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Reviewed, UniProtKB/Swiss-Prot O60671 (RAD1_HUMAN)

Last modified November 25, 2008. Version 59. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Cell cycle checkpoint protein RAD1
      Short name=hRAD1
    EC=3.1.11.2
Alternative name(s):
    DNA repair exonuclease rad1 homolog
    Rad1-like DNA damage checkpoint protein
Gene names
Name: RAD1
Synonyms: REC1
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length282 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

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. Isoform 1 possesses 3'->5' double stranded DNA exonuclease activity.

Catalytic activity

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

Subunit structure

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. RAD1 interacts with POLB, FEN1, HUS1, HUS1B, RAD9A and RAD9B.

Subcellular location

Nucleus.

Tissue specificity

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

Sequence similarities

Belongs to the rad1 family.

Ontologies

Keywords

   Biological processDNA damage
DNA repair
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   Molecular functionExonuclease
Hydrolase
Nuclease

Gene Ontology (GO)

   Biological processDNA damage checkpoint Ref.1

Traceable author statement. Source: ProtInc

DNA repair

Traceable author statement. Source: ProtInc

DNA replication

Inferred from Experiment. Source: Reactome

meiotic prophase I Ref.1

Traceable author statement. Source: ProtInc

   Cellular componentnucleus Ref.1 Ref.5

Inferred by curator. Source: UniProtKB

   Molecular function3'-5' exonuclease activity Ref.5

Inferred from direct assay. Source: UniProtKB

damaged DNA binding Ref.5

Non-traceable author statement. Source: UniProtKB

exodeoxyribonuclease III activity

Inferred from electronic annotation. Source: InterPro

protein binding Ref.12

Inferred from physical interaction. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O60671-1)

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.
Isoform 2 (identifier: O60671-2)

Also known as: Hrad1B;

The sequence of this isoform differs from the canonical sequence as follows:
     1-109: Missing.
Isoform 3 (identifier: O60671-3)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 282282Cell cycle checkpoint protein RAD1
PRO_0000225005

Natural variations

Alternative sequence1 – 109109Missing in isoform 2.
VSP_017334
Alternative sequence67 – 682AG → GL in isoform 3.
VSP_017335
Alternative sequence69 – 282214Missing in isoform 3.
VSP_017336

Experimental info

Mutagenesis226 – 2338SLLKPSTK → AAAAAAAA: Abolishes association of the 9-1-1 complex with RAD17
Sequence conflict1351N → T in AAC95466. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Hrad1A) [UniParc].

Last modified August 1, 1998. Version 1.
Checksum: 075FBD4CF8A4FDB2

FASTA28231,827
        10         20         30         40         50         60 
MPLLTQQIQD EDDQYSLVAS LDNVRNLSTI LKAIHFREHA TCFATKNGIK VTVENAKCVQ 

        70         80         90        100        110        120 
ANAFIQAGIF QEFKVQEESV TFRINLTVLL DCLSIFGSSP MPGTLTALRM CYQGYGYPLM 

       130        140        150        160        170        180 
LFLEEGGVVT VCKINTQEPE ETLDFDFCST NVINKIILQS EGLREAFSEL DMTSEVLQIT 

       190        200        210        220        230        240 
MSPDKPYFRL STFGNAGSSH LDYPKDSDLM EAFHCNQTQV NRYKISLLKP STKALVLSCK 

       250        260        270        280 
VSIRTDNRGF LSLQYMIRNE DGQICFVEYY CCPDEEVPES ES 

« Hide

Isoform 2 (Hrad1B) [UniParc].

Checksum: F599F0C6E4027A8A
Show »

17319,727
Isoform 3 [UniParc].

Checksum: 12B4E5E1CA5B9703
Show »

687,576

References

« Hide 'large scale' references
[1]"Human and mouse homologs of Schizosaccharomyces pombe rad1(+) and Saccharomyces cerevisiae RAD17: linkage to checkpoint control and mammalian meiosis."
Freire R., Murguia J.R., Tarsounas M., Lowndes N.F., Moens P.B., Jackson S.P.
Genes Dev. 12:2560-2573(1998) [PubMed: 9716408] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]"A human and mouse homolog of the Schizosaccharomyces pombe rad1+ cell cycle checkpoint control gene."
Bluyssen H.A.R., van Os R.I., Naus N.C., Jaspers I., Hoeijmakers J.H.J., de Klein A.
Genomics 54:331-337(1998) [PubMed: 9828137] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]"RAD1, a human structural homolog of the Schizosaccharomyces pombe RAD1 cell cycle checkpoint gene."
Marathi U.K., Dahlen M., Sunnerhagen P., Romero A.V., Ramagli L.S., Siciliano M.J., Li L., Legerski R.J.
Genomics 54:344-347(1998) [PubMed: 9828139] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Cervix carcinoma.
[4]"cDNA cloning and gene mapping of human homologs for Schizosaccharomyces pombe rad17, rad1, and hus1 and cloning of homologs from mouse, Caenorhabditis elegans, and Drosophila melanogaster."
Dean F.B., Lian L., O'Donnell M.
Genomics 54:424-436(1998) [PubMed: 9878245] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3).
[5]"A human homologue of the Schizosaccharomyces pombe rad1+ checkpoint gene encodes an exonuclease."
Parker A.E., Van de Weyer I., Laus M.C., Oostveen I., Yon J., Verhasselt P., Luyten W.H.M.L.
J. Biol. Chem. 273:18332-18339(1998) [PubMed: 9660799] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION IN EXONUCLEASE ACTIVITY.
[6]"HRAD1 and MRad1 encode mammalian homologues of the fission yeast rad1+ cell cycle checkpoint control gene."
Udell C.M., Lee S.K., Davey S.
Nucleic Acids Res. 26:3971-3976(1998) [PubMed: 9705507] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[7]"Identification and cloning of Hrad1, a human homolog of the Schizosaccharomyces pombe checkpoint protein."
Hao L., Chang M., Liu J., Chen L.B.
Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[8]"Mammalian REC1, encoding a 3'-5' exonuclease, is differentially expressed during meiosis."
Shannon M.E., Naureckiene S., Stubbs L., Holloman W.K., Thelen M.P.
Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
[9]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[10]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Bone marrow, Placenta and Testis.
[11]"Identification of novel polymorphisms in the RAD1 gene."
Saegusa K.K., Suga T.K., Imai T.
Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 104-188 AND 223-282.
[12]"The human G2 checkpoint control protein hRAD9 is a nuclear phosphoprotein that forms complexes with hRAD1 and hHUS1."
St Onge R.P., Udell C.M., Casselman R., Davey S.
Mol. Biol. Cell 10:1985-1995(1999) [PubMed: 10359610] [Abstract]
Cited for: INTERACTION WITH HUS1 AND RAD9A.
[13]"Physical interaction among human checkpoint control proteins HUS1p, RAD1p, and RAD9p, and implications for the regulation of cell cycle progression."
Hang H., Lieberman H.B.
Genomics 65:24-33(2000) [PubMed: 10777662] [Abstract]
Cited for: INTERACTION WITH HUS1 AND RAD9A.
[14]"HDAC1, a histone deacetylase, forms a complex with Hus1 and Rad9, two G2/M checkpoint Rad proteins."
Cai R.L., Yan-Neale Y., Cueto M.A., Xu H., Cohen D.
J. Biol. Chem. 275:27909-27916(2000) [PubMed: 10846170] [Abstract]
Cited for: IDENTIFICATION IN THE 9-1-1 COMPLEX ASSOCIATED WITH HDAC1.
[15]"The human checkpoint protein hRad17 interacts with the PCNA-like proteins hRad1, hHus1, and hRad9."
Rauen M., Burtelow M.A., Dufault V.M., Karnitz L.M.
J. Biol. Chem. 275:29767-29771(2000) [PubMed: 10884395] [Abstract]
Cited for: IDENTIFICATION IN THE 9-1-1 COMPLEX ASSOCIATED WITH RAD17, MUTAGENESIS OF 226-SER--LYS-233.
[16]"Identification and characterization of a paralog of human cell cycle checkpoint gene HUS1."
Hang H., Zhang Y., Dunbrack R.L. Jr., Wang C., Lieberman H.B.
Genomics 79:487-492(2002) [PubMed: 11944979] [Abstract]
Cited for: INTERACTION WITH HUS1B.
[17]"Expression of mammalian paralogues of HRAD9 and Mrad9 checkpoint control genes in normal and cancerous testicular tissue."
Hopkins K.M., Wang X., Berlin A., Hang H., Thaker H.M., Lieberman H.B.
Cancer Res. 63:5291-5298(2003) [PubMed: 14500360] [Abstract]
Cited for: INTERACTION WITH RAD9B.
[18]"Identification and characterization of RAD9B, a paralog of the RAD9 checkpoint gene."
Dufault V.M., Oestreich A.J., Vroman B.T., Karnitz L.M.
Genomics 82:644-651(2003) [PubMed: 14611806] [Abstract]
Cited for: INTERACTION WITH RAD9B.
[19]"Loading of the human 9-1-1 checkpoint complex onto DNA by the checkpoint clamp loader hRad17-replication factor C complex in vitro."
Bermudez V.P., Lindsey-Boltz L.A., Cesare A.J., Maniwa Y., Griffith J.D., Hurwitz J., Sancar A.
Proc. Natl. Acad. Sci. U.S.A. 100:1633-1638(2003) [PubMed: 12578958] [Abstract]
Cited for: ASSOCIATION OF THE 9-1-1 COMPLEX WITH THE RAD17-RFC COMPLEX, ELECTRON MICROSCOPY OF THE 9-1-1 AND RAD17-RFC COMPLEXES BOUND TO DNA.
[20]"The human Rad9/Rad1/Hus1 damage sensor clamp interacts with DNA polymerase beta and increases its DNA substrate utilisation efficiency: implications for DNA repair."
Toueille M., El-Andaloussi N., Frouin I., Freire R., Funk D., Shevelev I., Friedrich-Heineken E., Villani G., Hottiger M.O., Huebscher U.
Nucleic Acids Res. 32:3316-3324(2004) [PubMed: 15314187] [Abstract]
Cited for: IDENTIFICATION IN THE 9-1-1 COMPLEX ASSOCIATED WITH POLB, INTERACTION WITH POLB.
[21]"The human Rad9-Rad1-Hus1 checkpoint complex stimulates flap endonuclease 1."
Wang W., Brandt P., Rossi M.L., Lindsey-Boltz L., Podust V., Fanning E., Sancar A., Bambara R.A.
Proc. Natl. Acad. Sci. U.S.A. 101:16762-16767(2004) [PubMed: 15556996] [Abstract]
Cited for: IDENTIFICATION IN THE 9-1-1 COMPLEX ASSOCIATED WITH FEN1.
[22]"The human checkpoint sensor and alternative DNA clamp Rad9-Rad1-Hus1 modulates the activity of DNA ligase I, a component of the long-patch base excision repair machinery."
Smirnova E., Toueille M., Markkanen E., Huebscher U.
Biochem. J. 389:13-17(2005) [PubMed: 15871698] [Abstract]
Cited for: IDENTIFICATION IN THE 9-1-1 COMPLEX ASSOCIATED WITH LIG1.
[23]"The two DNA clamps Rad9/Rad1/Hus1 complex and proliferating cell nuclear antigen differentially regulate flap endonuclease 1 activity."
Friedrich-Heineken E., Toueille M., Taennler B., Buerki C., Ferrari E., Hottiger M.O., Huebscher U.
J. Mol. Biol. 353:980-989(2005) [PubMed: 16216273] [Abstract]
Cited for: IDENTIFICATION IN THE 9-1-1 COMPLEX ASSOCIATED WITH FEN1, INTERACTION WITH FEN1.
[24]"Interaction and colocalization of Rad9/Rad1/Hus1 checkpoint complex with replication protein A in human cells."
Wu X., Shell S.M., Zou Y.
Oncogene 24:4728-4735(2005) [PubMed: 15897895] [Abstract]
Cited for: IDENTIFICATION IN THE 9-1-1 COMPLEX ASSOCIATED WITH RPA1 AND RPA2.
+Additional computationally mapped references.

Cross-references

Sequence databases

AF074717 mRNA. Translation: AAC98093.1.
AF073524 mRNA. Translation: AAC95466.1.
AF030933 mRNA. Translation: AAC95427.1.
AF090170 mRNA. Translation: AAC95603.1.
AF076841 mRNA. Translation: AAC95523.1.
AJ004974 mRNA. Translation: CAA06248.1.
AJ004975 mRNA. Translation: CAA06249.1.
AF011905 mRNA. Translation: AAC27243.1.
AF058392 mRNA. Translation: AAC14138.1.
AF084512 mRNA. Translation: AAC35549.1.
AF084513 mRNA. Translation: AAC35550.1.
BT006908 mRNA. Translation: AAP35554.1.
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.
RefSeqNP_002844.1.
NP_596868.1.
UniGeneHs.531879

3D structure databases

ModBaseSearch...

Protein-protein interaction databases

IntActO60671.

Genome annotation databases

EnsemblENSG00000113456. Homo sapiens. [Contig view]
GeneID5810.
KEGGhsa:5810.

Organism-specific databases

H-InvDBHIX0004799.
HGNCHGNC:9806. RAD1.
MIM603153. gene.
PharmGKBPA142671554.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOGENOMO60671.
HOVERGENO60671.

Gene expression databases

ArrayExpressO60671.
CleanExHS_RAD1.
GermOnlineENSG00000113456. Homo sapiens.

Family and domain databases

InterProIPR003021. Rad1_Rec1.
IPR003011. Rad1_repair.
[Graphical view]
PANTHERPTHR10870. Rad1_Rec1. 1 hit.
PfamPF02144. Rad1. 1 hit.
[Graphical view]
PRINTSPR01245. RAD1REC1.
PR01246. RAD1REPAIR.
ProtoNetSearch...

Other Resources

LinkHubO60671.
NextBio22636.
SOURCESearch...

Entry information

Entry nameRAD1_HUMAN
AccessionPrimary (citable) accession number: O60671
Secondary accession number(s): O75572 expand/collapse secondary AC list , O95304, Q5KSM0, Q5KSM1, Q9UEP1
Entry history
Integrated into UniProtKB/Swiss-Prot: March 7, 2006
Last sequence update: August 1, 1998
Last modified: November 25, 2008
This is version 59 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents