. Translation: ABG67966.1.
DQ842021 mRNA. Translation: ABG67967.1.
RefSeqiNP_001028082.1. NM_001032910.1.
UniGeneiMmu.3751.

Genome annotation databases

EnsembliENSMMUT00000000490; ENSMMUP00000000454; ENSMMUG00000000335. [Q0PF16-1]
GeneIDi574288.
KEGGimcc:574288.

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiTRIM5_MACMU
AccessioniPrimary (citable) accession number: Q0PF16
Secondary accession number(s): Q0PF17
, Q2YEN1, Q6GX25, Q6QWE9, Q6QWF0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 23, 2007
Last sequence update: January 23, 2007
Last modified: August 30, 2017
This is version 96 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families