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RAD17

Protein FULL name:

cell cycle checkpoint protein RAD17 isoform 1 [Homo sapiens].


RAD17 (Homo sapiens) is product of expression of RAD17 gene.


RAD17 is involved in:

DDS in Homo sapiens
     





FUNCTION: 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 onto chromatin, and in CHEK1 activation. May also serve as a sensor of DNA replication progression, and may be involved in homologous recombination.

SUBUNIT: 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, NHP2L1 and MCM7. DNA damage promotes interaction with ATR or ATM and disrupts interaction with the RAD1-RAD9-HUS1 complex.

SUBCELLULAR LOCATION: Nucleus. Note=Phosphorylated form redistributes to discrete nuclear foci upon DNA damage.

TISSUE SPECIFICITY: 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).

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

PTM: 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.

SIMILARITY: Belongs to the rad17/RAD24 family.

WEB RESOURCE: Name=NIEHS-SNPs; [LINK]


NCBI GenPept GI number(s): 4506383
Species: Homo sapiens

Links to other databases:

Database ID Link
Uniprot O75943 O75943
PFAM: - O75943 (Link - using uniprot id)
InterPro: - O75943 (Link - using uniprot id)
CATH: - -
SCOP: - -
PDB: - -


Protein sequence:
MNQVTDWVDPSFDDFLECSGVSTITATSLGVNNSSHRRKNGPSTLESSRF
PARKRGNLSSLEQIYGLENSKEYLSENEPWVDKYKPETQHELAVHKKKIE
EVETWLKAQVLERQPKQGGSILLITGPPGCGKTTTLKILSKEHGIQVQEW
INPVLPDFQKDDFKGMFNTESSFHMFPYQSQIAVFKEFLLRATKYNKLQM
LGDDLRTDKKIILVEDLPNQFYRDSHTLHEVLRKYVRIGRCPLIFIISDS
LSGDNNQRLLFPKEIQEECSISNISFNPVAPTIMMKFLNRIVTIEANKNG
GKITVPDKTSLELLCQGCSGDIRSAINSLQFSSSKGENNLRPRKKGMSLK
SDAVLSKSKRRKKPDRVFENQEVQAIGGKDVSLFLFRALGKILYCKRASL
TELDSPRLPSHLSEYERDTLLVEPEEVVEMSHMPGDLFNLYLHQNYIDFF
MEIDDIVRASEFLSFADILSGDWNTRSLLREYSTSIATRGVMHSNKARGY
AHCQGGGSSFRPLHKPQWFLINKKYRENCLAAKALFPDFCLPALCLQTQL
LPYLALLTIPMRNQAQISFIQDIGRLPLKRHFGRLKMEALTDREHGMIDP
DSGDEAQLNGGHSAEESLGEPTQATVPETWSLPLSQNSASELPASQPQPF
SAQGDMEENIIIEDYESDGT

RAD17 (Homo sapiens) is able to recognize following damages:
RAD17 (Homo sapiens) belongs to following protein families:
References:

Title Authors Journal
Identification of a human homologue of the Schizosaccharomyces pombe rad17+ checkpoint gene. Parker AE, Van de Weyer I, Laus MC, Verhasselt P, Luyten WH J Biol Chem July 17, 1998
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 FB, Lian L, O'Donnell M Genomics Dec. 15, 1998
Human and mouse RAD17 genes: identification, localization, genomic structure and histological expression pattern in normal testis and seminoma. von Deimling F, Scharf JM, Liehr T, Rothe M, Kelter AR, Albers P, Dietrich WF, Kunkel LM, Wernert N, Wirth B Hum Genet Jan. 1, 1999
Human and mouse homologs of the Schizosaccharomyces pombe rad17+ cell cycle checkpoint control gene. Bluyssen HA, Naus NC, van Os RI, Jaspers I, Hoeijmakers JH, de Klein A Genomics Feb. 15, 1999
hRAD17, a structural homolog of the Schizosaccharomyces pombe RAD17 cell cycle checkpoint gene, stimulates p53 accumulation. Li L, Peterson CA, Kanter-Smoler G, Wei YF, Ramagli LS, Sunnerhagen P, Siciliano MJ, Legerski RJ Oncogene March 4, 1999
HRad17, a human homologue of the Schizosaccharomyces pombe checkpoint gene rad17, is overexpressed in colon carcinoma. Bao S, Chang MS, Auclair D, Sun Y, Wang Y, Wong WK, Zhang J, Liu Y, Qian X, Sutherland R, Magi-Galluzi C, Weisberg E, Cheng EY, Hao L, Sasaki H, Campbell MS, Kraeft SK, Loda M, Lo KM, Chen LB Cancer Res May 1, 1999
[Human hR24L gene is involved in DNA excision repair and recombination repair] Han Y, Zhu Y Zhonghua Yi Xue Za Zhi Dec. 1, 1999
HRad17 colocalizes with NHP2L1 in the nucleolus and redistributes after UV irradiation. Chang MS, Sasaki H, Campbell MS, Kraeft SK, Sutherland R, Yang CY, Liu Y, Auclair D, Hao L, Sonoda H, Ferland LH, Chen LB J Biol Chem Dec. 17, 1999
The human checkpoint protein hRad17 interacts with the PCNA-like proteins hRad1, hHus1, and hRad9. Rauen M, Burtelow MA, Dufault VM, Karnitz LM J Biol Chem Sept. 22, 2000
Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Bocher M, Blocker H, Bauersachs S, Blum H, Lauber J, Dusterhoft A, Beyer A, Kohrer K, Strack N, Mewes HW, Ottenwalder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A Genome Res March 1, 2001
ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses. Bao S, Tibbetts RS, Brumbaugh KM, Fang Y, Richardson DA, Ali A, Chen SM, Abraham RT, Wang XF Nature June 21, 2001
Purification and characterization of human DNA damage checkpoint Rad complexes. Lindsey-Boltz LA, Bermudez VP, Hurwitz J, Sancar A Proc Natl Acad Sci U S A Sept. 25, 2001
Multiple alternative splicing forms of human RAD17 and their differential response to ionizing radiation. Chen MS, Higashikubo R, Laszlo A, Roti Roti J Gene Oct. 17, 2001
Phosphorylation of serines 635 and 645 of human Rad17 is cell cycle regulated and is required for G(1)/S checkpoint activation in response to DNA damage. Post S, Weng YC, Cimprich K, Chen LB, Xu Y, Lee EY Proc Natl Acad Sci U S A Nov. 6, 2001
Regulation of ATR substrate selection by Rad17-dependent loading of Rad9 complexes onto chromatin. Zou L, Cortez D, Elledge SJ Genes Dev Feb. 15, 2002
Colocalization of human Rad17 and PCNA in late S phase of the cell cycle upon replication block. Dahm K, Hubscher U Oncogene Oct. 31, 2002
Loading of the human 9-1-1 checkpoint complex onto DNA by the checkpoint clamp loader hRad17-replication factor C complex in vitro. Bermudez VP, Lindsey-Boltz LA, Cesare AJ, Maniwa Y, Griffith JD, Hurwitz J, Sancar A Proc Natl Acad Sci U S A Jan. 18, 2003
Genomic instability and endoreduplication triggered by RAD17 deletion. Wang X, Zou L, Zheng H, Wei Q, Elledge SJ, Li L Genes Dev April 15, 2003
The human checkpoint Rad protein Rad17 is chromatin-associated throughout the cell cycle, localizes to DNA replication sites, and interacts with DNA polymerase epsilon. Post SM, Tomkinson AE, Lee EY Nucleic Acids Res Oct. 1, 2003
Biochemical characterization of DNA damage checkpoint complexes: clamp loader and clamp complexes with specificity for 5' recessed DNA. Ellison V, Stillman B PLoS Biol Nov. 1, 2003
Identification and characterization of RAD9B, a paralog of the RAD9 checkpoint gene. Dufault VM, Oestreich AJ, Vroman BT, Karnitz LM Genomics Dec. 1, 2003
Complete sequencing and characterization of 21,243 full-length human cDNAs. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S Nat Genet Feb. 1, 2004
Chromatin association of rad17 is required for an ataxia telangiectasia and rad-related kinase-mediated S-phase checkpoint in response to low-dose ultraviolet radiation. Garg R, Callens S, Lim DS, Canman CE, Kastan MB, Xu B Mol Cancer Res June 1, 2004
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J Genome Res Oct. 1, 2004
Interaction between human MCM7 and Rad17 proteins is required for replication checkpoint signaling. Tsao CC, Geisen C, Abraham RT EMBO J Nov. 24, 2004
The full-ORF clone resource of the German cDNA Consortium. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I BMC Genomics Jan. 1, 2007
Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra. Yu LR, Zhu Z, Chan KC, Issaq HJ, Dimitrov DS, Veenstra TD J Proteome Res Nov. 1, 2007


Last modification of this entry: Oct. 6, 2010.

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