O43502 · RA51C_HUMAN
- ProteinDNA repair protein RAD51 homolog 3
- GeneRAD51C
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids376 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Essential for the homologous recombination (HR) pathway of DNA repair. Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents. Part of the RAD51 paralog protein complexes BCDX2 and CX3 which act at different stages of the BRCA1-BRCA2-dependent HR pathway. Upon DNA damage, BCDX2 seems to act downstream of BRCA2 recruitment and upstream of RAD51 recruitment; CX3 seems to act downstream of RAD51 recruitment; both complexes bind predominantly to the intersection of the four duplex arms of the Holliday junction (HJ) and to junction of replication forks. The BCDX2 complex was originally reported to bind single-stranded DNA, single-stranded gaps in duplex DNA and specifically to nicks in duplex DNA. The BCDX2 subcomplex RAD51B:RAD51C exhibits single-stranded DNA-dependent ATPase activity suggesting an involvement in early stages of the HR pathway. Involved in RAD51 foci formation in response to DNA damage suggesting an involvement in early stages of HR probably in the invasion step. Has an early function in DNA repair in facilitating phosphorylation of the checkpoint kinase CHEK2 and thereby transduction of the damage signal, leading to cell cycle arrest and HR activation. Participates in branch migration and HJ resolution and thus is important for processing HR intermediates late in the DNA repair process; the function may be linked to the CX3 complex. Part of a PALB2-scaffolded HR complex containing BRCA2 and which is thought to play a role in DNA repair by HR. Protects RAD51 from ubiquitin-mediated degradation that is enhanced following DNA damage. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51 and XRCC3. Contributes to DNA cross-link resistance, sister chromatid cohesion and genomic stability. Involved in maintaining centrosome number in mitosis.
Features
Showing features for binding site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDNA repair protein RAD51 homolog 3
- Short namesR51H3
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO43502
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: DNA damage induces an increase in nuclear levels. Accumulates in DNA damage induced nuclear foci or RAD51C foci which is formed during the S or G2 phase of cell cycle. Accumulation at DNA lesions requires the presence of NBN/NBS1, ATM and RPA.
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Fanconi anemia complementation group O (FANCO)
- Note
- DescriptionA 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.
- See alsoMIM:613390
Natural variants in FANCO
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_064032 | 258 | R>H | in FANCO; possibly hypomorphic allele; reduces interaction with BRCA2 and to a lesser extent with PALB2 and RAD51; dbSNP:rs267606997 |
Breast-ovarian cancer, familial, 3 (BROVCA3)
- Note
- DescriptionA condition associated with familial predisposition to cancer of the breast and ovaries. Characteristic features in affected families are an early age of onset of breast cancer (often before age 50), increased chance of bilateral cancers (cancer that develop in both breasts, or both ovaries, independently), frequent occurrence of breast cancer among men, increased incidence of tumors of other specific organs, such as the prostate.
- See alsoMIM:613399
Natural variants in BROVCA3
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_063838 | 125 | G>V | in BROVCA3; dbSNP:rs267606998 | |
VAR_063840 | 138 | L>F | in BROVCA3; reduces interaction with BRCA2 and to a lesser extent with PALB2 and RAD51; dbSNP:rs267606999 | |
VAR_068017 | 162 | G>E | in BROVCA3; dbSNP:rs35151472 | |
VAR_068019 | 178 | Q>P | in BROVCA3; dbSNP:rs1598460753 | |
VAR_020520 | 287 | T>A | in BROVCA3; dbSNP:rs28363317 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_063837 | 3 | in dbSNP:rs376403182 | |||
Sequence: G → R | ||||||
Natural variant | VAR_068014 | 52 | in dbSNP:rs730881927 | |||
Sequence: I → L | ||||||
Natural variant | VAR_068015 | 103 | ||||
Sequence: Missing | ||||||
Natural variant | VAR_068016 | 114 | in dbSNP:rs1555593767 | |||
Sequence: G → V | ||||||
Natural variant | VAR_063838 | 125 | in BROVCA3; dbSNP:rs267606998 | |||
Sequence: G → V | ||||||
Natural variant | VAR_063839 | 126 | in dbSNP:rs61758784 | |||
Sequence: A → T | ||||||
Mutagenesis | 131 | Significant loss of function; abolishes Holliday junction resolution activity. | ||||
Sequence: K → A | ||||||
Mutagenesis | 131 | Partial loss of function. | ||||
Sequence: K → R | ||||||
Natural variant | VAR_063840 | 138 | in BROVCA3; reduces interaction with BRCA2 and to a lesser extent with PALB2 and RAD51; dbSNP:rs267606999 | |||
Sequence: L → F | ||||||
Natural variant | VAR_020518 | 144 | in dbSNP:rs28363307 | |||
Sequence: I → T | ||||||
Natural variant | VAR_063841 | 159 | reduces interaction with BRCA2 and to a lesser extent with PALB2 and RAD51; dbSNP:rs775213492 | |||
Sequence: D → N | ||||||
Natural variant | VAR_068017 | 162 | in BROVCA3; dbSNP:rs35151472 | |||
Sequence: G → E | ||||||
Natural variant | VAR_063842 | 169 | in dbSNP:rs587780256 | |||
Sequence: V → A | ||||||
Natural variant | VAR_068018 | 175 | in dbSNP:rs587780838 | |||
Sequence: A → T | ||||||
Natural variant | VAR_068019 | 178 | in BROVCA3; dbSNP:rs1598460753 | |||
Sequence: Q → P | ||||||
Natural variant | VAR_020519 | 249 | in dbSNP:rs28363311 | |||
Sequence: R → C | ||||||
Natural variant | VAR_064032 | 258 | in FANCO; possibly hypomorphic allele; reduces interaction with BRCA2 and to a lesser extent with PALB2 and RAD51; dbSNP:rs267606997 | |||
Sequence: R → H | ||||||
Natural variant | VAR_068020 | 262 | in dbSNP:rs149331537 | |||
Sequence: L → V | ||||||
Natural variant | VAR_063843 | 264 | in dbSNP:rs147241704 | |||
Sequence: G → S | ||||||
Natural variant | VAR_063844 | 264 | in dbSNP:rs1283065191 | |||
Sequence: G → V | ||||||
Natural variant | VAR_020520 | 287 | in BROVCA3; dbSNP:rs28363317 | |||
Sequence: T → A | ||||||
Natural variant | VAR_063845 | 366 | in dbSNP:rs577852020 | |||
Sequence: R → Q |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,732 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000122941 | 1-376 | UniProt | DNA repair protein RAD51 homolog 3 | |||
Sequence: MRGKTFRFEMQRDLVSFPLSPAVRVKLVSAGFQTAEELLEVKPSELSKEVGISKAEALETLQIIRRECLTNKPRYAGTSESHKKCTALELLEQEHTQGFIITFCSALDDILGGGVPLMKTTEICGAPGVGKTQLCMQLAVDVQIPECFGGVAGEAVFIDTEGSFMVDRVVDLATACIQHLQLIAEKHKGEEHRKALEDFTLDNILSHIYYFRCRDYTELLAQVYLLPDFLSEHSKVRLVIVDGIAFPFRHDLDDLSLRTRLLNGLAQQMISLANNHRLAVILTNQMTTKIDRNQALLVPALGESWGHAATIRLIFHWDRKQRLATLYKSPSQKECTVLFQIKPQGFRDTVVTSACSLQTEGSLSTRKRSRDPEEEL | |||||||
Modified residue | 20 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 20 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in a variety of tissues, with highest expression in testis, heart muscle, spleen and prostate.
Induction
Stress-induced increase in the mitochondrial levels is seen.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Part of the RAD51 paralog protein complexes BCDX2 and CX3; the complexes have a ring-like structure arranged into a flat disc around a central channel (PubMed:11751635, PubMed:11751636, PubMed:11842112, PubMed:11842113, PubMed:12427746, PubMed:14704354).
The BCDX2 complex consits of RAD51B, RAD51C, RAD51D and XRCC2; the CX3 complex consists of RAD51C and XRCC3 (PubMed:11751635, PubMed:11842113, PubMed:14704354).
The BCDX2 subcomplex RAD51B:RAD51C interacts with RAD51 (PubMed:12427746, PubMed:16395335).
Interacts with SWSAP1; involved in homologous recombination repair (PubMed:21965664).
Interacts directly with PALB2 which may serve as a scaffold for a HR complex containing PALB2, BRCA2, RAD51C, RAD51 and XRCC3 (PubMed:24141787).
Interacts with HELQ (PubMed:24005041).
Interacts with DNA damage up-regulated protein DDUP (PubMed:35849344).
The BCDX2 complex consits of RAD51B, RAD51C, RAD51D and XRCC2; the CX3 complex consists of RAD51C and XRCC3 (PubMed:11751635, PubMed:11842113, PubMed:14704354).
The BCDX2 subcomplex RAD51B:RAD51C interacts with RAD51 (PubMed:12427746, PubMed:16395335).
Interacts with SWSAP1; involved in homologous recombination repair (PubMed:21965664).
Interacts directly with PALB2 which may serve as a scaffold for a HR complex containing PALB2, BRCA2, RAD51C, RAD51 and XRCC3 (PubMed:24141787).
Interacts with HELQ (PubMed:24005041).
Interacts with DNA damage up-regulated protein DDUP (PubMed:35849344).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | O43502 | HELQ Q8TDG4 | 6 | EBI-2267048, EBI-2802156 | |
BINARY | O43502 | PALB2 Q86YC2 | 10 | EBI-2267048, EBI-1222653 | |
BINARY | O43502 | RAD51 Q06609 | 6 | EBI-2267048, EBI-297202 | |
BINARY | O43502 | RAD51B O15315 | 16 | EBI-2267048, EBI-2824089 | |
BINARY | O43502 | RAD51D O75771 | 8 | EBI-2267048, EBI-1055693 | |
BINARY | O43502 | SWSAP1 Q6NVH7 | 2 | EBI-2267048, EBI-5281637 | |
BINARY | O43502 | XRCC2 O43543 | 4 | EBI-2267048, EBI-3918457 | |
BINARY | O43502 | XRCC3 O43542 | 12 | EBI-2267048, EBI-2849976 | |
BINARY | O43502-2 | SPG21 Q9NZD8 | 3 | EBI-14233893, EBI-742688 |
Protein-protein interaction databases
Miscellaneous
Family & Domains
Features
Showing features for region, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-126 | Required for Holliday junction resolution activity | ||||
Sequence: MRGKTFRFEMQRDLVSFPLSPAVRVKLVSAGFQTAEELLEVKPSELSKEVGISKAEALETLQIIRRECLTNKPRYAGTSESHKKCTALELLEQEHTQGFIITFCSALDDILGGGVPLMKTTEICGA | ||||||
Region | 79-136 | Interaction with RAD51B, RAD51D and XRCC3 | ||||
Sequence: SESHKKCTALELLEQEHTQGFIITFCSALDDILGGGVPLMKTTEICGAPGVGKTQLCM | ||||||
Motif | 366-370 | Nuclear localization signal | ||||
Sequence: RKRSR |
Sequence similarities
Belongs to the RecA family. RAD51 subfamily.
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
O43502-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length376
- Mass (Da)42,190
- Last updated1998-06-01 v1
- Checksum3AAADD3C1C0851E0
O43502-2
- Name2
Computationally mapped potential isoform sequences
There are 13 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
H7C2Q5 | H7C2Q5_HUMAN | RAD51C | 213 | ||
H7C1R0 | H7C1R0_HUMAN | RAD51C | 257 | ||
E9PI66 | E9PI66_HUMAN | RAD51C | 52 | ||
A0A8V8TMU8 | A0A8V8TMU8_HUMAN | RAD51C | 305 | ||
A0A8V8TML3 | A0A8V8TML3_HUMAN | RAD51C | 286 | ||
A0A8V8TML8 | A0A8V8TML8_HUMAN | RAD51C | 259 | ||
A0A8V8TL64 | A0A8V8TL64_HUMAN | RAD51C | 74 | ||
Q7KZJ0 | Q7KZJ0_HUMAN | RAD51C | 134 | ||
J3QKK3 | J3QKK3_HUMAN | RAD51C | 346 | ||
J3QLB5 | J3QLB5_HUMAN | RAD51C | 47 | ||
J3QLQ2 | J3QLQ2_HUMAN | RAD51C | 107 | ||
J3QR58 | J3QR58_HUMAN | RAD51C | 229 | ||
A0A087WZ35 | A0A087WZ35_HUMAN | RAD51C | 131 |
Features
Showing features for alternative sequence.
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF029669 EMBL· GenBank· DDBJ | AAC39604.1 EMBL· GenBank· DDBJ | mRNA | ||
AF029670 EMBL· GenBank· DDBJ | AAC39605.1 EMBL· GenBank· DDBJ | mRNA | ||
AY623112 EMBL· GenBank· DDBJ | AAT38108.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AC011195 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC025521 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471109 EMBL· GenBank· DDBJ | EAW94432.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC107753 EMBL· GenBank· DDBJ | AAI07754.1 EMBL· GenBank· DDBJ | mRNA |