TRIM5_CHLTN
ID TRIM5_CHLTN Reviewed; 515 AA.
AC Q5C8U3; Q0NNX4; Q6J662;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 12-APR-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 Chlorocebus tantalus (Tantalus monkey) (Cercopithecus tantalus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Chlorocebus.
OX NCBI_TaxID=60712;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=15249687; DOI=10.1073/pnas.0402474101;
RA Keckesova Z., Ylinen L.M., Towers G.J.;
RT "The human and African green monkey TRIM5alpha genes encode Ref1 and Lv1
RT retroviral restriction factor activities.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:10780-10785(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 302-515.
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).
RN [4]
RP REVIEW, AND FUNCTION.
RX PubMed=22291694; DOI=10.3389/fmicb.2012.00013;
RA Nakayama E.E., Shioda T.;
RT "TRIM5alpha and species tropism of HIV/SIV.";
RL Front. Microbiol. 3:13-13(2012).
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. Restricts infection by human
CC immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus
CC (SIV-mac) and N-tropic murine leukemia viruse (N-MLV)
CC (PubMed:22291694). Plays a role in regulating autophagy through
CC activation of autophagy regulator BECN1 by causing its dissociation
CC from its inhibitors BCL2 and TAB2 (By similarity).
CC {ECO:0000250|UniProtKB:Q9C035, ECO:0000269|PubMed:22291694}.
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; AY593973; AAT10388.2; -; mRNA.
DR EMBL; AY740613; AAW72441.1; -; mRNA.
DR EMBL; DQ437606; ABE28408.1; -; Genomic_DNA.
DR AlphaFoldDB; Q5C8U3; -.
DR SMR; Q5C8U3; -.
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; TAS:UniProtKB.
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; 2.
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..515
FT /note="Tripartite motif-containing protein 5"
FT /id="PRO_0000273455"
FT DOMAIN 283..515
FT /note="B30.2/SPRY"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT ZN_FING 15..60
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 92..133
FT /note="B box-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT REGION 187..200
FT /note="Required for interaction with GABARAP and for
FT autophagy"
FT /evidence="ECO:0000250|UniProtKB:Q0PF16"
FT COILED 137..225
FT /evidence="ECO:0000255"
FT BINDING 97
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 100
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 119
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 125
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 87
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9C035"
FT CONFLICT 7
FT /note="V -> L (in Ref. 1; AAT10388)"
FT /evidence="ECO:0000305"
FT CONFLICT 165
FT /note="T -> I (in Ref. 1; AAT10388)"
FT /evidence="ECO:0000305"
FT CONFLICT 337
FT /note="L -> S (in Ref. 1; AAT10388)"
FT /evidence="ECO:0000305"
FT CONFLICT 347
FT /note="Y -> C (in Ref. 1; AAT10388 and 3; ABE28408)"
FT /evidence="ECO:0000305"
FT CONFLICT 351
FT /note="R -> L (in Ref. 1; AAT10388)"
FT /evidence="ECO:0000305"
FT CONFLICT 359
FT /note="G -> R (in Ref. 1; AAT10388)"
FT /evidence="ECO:0000305"
FT CONFLICT 438
FT /note="G -> S (in Ref. 3; ABE28408)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 515 AA; 59250 MW; 876A874F6F46AAD2 CRC64;
MASGILVNVK EEVTCPICLE LLTEPLSLPC GHSFCQACIT ANHKESMLYK EEERSCPVCR
ISYQPENIQP NRHVANIVEK LREVKLSPEE GQKVDHCARH GEKLLLFCQE DSKVICWLCE
RSQEHRGHHT FLMEEVAQEY HVKLQTALEM LRQKQQEAEK LEADTREEKA SWKIQIDYDK
TNVSADFEQL REILDWEESN ELQNLEKEEE DILKSLTKSE TEMVQQTQYM RELISDLEHR
LQGSMMELLQ GVDGIIKRIE NMTLKKPKTF HKNQRRVFRA PDLKGMLDMF RELTDVRRYW
VDVTLAPNNI SHAVIAEDKR QVSYQNPQIM YQAPGSLFGS LTNFNYYTGV RGSQSITSGK
LTNFNYCTGV LGSQSITSGK HYWEVDVSKK SAWILGVCAG FQPDATYNIE QNENYQPKYG
YWVIGLQEGD KYSVFQDGSS HTPFAPFIVP LSVIICPDRV GVFVDYEACT VSFFNITNHG
FLIYKFSQCS FSKPVFPYLN PRKCTVPMTL CSPSS
