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Protein

Checkpoint protein HUS1

Gene

HUS1

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. 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.1 Publication

GO - Biological processi

Keywordsi

Biological processDNA damage

Enzyme and pathway databases

BRENDAi2.3.2.B10 2681
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
SignaLinkiO60921

Names & Taxonomyi

Protein namesi
Recommended name:
Checkpoint protein HUS1
Short name:
hHUS1
Gene namesi
Name:HUS1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000136273.11
HGNCiHGNC:5309 HUS1
MIMi603760 gene
neXtProtiNX_O60921

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

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi3364
OpenTargetsiENSG00000136273
PharmGKBiPA29564

Polymorphism and mutation databases

BioMutaiHUS1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002250031 – 280Checkpoint protein HUS1Add BLAST280

Proteomic databases

EPDiO60921
MaxQBiO60921
PaxDbiO60921
PeptideAtlasiO60921
PRIDEiO60921
TopDownProteomicsiO60921-1 [O60921-1]

PTM databases

iPTMnetiO60921
PhosphoSitePlusiO60921

Expressioni

Tissue specificityi

Ubiquitous.1 Publication

Gene expression databases

BgeeiENSG00000136273
CleanExiHS_HUS1
ExpressionAtlasiO60921 baseline and differential
GenevisibleiO60921 HS

Organism-specific databases

HPAiHPA026787

Interactioni

Subunit structurei

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 DNAJC7.13 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi109596, 34 interactors
CORUMiO60921
DIPiDIP-40929N
IntActiO60921, 14 interactors
MINTiO60921
STRINGi9606.ENSP00000258774

Structurei

Secondary structure

1280
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi2 – 7Combined sources6
Helixi10 – 26Combined sources17
Beta strandi28 – 34Combined sources7
Beta strandi36 – 43Combined sources8
Beta strandi46 – 48Combined sources3
Beta strandi53 – 59Combined sources7
Helixi60 – 62Combined sources3
Beta strandi65 – 70Combined sources6
Beta strandi72 – 74Combined sources3
Beta strandi79 – 84Combined sources6
Helixi85 – 91Combined sources7
Helixi92 – 97Combined sources6
Beta strandi98 – 106Combined sources9
Beta strandi108 – 110Combined sources3
Beta strandi112 – 119Combined sources8
Beta strandi122 – 124Combined sources3
Beta strandi128 – 134Combined sources7
Beta strandi135 – 137Combined sources3
Helixi140 – 146Combined sources7
Beta strandi155 – 159Combined sources5
Helixi163 – 174Combined sources12
Beta strandi178 – 184Combined sources7
Beta strandi186 – 188Combined sources3
Beta strandi190 – 195Combined sources6
Beta strandi197 – 205Combined sources9
Beta strandi216 – 220Combined sources5
Beta strandi228 – 233Combined sources6
Helixi234 – 243Combined sources10
Beta strandi249 – 256Combined sources8
Turni257 – 259Combined sources3
Beta strandi260 – 269Combined sources10
Beta strandi271 – 277Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3A1JX-ray2.50B1-280[»]
3G65X-ray2.90C1-280[»]
3GGRX-ray3.20B2-280[»]
ProteinModelPortaliO60921
SMRiO60921
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO60921

Family & Domainsi

Sequence similaritiesi

Belongs to the HUS1 family.Curated

Phylogenomic databases

eggNOGiKOG3999 Eukaryota
ENOG410ZQ9J LUCA
GeneTreeiENSGT00390000000706
HOGENOMiHOG000253011
HOVERGENiHBG053069
InParanoidiO60921
KOiK10903
OMAiHNEIYLE
OrthoDBiEOG091G0H06
PhylomeDBiO60921
TreeFamiTF314491

Family and domain databases

InterProiView protein in InterPro
IPR016580 Cell_cycle_HUS1
IPR007150 Hus1/Mec3
PfamiView protein in Pfam
PF04005 Hus1, 1 hit
PIRSFiPIRSF011312 Cell_cycle_HUS1, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O60921-1) [UniParc]FASTAAdd to basket

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
MKFRAKIVDG ACLNHFTRIS NMIAKLAKTC TLRISPDKLN FILCDKLANG
60 70 80 90 100
GVSMWCELEQ ENFFNEFQME GVSAENNEIY LELTSENLSR ALKTAQNARA
110 120 130 140 150
LKIKLTNKHF PCLTVSVELL SMSSSSRIVT HDIPIKVIPR KLWKDLQEPV
160 170 180 190 200
VPDPDVSIYL PVLKTMKSVV EKMKNISNHL VIEANLDGEL NLKIETELVC
210 220 230 240 250
VTTHFKDLGN PPLASESTHE DRNVEHMAEV HIDIRKLLQF LAGQQVNPTK
260 270 280
ALCNIVNNKM VHFDLLHEDV SLQYFIPALS
Length:280
Mass (Da):31,691
Last modified:August 1, 1998 - v1
Checksum:i9C3ED2FD35C2ACB3
GO
Isoform 2 (identifier: O60921-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-21: Missing.

Note: No experimental confirmation available.
Show »
Length:259
Mass (Da):29,287
Checksum:iD97AE567F923089B
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_033999126S → G. Corresponds to variant dbSNP:rs2307261Ensembl.1
Natural variantiVAR_025414147Q → K1 PublicationCorresponds to variant dbSNP:rs2307254Ensembl.1
Natural variantiVAR_025415221D → E1 PublicationCorresponds to variant dbSNP:rs3176588Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0567021 – 21Missing in isoform 2. 1 PublicationAdd BLAST21

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y16893 mRNA Translation: CAA76518.1
AF076844 mRNA Translation: AAC95526.1
AF110393 mRNA Translation: AAD25350.1
AK294117 mRNA Translation: BAG57450.1
AC019066 Genomic DNA No translation available.
AC069282 Genomic DNA No translation available.
AC104696 Genomic DNA No translation available.
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
CCDSiCCDS34635.1 [O60921-1]
RefSeqiNP_004498.1, NM_004507.3 [O60921-1]
XP_016867604.1, XM_017012115.1 [O60921-2]
UniGeneiHs.152983

Genome annotation databases

EnsembliENST00000258774; ENSP00000258774; ENSG00000136273 [O60921-1]
ENST00000432325; ENSP00000416588; ENSG00000136273 [O60921-2]
ENST00000436444; ENSP00000403844; ENSG00000136273 [O60921-1]
ENST00000458191; ENSP00000400727; ENSG00000136273 [O60921-2]
GeneIDi3364
KEGGihsa:3364
UCSCiuc003tod.3 human [O60921-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiHUS1_HUMAN
AccessioniPrimary (citable) accession number: O60921
Secondary accession number(s): B4DFI9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 7, 2006
Last sequence update: August 1, 1998
Last modified: March 28, 2018
This is version 141 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
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Main funding by: National Institutes of Health