UniProt functional annotation for Q06609



	UniProt functional annotation for Q06609

UniProt code: Q06609.

Organism: Homo sapiens (Human).

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

Function: Plays an important role in homologous strand exchange, a key step in DNA repair through homologous recombination (HR) (PubMed:28575658). Binds to single and double-stranded DNA and exhibits DNA-dependent ATPase activity. Catalyzes the recognition of homology and strand exchange between homologous DNA partners to form a joint molecule between a processed DNA break and the repair template. Binds to single-stranded DNA in an ATP-dependent manner to form nucleoprotein filaments which are essential for the homology search and strand exchange (PubMed:26681308). Part of a PALB2-scaffolded HR complex containing BRCA2 and RAD51C and which is thought to play a role in DNA repair by HR. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51C and XRCC3. Also involved in interstrand cross-link repair (PubMed:26253028). {ECO:0000269|PubMed:12205100, ECO:0000269|PubMed:12442171, ECO:0000269|PubMed:18417535, ECO:0000269|PubMed:20231364, ECO:0000269|PubMed:20348101, ECO:0000269|PubMed:20413593, ECO:0000269|PubMed:23509288, ECO:0000269|PubMed:23754376, ECO:0000269|PubMed:26253028, ECO:0000269|PubMed:26681308, ECO:0000269|PubMed:28575658}.

Subunit: Forms linear homooligomers, giving rise to a RAD51 nucleoprotein filament, which is essential for strand-pairing reactions during DNA recombination. Interacts with BRCA1 and either directly or indirectly with p53. Interacts with XRCC3, RAD54L and RAD54B. Interacts with the BCDX2 subcomplex RAD51C:RAD51B. Component of the homologous recombination repair (HR) complex composed of ERCC5/XPG, BRCA2, PALB2, DSS1 and RAD51 (PubMed:26833090). Interacts directly with PALB2 which may serve as a scaffold for a HR complex containing PALB2, BRCA2, RAD51C, RAD51 and XRCC3. Interacts with RAD51AP1 and RAD51AP2. Interacts with CHEK1, and this may require prior phosphorylation of CHEK1. Interacts with the MND1-PSMC3IP heterodimer. Found in a complex, at least composed of BLM, RAD51 and SPIDR; the complex formation is mediated by SPIDR. Interacts with SPIDR; the interaction is direct and recruits RAD51 to DNA damage sites. Interacts with FIGNL1 (via N- terminal one-half region); the interaction is direct. Interacts with RAD51AP1 (via C-terminal region); the interaction is direct. Interacts with NABP2, RPA1, PALB2 and RAD51. Interacts with SWI5/C9orf119, and at lower level with SFR1/MEIR5. Interacts with hyperphosphorylated RPA2; this interaction is necessary for efficient recruitment to chromatin in response to DNA damage. Interacts with SWSAP1; involved in homologous recombination repair. Interacts with PARPBP, BRCA2 and RECQL5; these interactions interfere with the formation of the RAD51-DNA homologous recombination structure. Interacts with POLQ; POLQ acts as an inhibitor of homology-recombination repair (HR) pathway by limiting RAD51 accumulation at resected ends (PubMed:25642963). Interacts with FBH1 (PubMed:23393192). Interacts with POLN (PubMed:19995904). Interacts with RFWD3 (PubMed:28575658). Interacts with the MCM8-MCM9 complex; the interaction recruits RAD51 to DNA damage sites (PubMed:23401855). Component of a multiprotein complex with MEIOB and SPATA22. Interacts with the complex BRME1:HSF2BP:BRCA2 (By similarity). {ECO:0000250|UniProtKB:Q08297, ECO:0000269|PubMed:10851248, ECO:0000269|PubMed:11842113, ECO:0000269|PubMed:12427746, ECO:0000269|PubMed:12442171, ECO:0000269|PubMed:14580352, ECO:0000269|PubMed:15665856, ECO:0000269|PubMed:16990250, ECO:0000269|PubMed:18449195, ECO:0000269|PubMed:19995904, ECO:0000269|PubMed:20154705, ECO:0000269|PubMed:20231364, ECO:0000269|PubMed:20348101, ECO:0000269|PubMed:20705237, ECO:0000269|PubMed:20871615, ECO:0000269|PubMed:21252223, ECO:0000269|PubMed:21965664, ECO:0000269|PubMed:22153967, ECO:0000269|PubMed:23393192, ECO:0000269|PubMed:23401855, ECO:0000269|PubMed:23509288, ECO:0000269|PubMed:23754376, ECO:0000269|PubMed:24141787, ECO:0000269|PubMed:25642963, ECO:0000269|PubMed:26833090, ECO:0000269|PubMed:28575658, ECO:0000269|PubMed:9192668, ECO:0000269|PubMed:9321665, ECO:0000269|PubMed:9396801, ECO:0000269|PubMed:9461559}.

Subcellular location: Nucleus {ECO:0000269|PubMed:12442171, ECO:0000269|PubMed:15665856, ECO:0000269|PubMed:18417535, ECO:0000269|PubMed:19783859, ECO:0000269|PubMed:23401855, ECO:0000269|PubMed:23509288, ECO:0000269|PubMed:26681308, ECO:0000269|PubMed:26833090, ECO:0000269|PubMed:9192668}. Cytoplasm {ECO:0000269|PubMed:16215984, ECO:0000269|PubMed:26681308}. Cytoplasm, perinuclear region. Mitochondrion matrix {ECO:0000269|PubMed:20413593}. Chromosome {ECO:0000269|PubMed:23401855}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:21276791}. Note=Colocalizes with RAD51AP1 and RPA2 to multiple nuclear foci upon induction of DNA damage (PubMed:20154705). DNA damage induces an increase in nuclear levels (PubMed:20154705). Together with FIGNL1, redistributed in discrete nuclear DNA damage-induced foci after ionizing radiation (IR) or camptothecin (CPT) treatment (PubMed:23754376). Accumulated at sites of DNA damage in a SPIDR-dependent manner (PubMed:23509288). Recruited at sites of DNA damage in a MCM9-MCM8-dependent manner (PubMed:23401855). Colocalizes with ERCC5/XPG to nuclear foci in S phase (PubMed:26833090). {ECO:0000269|PubMed:20154705, ECO:0000269|PubMed:23401855, ECO:0000269|PubMed:23509288, ECO:0000269|PubMed:23754376, ECO:0000269|PubMed:26833090}.

Tissue specificity: Highly expressed in testis and thymus, followed by small intestine, placenta, colon, pancreas and ovary. Weakly expressed in breast.

Induction: Stress-induced increase in the mitochondrial levels is seen. {ECO:0000269|PubMed:20413593}.

Domain: The nuclear localization may reside in the C-terminus (between 259 and 339 AA).

Ptm: Ubiquitinated by the SCF(FBH1) E3 ubiquitin ligase complex, regulating RAD51 subcellular location and preventing its association with DNA. Ubiquitinated by RFWD3 in response to DNA damage: ubiquitination leads to degradation by the proteasome, promoting homologous recombination (PubMed:28575658). {ECO:0000269|PubMed:23393192, ECO:0000269|PubMed:28575658}.

Ptm: Phosphorylated. Phosphorylation of Thr-309 by CHEK1 may enhance association with chromatin at sites of DNA damage and promote DNA repair by homologous recombination. Phosphorylation by ABL1 inhibits function. {ECO:0000269|PubMed:15665856, ECO:0000269|PubMed:9461559}.

Disease: Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269|PubMed:10807537, ECO:0000269|PubMed:25539919}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.

Disease: Mirror movements 2 (MRMV2) [MIM:614508]: A disorder characterized by contralateral involuntary movements that mirror voluntary ones. While mirror movements are occasionally found in young children, persistence beyond the age of 10 is abnormal. Mirror movements occur more commonly in the upper extremities. {ECO:0000269|PubMed:22305526}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Fanconi anemia, complementation group R (FANCR) [MIM:617244]: 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:26253028, ECO:0000269|PubMed:26681308}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: [Isoform 3]: Mutagenesis of Arg-264 to Ala inhibits nuclear localization. Mutagenesis of Lys-264 to Gln inhibits nuclear localization. Deletion of 254-Arg-Lys-255 inhibits nuclear localization. {ECO:0000269|PubMed:18417535}.

Similarity: Belongs to the RecA family. RAD51 subfamily. {ECO:0000305}.

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:		Plays an important role in homologous strand exchange, a key step in DNA repair through homologous recombination (HR) (PubMed:28575658). Binds to single and double-stranded DNA and exhibits DNA-dependent ATPase activity. Catalyzes the recognition of homology and strand exchange between homologous DNA partners to form a joint molecule between a processed DNA break and the repair template. Binds to single-stranded DNA in an ATP-dependent manner to form nucleoprotein filaments which are essential for the homology search and strand exchange (PubMed:26681308). Part of a PALB2-scaffolded HR complex containing BRCA2 and RAD51C and which is thought to play a role in DNA repair by HR. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51C and XRCC3. Also involved in interstrand cross-link repair (PubMed:26253028). {ECO:0000269\|PubMed:12205100, ECO:0000269\|PubMed:12442171, ECO:0000269\|PubMed:18417535, ECO:0000269\|PubMed:20231364, ECO:0000269\|PubMed:20348101, ECO:0000269\|PubMed:20413593, ECO:0000269\|PubMed:23509288, ECO:0000269\|PubMed:23754376, ECO:0000269\|PubMed:26253028, ECO:0000269\|PubMed:26681308, ECO:0000269\|PubMed:28575658}.


Subunit:		Forms linear homooligomers, giving rise to a RAD51 nucleoprotein filament, which is essential for strand-pairing reactions during DNA recombination. Interacts with BRCA1 and either directly or indirectly with p53. Interacts with XRCC3, RAD54L and RAD54B. Interacts with the BCDX2 subcomplex RAD51C:RAD51B. Component of the homologous recombination repair (HR) complex composed of ERCC5/XPG, BRCA2, PALB2, DSS1 and RAD51 (PubMed:26833090). Interacts directly with PALB2 which may serve as a scaffold for a HR complex containing PALB2, BRCA2, RAD51C, RAD51 and XRCC3. Interacts with RAD51AP1 and RAD51AP2. Interacts with CHEK1, and this may require prior phosphorylation of CHEK1. Interacts with the MND1-PSMC3IP heterodimer. Found in a complex, at least composed of BLM, RAD51 and SPIDR; the complex formation is mediated by SPIDR. Interacts with SPIDR; the interaction is direct and recruits RAD51 to DNA damage sites. Interacts with FIGNL1 (via N- terminal one-half region); the interaction is direct. Interacts with RAD51AP1 (via C-terminal region); the interaction is direct. Interacts with NABP2, RPA1, PALB2 and RAD51. Interacts with SWI5/C9orf119, and at lower level with SFR1/MEIR5. Interacts with hyperphosphorylated RPA2; this interaction is necessary for efficient recruitment to chromatin in response to DNA damage. Interacts with SWSAP1; involved in homologous recombination repair. Interacts with PARPBP, BRCA2 and RECQL5; these interactions interfere with the formation of the RAD51-DNA homologous recombination structure. Interacts with POLQ; POLQ acts as an inhibitor of homology-recombination repair (HR) pathway by limiting RAD51 accumulation at resected ends (PubMed:25642963). Interacts with FBH1 (PubMed:23393192). Interacts with POLN (PubMed:19995904). Interacts with RFWD3 (PubMed:28575658). Interacts with the MCM8-MCM9 complex; the interaction recruits RAD51 to DNA damage sites (PubMed:23401855). Component of a multiprotein complex with MEIOB and SPATA22. Interacts with the complex BRME1:HSF2BP:BRCA2 (By similarity). {ECO:0000250\|UniProtKB:Q08297, ECO:0000269\|PubMed:10851248, ECO:0000269\|PubMed:11842113, ECO:0000269\|PubMed:12427746, ECO:0000269\|PubMed:12442171, ECO:0000269\|PubMed:14580352, ECO:0000269\|PubMed:15665856, ECO:0000269\|PubMed:16990250, ECO:0000269\|PubMed:18449195, ECO:0000269\|PubMed:19995904, ECO:0000269\|PubMed:20154705, ECO:0000269\|PubMed:20231364, ECO:0000269\|PubMed:20348101, ECO:0000269\|PubMed:20705237, ECO:0000269\|PubMed:20871615, ECO:0000269\|PubMed:21252223, ECO:0000269\|PubMed:21965664, ECO:0000269\|PubMed:22153967, ECO:0000269\|PubMed:23393192, ECO:0000269\|PubMed:23401855, ECO:0000269\|PubMed:23509288, ECO:0000269\|PubMed:23754376, ECO:0000269\|PubMed:24141787, ECO:0000269\|PubMed:25642963, ECO:0000269\|PubMed:26833090, ECO:0000269\|PubMed:28575658, ECO:0000269\|PubMed:9192668, ECO:0000269\|PubMed:9321665, ECO:0000269\|PubMed:9396801, ECO:0000269\|PubMed:9461559}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:12442171, ECO:0000269\|PubMed:15665856, ECO:0000269\|PubMed:18417535, ECO:0000269\|PubMed:19783859, ECO:0000269\|PubMed:23401855, ECO:0000269\|PubMed:23509288, ECO:0000269\|PubMed:26681308, ECO:0000269\|PubMed:26833090, ECO:0000269\|PubMed:9192668}. Cytoplasm {ECO:0000269\|PubMed:16215984, ECO:0000269\|PubMed:26681308}. Cytoplasm, perinuclear region. Mitochondrion matrix {ECO:0000269\|PubMed:20413593}. Chromosome {ECO:0000269\|PubMed:23401855}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269\|PubMed:21276791}. Note=Colocalizes with RAD51AP1 and RPA2 to multiple nuclear foci upon induction of DNA damage (PubMed:20154705). DNA damage induces an increase in nuclear levels (PubMed:20154705). Together with FIGNL1, redistributed in discrete nuclear DNA damage-induced foci after ionizing radiation (IR) or camptothecin (CPT) treatment (PubMed:23754376). Accumulated at sites of DNA damage in a SPIDR-dependent manner (PubMed:23509288). Recruited at sites of DNA damage in a MCM9-MCM8-dependent manner (PubMed:23401855). Colocalizes with ERCC5/XPG to nuclear foci in S phase (PubMed:26833090). {ECO:0000269\|PubMed:20154705, ECO:0000269\|PubMed:23401855, ECO:0000269\|PubMed:23509288, ECO:0000269\|PubMed:23754376, ECO:0000269\|PubMed:26833090}.
Tissue specificity:		Highly expressed in testis and thymus, followed by small intestine, placenta, colon, pancreas and ovary. Weakly expressed in breast.
Induction:		Stress-induced increase in the mitochondrial levels is seen. {ECO:0000269\|PubMed:20413593}.
Domain:		The nuclear localization may reside in the C-terminus (between 259 and 339 AA).
Ptm:		Ubiquitinated by the SCF(FBH1) E3 ubiquitin ligase complex, regulating RAD51 subcellular location and preventing its association with DNA. Ubiquitinated by RFWD3 in response to DNA damage: ubiquitination leads to degradation by the proteasome, promoting homologous recombination (PubMed:28575658). {ECO:0000269\|PubMed:23393192, ECO:0000269\|PubMed:28575658}.
Ptm:		Phosphorylated. Phosphorylation of Thr-309 by CHEK1 may enhance association with chromatin at sites of DNA damage and promote DNA repair by homologous recombination. Phosphorylation by ABL1 inhibits function. {ECO:0000269\|PubMed:15665856, ECO:0000269\|PubMed:9461559}.
Disease:		Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269\|PubMed:10807537, ECO:0000269\|PubMed:25539919}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
Disease:		Mirror movements 2 (MRMV2) [MIM:614508]: A disorder characterized by contralateral involuntary movements that mirror voluntary ones. While mirror movements are occasionally found in young children, persistence beyond the age of 10 is abnormal. Mirror movements occur more commonly in the upper extremities. {ECO:0000269\|PubMed:22305526}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Fanconi anemia, complementation group R (FANCR) [MIM:617244]: 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:26253028, ECO:0000269\|PubMed:26681308}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		[Isoform 3]: Mutagenesis of Arg-264 to Ala inhibits nuclear localization. Mutagenesis of Lys-264 to Gln inhibits nuclear localization. Deletion of 254-Arg-Lys-255 inhibits nuclear localization. {ECO:0000269\|PubMed:18417535}.
Similarity:		Belongs to the RecA family. RAD51 subfamily. {ECO:0000305}.