Reviewed, UniProtKB/Swiss-Prot O60671 (RAD1_HUMAN)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	282 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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 process	DNA damage DNA repair
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Molecular function	Exonuclease Hydrolase Nuclease
Gene Ontology (GO)
Biological process	DNA 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 component	nucleus Ref.1 Ref.5 Inferred by curator. Source: UniProtKB
Molecular function	3'-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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 282	282	Cell cycle checkpoint protein RAD1		PRO_0000225005
Natural variations
	Alternative sequence	1 – 109	109	Missing in isoform 2.		VSP_017334
	Alternative sequence	67 – 68	2	AG → GL in isoform 3.		VSP_017335
	Alternative sequence	69 – 282	214	Missing in isoform 3.		VSP_017336
Experimental info
	Mutagenesis	226 – 233	8	SLLKPSTK → AAAAAAAA: Abolishes association of the 9-1-1 complex with RAD17
	Sequence conflict	135	1	N → T in AAC95466. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Hrad1A) [UniParc]. Last modified August 1, 1998. Version 1. Checksum: 075FBD4CF8A4FDB2	FASTA	282	31,827
	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
	Isoform 2 (Hrad1B) [UniParc]. Checksum: F599F0C6E4027A8A		173	19,727
	10 20 30 40 50 60 MCYQGYGYPL MLFLEEGGVV TVCKINTQEP EETLDFDFCS TNVINKIILQ SEGLREAFSE 70 80 90 100 110 120 LDMTSEVLQI TMSPDKPYFR LSTFGNAGSS HLDYPKDSDL MEAFHCNQTQ VNRYKISLLK 130 140 150 160 170 PSTKALVLSC KVSIRTDNRG FLSLQYMIRN EDGQICFVEY YCCPDEEVPE SES
	Isoform 3 [UniParc]. Checksum: 12B4E5E1CA5B9703		68	7,576
	10 20 30 40 50 60 MPLLTQQIQD EDDQYSLVAS LDNVRNLSTI LKAIHFREHA TCFATKNGIK VTVENAKCVQ ANAFIQGL

References

	« Hide 'large scale' referencesShow '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
EMBLGenBankDDBJ	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.
RefSeq	NP_002844.1. NP_596868.1.
UniGene	Hs.531879
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	O60671.
Genome annotation databases
Ensembl	ENSG00000113456. Homo sapiens. [Contig view]
GeneID	5810.
KEGG	hsa:5810.
Organism-specific databases
H-InvDB	HIX0004799.
HGNC	HGNC:9806. RAD1.
MIM	603153. gene.
PharmGKB	PA142671554.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	O60671.
HOVERGEN	O60671.
Gene expression databases
ArrayExpress	O60671.
CleanEx	HS_RAD1.
GermOnline	ENSG00000113456. Homo sapiens.
Family and domain databases
InterPro	IPR003021. Rad1_Rec1. IPR003011. Rad1_repair. [Graphical view]
PANTHER	PTHR10870. Rad1_Rec1. 1 hit.
Pfam	PF02144. Rad1. 1 hit. [Graphical view]
PRINTS	PR01245. RAD1REC1. PR01246. RAD1REPAIR.
ProtoNet	Search...
Other Resources
LinkHub	O60671.
NextBio	22636.
SOURCE	Search...

Entry information

Entry name

RAD1_HUMAN

Accession

Primary (citable) accession number: O60671
Secondary accession number(s): O75572 , 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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)