UniProt functional annotation for P97929



	UniProt functional annotation for P97929

UniProt code: P97929.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51- ssDNA filaments by blocking ATP hydrolysis. Part of a PALB2-scaffolded HR complex containing RAD51C and which is thought to play a role in DNA repair by HR. May participate in S phase checkpoint activation. Binds selectively to ssDNA, and to ssDNA in tailed duplexes and replication fork structures. May play a role in the extension step after strand invasion at replication-dependent DNA double-strand breaks; together with PALB2 is involved in both POLH localization at collapsed replication forks and DNA polymerization activity. In concert with NPM1, regulates centrosome duplication. Interacts with the TREX-2 complex (transcription and export complex 2) subunits PCID2 and SEM1, and is required to prevent R-loop-associated DNA damage and thus transcription-associated genomic instability, independently of its known role in homologous recombination (By similarity). {ECO:0000250|UniProtKB:O35923, ECO:0000250|UniProtKB:P51587}.

Subunit: Monomer and dimer. Interacts with RAD51; regulates RAD51 recruitment and function at sites of DNA repair. Interacts with SEM1, WDR16, USP11, DMC1, ROCK2 and NPM1. Interacts with both nonubiquitinated and monoubiquitinated FANCD2; this complex also includes XRCC3 and phosphorylated FANCG. Part of a BRCA complex containing BRCA1, BRCA2 and PALB2. Component of the homologous recombination repair (HR) complex composed of ERCC5/XPG, BRCA2, PALB2, DSS1 and RAD51 (By similarity). Within the complex, interacts with ERCC5/XPG and PALB2 (By similarity). Interacts directly with PALB2 which may serve as a scaffold for a HR complex containing PALB2, BRCA2, RAD51C, RAD51 and XRCC3. Interacts with BRCA1 only in the presence of PALB2 which serves as the bridging protein. Interacts with POLH; the interaction is direct. Interacts with the TREX-2 complex subunits PCID2 and SEM1 (By similarity). Interacts with HSF2BP and BRME1; the interaction with HSF2BP is direct and allows the formation of a ternary complex (PubMed:32345962, PubMed:32460033, PubMed:31242413, PubMed:30760716, PubMed:32845237). The complex BRME1:HSF2BP:BRCA2 interacts with SPATA22, MEIOB and RAD51 (PubMed:32345962, PubMed:30760716). {ECO:0000250|UniProtKB:O35923, ECO:0000250|UniProtKB:P51587, ECO:0000269|PubMed:12228710, ECO:0000269|PubMed:30760716, ECO:0000269|PubMed:31242413, ECO:0000269|PubMed:32345962, ECO:0000269|PubMed:32460033, ECO:0000269|PubMed:32845237}.

Subcellular location: Nucleus {ECO:0000250|UniProtKB:P51587}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250|UniProtKB:P51587}.

Tissue specificity: Widely expressed. Highest expression in cerebellum, testis, ileum, appendix, epididymis, ovary and mammary gland. No expression in lung. {ECO:0000269|PubMed:32460033}.

Developmental stage: In the mammary gland, expression increases dramatically during pregnancy.

Ptm: Phosphorylated by ATM upon irradiation-induced DNA damage. Phosphorylation by CHEK1 and CHEK2 regulates interaction with RAD51. Phosphorylation at Ser-3291 by CDK1 and CDK2 is low in S phase when recombination is active, but increases as cells progress towards mitosis; this phosphorylation prevents homologous recombination- dependent repair during S phase and G2 by inhibiting RAD51 binding. {ECO:0000250|UniProtKB:P51587}.

Ptm: Ubiquitinated in the absence of DNA damage; this does not lead to proteasomal degradation. In contrast, ubiquitination in response to DNA damage leads to proteasomal degradation. {ECO:0000250|UniProtKB:P51587}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51- ssDNA filaments by blocking ATP hydrolysis. Part of a PALB2-scaffolded HR complex containing RAD51C and which is thought to play a role in DNA repair by HR. May participate in S phase checkpoint activation. Binds selectively to ssDNA, and to ssDNA in tailed duplexes and replication fork structures. May play a role in the extension step after strand invasion at replication-dependent DNA double-strand breaks; together with PALB2 is involved in both POLH localization at collapsed replication forks and DNA polymerization activity. In concert with NPM1, regulates centrosome duplication. Interacts with the TREX-2 complex (transcription and export complex 2) subunits PCID2 and SEM1, and is required to prevent R-loop-associated DNA damage and thus transcription-associated genomic instability, independently of its known role in homologous recombination (By similarity). {ECO:0000250\|UniProtKB:O35923, ECO:0000250\|UniProtKB:P51587}.


Subunit:		Monomer and dimer. Interacts with RAD51; regulates RAD51 recruitment and function at sites of DNA repair. Interacts with SEM1, WDR16, USP11, DMC1, ROCK2 and NPM1. Interacts with both nonubiquitinated and monoubiquitinated FANCD2; this complex also includes XRCC3 and phosphorylated FANCG. Part of a BRCA complex containing BRCA1, BRCA2 and PALB2. Component of the homologous recombination repair (HR) complex composed of ERCC5/XPG, BRCA2, PALB2, DSS1 and RAD51 (By similarity). Within the complex, interacts with ERCC5/XPG and PALB2 (By similarity). Interacts directly with PALB2 which may serve as a scaffold for a HR complex containing PALB2, BRCA2, RAD51C, RAD51 and XRCC3. Interacts with BRCA1 only in the presence of PALB2 which serves as the bridging protein. Interacts with POLH; the interaction is direct. Interacts with the TREX-2 complex subunits PCID2 and SEM1 (By similarity). Interacts with HSF2BP and BRME1; the interaction with HSF2BP is direct and allows the formation of a ternary complex (PubMed:32345962, PubMed:32460033, PubMed:31242413, PubMed:30760716, PubMed:32845237). The complex BRME1:HSF2BP:BRCA2 interacts with SPATA22, MEIOB and RAD51 (PubMed:32345962, PubMed:30760716). {ECO:0000250\|UniProtKB:O35923, ECO:0000250\|UniProtKB:P51587, ECO:0000269\|PubMed:12228710, ECO:0000269\|PubMed:30760716, ECO:0000269\|PubMed:31242413, ECO:0000269\|PubMed:32345962, ECO:0000269\|PubMed:32460033, ECO:0000269\|PubMed:32845237}.
Subcellular location:		Nucleus {ECO:0000250\|UniProtKB:P51587}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250\|UniProtKB:P51587}.
Tissue specificity:		Widely expressed. Highest expression in cerebellum, testis, ileum, appendix, epididymis, ovary and mammary gland. No expression in lung. {ECO:0000269\|PubMed:32460033}.
Developmental stage:		In the mammary gland, expression increases dramatically during pregnancy.
Ptm:		Phosphorylated by ATM upon irradiation-induced DNA damage. Phosphorylation by CHEK1 and CHEK2 regulates interaction with RAD51. Phosphorylation at Ser-3291 by CDK1 and CDK2 is low in S phase when recombination is active, but increases as cells progress towards mitosis; this phosphorylation prevents homologous recombination- dependent repair during S phase and G2 by inhibiting RAD51 binding. {ECO:0000250\|UniProtKB:P51587}.
Ptm:		Ubiquitinated in the absence of DNA damage; this does not lead to proteasomal degradation. In contrast, ubiquitination in response to DNA damage leads to proteasomal degradation. {ECO:0000250\|UniProtKB:P51587}.