O60921 (HUS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Checkpoint protein HUS1
Short name=hHUS1

Gene names

Name:

HUS1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	280 AA.
Sequence status	Complete.
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. 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 process	DNA damage DNA repair
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA 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 ionizing radiation Inferred from direct assay Ref.21. Source: UniProtKB double-strand break repair via homologous recombination Inferred from electronic annotation. Source: Compara embryo development Inferred from electronic annotation. Source: Compara negative regulation of DNA replication Inferred from electronic annotation. Source: Compara protein phosphorylation Inferred from electronic annotation. Source: Compara regulation of protein phosphorylation Inferred from electronic annotation. Source: Compara response to UV Inferred from electronic annotation. Source: Compara
Cellular_component	Golgi apparatus Inferred from direct assay. Source: HPA checkpoint clamp complex Inferred from electronic annotation. Source: InterPro nucleolus Inferred from direct assay. Source: HPA nucleoplasm Traceable author statement. Source: Reactome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RAD1	O60671	4	EBI-1056174,EBI-721835
RAD9A	Q99638	5	EBI-1056174,EBI-2606224

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 280

280

Checkpoint protein HUS1

PRO_0000225003

Natural variations

Natural variant

126

1

S → G.
Corresponds to variant rs2307261 [ dbSNP | Ensembl ].

VAR_033999

Natural variant

147

1

Q → K. Ref.6
Corresponds to variant rs2307254 [ dbSNP | Ensembl ].

VAR_025414

Natural variant

221

1

D → E. Ref.6
Corresponds to variant rs3176588 [ dbSNP | Ensembl ].

VAR_025415

Secondary structure

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280

Helix Strand Turn

Details...

Beta strand

2 – 7

6

Helix

10 – 26

17

Beta strand

28 – 34

7

Beta strand

36 – 43

8

Beta strand

46 – 48

3

Beta strand

53 – 59

7

Helix

60 – 62

3

Beta strand

65 – 70

6

Beta strand

72 – 74

3

Beta strand

79 – 84

6

Helix

85 – 91

7

Helix

92 – 97

6

Beta strand

98 – 106

9

Beta strand

108 – 110

3

Beta strand

112 – 119

8

Beta strand

122 – 124

3

Beta strand

128 – 134

7

Beta strand

135 – 137

3

Helix

140 – 146

7

Beta strand

155 – 159

5

Helix

163 – 174

12

Beta strand

178 – 184

7

Beta strand

186 – 188

3

Beta strand

190 – 195

6

Beta strand

197 – 205

9

Beta strand

216 – 220

5

Beta strand

228 – 233

6

Helix

234 – 243

10

Beta strand

249 – 256

8

Turn

257 – 259

3

Beta strand

260 – 269

10

Beta strand

271 – 277

7

Sequences

	Sequence		Length	Mass (Da)
	O60921 [UniParc]. Last modified August 1, 1998. Version 1. Checksum: 9C3ED2FD35C2ACB3	FASTA	280	31,691
	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

References

	« Hide 'large scale' referencesShow '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.

Web resources

NIEHS-SNPs

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.

IPI

IPI00004712.

RefSeq

NP_004498.1. NM_004507.3.

UniGene

Hs.152983.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3A1J	X-ray	2.50	B	1-280	[»]
3G65	X-ray	2.90	C	1-280	[»]
3GGR	X-ray	3.20	B	2-280	[»]

ProteinModelPortal

O60921.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-40929N.

IntAct

O60921. 3 interactions.

MINT

MINT-134822.

STRING

9606.ENSP00000258774.

PTM databases

PhosphoSite

O60921.

Proteomic databases

PaxDb

O60921.

PRIDE

O60921.

Protocols and materials databases

DNASU

3364.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000258774; ENSP00000258774; ENSG00000136273.
ENST00000436444; ENSP00000403844; ENSG00000136273.

GeneID

3364.

KEGG

hsa:3364.

UCSC

uc003tod.2. human.

Organism-specific databases

CTD

3364.

GeneCards

GC07M047735.

H-InvDB

HIX0033836.

HGNC

HGNC:5309. HUS1.

HPA

HPA026787.

MIM

603760. gene.

neXtProt

NX_O60921.

PharmGKB

PA29564.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG250864.

HOGENOM

HOG000253011.

HOVERGEN

HBG053069.

InParanoid

O60921.

KO

K10903.

OMA

QENFFSE.

OrthoDB

EOG4FTW1B.

PhylomeDB

O60921.

Enzyme and pathway databases

Pathway_Interaction_DB

telomerasepathway. Regulation of Telomerase.

Reactome

REACT_115566. Cell Cycle.

Gene expression databases

ArrayExpress

O60921.

Bgee

O60921.

CleanEx

HS_HUS1.

Genevestigator

O60921.

GermOnline

ENSG00000136273. Homo sapiens.

Family and domain databases

InterPro

IPR016580. Cell_cycle_HUS1.
IPR007150. Hus1/Mec3.
[Graphical view]

PANTHER

PTHR12900. PTHR12900. 1 hit.
PTHR12900:SF0. PTHR12900:SF0. 1 hit.

Pfam

PF04005. Hus1. 1 hit.
[Graphical view]

PIRSF

PIRSF011312. Cell_cycle_HUS1. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

O60921.

GenomeRNAi

3364.

NextBio

13320.

SOURCE

Search...

Entry information

Entry name

HUS1_HUMAN

Accession

Primary (citable) accession number: O60921

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 7, 2006
Last sequence update:	August 1, 1998
Last modified:	May 1, 2013
This is version 98 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.