UniProt functional annotation for P61088



	UniProt functional annotation for P61088

UniProt code: P61088.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: The UBE2V1-UBE2N and UBE2V2-UBE2N heterodimers catalyze the synthesis of non-canonical 'Lys-63'-linked polyubiquitin chains. This type of polyubiquitination does not lead to protein degradation by the proteasome. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Acts together with the E3 ligases, HLTF and SHPRH, in the 'Lys-63'-linked poly- ubiquitination of PCNA upon genotoxic stress, which is required for DNA repair. Appears to act together with E3 ligase RNF5 in the 'Lys-63'- linked polyubiquitination of JKAMP thereby regulating JKAMP function by decreasing its association with components of the proteasome and ERAD. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1- UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'- linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes. Together with RNF135 and UB2V1, catalyzes the viral RNA-dependent 'Lys-63'-linked polyubiquitination of RIG-I/DDX58 to activate the downstream signaling pathway that leads to interferon beta production (PubMed:28469175, PubMed:31006531). UBE2V1- UBE2N together with TRAF3IP2 E3 ubiquitin ligase mediate 'Lys-63'- linked polyubiquitination of TRAF6, a component of IL17A-mediated signaling pathway. {ECO:0000269|PubMed:10089880, ECO:0000269|PubMed:14562038, ECO:0000269|PubMed:19269966, ECO:0000269|PubMed:19825828, ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:21512573, ECO:0000269|PubMed:28469175, ECO:0000269|PubMed:31006531}.

Catalytic activity: Reaction=S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine = [E1 ubiquitin- activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin- conjugating enzyme]-L-cysteine.; EC=2.3.2.23; Evidence={ECO:0000255|PROSITE-ProRule:PRU00388, ECO:0000255|PROSITE- ProRule:PRU10133, ECO:0000269|PubMed:20061386};

Activity regulation: Activity is inhibited by binding to OTUB1, which prevents 'Lys-63'-linked polyubiquitination (PubMed:20725033, PubMed:22325355, PubMed:22367539). Activity is inhibited by GPS2, leading to prevent 'Lys-63'-linked polyubiquitination (By similarity). {ECO:0000250|UniProtKB:P61089, ECO:0000269|PubMed:20725033, ECO:0000269|PubMed:22325355, ECO:0000269|PubMed:22367539}.

Pathway: Protein modification; protein ubiquitination. {ECO:0000255|PROSITE-ProRule:PRU00388}.

Subunit: Heterodimer with UBE2V2 (PubMed:10089880, PubMed:11473255, PubMed:14562038, PubMed:16307917, PubMed:16307917). Interacts (UBE2V2- UBE2N heterodimer) with the E3 ligase STUB1 (via the U-box domain); the complex has a specific 'Lys-63'-linked polyubiquitination activity (PubMed:16307917). Interacts with RNF8 and RNF168 (PubMed:16215985, PubMed:19203578). Interacts with RNF11 (PubMed:18615712). Interacts with the E3 ligases, HLTF and SHPRH; the interactions promote the 'Lys- 63'-linked polyubiquitination of PCNA upon genotoxic stress and lead to DNA repair (PubMed:17108083, PubMed:17130289, PubMed:18316726, PubMed:18719106). Interacts with ARIH2 (via RING-type 2) (PubMed:19340006). Interacts with OTUB1; leading to inhibit E2- conjugating activity (PubMed:20725033, PubMed:22325355, PubMed:22367539). Interacts with GPS2; leading to inhibit E2- conjugating activity (By similarity). Interacts with DDX58 and RNF135; involved in DDX58 ubiquitination and activation (PubMed:28469175). {ECO:0000250|UniProtKB:P61089, ECO:0000269|PubMed:10089880, ECO:0000269|PubMed:11473255, ECO:0000269|PubMed:14562038, ECO:0000269|PubMed:16215985, ECO:0000269|PubMed:16307917, ECO:0000269|PubMed:17108083, ECO:0000269|PubMed:17130289, ECO:0000269|PubMed:18316726, ECO:0000269|PubMed:18615712, ECO:0000269|PubMed:18719106, ECO:0000269|PubMed:19203578, ECO:0000269|PubMed:19340006, ECO:0000269|PubMed:20725033, ECO:0000269|PubMed:22325355, ECO:0000269|PubMed:22367539, ECO:0000269|PubMed:22589545, ECO:0000269|PubMed:28469175}.

Subcellular location: Nucleus {ECO:0000269|PubMed:19340006}. Cytoplasm {ECO:0000269|PubMed:19340006}.

Ptm: Conjugation to ISG15 impairs formation of the thioester bond with ubiquitin but not interaction with UBE2V2. {ECO:0000269|PubMed:16112642}.

Similarity: Belongs to the ubiquitin-conjugating enzyme family. {ECO:0000255|PROSITE-ProRule:PRU00388}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		The UBE2V1-UBE2N and UBE2V2-UBE2N heterodimers catalyze the synthesis of non-canonical 'Lys-63'-linked polyubiquitin chains. This type of polyubiquitination does not lead to protein degradation by the proteasome. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Acts together with the E3 ligases, HLTF and SHPRH, in the 'Lys-63'-linked poly- ubiquitination of PCNA upon genotoxic stress, which is required for DNA repair. Appears to act together with E3 ligase RNF5 in the 'Lys-63'- linked polyubiquitination of JKAMP thereby regulating JKAMP function by decreasing its association with components of the proteasome and ERAD. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1- UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'- linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes. Together with RNF135 and UB2V1, catalyzes the viral RNA-dependent 'Lys-63'-linked polyubiquitination of RIG-I/DDX58 to activate the downstream signaling pathway that leads to interferon beta production (PubMed:28469175, PubMed:31006531). UBE2V1- UBE2N together with TRAF3IP2 E3 ubiquitin ligase mediate 'Lys-63'- linked polyubiquitination of TRAF6, a component of IL17A-mediated signaling pathway. {ECO:0000269\|PubMed:10089880, ECO:0000269\|PubMed:14562038, ECO:0000269\|PubMed:19269966, ECO:0000269\|PubMed:19825828, ECO:0000269\|PubMed:20061386, ECO:0000269\|PubMed:21512573, ECO:0000269\|PubMed:28469175, ECO:0000269\|PubMed:31006531}.


Catalytic activity:		Reaction=S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine = [E1 ubiquitin- activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin- conjugating enzyme]-L-cysteine.; EC=2.3.2.23; Evidence={ECO:0000255\|PROSITE-ProRule:PRU00388, ECO:0000255\|PROSITE- ProRule:PRU10133, ECO:0000269\|PubMed:20061386};
Activity regulation:		Activity is inhibited by binding to OTUB1, which prevents 'Lys-63'-linked polyubiquitination (PubMed:20725033, PubMed:22325355, PubMed:22367539). Activity is inhibited by GPS2, leading to prevent 'Lys-63'-linked polyubiquitination (By similarity). {ECO:0000250\|UniProtKB:P61089, ECO:0000269\|PubMed:20725033, ECO:0000269\|PubMed:22325355, ECO:0000269\|PubMed:22367539}.
Pathway:		Protein modification; protein ubiquitination. {ECO:0000255\|PROSITE-ProRule:PRU00388}.
Subunit:		Heterodimer with UBE2V2 (PubMed:10089880, PubMed:11473255, PubMed:14562038, PubMed:16307917, PubMed:16307917). Interacts (UBE2V2- UBE2N heterodimer) with the E3 ligase STUB1 (via the U-box domain); the complex has a specific 'Lys-63'-linked polyubiquitination activity (PubMed:16307917). Interacts with RNF8 and RNF168 (PubMed:16215985, PubMed:19203578). Interacts with RNF11 (PubMed:18615712). Interacts with the E3 ligases, HLTF and SHPRH; the interactions promote the 'Lys- 63'-linked polyubiquitination of PCNA upon genotoxic stress and lead to DNA repair (PubMed:17108083, PubMed:17130289, PubMed:18316726, PubMed:18719106). Interacts with ARIH2 (via RING-type 2) (PubMed:19340006). Interacts with OTUB1; leading to inhibit E2- conjugating activity (PubMed:20725033, PubMed:22325355, PubMed:22367539). Interacts with GPS2; leading to inhibit E2- conjugating activity (By similarity). Interacts with DDX58 and RNF135; involved in DDX58 ubiquitination and activation (PubMed:28469175). {ECO:0000250\|UniProtKB:P61089, ECO:0000269\|PubMed:10089880, ECO:0000269\|PubMed:11473255, ECO:0000269\|PubMed:14562038, ECO:0000269\|PubMed:16215985, ECO:0000269\|PubMed:16307917, ECO:0000269\|PubMed:17108083, ECO:0000269\|PubMed:17130289, ECO:0000269\|PubMed:18316726, ECO:0000269\|PubMed:18615712, ECO:0000269\|PubMed:18719106, ECO:0000269\|PubMed:19203578, ECO:0000269\|PubMed:19340006, ECO:0000269\|PubMed:20725033, ECO:0000269\|PubMed:22325355, ECO:0000269\|PubMed:22367539, ECO:0000269\|PubMed:22589545, ECO:0000269\|PubMed:28469175}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:19340006}. Cytoplasm {ECO:0000269\|PubMed:19340006}.
Ptm:		Conjugation to ISG15 impairs formation of the thioester bond with ubiquitin but not interaction with UBE2V2. {ECO:0000269\|PubMed:16112642}.
Similarity:		Belongs to the ubiquitin-conjugating enzyme family. {ECO:0000255\|PROSITE-ProRule:PRU00388}.