UniProt functional annotation for Q0PF16



	UniProt functional annotation for Q0PF16

UniProt code: Q0PF16.

Organism: Macaca mulatta (Rhesus macaque).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Cercopithecidae; Cercopithecinae; Macaca.

Function: 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). {ECO:0000269|PubMed:21035162, ECO:0000269|PubMed:21734049, ECO:0000269|PubMed:22291694, ECO:0000269|PubMed:25127057}.

Catalytic activity: Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27;

Pathway: Protein modification; protein ubiquitination.

Subunit: 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). {ECO:0000250|UniProtKB:Q9C035, ECO:0000269|PubMed:17156811, ECO:0000269|PubMed:20053985, ECO:0000269|PubMed:20357094, ECO:0000269|PubMed:21187419, ECO:0000269|PubMed:21680743, ECO:0000269|PubMed:21734049, ECO:0000269|PubMed:22078707, ECO:0000269|PubMed:25127057}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:17156811}. Nucleus {ECO:0000269|PubMed:17156811}. Note=Predominantly localizes in cytoplasmic bodies (PubMed:20357094, PubMed:22078707). Localization may be influenced by the coexpression of other TRIM proteins, hence partial nuclear localization is observed in the presence of TRIM22 or TRIM27 (PubMed:17156811). In cytoplasmic bodies, colocalizes with proteasomal subunits and SQSTM1 (PubMed:20357094). {ECO:0000269|PubMed:17156811, ECO:0000269|PubMed:20357094, ECO:0000269|PubMed:22078707}.

Domain: 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). {ECO:0000250|UniProtKB:Q9C035, ECO:0000269|PubMed:21680743}.

Domain: The B30.2/SPRY domain acts as a capsid recognition domain. Polymorphisms in this domain explain the observed species-specific differences among orthologs. {ECO:0000269|PubMed:21734049}.

Domain: The RING-type zinc finger domain confers E3 ubiquitin ligase activity and is essential for retrovirus restriction activity, autoubiquitination and higher-order multimerization. {ECO:0000269|PubMed:17156811, ECO:0000269|PubMed:21734049}.

Ptm: Degraded in a proteasome-independent fashion in the absence of viral infection but in a proteasome-dependent fashion following exposure to restriction sensitive virus. {ECO:0000250}.

Ptm: Autoubiquitinated in a RING finger- and UBE2D2-dependent manner. Monoubiquitinated by TRIM21. Deubiquitinated by Yersinia YopJ. Ubiquitination may not lead to proteasomal degradation. {ECO:0000269|PubMed:20053985, ECO:0000269|PubMed:21734049}.

Similarity: Belongs to the TRIM/RBCC family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Macaca mulatta (Rhesus macaque).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Cercopithecidae; Cercopithecinae; Macaca.



Function:		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). {ECO:0000269\|PubMed:21035162, ECO:0000269\|PubMed:21734049, ECO:0000269\|PubMed:22291694, ECO:0000269\|PubMed:25127057}.


Catalytic activity:		Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27;
Pathway:		Protein modification; protein ubiquitination.
Subunit:		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). {ECO:0000250\|UniProtKB:Q9C035, ECO:0000269\|PubMed:17156811, ECO:0000269\|PubMed:20053985, ECO:0000269\|PubMed:20357094, ECO:0000269\|PubMed:21187419, ECO:0000269\|PubMed:21680743, ECO:0000269\|PubMed:21734049, ECO:0000269\|PubMed:22078707, ECO:0000269\|PubMed:25127057}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:17156811}. Nucleus {ECO:0000269\|PubMed:17156811}. Note=Predominantly localizes in cytoplasmic bodies (PubMed:20357094, PubMed:22078707). Localization may be influenced by the coexpression of other TRIM proteins, hence partial nuclear localization is observed in the presence of TRIM22 or TRIM27 (PubMed:17156811). In cytoplasmic bodies, colocalizes with proteasomal subunits and SQSTM1 (PubMed:20357094). {ECO:0000269\|PubMed:17156811, ECO:0000269\|PubMed:20357094, ECO:0000269\|PubMed:22078707}.
Domain:		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). {ECO:0000250\|UniProtKB:Q9C035, ECO:0000269\|PubMed:21680743}.
Domain:		The B30.2/SPRY domain acts as a capsid recognition domain. Polymorphisms in this domain explain the observed species-specific differences among orthologs. {ECO:0000269\|PubMed:21734049}.
Domain:		The RING-type zinc finger domain confers E3 ubiquitin ligase activity and is essential for retrovirus restriction activity, autoubiquitination and higher-order multimerization. {ECO:0000269\|PubMed:17156811, ECO:0000269\|PubMed:21734049}.
Ptm:		Degraded in a proteasome-independent fashion in the absence of viral infection but in a proteasome-dependent fashion following exposure to restriction sensitive virus. {ECO:0000250}.
Ptm:		Autoubiquitinated in a RING finger- and UBE2D2-dependent manner. Monoubiquitinated by TRIM21. Deubiquitinated by Yersinia YopJ. Ubiquitination may not lead to proteasomal degradation. {ECO:0000269\|PubMed:20053985, ECO:0000269\|PubMed:21734049}.
Similarity:		Belongs to the TRIM/RBCC family. {ECO:0000305}.