Human Gene RAD17 (ENST00000361732.6) from GENCODE V44
Description: Homo sapiens RAD17 checkpoint clamp loader component (RAD17), transcript variant 6, mRNA. (from RefSeq NM_133343) RefSeq Summary (NM_133343): The protein encoded by this gene is highly similar to the gene product of Schizosaccharomyces pombe rad17, a cell cycle checkpoint gene required for cell cycle arrest and DNA damage repair in response to DNA damage. This protein shares strong similarity with DNA replication factor C (RFC), and can form a complex with RFCs. This protein binds to chromatin prior to DNA damage and is phosphorylated by the checkpoint kinase ATR following damage. This protein recruits the RAD1-RAD9-HUS1 checkpoint protein complex onto chromatin after DNA damage, which may be required for its phosphorylation. The phosphorylation of this protein is required for the DNA-damage-induced cell cycle G2 arrest, and is thought to be a critical early event during checkpoint signaling in DNA-damaged cells. Multiple alternatively spliced transcript variants of this gene, which encode four distinct protein isoforms, have been reported. Two pseudogenes, located on chromosomes 7 and 13, have been identified. [provided by RefSeq, Jul 2013]. Gencode Transcript: ENST00000361732.6 Gencode Gene: ENSG00000152942.19 Transcript (Including UTRs) Position: hg38 chr5:69,369,297-69,414,801 Size: 45,505 Total Exon Count: 18 Strand: + Coding Region Position: hg38 chr5:69,372,209-69,414,292 Size: 42,084 Coding Exon Count: 16
ID:RAD17_HUMAN DESCRIPTION: RecName: Full=Cell cycle checkpoint protein RAD17; Short=hRad17; AltName: Full=RF-C/activator 1 homolog; 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 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. 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; URL="http://egp.gs.washington.edu/data/rad17/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O75943
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
AL122068 - Homo sapiens mRNA; cDNA DKFZp434A1135 (from clone DKFZp434A1135). JD387012 - Sequence 368036 from Patent EP1572962. JD382460 - Sequence 363484 from Patent EP1572962. JD537941 - Sequence 518965 from Patent EP1572962. JD405711 - Sequence 386735 from Patent EP1572962. AK292487 - Homo sapiens cDNA FLJ77610 complete cds, highly similar to Homo sapiens RAD17 homolog (S. pombe) (RAD17), transcript variant 5, mRNA. AF126424 - Homo sapiens cell cycle checkpoint protein (R24L) mRNA, complete cds. BC018110 - Homo sapiens cDNA clone IMAGE:3903087, containing frame-shift errors. AF017748 - Homo sapiens cell cycle checkpoint protein RAD17 mRNA, complete cds. BX537441 - Homo sapiens mRNA; cDNA DKFZp686C19204 (from clone DKFZp686C19204); complete cds. AK123514 - Homo sapiens cDNA FLJ41520 fis, clone BRTHA2012466, highly similar to Homo sapiens cell cycle checkpoint protein RAD17 mRNA. AF076838 - Homo sapiens Rad17-like protein (RAD17) mRNA, complete cds. AJ001642 - Homo sapiens mRNA for cell cycle checkpoint protein. AJ004977 - Homo sapiens mRNA for cell cycle checkpoint protein rad17. AF098533 - Homo sapiens RAD17 isoform 3 (RAD17) mRNA, complete cds. AF098534 - Homo sapiens RAD17 isoform 4 (RAD17) mRNA, complete cds. AF085736 - Homo sapiens RF-C/activator 1 homolog (RAD17) mRNA, complete cds. BC032304 - Homo sapiens RAD17 homolog (S. pombe), mRNA (cDNA clone MGC:40346 IMAGE:5170876), complete cds. AF112263 - Homo sapiens hRad17 protein mRNA, complete cds. AM393045 - Synthetic construct Homo sapiens clone IMAGE:100001900 for hypothetical protein (RAD17 gene). AB384388 - Synthetic construct DNA, clone: pF1KSDB0062, Homo sapiens RAD17 gene for cell cycle checkpoint protein RAD17, complete cds, without stop codon, in Flexi system. KJ897441 - Synthetic construct Homo sapiens clone ccsbBroadEn_06835 RAD17 gene, encodes complete protein. DQ891608 - Synthetic construct clone IMAGE:100004238; FLH178593.01X; RZPDo839E11128D RAD17 homolog (S. pombe) (RAD17) gene, encodes complete protein. DQ894801 - Synthetic construct Homo sapiens clone IMAGE:100009261; FLH178589.01L; RZPDo839E11127D RAD17 homolog (S. pombe) (RAD17) gene, encodes complete protein. JD250664 - Sequence 231688 from Patent EP1572962. JD113114 - Sequence 94138 from Patent EP1572962. JD177357 - Sequence 158381 from Patent EP1572962. JD538651 - Sequence 519675 from Patent EP1572962. JD091410 - Sequence 72434 from Patent EP1572962. JD093771 - Sequence 74795 from Patent EP1572962. JD288334 - Sequence 269358 from Patent EP1572962. JD530538 - Sequence 511562 from Patent EP1572962. JD501540 - Sequence 482564 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_atrbrcaPathway - Role of BRCA1, BRCA2 and ATR in Cancer Susceptibility
Reactome (by CSHL, EBI, and GO)
Protein O75943 (Reactome details) participates in the following event(s):
R-HSA-176101 Recruitment of Rad17-RFC complex to DNA R-HSA-5685011 ATR activation at DNA DSBs R-HSA-5686657 ERCC1:XPF cleaves flaps generated by SSA R-HSA-5693561 RAD51 binds BRCA2 at resected DNA DSBs R-HSA-176264 Recruitment of the Rad9-Hus1-Rad1 complex to DNA R-HSA-5684887 Activation of CHEK1 at resected DNA DSBs R-HSA-5684882 CHEK1 is recruited to resected DNA DSBs R-HSA-5685156 ATR phosphorylates RPA2 R-HSA-5693580 Association of RAD52 with the RPA complex at resected DNA DSBs R-HSA-6799332 ATR phosphorylates TP53 R-HSA-5693564 Association of RAD51 with RAD52:DNA double-strand break ends R-HSA-5686642 RAD52 promotes single strand annealing at resected DNA DSBs R-HSA-176187 Activation of ATR in response to replication stress R-HSA-5693607 Processing of DNA double-strand break ends R-HSA-5685938 HDR through Single Strand Annealing (SSA) R-HSA-5693616 Presynaptic phase of homologous DNA pairing and strand exchange R-HSA-69481 G2/M Checkpoints R-HSA-5693567 HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA) R-HSA-5693579 Homologous DNA Pairing and Strand Exchange R-HSA-69473 G2/M DNA damage checkpoint R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation R-HSA-69620 Cell Cycle Checkpoints R-HSA-5693538 Homology Directed Repair R-HSA-5685942 HDR through Homologous Recombination (HRR) R-HSA-5633007 Regulation of TP53 Activity R-HSA-1640170 Cell Cycle R-HSA-5693532 DNA Double-Strand Break Repair R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-73894 DNA Repair R-HSA-212436 Generic Transcription Pathway R-HSA-73857 RNA Polymerase II Transcription R-HSA-74160 Gene expression (Transcription)
US Server
