O75943 · RAD17_HUMAN
- ProteinCell cycle checkpoint protein RAD17
- GeneRAD17
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids681 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Has a weak ATPase activity required for binding to chromatin (PubMed:10208430, PubMed:11418864, PubMed:11687627, PubMed:11799063, PubMed:12672690, PubMed:14624239, PubMed:15235112).
Participates in the recruitment of the 9-1-1 (RAD1-RAD9-HUS1) complex and RHNO1 onto chromatin, and in CHEK1 activation (PubMed:21659603).
Involved in homologous recombination by mediating recruitment of the MRN complex to DNA damage sites (PubMed:24534091).
May also serve as a sensor of DNA replication progression (PubMed:12578958, PubMed:14500819, PubMed:15538388).
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | nucleolus | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Cellular Component | Rad17 RFC-like complex | |
Cellular Component | site of double-strand break | |
Molecular Function | ATP binding | |
Molecular Function | chromatin binding | |
Molecular Function | chromatin-protein adaptor activity | |
Molecular Function | DNA clamp loader activity | |
Biological Process | DNA damage checkpoint signaling | |
Biological Process | DNA damage response | |
Biological Process | DNA repair | |
Biological Process | DNA replication checkpoint signaling | |
Biological Process | mitotic DNA replication checkpoint signaling | |
Biological Process | mitotic intra-S DNA damage checkpoint signaling | |
Biological Process | negative regulation of DNA replication | |
Biological Process | protein localization to site of double-strand break | |
Biological Process | regulation of phosphorylation |
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameCell cycle checkpoint protein RAD17
- Short nameshRad17
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO75943
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 18-23 | Strongly reduced interaction with RAD1. | ||||
Sequence: WVDPSF → AADPSA | ||||||
Natural variant | VAR_021574 | 32 | in dbSNP:rs17229831 | |||
Sequence: V → I | ||||||
Mutagenesis | 143 | Impairs phosphorylation on S-656. Abolishes interaction with the RAD1-RAD9-HUS1 complex; does not affect interaction with RFC3. | ||||
Sequence: K → E | ||||||
Mutagenesis | 143 | Impairs phosphorylation. Impairs interaction with DNA and the RAD1-RAD9-HUS1 complex; does not affect interaction with RFC3. | ||||
Sequence: K → G | ||||||
Mutagenesis | 191 | No effect on phosphorylation by ATR. | ||||
Sequence: S → A | ||||||
Natural variant | VAR_021575 | 487 | in dbSNP:rs17236478 | |||
Sequence: R → L | ||||||
Natural variant | VAR_021576 | 535 | in dbSNP:rs17236485 | |||
Sequence: K → E | ||||||
Natural variant | VAR_021577 | 557 | in dbSNP:rs1045051 | |||
Sequence: L → R | ||||||
Mutagenesis | 633 | Impaired phosphorylation by ATM and interaction with NBN. | ||||
Sequence: T → A | ||||||
Mutagenesis | 646 | Reduces by 50% phosphorylation by ATR, and abolishes interaction with RAD1. Abolishes phosphorylation by ATR and checkpoint activation without affecting interaction with RAD17, RFC3, RFC4, ATM or ATR; when associated with A-656. | ||||
Sequence: S → A | ||||||
Mutagenesis | 646 | Abolishes interaction with RAD1; when associated with D-656. | ||||
Sequence: S → D | ||||||
Mutagenesis | 656 | Reduces by 50% phosphorylation by ATR, and abolishes interaction with RAD1. Abolishes phosphorylation by ATR and checkpoint activation without affecting interaction with RAD17, RFC3, RFC4, ATM or ATR; when associated with A-646. | ||||
Sequence: S → A | ||||||
Mutagenesis | 656 | Abolishes interaction with RAD1; when associated with D-646. | ||||
Sequence: S → D |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 757 variants from UniProt as well as other sources including ClinVar and dbSNP.
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_0000209948 | 1-681 | UniProt | Cell cycle checkpoint protein RAD17 | |||
Sequence: MSKTFLRPKVSSTKVTDWVDPSFDDFLECSGVSTITATSLGVNNSSHRRKNGPSTLESSRFPARKRGNLSSLEQIYGLENSKEYLSENEPWVDKYKPETQHELAVHKKKIEEVETWLKAQVLERQPKQGGSILLITGPPGCGKTTTLKILSKEHGIQVQEWINPVLPDFQKDDFKGMFNTESSFHMFPYQSQIAVFKEFLLRATKYNKLQMLGDDLRTDKKIILVEDLPNQFYRDSHTLHEVLRKYVRIGRCPLIFIISDSLSGDNNQRLLFPKEIQEECSISNISFNPVAPTIMMKFLNRIVTIEANKNGGKITVPDKTSLELLCQGCSGDIRSAINSLQFSSSKGENNLRPRKKGMSLKSDAVLSKSKRRKKPDRVFENQEVQAIGGKDVSLFLFRALGKILYCKRASLTELDSPRLPSHLSEYERDTLLVEPEEVVEMSHMPGDLFNLYLHQNYIDFFMEIDDIVRASEFLSFADILSGDWNTRSLLREYSTSIATRGVMHSNKARGYAHCQGGGSSFRPLHKPQWFLINKKYRENCLAAKALFPDFCLPALCLQTQLLPYLALLTIPMRNQAQISFIQDIGRLPLKRHFGRLKMEALTDREHGMIDPDSGDEAQLNGGHSAEESLGEPTQATVPETWSLPLSQNSASELPASQPQPFSAQGDMEENIIIEDYESDGT | |||||||
Modified residue | 55 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 71 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 86 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 86 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 359 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 359 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 410 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 416 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 633 | UniProt | Phosphothreonine; by ATM | ||||
Sequence: T | |||||||
Modified residue | 646 | UniProt | Phosphoserine; by ATR and ATM | ||||
Sequence: S | |||||||
Modified residue | 656 | UniProt | Phosphoserine; by ATR and ATM | ||||
Sequence: S |
Post-translational modification
Phosphorylation is mediated by ATR upon UV or replication arrest, whereas it may be mediated both by ATR and ATM upon ionizing radiation (PubMed:11418864, PubMed:11799063).
Phosphorylation on both sites is required for interaction with RAD1 but dispensable for interaction with RFC3 or RFC4 (PubMed:11687627).
Phosphorylation at Thr-633 by ATM in response to DNA damage promotes interaction with NBN and recruitment of the MRN complex to DNA damage sites (PubMed:24534091).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Induction
Isoform 1
Isoform 3
Isoform 4
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with RAD1 and RAD9 within the 9-1-1 (RAD1-RAD9-HUS1) complex (PubMed:10884395, PubMed:11418864, PubMed:12578958, PubMed:36841485, PubMed:9660800).
Interacts with RAD9B, POLE, SNU13 and MCM7 (PubMed:10593953, PubMed:14500819, PubMed:14611806, PubMed:15538388).
DNA damage promotes interaction with ATR or ATM and disrupts interaction with the 9-1-1 (RAD1-RAD9-HUS1) complex (PubMed:10884395, PubMed:11418864, PubMed:12578958).
Interacts (when phosphorylated) with NBN; promoting recruitment of the MRN complex to DNA damage sites (PubMed:24534091).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | O75943 | FZR1 Q9UM11 | 2 | EBI-968231, EBI-724997 | |
BINARY | O75943 | MRE11 P49959 | 2 | EBI-968231, EBI-396513 | |
BINARY | O75943 | NBN O60934 | 5 | EBI-968231, EBI-494844 | |
BINARY | O75943 | RAD50 Q92878 | 2 | EBI-968231, EBI-495494 | |
BINARY | O75943 | RAD9A Q99638 | 2 | EBI-968231, EBI-2606224 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for motif, compositional bias, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 17-25 | RAD1-binding motif | ||||
Sequence: DWVDPSFDD | ||||||
Compositional bias | 42-58 | Polar residues | ||||
Sequence: VNNSSHRRKNGPSTLES | ||||||
Region | 42-61 | Disordered | ||||
Sequence: VNNSSHRRKNGPSTLESSRF | ||||||
Region | 344-377 | Disordered | ||||
Sequence: SSKGENNLRPRKKGMSLKSDAVLSKSKRRKKPDR | ||||||
Compositional bias | 349-377 | Basic and acidic residues | ||||
Sequence: NNLRPRKKGMSLKSDAVLSKSKRRKKPDR | ||||||
Region | 432-681 | Interaction with MCM7 | ||||
Sequence: LVEPEEVVEMSHMPGDLFNLYLHQNYIDFFMEIDDIVRASEFLSFADILSGDWNTRSLLREYSTSIATRGVMHSNKARGYAHCQGGGSSFRPLHKPQWFLINKKYRENCLAAKALFPDFCLPALCLQTQLLPYLALLTIPMRNQAQISFIQDIGRLPLKRHFGRLKMEALTDREHGMIDPDSGDEAQLNGGHSAEESLGEPTQATVPETWSLPLSQNSASELPASQPQPFSAQGDMEENIIIEDYESDGT | ||||||
Region | 606-681 | Disordered | ||||
Sequence: HGMIDPDSGDEAQLNGGHSAEESLGEPTQATVPETWSLPLSQNSASELPASQPQPFSAQGDMEENIIIEDYESDGT | ||||||
Compositional bias | 627-664 | Polar residues | ||||
Sequence: ESLGEPTQATVPETWSLPLSQNSASELPASQPQPFSAQ |
Sequence similarities
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 4 isoforms produced by Alternative splicing.
O75943-1
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
- SynonymsRad17Sp, FM2
- Length681
- Mass (Da)77,055
- Last updated2005-03-29 v2
- Checksum796C2BD48F7995A3
O75943-2
- Name2
- SynonymsRad17Sp2, FM1
- Differences from canonical
- 1-14: MSKTFLRPKVSSTK → MNQ
O75943-3
- Name3
- SynonymsFM3
- Differences from canonical
- 1-176: Missing
O75943-4
- Name4
- SynonymsFM4
Computationally mapped potential isoform sequences
There are 9 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
D6RHU1 | D6RHU1_HUMAN | RAD17 | 50 | ||
D6RAW6 | D6RAW6_HUMAN | RAD17 | 169 | ||
D6RA84 | D6RA84_HUMAN | RAD17 | 20 | ||
H0Y9J8 | H0Y9J8_HUMAN | RAD17 | 165 | ||
H0Y9T7 | H0Y9T7_HUMAN | RAD17 | 184 | ||
A0A0G2JP78 | A0A0G2JP78_HUMAN | RAD17 | 584 | ||
A0A0G2JP31 | A0A0G2JP31_HUMAN | RAD17 | 184 | ||
A0A0G2JPT5 | A0A0G2JPT5_HUMAN | RAD17 | 681 | ||
A0A0G2JNH5 | A0A0G2JNH5_HUMAN | RAD17 | 505 |
Features
Showing features for alternative sequence, compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_013308 | 1-14 | in isoform 2 | |||
Sequence: MSKTFLRPKVSSTK → MNQ | ||||||
Alternative sequence | VSP_013307 | 1-97 | in isoform 4 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_013306 | 1-176 | in isoform 3 | |||
Sequence: Missing | ||||||
Compositional bias | 42-58 | Polar residues | ||||
Sequence: VNNSSHRRKNGPSTLES | ||||||
Sequence conflict | 75 | in Ref. 12; CAD97683 | ||||
Sequence: I → V | ||||||
Alternative sequence | VSP_013309 | 98-99 | in isoform 4 | |||
Sequence: ET → MN | ||||||
Sequence conflict | 187 | in Ref. 5; AAC36334 | ||||
Sequence: F → L | ||||||
Sequence conflict | 194 | in Ref. 7; AAD01620 | ||||
Sequence: A → S | ||||||
Sequence conflict | 340 | in Ref. 5; AAC36334 | ||||
Sequence: L → P | ||||||
Compositional bias | 349-377 | Basic and acidic residues | ||||
Sequence: NNLRPRKKGMSLKSDAVLSKSKRRKKPDR | ||||||
Sequence conflict | 445 | in Ref. 5; AAC36334 | ||||
Sequence: P → S | ||||||
Sequence conflict | 462 | in Ref. 5; AAC36334 | ||||
Sequence: M → T | ||||||
Compositional bias | 627-664 | Polar residues | ||||
Sequence: ESLGEPTQATVPETWSLPLSQNSASELPASQPQPFSAQ | ||||||
Sequence conflict | 648 | in Ref. 5; AAC36334 | ||||
Sequence: N → D | ||||||
Sequence conflict | 672 | in Ref. 5; AAC36334 | ||||
Sequence: I → M |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF076838 EMBL· GenBank· DDBJ | AAC95520.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ004977 EMBL· GenBank· DDBJ | CAA06251.1 EMBL· GenBank· DDBJ | mRNA | ||
AF112263 EMBL· GenBank· DDBJ | AAD38878.1 EMBL· GenBank· DDBJ | mRNA | ||
AF085736 EMBL· GenBank· DDBJ | AAC36334.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ001642 EMBL· GenBank· DDBJ | CAA04894.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ131296 EMBL· GenBank· DDBJ | CAB46364.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ131297 EMBL· GenBank· DDBJ | CAB46364.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ131298 EMBL· GenBank· DDBJ | CAB46364.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ131299 EMBL· GenBank· DDBJ | CAB46364.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ131300 EMBL· GenBank· DDBJ | CAB46364.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ131301 EMBL· GenBank· DDBJ | CAB46364.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ131302 EMBL· GenBank· DDBJ | CAB46364.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ131303 EMBL· GenBank· DDBJ | CAB46364.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ131304 EMBL· GenBank· DDBJ | CAB46364.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ131305 EMBL· GenBank· DDBJ | CAB46364.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ131306 EMBL· GenBank· DDBJ | CAB46364.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ131307 EMBL· GenBank· DDBJ | CAB46364.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ131308 EMBL· GenBank· DDBJ | CAB46364.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF017748 EMBL· GenBank· DDBJ | AAD01620.1 EMBL· GenBank· DDBJ | mRNA | ||
AF126424 EMBL· GenBank· DDBJ | AAD17334.1 EMBL· GenBank· DDBJ | mRNA | ||
AF098533 EMBL· GenBank· DDBJ | AAC97950.1 EMBL· GenBank· DDBJ | mRNA | ||
AF098534 EMBL· GenBank· DDBJ | AAC97951.1 EMBL· GenBank· DDBJ | mRNA | ||
AL122068 EMBL· GenBank· DDBJ | CAB59244.1 EMBL· GenBank· DDBJ | mRNA | ||
AK292487 EMBL· GenBank· DDBJ | BAF85176.1 EMBL· GenBank· DDBJ | mRNA | ||
BX537441 EMBL· GenBank· DDBJ | CAD97683.1 EMBL· GenBank· DDBJ | mRNA | ||
AY612854 EMBL· GenBank· DDBJ | AAT09763.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471137 EMBL· GenBank· DDBJ | EAW51283.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471137 EMBL· GenBank· DDBJ | EAW51284.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471137 EMBL· GenBank· DDBJ | EAW51285.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471137 EMBL· GenBank· DDBJ | EAW51286.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471137 EMBL· GenBank· DDBJ | EAW51288.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC032304 EMBL· GenBank· DDBJ | AAH32304.1 EMBL· GenBank· DDBJ | mRNA |