TRIM5_PONPY
ID TRIM5_PONPY Reviewed; 493 AA.
AC Q2YEM9; Q0NNX9; Q3ZEE6; Q50EW8; Q5D7I4; Q5RFC7;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-DEC-2005, sequence version 1.
DT 03-AUG-2022, entry version 95.
DE RecName: Full=Tripartite motif-containing protein 5;
DE EC=2.3.2.27;
DE AltName: Full=RING-type E3 ubiquitin transferase TRIM5 {ECO:0000305};
DE AltName: Full=TRIM5alpha;
GN Name=TRIM5;
OS Pongo pygmaeus (Bornean orangutan).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9600;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=16226405; DOI=10.1016/j.gene.2005.06.045;
RA Liu H.L., Wang Y.Q., Liao C.H., Kuang Y.Q., Zheng Y.T., Su B.;
RT "Adaptive evolution of primate TRIM5alpha, a gene restricting HIV-1
RT infection.";
RL Gene 362:109-116(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=15689398; DOI=10.1073/pnas.0409853102;
RA Sawyer S.L., Wu L.I., Emerman M., Malik H.S.;
RT "Positive selection of primate TRIM5alpha identifies a critical species-
RT specific retroviral restriction domain.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:2832-2837(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=16460575; DOI=10.1186/1742-4690-3-11;
RA Ortiz M., Bleiber G., Martinez R., Kaessmann H., Telenti A.;
RT "Patterns of evolution of host proteins involved in retroviral
RT pathogenesis.";
RL Retrovirology 3:11-11(2006).
RN [4]
RP SEQUENCE REVISION TO 384-385; 389; 396 AND 420.
RA Ortiz M., Bleiber G., Martinez R., Telenti A.;
RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 299-493.
RX PubMed=15857996; DOI=10.1128/jvi.79.10.6111-6121.2005;
RA Song B., Gold B., O'Huigin C., Javanbakht H., Li X., Stremlau M.,
RA Winkler C., Dean M., Sodroski J.;
RT "The B30.2(SPRY) domain of the retroviral restriction factor TRIM5alpha
RT exhibits lineage-specific length and sequence variation in primates.";
RL J. Virol. 79:6111-6121(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 300-493.
RX PubMed=16912305; DOI=10.1128/jvi.00688-06;
RA Ohkura S., Yap M.W., Sheldon T., Stoye J.P.;
RT "All three variable regions of the TRIM5alpha B30.2 domain can contribute
RT to the specificity of retrovirus restriction.";
RL J. Virol. 80:8554-8565(2006).
CC -!- FUNCTION: Capsid-specific restriction factor that prevents infection
CC from non-host-adapted retroviruses. Blocks viral replication early in
CC the life cycle, after viral entry but before reverse transcription. In
CC addition to acting as a capsid-specific restriction factor, also acts
CC as a pattern recognition receptor that activates innate immune
CC signaling in response to the retroviral capsid lattice. Binding to the
CC viral capsid triggers its E3 ubiquitin ligase activity, and in concert
CC with the heterodimeric ubiquitin conjugating enzyme complex UBE2V1-
CC UBE2N (also known as UBC13-UEV1A complex) generates 'Lys-63'-linked
CC polyubiquitin chains, which in turn are catalysts in the
CC autophosphorylation of the MAP3K7/TAK1 complex (includes TAK1, TAB2,
CC and TAB3). Activation of the MAP3K7/TAK1 complex by autophosphorylation
CC results in the induction and expression of NF-kappa-B and MAPK-
CC responsive inflammatory genes, thereby leading to an innate immune
CC response in the infected cell. Plays a role in regulating autophagy
CC through activation of autophagy regulator BECN1 by causing its
CC dissociation from its inhibitors BCL2 and TAB2.
CC {ECO:0000250|UniProtKB:Q9C035}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Can form homodimers and homotrimers. In addition to lower-
CC order dimerization, also exhibits a higher-order multimerization and
CC both low- and high-order multimerizations are essential for its
CC restriction activity. Interacts with BTBD1 and BTBD2. Interacts with
CC PSMC4, PSMC5, PSMD7 and HSPA8/HSC70. Interacts (via B30.2/SPRY domain)
CC with HSPA1A/B. Interacts with PSMC2, MAP3K7/TAK1, TAB2 and TAB3.
CC Interacts with SQSTM1. Interacts with TRIM6 and TRIM34. Interacts with
CC ULK1 (phosphorylated form), GABARAP, GABARAPL1, GABARAPL2, MAP1LC3A,
CC MAP1LC3C and BECN1. {ECO:0000250|UniProtKB:Q0PF16,
CC ECO:0000250|UniProtKB:Q9C035}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q0PF16}. Nucleus
CC {ECO:0000250|UniProtKB:Q0PF16}. Note=Predominantly localizes in
CC cytoplasmic bodies. Localization may be influenced by the coexpression
CC of other TRIM proteins, hence partial nuclear localization is observed
CC in the presence of TRIM22 or TRIM27. In cytoplasmic bodies, colocalizes
CC with proteasomal subunits and SQSTM1. {ECO:0000250|UniProtKB:Q0PF16}.
CC -!- DOMAIN: The B box-type zinc finger domain and the coiled-coil domain
CC contribute to the higher and low order multimerization respectively
CC which is essential for restriction activity. The coiled coil domain is
CC important for higher order multimerization by promoting the initial
CC dimerization. {ECO:0000250|UniProtKB:Q0PF16,
CC ECO:0000250|UniProtKB:Q9C035}.
CC -!- DOMAIN: The B30.2/SPRY domain acts as a capsid recognition domain.
CC Polymorphisms in this domain explain the observed species-specific
CC differences among orthologs (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The RING-type zinc finger domain confers E3 ubiquitin ligase
CC activity and is essential for retrovirus restriction activity,
CC autoubiquitination and higher-order multimerization. {ECO:0000250}.
CC -!- PTM: Degraded in a proteasome-independent fashion in the absence of
CC viral infection but in a proteasome-dependent fashion following
CC exposure to restriction sensitive virus. {ECO:0000250}.
CC -!- PTM: Autoubiquitinated in a RING finger- and UBE2D2-dependent manner.
CC Monoubiquitinated by TRIM21. Deubiquitinated by Yersinia YopJ.
CC Ubiquitination may not lead to proteasomal degradation (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the TRIM/RBCC family. {ECO:0000305}.
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DR EMBL; AY899900; AAX86684.1; -; Genomic_DNA.
DR EMBL; AY899894; AAX86684.1; JOINED; Genomic_DNA.
DR EMBL; AY899895; AAX86684.1; JOINED; Genomic_DNA.
DR EMBL; AY899896; AAX86684.1; JOINED; Genomic_DNA.
DR EMBL; AY899897; AAX86684.1; JOINED; Genomic_DNA.
DR EMBL; AY899898; AAX86684.1; JOINED; Genomic_DNA.
DR EMBL; AY899899; AAX86684.1; JOINED; Genomic_DNA.
DR EMBL; AY843513; AAV91984.1; -; Genomic_DNA.
DR EMBL; AY923179; AAY23161.2; -; Genomic_DNA.
DR EMBL; CR857231; CAH89530.1; -; mRNA.
DR EMBL; AY710302; AAW55821.1; -; Genomic_DNA.
DR EMBL; DQ437601; ABE28403.1; -; Genomic_DNA.
DR AlphaFoldDB; Q2YEM9; -.
DR SMR; Q2YEM9; -.
DR UniPathway; UPA00143; -.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0000932; C:P-body; ISS:UniProtKB.
DR GO; GO:0038187; F:pattern recognition receptor activity; ISS:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0002218; P:activation of innate immune response; ISS:UniProtKB.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0031664; P:regulation of lipopolysaccharide-mediated signaling pathway; ISS:UniProtKB.
DR Gene3D; 2.60.120.920; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR001870; B30.2/SPRY.
DR InterPro; IPR043136; B30.2/SPRY_sf.
DR InterPro; IPR003879; Butyrophylin_SPRY.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR003877; SPRY_dom.
DR InterPro; IPR027370; Znf-RING_LisH.
DR InterPro; IPR000315; Znf_B-box.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR Pfam; PF00622; SPRY; 1.
DR Pfam; PF00643; zf-B_box; 1.
DR Pfam; PF13445; zf-RING_UBOX; 1.
DR PRINTS; PR01407; BUTYPHLNCDUF.
DR SMART; SM00336; BBOX; 1.
DR SMART; SM00184; RING; 1.
DR SMART; SM00449; SPRY; 1.
DR SUPFAM; SSF49899; SSF49899; 1.
DR PROSITE; PS50188; B302_SPRY; 1.
DR PROSITE; PS50119; ZF_BBOX; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Antiviral defense; Autophagy; Coiled coil; Cytoplasm;
KW Immunity; Innate immunity; Metal-binding; Nucleus; Phosphoprotein;
KW Transferase; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9C035"
FT CHAIN 2..493
FT /note="Tripartite motif-containing protein 5"
FT /id="PRO_0000273472"
FT DOMAIN 281..493
FT /note="B30.2/SPRY"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT ZN_FING 15..59
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 90..132
FT /note="B box-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT REGION 185..198
FT /note="Required for interaction with GABARAP and for
FT autophagy"
FT /evidence="ECO:0000250|UniProtKB:Q0PF16"
FT COILED 131..223
FT /evidence="ECO:0000255"
FT BINDING 95
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 98
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 117
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 123
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q9C035"
FT MOD_RES 86
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9C035"
FT CONFLICT 33
FT /note="S -> N (in Ref. 5; CAH89530)"
FT /evidence="ECO:0000305"
FT CONFLICT 180
FT /note="S -> N (in Ref. 3; AAY23161)"
FT /evidence="ECO:0000305"
FT CONFLICT 253
FT /note="V -> I (in Ref. 2; AAV91984, 3; AAY23161 and 5;
FT CAH89530)"
FT /evidence="ECO:0000305"
FT CONFLICT 343
FT /note="N -> S (in Ref. 3; AAY23161)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 493 AA; 56434 MW; EDBEB9F0C978CDF7 CRC64;
MASGILVNVK EEVTCPICLE LLTQPLSLDC GHSFCQACLT ANHKKSTLDK GERSCPVCRV
SYQPKNIRPN RHVANIVEKL REVKLSPEGQ KVDHCARHGE KLLLFCKEDG KVICWLCERS
QEHRGHHTFL TEEVAQKYQV KLQAALEMLR QKQQEAEELE ADIREEKASW KTQIQYDKTS
VLADFEQLRD ILDWEESNEL QNLEKEEEDI LKSLTKSETE MVQQTQSVRE LISDVEHRLQ
GSVMELLQGV DGVIKRMQNV TLKKPETFPK NQRRVFRAPN LKGMLEVFRE LTDVRRYWVD
VTVAPNDISY AVISEDMRQV SCPEPQIIYG AQGTTYQTYV NFNYCTGILG SQSITSGKHY
WEVDVSKKSA WILGVCAGFQ PDAMYNIEQN ENYQPQYGYW VIGLEEGVKC SAFQDGSFHN
PSAPFIVPLS VIICPDRVGV FLDYEACTVS FFNITNHGFL IYKFSHCSFS QPVFPYLNPR
KCRVPMTLCS PSS
