ID   RAD9A_MOUSE             Reviewed;         389 AA.
AC   Q9Z0F6; Q8QZZ3;
DT   07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 1.
DT   27-MAR-2024, entry version 144.
DE   RecName: Full=Cell cycle checkpoint control protein RAD9A;
DE            Short=mRAD9;
DE            EC=3.1.11.2;
DE   AltName: Full=DNA repair exonuclease rad9 homolog A;
DE   AltName: Full=Rad9-like protein;
GN   Name=Rad9a; Synonyms=Rad9;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND TISSUE SPECIFICITY.
RX   PubMed=9766521;
RX   DOI=10.1002/(sici)1097-4652(199811)177:2<241::aid-jcp6>3.0.co;2-n;
RA   Hang H., Rauth S.J., Hopkins K.M., Davey S.K., Lieberman H.B.;
RT   "Molecular cloning and tissue-specific expression of Mrad9, a murine
RT   orthologue of the Schizosaccharomyces pombe rad9+ checkpoint control
RT   gene.";
RL   J. Cell. Physiol. 177:241-247(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Fetal testis;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Eye;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 292-389.
RC   STRAIN=AKR/J, C58/J, DBA/2J, FVB/NJ, I/LnJ, MOLF/EiJ, and NZB/BlNJ;
RA   Park Y.-G., Lukes L., Yang H., Debies M.T., Samant R.S., Welch D.R.,
RA   Lee M., Hunter K.W.;
RL   Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   INTERACTION WITH ATAD5.
RX   PubMed=15983387; DOI=10.1073/pnas.0504222102;
RA   Ishii H., Inageta T., Mimori K., Saito T., Sasaki H., Isobe M., Mori M.,
RA   Croce C.M., Huebner K., Ozawa K., Furukawa Y.;
RT   "Frag1, a homolog of alternative replication factor C subunits, links
RT   replication stress surveillance with apoptosis.";
RL   Proc. Natl. Acad. Sci. U.S.A. 102:9655-9660(2005).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-385, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Embryonic fibroblast;
RX   PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA   Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT   "Large scale localization of protein phosphorylation by use of electron
RT   capture dissociation mass spectrometry.";
RL   Mol. Cell. Proteomics 8:904-912(2009).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-373 AND SER-385, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brown adipose tissue, and Spleen;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: Component of the 9-1-1 cell-cycle checkpoint response complex
CC       that plays a major role in DNA repair. The 9-1-1 complex is recruited
CC       to DNA lesion upon damage by the RAD17-replication factor C (RFC) clamp
CC       loader complex. Acts then as a sliding clamp platform on DNA for
CC       several proteins involved in long-patch base excision repair (LP-BER).
CC       The 9-1-1 complex stimulates DNA polymerase beta (POLB) activity by
CC       increasing its affinity for the 3'-OH end of the primer-template and
CC       stabilizes POLB to those sites where LP-BER proceeds; endonuclease FEN1
CC       cleavage activity on substrates with double, nick, or gap flaps of
CC       distinct sequences and lengths; and DNA ligase I (LIG1) on long-patch
CC       base excision repair substrates. The 9-1-1 complex is necessary for the
CC       recruitment of RHNO1 to sites of double-stranded breaks (DSB) occurring
CC       during the S phase. RAD9A possesses 3'->5' double stranded DNA
CC       exonuclease activity. {ECO:0000250|UniProtKB:Q99638}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Exonucleolytic cleavage in the 3'- to 5'-direction to yield
CC         nucleoside 5'-phosphates.; EC=3.1.11.2;
CC         Evidence={ECO:0000250|UniProtKB:Q99638};
CC   -!- SUBUNIT: Component of the toroidal 9-1-1 (RAD9-RAD1-HUS1) complex,
CC       composed of RAD9A, RAD1 and HUS1 (By similarity). The 9-1-1 complex
CC       associates with LIG1, POLB, FEN1, RAD17, HDAC1, RPA1 and RPA2 (By
CC       similarity). The 9-1-1 complex associates with the RAD17-RFC complex
CC       (By similarity). RAD9A interacts with BCL2L1, FEN1, RAD9B, ABL1, RPA1,
CC       ATAD5 and RPA2 (PubMed:15983387). Interacts with DNAJC7 (By
CC       similarity). Interacts with DNAJC7. Interacts (when phosphorylated)
CC       with TOPBP1 (By similarity). {ECO:0000250|UniProtKB:Q99638,
CC       ECO:0000269|PubMed:15983387}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q99638}.
CC   -!- TISSUE SPECIFICITY: Expressed in heart, brain, spleen, lung, liver,
CC       skeletal muscle, kidney and testis. {ECO:0000269|PubMed:9766521}.
CC   -!- PTM: Constitutively phosphorylated on serine and threonine amino acids
CC       in absence of DNA damage. Hyperphosphorylated by PRKCD and ABL1 upon
CC       DNA damage. Its phosphorylation by PRKCD may be required for the
CC       formation of the 9-1-1 complex. Phosphorylated at Ser-341 and Ser-385
CC       by CK2, promoting interaction with TOPBP1.
CC       {ECO:0000250|UniProtKB:Q99638}.
CC   -!- SIMILARITY: Belongs to the rad9 family. {ECO:0000305}.
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DR   EMBL; AF045663; AAC77365.1; -; mRNA.
DR   EMBL; AF045662; AAC77364.1; -; Genomic_DNA.
DR   EMBL; AK134293; BAE22086.1; -; mRNA.
DR   EMBL; BC082556; AAH82556.1; -; mRNA.
DR   EMBL; AF469747; AAL82448.1; -; Genomic_DNA.
DR   EMBL; AF469748; AAL82449.1; -; Genomic_DNA.
DR   EMBL; AF469749; AAL82450.1; -; Genomic_DNA.
DR   EMBL; AF469750; AAL82451.1; -; Genomic_DNA.
DR   EMBL; AF469752; AAL82453.1; -; Genomic_DNA.
DR   EMBL; AF469753; AAL82454.1; -; Genomic_DNA.
DR   EMBL; AF469751; AAL82452.1; -; Genomic_DNA.
DR   CCDS; CCDS29422.1; -.
DR   RefSeq; NP_035367.1; NM_011237.2.
DR   AlphaFoldDB; Q9Z0F6; -.
DR   SMR; Q9Z0F6; -.
DR   BioGRID; 202570; 2.
DR   STRING; 10090.ENSMUSP00000025740; -.
DR   GlyGen; Q9Z0F6; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9Z0F6; -.
DR   PhosphoSitePlus; Q9Z0F6; -.
DR   EPD; Q9Z0F6; -.
DR   jPOST; Q9Z0F6; -.
DR   MaxQB; Q9Z0F6; -.
DR   PaxDb; 10090-ENSMUSP00000025740; -.
DR   PeptideAtlas; Q9Z0F6; -.
DR   ProteomicsDB; 255024; -.
DR   Pumba; Q9Z0F6; -.
DR   Antibodypedia; 1880; 1255 antibodies from 38 providers.
DR   DNASU; 19367; -.
DR   Ensembl; ENSMUST00000025740.8; ENSMUSP00000025740.7; ENSMUSG00000024824.8.
DR   GeneID; 19367; -.
DR   KEGG; mmu:19367; -.
DR   UCSC; uc008fzh.1; mouse.
DR   AGR; MGI:1328356; -.
DR   CTD; 5883; -.
DR   MGI; MGI:1328356; Rad9a.
DR   VEuPathDB; HostDB:ENSMUSG00000024824; -.
DR   eggNOG; KOG2810; Eukaryota.
DR   GeneTree; ENSGT00390000005767; -.
DR   HOGENOM; CLU_049242_0_0_1; -.
DR   InParanoid; Q9Z0F6; -.
DR   OMA; YQLHDAL; -.
DR   OrthoDB; 3061362at2759; -.
DR   PhylomeDB; Q9Z0F6; -.
DR   TreeFam; TF101212; -.
DR   Reactome; R-MMU-176187; Activation of ATR in response to replication stress.
DR   Reactome; R-MMU-5685938; HDR through Single Strand Annealing (SSA).
DR   Reactome; R-MMU-5693607; Processing of DNA double-strand break ends.
DR   Reactome; R-MMU-6804756; Regulation of TP53 Activity through Phosphorylation.
DR   Reactome; R-MMU-69473; G2/M DNA damage checkpoint.
DR   BioGRID-ORCS; 19367; 34 hits in 110 CRISPR screens.
DR   ChiTaRS; Rad9a; mouse.
DR   PRO; PR:Q9Z0F6; -.
DR   Proteomes; UP000000589; Chromosome 19.
DR   RNAct; Q9Z0F6; Protein.
DR   Bgee; ENSMUSG00000024824; Expressed in undifferentiated genital tubercle and 74 other cell types or tissues.
DR   ExpressionAtlas; Q9Z0F6; baseline and differential.
DR   GO; GO:0030896; C:checkpoint clamp complex; ISO:MGI.
DR   GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0008408; F:3'-5' exonuclease activity; ISO:MGI.
DR   GO; GO:0008311; F:double-stranded DNA 3'-5' DNA exonuclease activity; IEA:UniProtKB-EC.
DR   GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR   GO; GO:0042826; F:histone deacetylase binding; ISO:MGI.
DR   GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR   GO; GO:0017124; F:SH3 domain binding; ISO:MGI.
DR   GO; GO:0071479; P:cellular response to ionizing radiation; ISO:MGI.
DR   GO; GO:0000077; P:DNA damage checkpoint signaling; ISO:MGI.
DR   GO; GO:0006974; P:DNA damage response; ISO:MGI.
DR   GO; GO:0006281; P:DNA repair; IBA:GO_Central.
DR   GO; GO:0000076; P:DNA replication checkpoint signaling; IBA:GO_Central.
DR   GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IMP:MGI.
DR   GO; GO:0031573; P:mitotic intra-S DNA damage checkpoint signaling; IGI:MGI.
DR   GO; GO:1902231; P:positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage; IMP:MGI.
DR   CDD; cd00577; PCNA; 1.
DR   Gene3D; 3.70.10.10; -; 1.
DR   InterPro; IPR046938; DNA_clamp_sf.
DR   InterPro; IPR026584; Rad9.
DR   InterPro; IPR007268; Rad9/Ddc1.
DR   PANTHER; PTHR15237:SF1; CELL CYCLE CHECKPOINT CONTROL PROTEIN RAD9A; 1.
DR   PANTHER; PTHR15237; DNA REPAIR PROTEIN RAD9; 1.
DR   Pfam; PF04139; Rad9; 1.
DR   PIRSF; PIRSF009303; Cell_cycle_RAD9; 1.
DR   SUPFAM; SSF55979; DNA clamp; 1.
DR   Genevisible; Q9Z0F6; MM.
PE   1: Evidence at protein level;
KW   DNA damage; Exonuclease; Hydrolase; Nuclease; Nucleus; Phosphoprotein;
KW   Reference proteome.
FT   CHAIN           1..389
FT                   /note="Cell cycle checkpoint control protein RAD9A"
FT                   /id="PRO_0000225001"
FT   REGION          51..91
FT                   /note="Possesses 3'-5' exonuclease activity"
FT                   /evidence="ECO:0000250"
FT   REGION          266..389
FT                   /note="Sufficient for interaction with ABL1"
FT                   /evidence="ECO:0000250"
FT   REGION          271..296
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          312..389
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        315..331
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         28
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:Q99638"
FT   MOD_RES         272
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q99638"
FT   MOD_RES         277
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q99638"
FT   MOD_RES         341
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q99638"
FT   MOD_RES         373
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         385
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19131326,
FT                   ECO:0007744|PubMed:21183079"
SQ   SEQUENCE   389 AA;  42059 MW;  2AE8FF75385C668D CRC64;
     MKCLITGGNV KVLGKAVHSL SRIGDELYLE PLKDGLSLRT VNSSRSAYAC FLFAPLFFQQ
     YQAASPGQDL LRCKILMKAF LSVFRSLAIV EKSVEKCCIS LSGSHSHLVV QLHCKYGVKK
     THNLSFQDCE SLQAVFDPAS CPHLLRTPAR VLAEAVLSFP LALTEVTLGI GRGRRVILRS
     YQEEEADSTS KAMVTETSIG DEDFQQLHAP EGIAVTFCLK EFRGLLSFAE SANLPLTIHF
     DVPGRPVIFT IEDSLLDAHF VLATLLEQDS CSQGPCSPKP HQPVPQKQAH STPHLDDFTS
     DDIDCYMIAM ETTGGNEGSG AQPSTSLPPV SLASHDLAPT SEEEAEPSTV PGTPPPKKFR
     SLFFGSILAP VHSPQGPNPV LAEDSDGEG
//