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Protein

Cell cycle checkpoint protein RAD17

Gene

RAD17

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Essential for sustained cell growth, maintenance of chromosomal stability, and ATR-dependent checkpoint activation upon DNA damage. Has a weak ATPase activity required for binding to chromatin. Participates in the recruitment of the RAD1-RAD9-HUS1 complex and RHNO1 onto chromatin, and in CHEK1 activation. May also serve as a sensor of DNA replication progression, and may be involved in homologous recombination.11 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi137 – 144ATPSequence analysis8

GO - Molecular functioni

GO - Biological processi

  • cellular response to DNA damage stimulus Source: UniProtKB
  • DNA damage checkpoint Source: UniProtKB
  • DNA repair Source: GO_Central
  • DNA replication Source: Reactome
  • DNA replication checkpoint Source: ProtInc
  • mitotic cell cycle checkpoint Source: UniProtKB
  • mitotic DNA replication checkpoint Source: GO_Central
  • negative regulation of DNA replication Source: UniProtKB
  • regulation of phosphorylation Source: UniProtKB

Keywordsi

Biological processCell cycle, DNA damage
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

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
SIGNORiO75943

Names & Taxonomyi

Protein namesi
Recommended name:
Cell cycle checkpoint protein RAD17
Short name:
hRad17
Alternative name(s):
RF-C/activator 1 homolog
Gene namesi
Name:RAD17
Synonyms:R24L
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000152942.18
HGNCiHGNC:9807 RAD17
MIMi603139 gene
neXtProtiNX_O75943

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

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi143K → E: Impairs phosphorylation on S-656. Abolishes interaction with the RAD1-RAD9-HUS1 complex; does not affect interaction with RFC3. 3 Publications1
Mutagenesisi143K → G: Impairs phosphorylation. Impairs interaction with DNA and the RAD1-RAD9-HUS1 complex; does not affect interaction with RFC3. 3 Publications1
Mutagenesisi191S → A: No effect on phosphorylation by ATR. 1 Publication1
Mutagenesisi646S → A: Reduces by 50% phosphorylation by ATR, and abolishes interaction with RAD1. Abolishes phosphorylation by ATR and checkpoint activation without affecting interaction with RFC3, RFC4, ATM or ATR; when associated with A-656. 4 Publications1
Mutagenesisi646S → D: Abolishes interaction with RAD1; when associated with D-656. 4 Publications1
Mutagenesisi656S → A: Reduces by 50% phosphorylation by ATR, and abolishes interaction with RAD1. Abolishes phosphorylation by ATR and checkpoint activation without affecting interaction with RFC3, RFC4, ATM or ATR; when associated with A-646. 4 Publications1
Mutagenesisi656S → D: Abolishes interaction with RAD1; when associated with D-646. 4 Publications1

Organism-specific databases

DisGeNETi5884
OpenTargetsiENSG00000152942
PharmGKBiPA34167

Polymorphism and mutation databases

BioMutaiRAD17

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002099481 – 681Cell cycle checkpoint protein RAD17Add BLAST681

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei55PhosphothreonineBy similarity1
Modified residuei71PhosphoserineCombined sources1
Modified residuei86PhosphoserineCombined sources1
Modified residuei359PhosphoserineCombined sources1
Modified residuei646Phosphoserine; by ATR and ATM4 Publications1
Modified residuei656Phosphoserine; by ATR and ATM3 Publications1

Post-translational modificationi

Phosphorylated. Phosphorylation on Ser-646 and Ser-656 is cell cycle-regulated, enhanced by genotoxic stress, and required for activation of checkpoint signaling. Phosphorylation is mediated by ATR upon UV or replication arrest, whereas it may be mediated both by ATR and ATM upon ionizing radiation. Phosphorylation on both sites is required for interaction with RAD1 but dispensable for interaction with RFC3 or RFC4.5 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiO75943
PaxDbiO75943
PeptideAtlasiO75943
PRIDEiO75943

PTM databases

iPTMnetiO75943
PhosphoSitePlusiO75943

Expressioni

Tissue specificityi

Overexpressed in various cancer cell lines and in colon carcinoma (at protein level). Isoform 2 and isoform 3 are the most abundant isoforms in non irradiated cells (at protein level). Ubiquitous at low levels. Highly expressed in testis, where it is expressed within the germinal epithelium of the seminiferous tubuli. Weakly expressed in seminomas (testicular tumors).5 Publications

Inductioni

Isoform 1, isoform 3 and isoform 4 are induced by X-ray irradiation.1 Publication

Gene expression databases

BgeeiENSG00000152942
CleanExiHS_RAD17
ExpressionAtlasiO75943 baseline and differential
GenevisibleiO75943 HS

Organism-specific databases

HPAiCAB004551
HPA005448

Interactioni

Subunit structurei

Part of a DNA-binding complex containing RFC2, RFC3, RFC4 and RFC5. Interacts with RAD1 and RAD9 within the RAD1-RAD9-HUS1 complex. Interacts with RAD9B, POLE, SNU13 and MCM7. DNA damage promotes interaction with ATR or ATM and disrupts interaction with the RAD1-RAD9-HUS1 complex.13 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi111821, 33 interactors
CORUMiO75943
DIPiDIP-24254N
DIP-34896N
IntActiO75943, 15 interactors
MINTiO75943
STRINGi9606.ENSP00000370151

Structurei

3D structure databases

ProteinModelPortaliO75943
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni432 – 681Interaction with MCM71 PublicationAdd BLAST250

Sequence similaritiesi

Belongs to the rad17/RAD24 family.Curated

Phylogenomic databases

eggNOGiKOG1970 Eukaryota
COG0470 LUCA
GeneTreeiENSGT00440000039046
HOVERGENiHBG059834
InParanoidiO75943
KOiK06662
OMAiPRNFVNF
OrthoDBiEOG091G0B7G
PhylomeDBiO75943

Family and domain databases

InterProiView protein in InterPro
IPR004582 Checkpoint_prot_Rad17_Rad24
IPR027417 P-loop_NTPase
IPR018324 Rad17/Rad24_fun/met
PANTHERiPTHR12172 PTHR12172, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
TIGRFAMsiTIGR00602 rad24, 1 hit

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O75943-1) [UniParc]FASTAAdd to basket
Also known as: Rad17Sp, FM2

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
MSKTFLRPKV SSTKVTDWVD PSFDDFLECS GVSTITATSL GVNNSSHRRK
60 70 80 90 100
NGPSTLESSR FPARKRGNLS SLEQIYGLEN SKEYLSENEP WVDKYKPETQ
110 120 130 140 150
HELAVHKKKI EEVETWLKAQ VLERQPKQGG SILLITGPPG CGKTTTLKIL
160 170 180 190 200
SKEHGIQVQE WINPVLPDFQ KDDFKGMFNT ESSFHMFPYQ SQIAVFKEFL
210 220 230 240 250
LRATKYNKLQ MLGDDLRTDK KIILVEDLPN QFYRDSHTLH EVLRKYVRIG
260 270 280 290 300
RCPLIFIISD SLSGDNNQRL LFPKEIQEEC SISNISFNPV APTIMMKFLN
310 320 330 340 350
RIVTIEANKN GGKITVPDKT SLELLCQGCS GDIRSAINSL QFSSSKGENN
360 370 380 390 400
LRPRKKGMSL KSDAVLSKSK RRKKPDRVFE NQEVQAIGGK DVSLFLFRAL
410 420 430 440 450
GKILYCKRAS LTELDSPRLP SHLSEYERDT LLVEPEEVVE MSHMPGDLFN
460 470 480 490 500
LYLHQNYIDF FMEIDDIVRA SEFLSFADIL SGDWNTRSLL REYSTSIATR
510 520 530 540 550
GVMHSNKARG YAHCQGGGSS FRPLHKPQWF LINKKYRENC LAAKALFPDF
560 570 580 590 600
CLPALCLQTQ LLPYLALLTI PMRNQAQISF IQDIGRLPLK RHFGRLKMEA
610 620 630 640 650
LTDREHGMID PDSGDEAQLN GGHSAEESLG EPTQATVPET WSLPLSQNSA
660 670 680
SELPASQPQP FSAQGDMEEN IIIEDYESDG T
Length:681
Mass (Da):77,055
Last modified:March 29, 2005 - v2
Checksum:i796C2BD48F7995A3
GO
Isoform 2 (identifier: O75943-2) [UniParc]FASTAAdd to basket
Also known as: Rad17Sp2, FM1

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: MSKTFLRPKVSSTK → MNQ

Show »
Length:670
Mass (Da):75,836
Checksum:i2C8053B065996228
GO
Isoform 3 (identifier: O75943-3) [UniParc]FASTAAdd to basket
Also known as: FM3

The sequence of this isoform differs from the canonical sequence as follows:
     1-176: Missing.

Show »
Length:505
Mass (Da):57,244
Checksum:i3F873BE5F9EF5F85
GO
Isoform 4 (identifier: O75943-4) [UniParc]FASTAAdd to basket
Also known as: FM4

The sequence of this isoform differs from the canonical sequence as follows:
     1-97: Missing.
     98-99: ET → MN

Show »
Length:584
Mass (Da):66,156
Checksum:i54FE8CE0D06C1971
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti75I → V in CAD97683 (PubMed:17974005).Curated1
Sequence conflicti187F → L in AAC36334 (PubMed:9933569).Curated1
Sequence conflicti194A → S in AAD01620 (PubMed:10208430).Curated1
Sequence conflicti340L → P in AAC36334 (PubMed:9933569).Curated1
Sequence conflicti445P → S in AAC36334 (PubMed:9933569).Curated1
Sequence conflicti462M → T in AAC36334 (PubMed:9933569).Curated1
Sequence conflicti648N → D in AAC36334 (PubMed:9933569).Curated1
Sequence conflicti672I → M in AAC36334 (PubMed:9933569).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02157432V → I1 PublicationCorresponds to variant dbSNP:rs17229831Ensembl.1
Natural variantiVAR_021575487R → L1 PublicationCorresponds to variant dbSNP:rs17236478Ensembl.1
Natural variantiVAR_021576535K → E1 PublicationCorresponds to variant dbSNP:rs17236485Ensembl.1
Natural variantiVAR_021577557L → R3 PublicationsCorresponds to variant dbSNP:rs1045051Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0133061 – 176Missing in isoform 3. 1 PublicationAdd BLAST176
Alternative sequenceiVSP_0133071 – 97Missing in isoform 4. 1 PublicationAdd BLAST97
Alternative sequenceiVSP_0133081 – 14MSKTF…VSSTK → MNQ in isoform 2. 11 PublicationsAdd BLAST14
Alternative sequenceiVSP_01330998 – 99ET → MN in isoform 4. 1 Publication2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF076838 mRNA Translation: AAC95520.1
AJ004977 mRNA Translation: CAA06251.1
AF112263 mRNA Translation: AAD38878.1
AF085736 mRNA Translation: AAC36334.1
AJ001642 mRNA Translation: CAA04894.1
AJ131296
, AJ131297, AJ131298, AJ131299, AJ131300, AJ131301, AJ131302, AJ131303, AJ131304, AJ131305, AJ131306, AJ131307, AJ131308 Genomic DNA Translation: CAB46364.1
AF017748 mRNA Translation: AAD01620.1
AF126424 mRNA Translation: AAD17334.1
AF098533 mRNA Translation: AAC97950.1
AF098534 mRNA Translation: AAC97951.1
AL122068 mRNA Translation: CAB59244.1
AK292487 mRNA Translation: BAF85176.1
BX537441 mRNA Translation: CAD97683.1
AY612854 Genomic DNA Translation: AAT09763.1
CH471137 Genomic DNA Translation: EAW51283.1
CH471137 Genomic DNA Translation: EAW51284.1
CH471137 Genomic DNA Translation: EAW51285.1
CH471137 Genomic DNA Translation: EAW51286.1
CH471137 Genomic DNA Translation: EAW51288.1
BC032304 mRNA Translation: AAH32304.1
CCDSiCCDS4003.1 [O75943-1]
CCDS4004.1 [O75943-2]
CCDS4005.1 [O75943-4]
CCDS47226.1 [O75943-3]
PIRiT34548
RefSeqiNP_001265551.1, NM_001278622.1 [O75943-2]
NP_002864.1, NM_002873.1 [O75943-2]
NP_579916.1, NM_133338.2 [O75943-2]
NP_579917.1, NM_133339.2 [O75943-1]
NP_579918.1, NM_133340.2 [O75943-3]
NP_579919.1, NM_133341.2 [O75943-4]
NP_579920.1, NM_133342.2 [O75943-2]
NP_579921.1, NM_133343.1 [O75943-2]
NP_579922.1, NM_133344.2 [O75943-2]
XP_016865168.1, XM_017009679.1 [O75943-2]
XP_016865169.1, XM_017009680.1 [O75943-2]
XP_016865170.1, XM_017009681.1 [O75943-2]
UniGeneiHs.16184

Genome annotation databases

EnsembliENST00000282891; ENSP00000282891; ENSG00000152942 [O75943-4]
ENST00000305138; ENSP00000303134; ENSG00000152942 [O75943-2]
ENST00000345306; ENSP00000311227; ENSG00000152942 [O75943-2]
ENST00000354312; ENSP00000346271; ENSG00000152942 [O75943-2]
ENST00000354868; ENSP00000346938; ENSG00000152942 [O75943-2]
ENST00000358030; ENSP00000350725; ENSG00000152942 [O75943-3]
ENST00000361732; ENSP00000355226; ENSG00000152942 [O75943-2]
ENST00000380774; ENSP00000370151; ENSG00000152942 [O75943-1]
ENST00000509734; ENSP00000426191; ENSG00000152942 [O75943-1]
ENST00000521422; ENSP00000427743; ENSG00000152942 [O75943-3]
ENST00000610770; ENSP00000478167; ENSG00000276618
ENST00000611523; ENSP00000477962; ENSG00000276618
ENST00000612044; ENSP00000477996; ENSG00000276618
ENST00000616488; ENSP00000484854; ENSG00000276618
ENST00000616683; ENSP00000482775; ENSG00000152942 [O75943-2]
ENST00000616759; ENSP00000479160; ENSG00000276618
ENST00000620889; ENSP00000482371; ENSG00000276618
GeneIDi5884
KEGGihsa:5884
UCSCiuc003jwg.4 human [O75943-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiRAD17_HUMAN
AccessioniPrimary (citable) accession number: O75943
Secondary accession number(s): A8K8X2
, D3DWA5, O75714, Q7Z3S4, Q9UNK7, Q9UNR7, Q9UNR8, Q9UPF5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 29, 2005
Last sequence update: March 29, 2005
Last modified: May 23, 2018
This is version 162 of the entry and version 2 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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