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O60921 (HUS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Checkpoint protein HUS1

Short name=hHUS1
Gene names
Name:HUS1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length280 AA.
Sequence statusComplete.
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. The 9-1-1 complex is necessary for the recruitment of RHNO1 to sites of double-stranded breaks (DSB) occurring during the S phase. Ref.21

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. HUS1 interacts with POLB, HDAC1, FEN1, PCNA, RAD1, RAD9A and RAD9B. HUS1 does not interact with RAD17. Interacts with DNAJC7. Ref.3 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20

Subcellular location

Nucleus. Cytoplasm. Note: In discrete nuclear foci upon DNA damage. According to Ref.13, localized also in the cytoplasm. DNA damage induces its nuclear translocation. Shuttles between the nucleus and the cytoplasm. Ref.9 Ref.11

Tissue specificity

Ubiquitous. Ref.3

Sequence similarities

Belongs to the HUS1 family.

Ontologies

Keywords
   Biological processDNA damage
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA damage checkpoint

Inferred from mutant phenotype Ref.21. Source: UniProtKB

DNA repair

Traceable author statement PubMed 9872989. Source: ProtInc

DNA replication

Traceable author statement. Source: Reactome

cellular response to DNA damage stimulus

Traceable author statement PubMed 9872989. Source: ProtInc

cellular response to ionizing radiation

Inferred from direct assay Ref.21. Source: UniProtKB

double-strand break repair via homologous recombination

Inferred from electronic annotation. Source: Ensembl

embryo development

Inferred from electronic annotation. Source: Ensembl

mitotic cell cycle checkpoint

Inferred from electronic annotation. Source: Ensembl

negative regulation of DNA replication

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from electronic annotation. Source: Ensembl

regulation of protein phosphorylation

Inferred from electronic annotation. Source: Ensembl

response to UV

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcheckpoint clamp complex

Inferred from electronic annotation. Source: InterPro

cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleolus

Inferred from electronic annotation. Source: InterPro

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.9. Source: UniProtKB

   Molecular_functionprotein binding

Inferred from physical interaction Ref.8Ref.9Ref.10. Source: UniProtKB

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 280280Checkpoint protein HUS1
PRO_0000225003

Natural variations

Natural variant1261S → G.
Corresponds to variant rs2307261 [ dbSNP | Ensembl ].
VAR_033999
Natural variant1471Q → K. Ref.6
Corresponds to variant rs2307254 [ dbSNP | Ensembl ].
VAR_025414
Natural variant2211D → E. Ref.6
Corresponds to variant rs3176588 [ dbSNP | Ensembl ].
VAR_025415

Secondary structure

......................................................... 280
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O60921 [UniParc].

Last modified August 1, 1998. Version 1.
Checksum: 9C3ED2FD35C2ACB3

FASTA28031,691
        10         20         30         40         50         60 
MKFRAKIVDG ACLNHFTRIS NMIAKLAKTC TLRISPDKLN FILCDKLANG GVSMWCELEQ 

        70         80         90        100        110        120 
ENFFNEFQME GVSAENNEIY LELTSENLSR ALKTAQNARA LKIKLTNKHF PCLTVSVELL 

       130        140        150        160        170        180 
SMSSSSRIVT HDIPIKVIPR KLWKDLQEPV VPDPDVSIYL PVLKTMKSVV EKMKNISNHL 

       190        200        210        220        230        240 
VIEANLDGEL NLKIETELVC VTTHFKDLGN PPLASESTHE DRNVEHMAEV HIDIRKLLQF 

       250        260        270        280 
LAGQQVNPTK ALCNIVNNKM VHFDLLHEDV SLQYFIPALS 

« Hide

References

« Hide 'large scale' references
[1]"Hus1p, a conserved fission yeast checkpoint protein, interacts with Rad1p and is phosphorylated in response to DNA damage."
Kostrub C.F., Knudsen K., Subramani S., Enoch T.
EMBO J. 17:2055-2066(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH RAD1 AND RAD9A, TISSUE SPECIFICITY.
Tissue: T-cell.
[4]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"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 (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]NIEHS SNPs program
Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LYS-147 AND GLU-221.
[7]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Urinary bladder.
[8]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RAD1 AND RAD9A.
[9]"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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE 9-1-1 COMPLEX ASSOCIATED WITH HDAC1, INTERACTION WITH HDAC1, SUBCELLULAR LOCATION.
[10]"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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE 9-1-1 COMPLEX ASSOCIATED WITH RAD17.
[11]"PCNA interacts with hHus1/hRad9 in response to DNA damage and replication inhibition."
Komatsu K., Wharton W., Hang H., Wu C., Singh S., Lieberman H.B., Pledger W.J., Wang H.-G.
Oncogene 19:5291-5297(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PCNA, SUBCELLULAR LOCATION.
[12]"The J domain of Tpr2 regulates its interaction with the proapoptotic and cell-cycle checkpoint protein, Rad9."
Xiang S.L., Kumano T., Iwasaki S.I., Sun X., Yoshioka K., Yamamoto K.C.
Biochem. Biophys. Res. Commun. 287:932-940(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DNAJC7.
[13]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RAD9B.
[14]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RAD9B.
[15]"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] [Europe PMC] [Abstract]
Cited for: ASSOCIATION OF THE 9-1-1 COMPLEX WITH THE RAD17-RFC COMPLEX, LACK OF INTERACTION WITH RAD17, ELECTRON MICROSCOPY OF THE 9-1-1 AND RAD17-RFC COMPLEXES BOUND TO DNA.
[16]"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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE 9-1-1 COMPLEX ASSOCIATED WITH POLB, INTERACTION WITH POLB.
[17]"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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE 9-1-1 COMPLEX ASSOCIATED WITH FEN1.
[18]"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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE 9-1-1 COMPLEX ASSOCIATED WITH LIG1.
[19]"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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE 9-1-1 COMPLEX ASSOCIATED WITH FEN1, INTERACTION WITH FEN1.
[20]"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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE 9-1-1 COMPLEX ASSOCIATED WITH RPA1 AND RPA2.
[21]"A DNA damage response screen identifies RHINO, a 9-1-1 and TopBP1 interacting protein required for ATR signaling."
Cotta-Ramusino C., McDonald E.R. III, Hurov K., Sowa M.E., Harper J.W., Elledge S.J.
Science 332:1313-1317(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y16893 mRNA. Translation: CAA76518.1.
AF076844 mRNA. Translation: AAC95526.1.
AF110393 mRNA. Translation: AAD25350.1.
CR536552 mRNA. Translation: CAG38789.1.
BT019481 mRNA. Translation: AAV38288.1.
BT019482 mRNA. Translation: AAV38289.1.
AF503165 Genomic DNA. Translation: AAM18968.1.
BC007013 mRNA. Translation: AAH07013.1.
CCDSCCDS34635.1.
RefSeqNP_004498.1. NM_004507.3.
UniGeneHs.152983.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3A1JX-ray2.50B1-280[»]
3G65X-ray2.90C1-280[»]
3GGRX-ray3.20B2-280[»]
ProteinModelPortalO60921.
SMRO60921. Positions 3-280.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109596. 21 interactions.
DIPDIP-40929N.
IntActO60921. 4 interactions.
MINTMINT-134822.
STRING9606.ENSP00000258774.

PTM databases

PhosphoSiteO60921.

Proteomic databases

MaxQBO60921.
PaxDbO60921.
PRIDEO60921.

Protocols and materials databases

DNASU3364.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000258774; ENSP00000258774; ENSG00000136273.
ENST00000436444; ENSP00000403844; ENSG00000136273.
GeneID3364.
KEGGhsa:3364.
UCSCuc003tod.2. human.

Organism-specific databases

CTD3364.
GeneCardsGC07M047735.
H-InvDBHIX0033836.
HGNCHGNC:5309. HUS1.
HPAHPA026787.
MIM603760. gene.
neXtProtNX_O60921.
PharmGKBPA29564.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG250864.
HOGENOMHOG000253011.
HOVERGENHBG053069.
InParanoidO60921.
KOK10903.
OMACMILYVY.
PhylomeDBO60921.
TreeFamTF314491.

Enzyme and pathway databases

ReactomeREACT_115566. Cell Cycle.
SignaLinkO60921.

Gene expression databases

ArrayExpressO60921.
BgeeO60921.
CleanExHS_HUS1.
GenevestigatorO60921.

Family and domain databases

InterProIPR016580. Cell_cycle_HUS1.
IPR007150. Hus1/Mec3.
[Graphical view]
PANTHERPTHR12900. PTHR12900. 1 hit.
PfamPF04005. Hus1. 1 hit.
[Graphical view]
PIRSFPIRSF011312. Cell_cycle_HUS1. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceO60921.
GeneWikiHUS1.
GenomeRNAi3364.
NextBio13320.
PROO60921.
SOURCESearch...

Entry information

Entry nameHUS1_HUMAN
AccessionPrimary (citable) accession number: O60921
Entry history
Integrated into UniProtKB/Swiss-Prot: March 7, 2006
Last sequence update: August 1, 1998
Last modified: July 9, 2014
This is version 109 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM