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Protein

Cell cycle checkpoint protein RAD1

Gene

RAD1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 (PubMed:10846170, PubMed:10884395). The 9-1-1 complex is recruited to DNA lesion upon damage by the RAD17-replication factor C (RFC) clamp loader complex (PubMed:12578958). Acts then as a sliding clamp platform on DNA for several proteins involved in long-patch base excision repair (LP-BER) (PubMed:15871698). 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 (PubMed:15314187, PubMed:15556996, PubMed:15871698). The 9-1-1 complex is necessary for the recruitment of RHNO1 to sites of double-stranded breaks (DSB) occurring during the S phase (PubMed:21659603). Isoform 1 possesses 3'->5' double stranded DNA exonuclease activity (PubMed:9660799).8 Publications

Catalytic activityi

Exonucleolytic cleavage in the 3'- to 5'-direction to yield nucleoside 5'-phosphates.1 Publication

GO - Molecular functioni

  • 3'-5' exonuclease activity Source: UniProtKB
  • damaged DNA binding Source: ProtInc
  • exodeoxyribonuclease III activity Source: UniProtKB-EC

GO - Biological processi

  • cellular response to DNA damage stimulus Source: ProtInc
  • cellular response to ionizing radiation Source: UniProtKB
  • DNA damage checkpoint Source: UniProtKB
  • DNA repair Source: GO_Central
  • meiotic recombination checkpoint Source: UniProtKB
  • substantia nigra development Source: UniProtKB

Keywordsi

Molecular functionExonuclease, Hydrolase, Nuclease
Biological processDNA damage, DNA repair

Enzyme and pathway databases

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
SIGNORiO60671

Names & Taxonomyi

Protein namesi
Recommended name:
Cell cycle checkpoint protein RAD1 (EC:3.1.11.21 Publication)
Short name:
hRAD1
Alternative name(s):
DNA repair exonuclease rad1 homolog
Rad1-like DNA damage checkpoint protein
Gene namesi
Name:RAD1
Synonyms:REC1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000113456.18
HGNCiHGNC:9806 RAD1
MIMi603153 gene
neXtProtiNX_O60671

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi226 – 233SLLKPSTK → AAAAAAAA: Abolishes association of the 9-1-1 complex with RAD17. 1 Publication8

Organism-specific databases

DisGeNETi5810
OpenTargetsiENSG00000113456
PharmGKBiPA34166

Chemistry databases

ChEMBLiCHEMBL3309116

Polymorphism and mutation databases

BioMutaiRAD1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002250051 – 282Cell cycle checkpoint protein RAD1Add BLAST282

Proteomic databases

EPDiO60671
MaxQBiO60671
PaxDbiO60671
PeptideAtlasiO60671
PRIDEiO60671
ProteomicsDBi49514
49515 [O60671-2]
49516 [O60671-3]

PTM databases

iPTMnetiO60671
PhosphoSitePlusiO60671

Expressioni

Tissue specificityi

Expressed in testis, uterus, bladder, spleen, ovaries, lung, brain and muscle (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000113456
CleanExiHS_RAD1
ExpressionAtlasiO60671 baseline and differential
GenevisibleiO60671 HS

Organism-specific databases

HPAiHPA006692

Interactioni

Subunit structurei

Component of the toroidal 9-1-1 (RAD9-RAD1-HUS1) complex, composed of RAD9A, RAD1 and HUS1 (PubMed:10846170, PubMed:10884395). The 9-1-1 complex associates with LIG1, POLB, FEN1, RAD17, HDAC1, RPA1 and RPA2 (PubMed:10846170, PubMed:10884395, PubMed:15314187, PubMed:15556996, PubMed:15871698, PubMed:15897895, PubMed:16216273). The 9-1-1 complex associates with the RAD17-RFC complex (PubMed:12578958). RAD1 interacts with POLB, FEN1, HUS1, HUS1B, RAD9A and RAD9B (PubMed:10359610, PubMed:10777662, PubMed:11944979, PubMed:14500360, PubMed:14611806, PubMed:15314187, PubMed:15556996, PubMed:16216273). Interacts with DNAJC7 (PubMed:11573955).14 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi111771, 19 interactors
ComplexPortaliCPX-1829 Checkpoint clamp complex
CORUMiO60671
DIPiDIP-46061N
IntActiO60671, 4 interactors
STRINGi9606.ENSP00000340879

Chemistry databases

BindingDBiO60671

Structurei

Secondary structure

1282
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi16 – 22Combined sources7
Helixi25 – 32Combined sources8
Beta strandi36 – 45Combined sources10
Beta strandi48 – 55Combined sources8
Turni56 – 58Combined sources3
Beta strandi59 – 66Combined sources8
Helixi67 – 69Combined sources3
Beta strandi70 – 78Combined sources9
Beta strandi80 – 85Combined sources6
Helixi86 – 93Combined sources8
Turni94 – 96Combined sources3
Beta strandi107 – 112Combined sources6
Beta strandi114 – 117Combined sources4
Beta strandi119 – 125Combined sources7
Beta strandi128 – 134Combined sources7
Turni149 – 151Combined sources3
Beta strandi152 – 159Combined sources8
Helixi160 – 163Combined sources4
Helixi164 – 168Combined sources5
Beta strandi174 – 181Combined sources8
Beta strandi183 – 194Combined sources12
Beta strandi197 – 203Combined sources7
Beta strandi205 – 207Combined sources3
Beta strandi208 – 215Combined sources8
Beta strandi219 – 224Combined sources6
Helixi225 – 228Combined sources4
Helixi231 – 237Combined sources7
Beta strandi239 – 246Combined sources8
Beta strandi247 – 249Combined sources3
Beta strandi251 – 258Combined sources8
Beta strandi260 – 262Combined sources3
Beta strandi264 – 271Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3A1JX-ray2.50C13-275[»]
3G65X-ray2.90B1-282[»]
3GGRX-ray3.20C1-282[»]
ProteinModelPortaliO60671
SMRiO60671
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO60671

Family & Domainsi

Sequence similaritiesi

Belongs to the rad1 family.Curated

Phylogenomic databases

eggNOGiKOG3194 Eukaryota
ENOG410YHQU LUCA
GeneTreeiENSGT00500000044913
HOGENOMiHOG000008015
HOVERGENiHBG053058
InParanoidiO60671
KOiK02830
OMAiCKVSVRT
OrthoDBiEOG091G0HS8
PhylomeDBiO60671
TreeFamiTF101211

Family and domain databases

InterProiView protein in InterPro
IPR003011 Cell_cycle_checkpoint_Rad1
IPR003021 Rad1_Rec1_Rad17
PANTHERiPTHR10870 PTHR10870, 1 hit
PfamiView protein in Pfam
PF02144 Rad1, 1 hit
PRINTSiPR01245 RAD1REC1
PR01246 RAD1REPAIR

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O60671-1) [UniParc]FASTAAdd to basket
Also known as: Hrad1A

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.

« Hide

        10         20         30         40         50
MPLLTQQIQD EDDQYSLVAS LDNVRNLSTI LKAIHFREHA TCFATKNGIK
60 70 80 90 100
VTVENAKCVQ ANAFIQAGIF QEFKVQEESV TFRINLTVLL DCLSIFGSSP
110 120 130 140 150
MPGTLTALRM CYQGYGYPLM LFLEEGGVVT VCKINTQEPE ETLDFDFCST
160 170 180 190 200
NVINKIILQS EGLREAFSEL DMTSEVLQIT MSPDKPYFRL STFGNAGSSH
210 220 230 240 250
LDYPKDSDLM EAFHCNQTQV NRYKISLLKP STKALVLSCK VSIRTDNRGF
260 270 280
LSLQYMIRNE DGQICFVEYY CCPDEEVPES ES
Length:282
Mass (Da):31,827
Last modified:August 1, 1998 - v1
Checksum:i075FBD4CF8A4FDB2
GO
Isoform 2 (identifier: O60671-2) [UniParc]FASTAAdd to basket
Also known as: Hrad1B

The sequence of this isoform differs from the canonical sequence as follows:
     67-102: Missing.

Show »
Length:246
Mass (Da):27,828
Checksum:iE96C130821B8D2D0
GO
Isoform 3 (identifier: O60671-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     67-68: AG → GL
     69-282: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:68
Mass (Da):7,576
Checksum:i12B4E5E1CA5B9703
GO

Sequence cautioni

The sequence AAC35550 differs from that shown. Reason: Frameshift at position 103.Curated
The sequence AAC35550 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAA06249 differs from that shown. Reason: Frameshift at position 103.Curated
The sequence CAA06249 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti135N → T in AAC95466 (PubMed:9828137).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05171833A → G. Corresponds to variant dbSNP:rs2308951Ensembl.1
Natural variantiVAR_05537639H → Q1 PublicationCorresponds to variant dbSNP:rs41271673Ensembl.1
Natural variantiVAR_051719104T → S. Corresponds to variant dbSNP:rs1805328Ensembl.1
Natural variantiVAR_051720114G → D. Corresponds to variant dbSNP:rs2308957Ensembl.1
Natural variantiVAR_051721281E → G1 PublicationCorresponds to variant dbSNP:rs1805327Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01733467 – 102Missing in isoform 2. 2 PublicationsAdd BLAST36
Alternative sequenceiVSP_01733567 – 68AG → GL in isoform 3. 1 Publication2
Alternative sequenceiVSP_01733669 – 282Missing in isoform 3. 1 PublicationAdd BLAST214

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF074717 mRNA Translation: AAC98093.1
AF073524 mRNA Translation: AAC95466.1
AF030933 mRNA Translation: AAC95427.1
AF076841 mRNA Translation: AAC95523.1
AF090170 mRNA Translation: AAC95603.1
AJ004974 mRNA Translation: CAA06248.1
AJ004975 mRNA Translation: CAA06249.1 Sequence problems.
AF011905 mRNA Translation: AAC27243.1
AF058392 mRNA Translation: AAC14138.1
AF084512 mRNA Translation: AAC35549.1
AF084513 mRNA Translation: AAC35550.1 Sequence problems.
AK002112 mRNA Translation: BAG51017.1
BT006908 mRNA Translation: AAP35554.1
DQ451401 Genomic DNA Translation: ABD96829.1
CH471119 Genomic DNA Translation: EAW55904.1
BC006837 mRNA Translation: AAH06837.1
BC009804 mRNA Translation: AAH09804.1
BC037857 mRNA Translation: AAH37857.1
AB183821 Genomic DNA Translation: BAD86789.1
AB183822 Genomic DNA Translation: BAD86790.1
CCDSiCCDS3905.1 [O60671-1]
RefSeqiNP_002844.1, NM_002853.3 [O60671-1]
UniGeneiHs.38114

Genome annotation databases

EnsembliENST00000325577; ENSP00000313467; ENSG00000113456 [O60671-3]
ENST00000341754; ENSP00000340879; ENSG00000113456 [O60671-1]
ENST00000382038; ENSP00000371469; ENSG00000113456 [O60671-1]
GeneIDi5810
KEGGihsa:5810
UCSCiuc003jix.4 human [O60671-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiRAD1_HUMAN
AccessioniPrimary (citable) accession number: O60671
Secondary accession number(s): O75572
, O95304, Q1W161, Q5KSM0, Q5KSM1, Q9UEP1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 7, 2006
Last sequence update: August 1, 1998
Last modified: June 20, 2018
This is version 152 of the entry and version 1 of the sequence. See 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, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: 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

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