Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Cell cycle checkpoint control protein RAD9A

Gene

RAD9A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Component of the 9-1-1 cell-cycle checkpoint response complex that plays a major role in DNA repair. The 9-1-1 complex is recruited to DNA lesion upon damage by the RAD17-replication factor C (RFC) clamp loader complex. Acts then as a sliding clamp platform on DNA for several proteins involved in long-patch base excision repair (LP-BER). The 9-1-1 complex stimulates DNA polymerase beta (POLB) activity by increasing its affinity for the 3'-OH end of the primer-template and stabilizes POLB to those sites where LP-BER proceeds; endonuclease FEN1 cleavage activity on substrates with double, nick, or gap flaps of distinct sequences and lengths; and DNA ligase I (LIG1) on long-patch base excision repair substrates. The 9-1-1 complex is necessary for the recruitment of RHNO1 to sites of double-stranded breaks (DSB) occurring during the S phase. RAD9A possesses 3'->5' double stranded DNA exonuclease activity. Its phosphorylation by PRKCD may be required for the formation of the 9-1-1 complex.2 Publications

Catalytic activityi

Exonucleolytic cleavage in the 3'- to 5'-direction to yield nucleoside 5'-phosphates.

GO - Molecular functioni

  • 3'-5' exonuclease activity Source: UniProtKB
  • enzyme binding Source: UniProtKB
  • exodeoxyribonuclease III activity Source: UniProtKB-EC
  • histone deacetylase binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • SH3 domain binding Source: UniProtKB

GO - Biological processi

  • cellular response to DNA damage stimulus Source: UniProtKB
  • cellular response to ionizing radiation Source: UniProtKB
  • DNA damage checkpoint Source: UniProtKB
  • DNA repair Source: ProtInc
  • DNA replication Source: Reactome
  • DNA replication checkpoint Source: ProtInc
  • intra-S DNA damage checkpoint Source: GO_Central
  • positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage Source: Ensembl
  • regulation of signal transduction by p53 class mediator Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Exonuclease, Hydrolase, Nuclease

Keywords - Biological processi

DNA damage

Enzyme and pathway databases

BioCyciZFISH:HS10543-MONOMER.
ReactomeiR-HSA-176187. Activation of ATR in response to replication stress.
R-HSA-5685938. HDR through Single Strand Annealing (SSA).
R-HSA-5693607. Processing of DNA double-strand break ends.
R-HSA-5693616. Presynaptic phase of homologous DNA pairing and strand exchange.
R-HSA-6804756. Regulation of TP53 Activity through Phosphorylation.
R-HSA-69473. G2/M DNA damage checkpoint.
SignaLinkiQ99638.
SIGNORiQ99638.

Names & Taxonomyi

Protein namesi
Recommended name:
Cell cycle checkpoint control protein RAD9A (EC:3.1.11.2)
Short name:
hRAD9
Alternative name(s):
DNA repair exonuclease rad9 homolog A
Gene namesi
Name:RAD9A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:9827. RAD9A.

Subcellular locationi

  • Nucleus 1 Publication

GO - Cellular componenti

  • checkpoint clamp complex Source: GO_Central
  • cytoplasm Source: Ensembl
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi28Y → F: Abolishes phosphorylation by ABL1. 1 Publication1
Mutagenesisi272S → A: Complete loss of phosphorylation and no loss of interaction with the 9-1-1 complex; when associated with A-277; A-328; A-341; A-375; A-380 and A-387. 1 Publication1
Mutagenesisi277S → A: Complete loss of phosphorylation and no loss of interaction with the 9-1-1 complex; when associated with A-272; A-328; A-341; A-375; A-380 and A-387. 1 Publication1
Mutagenesisi328S → A: Complete loss of phosphorylation and no loss of interaction with the 9-1-1 complex; when associated with A-272; A-277; A-341; A-375; A-380 and A-387. 1 Publication1
Mutagenesisi341S → A: Complete loss of phosphorylation and no loss of interaction with the 9-1-1 complex; when associated with A-272; A-277; A-328; A-375; A-380 and A-387. 1 Publication1
Mutagenesisi375S → A: Complete loss of phosphorylation and no loss of interaction with the 9-1-1 complex; when associated with A-272; A-277; A-328; A-341; A-380 and A-387. 1 Publication1
Mutagenesisi380S → A: Complete loss of phosphorylation and no loss of interaction with the 9-1-1 complex; when associated with A-272; A-277; A-328; A-341; A-375 and A-387. 1 Publication1
Mutagenesisi387S → A: Complete loss of phosphorylation and no loss of interaction with the 9-1-1 complex; when associated with A-272; A-277; A-328; A-341; A-375 and A-380. 1 Publication1

Organism-specific databases

DisGeNETi5883.
OpenTargetsiENSG00000172613.
PharmGKBiPA294.

Polymorphism and mutation databases

BioMutaiRAD9A.
DMDMi74717382.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002250001 – 391Cell cycle checkpoint control protein RAD9AAdd BLAST391

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei28Phosphotyrosine1 Publication1
Modified residuei272Phosphoserine1 Publication1
Modified residuei277PhosphoserineCombined sources1 Publication1
Modified residuei328PhosphoserineCombined sources1 Publication1
Modified residuei341Phosphoserine1 Publication1
Modified residuei375PhosphoserineCombined sources1 Publication1
Modified residuei380PhosphoserineCombined sources1 Publication1
Modified residuei387PhosphoserineCombined sources1 Publication1

Post-translational modificationi

Constitutively phosphorylated on serine and threonine amino acids in absence of DNA damage. Hyperphosphorylated by PRKCD and ABL1 upon DNA damage. Its phosphorylation by PRKCD may be required for the formation of the 9-1-1 complex.3 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ99638.
MaxQBiQ99638.
PaxDbiQ99638.
PeptideAtlasiQ99638.
PRIDEiQ99638.

PTM databases

iPTMnetiQ99638.
PhosphoSitePlusiQ99638.

Expressioni

Gene expression databases

BgeeiENSG00000172613.
CleanExiHS_RAD9A.
ExpressionAtlasiQ99638. baseline and differential.
GenevisibleiQ99638. HS.

Organism-specific databases

HPAiHPA006725.
HPA048155.

Interactioni

Subunit structurei

Component of the toroidal 9-1-1 (RAD9-RAD1-HUS1) complex, composed of RAD9A, RAD1 and HUS1. The 9-1-1 complex associates with LIG1, POLB, FEN1, RAD17, HDAC1, RPA1 and RPA2. The 9-1-1 complex associates with the RAD17-RFC complex. RAD9A interacts with BCL2L1, FEN1, PRKCD, RAD9B, HUS1, RAD1, ABL1, RPA1, ATAD5 and RPA2. Interacts with DNAJC7 and RHNO1.14 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
HUS1O609215EBI-2606224,EBI-1056174
RAD1O606712EBI-2606224,EBI-721835

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • histone deacetylase binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • SH3 domain binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111820. 32 interactors.
DIPiDIP-24255N.
DIP-40930N.
IntActiQ99638. 7 interactors.
MINTiMINT-134869.
STRINGi9606.ENSP00000311360.

Structurei

Secondary structure

1391
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi2 – 6Combined sources5
Helixi8 – 21Combined sources14
Beta strandi25 – 32Combined sources8
Beta strandi35 – 41Combined sources7
Beta strandi47 – 53Combined sources7
Helixi55 – 57Combined sources3
Beta strandi58 – 62Combined sources5
Beta strandi66 – 68Combined sources3
Beta strandi73 – 76Combined sources4
Helixi77 – 84Combined sources8
Helixi87 – 93Combined sources7
Beta strandi94 – 100Combined sources7
Beta strandi106 – 114Combined sources9
Helixi115 – 117Combined sources3
Beta strandi119 – 125Combined sources7
Helixi138 – 140Combined sources3
Beta strandi142 – 148Combined sources7
Helixi149 – 156Combined sources8
Beta strandi165 – 170Combined sources6
Helixi172 – 174Combined sources3
Beta strandi176 – 181Combined sources6
Beta strandi187 – 189Combined sources3
Beta strandi194 – 199Combined sources6
Helixi201 – 203Combined sources3
Beta strandi205 – 208Combined sources4
Beta strandi214 – 218Combined sources5
Helixi219 – 231Combined sources13
Beta strandi235 – 240Combined sources6
Beta strandi241 – 245Combined sources5
Beta strandi247 – 252Combined sources6
Beta strandi254 – 262Combined sources9
Beta strandi267 – 269Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3A1JX-ray2.50A1-266[»]
3G65X-ray2.90A1-270[»]
3GGRX-ray3.20A1-270[»]
ProteinModelPortaliQ99638.
SMRiQ99638.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99638.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni51 – 91Possesses 3'-5' exonuclease activityAdd BLAST41
Regioni266 – 391Sufficient for interaction with ABL11 PublicationAdd BLAST126

Sequence similaritiesi

Belongs to the rad9 family.Curated

Phylogenomic databases

eggNOGiKOG2810. Eukaryota.
ENOG410XYYN. LUCA.
GeneTreeiENSGT00390000005767.
HOGENOMiHOG000059650.
HOVERGENiHBG058989.
InParanoidiQ99638.
KOiK10994.
OMAiLHCKHGL.
OrthoDBiEOG091G0B2E.
PhylomeDBiQ99638.
TreeFamiTF101212.

Family and domain databases

InterProiIPR026584. Rad9.
IPR007268. Rad9/Ddc1.
[Graphical view]
PANTHERiPTHR15237. PTHR15237. 1 hit.
PfamiPF04139. Rad9. 1 hit.
[Graphical view]
PIRSFiPIRSF009303. Cell_cycle_RAD9. 1 hit.

Sequencei

Sequence statusi: Complete.

Q99638-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKCLVTGGNV KVLGKAVHSL SRIGDELYLE PLEDGLSLRT VNSSRSAYAC
60 70 80 90 100
FLFAPLFFQQ YQAATPGQDL LRCKILMKSF LSVFRSLAML EKTVEKCCIS
110 120 130 140 150
LNGRSSRLVV QLHCKFGVRK THNLSFQDCE SLQAVFDPAS CPHMLRAPAR
160 170 180 190 200
VLGEAVLPFS PALAEVTLGI GRGRRVILRS YHEEEADSTA KAMVTEMCLG
210 220 230 240 250
EEDFQQLQAQ EGVAITFCLK EFRGLLSFAE SANLNLSIHF DAPGRPAIFT
260 270 280 290 300
IKDSLLDGHF VLATLSDTDS HSQDLGSPER HQPVPQLQAH STPHPDDFAN
310 320 330 340 350
DDIDSYMIAM ETTIGNEGSR VLPSISLSPG PQPPKSPGPH SEEEDEAEPS
360 370 380 390
TVPGTPPPKK FRSLFFGSIL APVRSPQGPS PVLAEDSEGE G
Length:391
Mass (Da):42,547
Last modified:May 1, 1997 - v1
Checksum:i4D4D6D4C6E1057D3
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti12V → A in CAG38746 (Ref. 2) Curated1
Sequence conflicti130E → A in AAH14848 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0254103C → F.1 PublicationCorresponds to variant rs11575913dbSNPEnsembl.1
Natural variantiVAR_05172471L → Q.Corresponds to variant rs2422490dbSNPEnsembl.1
Natural variantiVAR_025411100S → A.1 PublicationCorresponds to variant rs2066492dbSNPEnsembl.1
Natural variantiVAR_025412239H → R.1 PublicationCorresponds to variant rs17880039dbSNPEnsembl.1
Natural variantiVAR_025413307M → T.1 PublicationCorresponds to variant rs17882466dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U53174 mRNA. Translation: AAB39928.1.
CR536508 mRNA. Translation: CAG38746.1.
AY766122 Genomic DNA. Translation: AAU89725.1.
AK315348 mRNA. Translation: BAG37745.1.
CH471076 Genomic DNA. Translation: EAW74605.1.
BC014848 mRNA. Translation: AAH14848.1.
CCDSiCCDS8159.1.
RefSeqiNP_001230153.1. NM_001243224.1.
NP_004575.1. NM_004584.2.
UniGeneiHs.655354.

Genome annotation databases

EnsembliENST00000307980; ENSP00000311360; ENSG00000172613.
GeneIDi5883.
KEGGihsa:5883.
UCSCiuc001okr.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs
Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U53174 mRNA. Translation: AAB39928.1.
CR536508 mRNA. Translation: CAG38746.1.
AY766122 Genomic DNA. Translation: AAU89725.1.
AK315348 mRNA. Translation: BAG37745.1.
CH471076 Genomic DNA. Translation: EAW74605.1.
BC014848 mRNA. Translation: AAH14848.1.
CCDSiCCDS8159.1.
RefSeqiNP_001230153.1. NM_001243224.1.
NP_004575.1. NM_004584.2.
UniGeneiHs.655354.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3A1JX-ray2.50A1-266[»]
3G65X-ray2.90A1-270[»]
3GGRX-ray3.20A1-270[»]
ProteinModelPortaliQ99638.
SMRiQ99638.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111820. 32 interactors.
DIPiDIP-24255N.
DIP-40930N.
IntActiQ99638. 7 interactors.
MINTiMINT-134869.
STRINGi9606.ENSP00000311360.

PTM databases

iPTMnetiQ99638.
PhosphoSitePlusiQ99638.

Polymorphism and mutation databases

BioMutaiRAD9A.
DMDMi74717382.

Proteomic databases

EPDiQ99638.
MaxQBiQ99638.
PaxDbiQ99638.
PeptideAtlasiQ99638.
PRIDEiQ99638.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000307980; ENSP00000311360; ENSG00000172613.
GeneIDi5883.
KEGGihsa:5883.
UCSCiuc001okr.4. human.

Organism-specific databases

CTDi5883.
DisGeNETi5883.
GeneCardsiRAD9A.
HGNCiHGNC:9827. RAD9A.
HPAiHPA006725.
HPA048155.
MIMi603761. gene.
neXtProtiNX_Q99638.
OpenTargetsiENSG00000172613.
PharmGKBiPA294.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2810. Eukaryota.
ENOG410XYYN. LUCA.
GeneTreeiENSGT00390000005767.
HOGENOMiHOG000059650.
HOVERGENiHBG058989.
InParanoidiQ99638.
KOiK10994.
OMAiLHCKHGL.
OrthoDBiEOG091G0B2E.
PhylomeDBiQ99638.
TreeFamiTF101212.

Enzyme and pathway databases

BioCyciZFISH:HS10543-MONOMER.
ReactomeiR-HSA-176187. Activation of ATR in response to replication stress.
R-HSA-5685938. HDR through Single Strand Annealing (SSA).
R-HSA-5693607. Processing of DNA double-strand break ends.
R-HSA-5693616. Presynaptic phase of homologous DNA pairing and strand exchange.
R-HSA-6804756. Regulation of TP53 Activity through Phosphorylation.
R-HSA-69473. G2/M DNA damage checkpoint.
SignaLinkiQ99638.
SIGNORiQ99638.

Miscellaneous databases

ChiTaRSiRAD9A. human.
EvolutionaryTraceiQ99638.
GeneWikiiRAD9A.
GenomeRNAii5883.
PROiQ99638.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000172613.
CleanExiHS_RAD9A.
ExpressionAtlasiQ99638. baseline and differential.
GenevisibleiQ99638. HS.

Family and domain databases

InterProiIPR026584. Rad9.
IPR007268. Rad9/Ddc1.
[Graphical view]
PANTHERiPTHR15237. PTHR15237. 1 hit.
PfamiPF04139. Rad9. 1 hit.
[Graphical view]
PIRSFiPIRSF009303. Cell_cycle_RAD9. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiRAD9A_HUMAN
AccessioniPrimary (citable) accession number: Q99638
Secondary accession number(s): B2RCZ8, Q6FI29, Q96C41
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 7, 2006
Last sequence update: May 1, 1997
Last modified: November 2, 2016
This is version 126 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.