UniProt functional annotation for Q9UI95



	UniProt functional annotation for Q9UI95

UniProt code: Q9UI95.

Organism: Homo sapiens (Human).

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

Function: Adapter protein able to interact with different proteins and involved in different biological processes (PubMed:11459825, PubMed:11459826, PubMed:17719540, PubMed:17296730, PubMed:19443654, PubMed:29656893). Mediates the interaction between the error-prone DNA polymerase zeta catalytic subunit REV3L and the inserter polymerase REV1, thereby mediating the second polymerase switching in translesion DNA synthesis (PubMed:20164194). Translesion DNA synthesis releases the replication blockade of replicative polymerases, stalled in presence of DNA lesions (PubMed:20164194). Component of the shieldin complex, which plays an important role in repair of DNA double-stranded breaks (DSBs) (PubMed:29656893). During G1 and S phase of the cell cycle, the complex functions downstream of TP53BP1 to promote non-homologous end joining (NHEJ) and suppress DNA end resection (PubMed:29656893). Mediates various NHEJ-dependent processes including immunoglobulin class-switch recombination, and fusion of unprotected telomeres (PubMed:29656893). May also regulate another aspect of cellular response to DNA damage through regulation of the JNK-mediated phosphorylation and activation of the transcriptional activator ELK1 (PubMed:17296730). Inhibits the FZR1- and probably CDC20-mediated activation of the anaphase promoting complex APC thereby regulating progression through the cell cycle (PubMed:11459825, PubMed:17719540). Regulates TCF7L2-mediated gene transcription and may play a role in epithelial-mesenchymal transdifferentiation (PubMed:19443654). {ECO:0000269|PubMed:11459825, ECO:0000269|PubMed:11459826, ECO:0000269|PubMed:17296730, ECO:0000269|PubMed:17719540, ECO:0000269|PubMed:19443654, ECO:0000269|PubMed:20164194, ECO:0000269|PubMed:29656893}.

Subunit: Homooligomer (Probable). Heterodimer with REV3L (PubMed:10660610, PubMed:11485998). This dimer forms the minimal DNA polymerase zeta complex (Pol-zeta2), with REV3L bearing DNA polymerase catalytic activity, although its activity is very low in this context (PubMed:11485998). Component of the tetrameric Pol-zeta complex (Pol- zeta4), which consists of REV3L, MAD2L2, POLD2 and POLD3; Pol-zeta4 is the fully active form of DNA polymerase zeta (PubMed:24449906). Component of the shieldin complex, consisting of SHLD1, SHLD2, SHLD3 and MAD2L2/REV7 (PubMed:29656893, PubMed:29789392). Within the complex, SHLD2 forms a scaffold which interacts with a SHLD3-MAD2L2 subcomplex via its N-terminus, and with SHLD1 via its C-terminus (PubMed:29656893). Interacts with REV1 (PubMed:11485998, PubMed:20164194). Interacts with ADAM9 (PubMed:10527948). Interacts with CHAMP1 (PubMed:21063390). Interacts with FZR1 (in complex with the anaphase promoting complex APC) (PubMed:11459825, PubMed:11459826). Interacts with CDC20; PubMed:11459825 could not detect the interaction (PubMed:11459826). Interacts with RAN (PubMed:19753112). Interacts with ELK1; the interaction is direct and recruits MAD2L2 to ELK1-specific promoters (PubMed:17296730). May interact with the JNK kinases MAPK8 and/or MAPK9 to stimulate ELK1 phosphorylation and transcriptional activity upon DNA damage (PubMed:17296730). Interacts with TCF7L2; prevents its binding to promoters and negatively modulates its transcriptional activity (PubMed:19443654). Interacts with YY1AP1 (PubMed:17541814). Interacts with S.flexneri protein ipaB; prevents the interaction of MAD2L2 with FZR1 and CDC20 resulting in an activation of the anaphase-promoting complex APC and a cell cycle arrest (PubMed:17719540). Interacts with PRCC; the interaction is direct (PubMed:11717438). Interacts with POGZ (PubMed:20850016). {ECO:0000269|PubMed:10527948, ECO:0000269|PubMed:10660610, ECO:0000269|PubMed:11459825, ECO:0000269|PubMed:11459826, ECO:0000269|PubMed:11485998, ECO:0000269|PubMed:11717438, ECO:0000269|PubMed:17296730, ECO:0000269|PubMed:17541814, ECO:0000269|PubMed:17719540, ECO:0000269|PubMed:19443654, ECO:0000269|PubMed:19753112, ECO:0000269|PubMed:20164194, ECO:0000269|PubMed:20850016, ECO:0000269|PubMed:21063390, ECO:0000269|PubMed:24449906, ECO:0000269|PubMed:29656893, ECO:0000269|PubMed:29789392, ECO:0000305}.

Subcellular location: Nucleus {ECO:0000269|PubMed:11717438, ECO:0000269|PubMed:17541814, ECO:0000269|PubMed:17719540, ECO:0000269|PubMed:19753112}. Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:19753112, ECO:0000269|PubMed:21063390}. Cytoplasm {ECO:0000269|PubMed:11717438, ECO:0000269|PubMed:17719540}. Chromosome {ECO:0000269|PubMed:29656893}. Note=Recruited to sites of chromosomal double-stranded breaks during G1 and S phase of the cell cycle. {ECO:0000269|PubMed:29656893}.

Tissue specificity: Ubiquitously expressed. {ECO:0000269|PubMed:11717438}.

Disease: Fanconi anemia, complementation group V (FANCV) [MIM:617243]: A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair. {ECO:0000269|PubMed:27500492}. Note=The disease is caused by variants affecting the gene represented in this entry.

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:		Adapter protein able to interact with different proteins and involved in different biological processes (PubMed:11459825, PubMed:11459826, PubMed:17719540, PubMed:17296730, PubMed:19443654, PubMed:29656893). Mediates the interaction between the error-prone DNA polymerase zeta catalytic subunit REV3L and the inserter polymerase REV1, thereby mediating the second polymerase switching in translesion DNA synthesis (PubMed:20164194). Translesion DNA synthesis releases the replication blockade of replicative polymerases, stalled in presence of DNA lesions (PubMed:20164194). Component of the shieldin complex, which plays an important role in repair of DNA double-stranded breaks (DSBs) (PubMed:29656893). During G1 and S phase of the cell cycle, the complex functions downstream of TP53BP1 to promote non-homologous end joining (NHEJ) and suppress DNA end resection (PubMed:29656893). Mediates various NHEJ-dependent processes including immunoglobulin class-switch recombination, and fusion of unprotected telomeres (PubMed:29656893). May also regulate another aspect of cellular response to DNA damage through regulation of the JNK-mediated phosphorylation and activation of the transcriptional activator ELK1 (PubMed:17296730). Inhibits the FZR1- and probably CDC20-mediated activation of the anaphase promoting complex APC thereby regulating progression through the cell cycle (PubMed:11459825, PubMed:17719540). Regulates TCF7L2-mediated gene transcription and may play a role in epithelial-mesenchymal transdifferentiation (PubMed:19443654). {ECO:0000269\|PubMed:11459825, ECO:0000269\|PubMed:11459826, ECO:0000269\|PubMed:17296730, ECO:0000269\|PubMed:17719540, ECO:0000269\|PubMed:19443654, ECO:0000269\|PubMed:20164194, ECO:0000269\|PubMed:29656893}.


Subunit:		Homooligomer (Probable). Heterodimer with REV3L (PubMed:10660610, PubMed:11485998). This dimer forms the minimal DNA polymerase zeta complex (Pol-zeta2), with REV3L bearing DNA polymerase catalytic activity, although its activity is very low in this context (PubMed:11485998). Component of the tetrameric Pol-zeta complex (Pol- zeta4), which consists of REV3L, MAD2L2, POLD2 and POLD3; Pol-zeta4 is the fully active form of DNA polymerase zeta (PubMed:24449906). Component of the shieldin complex, consisting of SHLD1, SHLD2, SHLD3 and MAD2L2/REV7 (PubMed:29656893, PubMed:29789392). Within the complex, SHLD2 forms a scaffold which interacts with a SHLD3-MAD2L2 subcomplex via its N-terminus, and with SHLD1 via its C-terminus (PubMed:29656893). Interacts with REV1 (PubMed:11485998, PubMed:20164194). Interacts with ADAM9 (PubMed:10527948). Interacts with CHAMP1 (PubMed:21063390). Interacts with FZR1 (in complex with the anaphase promoting complex APC) (PubMed:11459825, PubMed:11459826). Interacts with CDC20; PubMed:11459825 could not detect the interaction (PubMed:11459826). Interacts with RAN (PubMed:19753112). Interacts with ELK1; the interaction is direct and recruits MAD2L2 to ELK1-specific promoters (PubMed:17296730). May interact with the JNK kinases MAPK8 and/or MAPK9 to stimulate ELK1 phosphorylation and transcriptional activity upon DNA damage (PubMed:17296730). Interacts with TCF7L2; prevents its binding to promoters and negatively modulates its transcriptional activity (PubMed:19443654). Interacts with YY1AP1 (PubMed:17541814). Interacts with S.flexneri protein ipaB; prevents the interaction of MAD2L2 with FZR1 and CDC20 resulting in an activation of the anaphase-promoting complex APC and a cell cycle arrest (PubMed:17719540). Interacts with PRCC; the interaction is direct (PubMed:11717438). Interacts with POGZ (PubMed:20850016). {ECO:0000269\|PubMed:10527948, ECO:0000269\|PubMed:10660610, ECO:0000269\|PubMed:11459825, ECO:0000269\|PubMed:11459826, ECO:0000269\|PubMed:11485998, ECO:0000269\|PubMed:11717438, ECO:0000269\|PubMed:17296730, ECO:0000269\|PubMed:17541814, ECO:0000269\|PubMed:17719540, ECO:0000269\|PubMed:19443654, ECO:0000269\|PubMed:19753112, ECO:0000269\|PubMed:20164194, ECO:0000269\|PubMed:20850016, ECO:0000269\|PubMed:21063390, ECO:0000269\|PubMed:24449906, ECO:0000269\|PubMed:29656893, ECO:0000269\|PubMed:29789392, ECO:0000305}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:11717438, ECO:0000269\|PubMed:17541814, ECO:0000269\|PubMed:17719540, ECO:0000269\|PubMed:19753112}. Cytoplasm, cytoskeleton, spindle {ECO:0000269\|PubMed:19753112, ECO:0000269\|PubMed:21063390}. Cytoplasm {ECO:0000269\|PubMed:11717438, ECO:0000269\|PubMed:17719540}. Chromosome {ECO:0000269\|PubMed:29656893}. Note=Recruited to sites of chromosomal double-stranded breaks during G1 and S phase of the cell cycle. {ECO:0000269\|PubMed:29656893}.
Tissue specificity:		Ubiquitously expressed. {ECO:0000269\|PubMed:11717438}.
Disease:		Fanconi anemia, complementation group V (FANCV) [MIM:617243]: A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair. {ECO:0000269\|PubMed:27500492}. Note=The disease is caused by variants affecting the gene represented in this entry.