ATAD5_HUMAN
ID ATAD5_HUMAN Reviewed; 1844 AA.
AC Q96QE3; Q05DH0; Q69YR6; Q9H9I1;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 4.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=ATPase family AAA domain-containing protein 5 {ECO:0000312|HGNC:HGNC:25752};
DE AltName: Full=Chromosome fragility-associated gene 1 protein;
GN Name=ATAD5 {ECO:0000312|HGNC:HGNC:25752};
GN Synonyms=C17orf41, Elg1 {ECO:0000303|PubMed:13678589},
GN FRAG1 {ECO:0000303|PubMed:15983387};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=11468690; DOI=10.1086/323043;
RA Jenne D.E., Tinschert S., Reimann H., Lasinger W., Thiel G., Hameister H.,
RA Kehrer-Sawatzki H.;
RT "Molecular characterization and gene content of breakpoint boundaries in
RT patients with neurofibromatosis type 1 with 17q11.2 microdeletions.";
RL Am. J. Hum. Genet. 69:516-527(2001).
RN [2]
RP SEQUENCE REVISION.
RA Jenne D.E.;
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH RAD9A,
RP AND MUTAGENESIS OF SER-1169; SER-1187; CYS-1430 AND GLU-1432.
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1224 (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-474 (ISOFORM 1), AND VARIANT
RP GLY-135.
RC TISSUE=Uterus;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 377-1844 (ISOFORM 2).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [8]
RP INTERACTION WITH RFC2.
RX PubMed=13678589; DOI=10.1016/s0960-9822(03)00578-5;
RA Kanellis P., Agyei R., Durocher D.;
RT "Elg1 forms an alternative PCNA-interacting RFC complex required to
RT maintain genome stability.";
RL Curr. Biol. 13:1583-1595(2003).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-621, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-44; SER-306; SER-369 AND
RP SER-1116, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19755857; DOI=10.4161/cc.8.19.9752;
RA Sikdar N., Banerjee S., Lee K.Y., Wincovitch S., Pak E., Nakanishi K.,
RA Jasin M., Dutra A., Myung K.;
RT "DNA damage responses by human ELG1 in S phase are important to maintain
RT genomic integrity.";
RL Cell Cycle 8:3199-3207(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306; SER-311 AND SER-614, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [14]
RP FUNCTION, INTERACTION WITH USP1; WDR48; PCNA AND RFC4, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF 368-LYS--GLU-384.
RX PubMed=20147293; DOI=10.1074/jbc.m109.092544;
RA Lee K.Y., Yang K., Cohn M.A., Sikdar N., D'Andrea A.D., Myung K.;
RT "Human ELG1 regulates the level of ubiquitinated proliferating cell nuclear
RT antigen (PCNA) through Its interactions with PCNA and USP1.";
RL J. Biol. Chem. 285:10362-10369(2010).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-219, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
RP INTERACTION WITH BRD4.
RX PubMed=21555454; DOI=10.1128/mcb.01341-10;
RA Rahman S., Sowa M.E., Ottinger M., Smith J.A., Shi Y., Harper J.W.,
RA Howley P.M.;
RT "The Brd4 extraterminal domain confers transcription activation independent
RT of pTEFb by recruiting multiple proteins, including NSD3.";
RL Mol. Cell. Biol. 31:2641-2652(2011).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-614, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [18]
RP FUNCTION.
RX PubMed=23937667; DOI=10.1111/gtc.12087;
RA Shiomi Y., Nishitani H.;
RT "Alternative replication factor C protein, Elg1, maintains chromosome
RT stability by regulating PCNA levels on chromatin.";
RL Genes Cells 18:946-959(2013).
RN [19]
RP FUNCTION, INTERACTION WITH RFC4 AND PCNA, AND MUTAGENESIS OF
RP 368-LYS--GLU-384 AND LYS-1138.
RX PubMed=23277426; DOI=10.1083/jcb.201206084;
RA Lee K.Y., Fu H., Aladjem M.I., Myung K.;
RT "ATAD5 regulates the lifespan of DNA replication factories by modulating
RT PCNA level on the chromatin.";
RL J. Cell Biol. 200:31-44(2013).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306; SER-602 AND SER-817, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [21]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-127, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [22]
RP FUNCTION, INTERACTION WITH RAD51; RFC5 AND WDR48, AND MUTAGENESIS OF
RP 368-LYS--GLU-384; 642-ALA--ILE-645 AND LYS-1138.
RX PubMed=31844045; DOI=10.1038/s41467-019-13667-4;
RA Park S.H., Kang N., Song E., Wie M., Lee E.A., Hwang S., Lee D., Ra J.S.,
RA Park I.B., Park J., Kang S., Park J.H., Hohng S., Lee K.Y., Myung K.;
RT "ATAD5 promotes replication restart by regulating RAD51 and PCNA in
RT response to replication stress.";
RL Nat. Commun. 10:5718-5718(2019).
RN [23]
RP VARIANT ASN-215.
RX PubMed=26282398; DOI=10.1186/s13023-015-0316-8;
RA Dahmani M., Ammar-Khodja F., Bonnet C., Lefevre G.M., Hardelin J.P.,
RA Ibrahim H., Mallek Z., Petit C.;
RT "EPS8L2 is a new causal gene for childhood onset autosomal recessive
RT progressive hearing loss.";
RL Orphanet J. Rare Dis. 10:96-96(2015).
CC -!- FUNCTION: Has an imporant role in DNA replication and in maintaining
CC genome integrity during replication stress (PubMed:15983387,
CC PubMed:19755857). Involved in a RAD9A-related damage checkpoint, a
CC pathway that is important in determining whether DNA damage is
CC compatible with cell survival or whether it requires cell elimination
CC by apoptosis (PubMed:15983387). Modulates the RAD9A interaction with
CC BCL2 and thereby induces DNA damage-induced apoptosis
CC (PubMed:15983387). Promotes PCNA deubiquitination by recruiting the
CC ubiquitin-specific protease 1 (USP1) and WDR48 thereby down-regulating
CC the error-prone damage bypass pathway (PubMed:20147293). As component
CC of the ATAD5 RFC-like complex, regulates the function of the DNA
CC polymerase processivity factor PCNA by unloading the ring-shaped PCNA
CC homotrimer from DNA after replication during the S phase of the cell
CC cycle (PubMed:23277426, PubMed:23937667). This seems to be dependent on
CC its ATPase activity (PubMed:23277426). Plays important roles in
CC restarting stalled replication forks under replication stress, by
CC unloading the PCNA homotrimer from DNA and recruiting RAD51 possibly
CC through an ATR-dependent manner (PubMed:31844045). Ultimately this
CC enables replication fork regression, breakage, and eventual fork
CC restart (PubMed:31844045). Both the PCNA unloading activity and the
CC interaction with WDR48 are required to efficiently recruit RAD51 to
CC stalled replication forks (PubMed:31844045). Promotes the generation of
CC MUS81-mediated single-stranded DNA-associated breaks in response to
CC replication stress, which is an alternative pathway to restart
CC stalled/regressed replication forks (PubMed:31844045).
CC {ECO:0000269|PubMed:15983387, ECO:0000269|PubMed:19755857,
CC ECO:0000269|PubMed:20147293, ECO:0000269|PubMed:23277426,
CC ECO:0000269|PubMed:23937667, ECO:0000269|PubMed:31844045}.
CC -!- SUBUNIT: Component of a heteropentameric replication factor ATAD5 RFC-
CC like complex composed of one large subunit (ATAD5) and four small
CC subunits (RFC2, RFC3, RFC4 and RFC5) (PubMed:13678589, PubMed:20147293,
CC PubMed:23277426). Within the ATAD5 RFC-like complex, interacts with
CC RFC2, RFC4 and RFC5 (PubMed:13678589, PubMed:20147293, PubMed:23277426,
CC PubMed:31844045). Within the ATAD5 RFC-like complex, interacts directly
CC via-N terminal with RAD51; the interactions is enhanced under
CC replication stress (PubMed:31844045). Interacts with RB1 predominantly
CC in G1 phase via its LXCXE motif (By similarity). Interacts with RAD9A
CC in growing cells (PubMed:15983387). The interaction with RAD9A is
CC reduced after exposure to DNA replication-inhibiting agents
CC (PubMed:15983387). Interacts with BRD4 (PubMed:21555454). Interacts
CC with PCNA (PubMed:20147293, PubMed:23277426). Interacts with
CC deubiquitinating enzyme USP1, and its associated factor, WDR48
CC (PubMed:20147293, PubMed:31844045). {ECO:0000250|UniProtKB:Q4QY64,
CC ECO:0000269|PubMed:13678589, ECO:0000269|PubMed:15983387,
CC ECO:0000269|PubMed:20147293, ECO:0000269|PubMed:21555454,
CC ECO:0000269|PubMed:23277426, ECO:0000269|PubMed:31844045,
CC ECO:0000303|PubMed:13678589, ECO:0000303|PubMed:20147293,
CC ECO:0000303|PubMed:23277426}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19755857,
CC ECO:0000269|PubMed:20147293}. Note=Accumulates in nuclear foci at sites
CC of stalled DNA replication forks in response to DNA damage.
CC {ECO:0000269|PubMed:19755857}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96QE3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96QE3-2; Sequence=VSP_031097;
CC -!- PTM: ATR may stimulate the RAD9A dissociation.
CC -!- SIMILARITY: Belongs to the AAA ATPase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH15051.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=BAB14248.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AJ314648; CAC44537.2; -; mRNA.
DR EMBL; AY557611; AAT52049.1; -; mRNA.
DR EMBL; AL832103; CAH10412.1; -; mRNA.
DR EMBL; BC015051; AAH15051.1; ALT_SEQ; mRNA.
DR EMBL; AK022797; BAB14248.1; ALT_INIT; mRNA.
DR EMBL; AC127024; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC130324; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS11260.1; -. [Q96QE3-1]
DR RefSeq; NP_079133.3; NM_024857.4. [Q96QE3-1]
DR AlphaFoldDB; Q96QE3; -.
DR BioGRID; 122994; 72.
DR DIP; DIP-62118N; -.
DR IntAct; Q96QE3; 23.
DR MINT; Q96QE3; -.
DR STRING; 9606.ENSP00000313171; -.
DR ChEMBL; CHEMBL1741209; -.
DR iPTMnet; Q96QE3; -.
DR PhosphoSitePlus; Q96QE3; -.
DR BioMuta; ATAD5; -.
DR DMDM; 296439460; -.
DR EPD; Q96QE3; -.
DR jPOST; Q96QE3; -.
DR MassIVE; Q96QE3; -.
DR MaxQB; Q96QE3; -.
DR PaxDb; Q96QE3; -.
DR PeptideAtlas; Q96QE3; -.
DR PRIDE; Q96QE3; -.
DR ProteomicsDB; 77862; -. [Q96QE3-1]
DR ProteomicsDB; 77863; -. [Q96QE3-2]
DR Antibodypedia; 15166; 161 antibodies from 28 providers.
DR DNASU; 79915; -.
DR Ensembl; ENST00000321990.5; ENSP00000313171.4; ENSG00000176208.9. [Q96QE3-1]
DR GeneID; 79915; -.
DR KEGG; hsa:79915; -.
DR MANE-Select; ENST00000321990.5; ENSP00000313171.4; NM_024857.5; NP_079133.3.
DR UCSC; uc002hfs.2; human. [Q96QE3-1]
DR CTD; 79915; -.
DR DisGeNET; 79915; -.
DR GeneCards; ATAD5; -.
DR HGNC; HGNC:25752; ATAD5.
DR HPA; ENSG00000176208; Tissue enhanced (bone).
DR MIM; 609534; gene.
DR neXtProt; NX_Q96QE3; -.
DR OpenTargets; ENSG00000176208; -.
DR PharmGKB; PA162377100; -.
DR VEuPathDB; HostDB:ENSG00000176208; -.
DR eggNOG; KOG1968; Eukaryota.
DR GeneTree; ENSGT00940000153469; -.
DR HOGENOM; CLU_002810_0_0_1; -.
DR InParanoid; Q96QE3; -.
DR OMA; ANLDNAW; -.
DR PhylomeDB; Q96QE3; -.
DR TreeFam; TF329112; -.
DR PathwayCommons; Q96QE3; -.
DR SignaLink; Q96QE3; -.
DR SIGNOR; Q96QE3; -.
DR BioGRID-ORCS; 79915; 85 hits in 1082 CRISPR screens.
DR ChiTaRS; ATAD5; human.
DR GenomeRNAi; 79915; -.
DR Pharos; Q96QE3; Tbio.
DR PRO; PR:Q96QE3; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q96QE3; protein.
DR Bgee; ENSG00000176208; Expressed in buccal mucosa cell and 99 other tissues.
DR ExpressionAtlas; Q96QE3; baseline and differential.
DR Genevisible; Q96QE3; HS.
DR GO; GO:0031391; C:Elg1 RFC-like complex; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0003677; F:DNA binding; IBA:GO_Central.
DR GO; GO:0061860; F:DNA clamp unloader activity; IMP:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0090618; P:DNA clamp unloading; IMP:UniProtKB.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IEA:Ensembl.
DR GO; GO:0045190; P:isotype switching; IEA:Ensembl.
DR GO; GO:1902166; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IEA:Ensembl.
DR GO; GO:0033260; P:nuclear DNA replication; IEA:Ensembl.
DR GO; GO:0090305; P:nucleic acid phosphodiester bond hydrolysis; IEA:Ensembl.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; IEA:Ensembl.
DR GO; GO:1902751; P:positive regulation of cell cycle G2/M phase transition; IMP:UniProtKB.
DR GO; GO:0045740; P:positive regulation of DNA replication; IMP:UniProtKB.
DR GO; GO:0048304; P:positive regulation of isotype switching to IgG isotypes; IEA:Ensembl.
DR GO; GO:1901990; P:regulation of mitotic cell cycle phase transition; IEA:Ensembl.
DR GO; GO:0042770; P:signal transduction in response to DNA damage; IEA:Ensembl.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR003959; ATPase_AAA_core.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF00004; AAA; 1.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; DNA damage; Isopeptide bond;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..1844
FT /note="ATPase family AAA domain-containing protein 5"
FT /id="PRO_0000317618"
FT REGION 178..204
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 368..384
FT /note="Interaction with WDR48"
FT /evidence="ECO:0000269|PubMed:20147293"
FT REGION 477..499
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 580..623
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 658..700
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 987..1047
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1092..1118
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1203..1235
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1272..1292
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1591..1635
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1630..1719
FT /note="Interaction with RAD51 and RFC5"
FT /evidence="ECO:0000269|PubMed:31844045"
FT MOTIF 1428..1432
FT /note="LXCXE motif"
FT COMPBIAS 178..195
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 682..700
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 987..1035
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1214..1228
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1272..1288
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1603..1621
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1132..1139
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00499"
FT MOD_RES 44
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 219
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 306
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 311
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 354
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4QY64"
FT MOD_RES 369
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 602
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 614
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 621
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332"
FT MOD_RES 817
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1116
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT CROSSLNK 127
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1205..1844
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_031097"
FT VARIANT 35
FT /note="T -> S (in dbSNP:rs9910051)"
FT /id="VAR_038572"
FT VARIANT 87
FT /note="P -> S (in dbSNP:rs3816780)"
FT /id="VAR_038573"
FT VARIANT 135
FT /note="E -> G (in dbSNP:rs11080134)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_038574"
FT VARIANT 215
FT /note="D -> N (in dbSNP:rs367699401)"
FT /evidence="ECO:0000269|PubMed:26282398"
FT /id="VAR_079496"
FT VARIANT 249
FT /note="R -> K (in dbSNP:rs17826219)"
FT /id="VAR_038575"
FT VARIANT 699
FT /note="N -> H (in dbSNP:rs3764421)"
FT /id="VAR_038576"
FT VARIANT 1419
FT /note="Y -> H (in dbSNP:rs11657270)"
FT /id="VAR_038577"
FT MUTAGEN 368..384
FT /note="Missing: Abolishes interaction with WDR48 and
FT recruitment of RAD51 at site of stalled replication forks
FT under replication stress. Reduces down-regulation of PCNA
FT monoubiquitination but retains the ability to unload PCNA
FT from chromatin."
FT /evidence="ECO:0000269|PubMed:20147293,
FT ECO:0000269|PubMed:23277426, ECO:0000269|PubMed:31844045"
FT MUTAGEN 642..645
FT /note="Missing: Loss of interaction with RAD51 and loading
FT of RAD51 to stalled replication forks during replication
FT stress. Loss of processing of stalled replication forks.
FT Retains PCNA-unloading ability."
FT /evidence="ECO:0000269|PubMed:31844045"
FT MUTAGEN 1138
FT /note="K->E: Results in defective PCNA removal from
FT chromatin and recruitment of RAD51 at site of stalled
FT replication forks under replication stress. Loss of
FT processing of stalled replication forks. Retains
FT interaction with PCNA and RFC4."
FT /evidence="ECO:0000269|PubMed:23277426,
FT ECO:0000269|PubMed:31844045"
FT MUTAGEN 1169
FT /note="S->A: No effect on the RAD9A interaction after MMS
FT exposure. Resists to DNA damage after MMS exposure."
FT /evidence="ECO:0000269|PubMed:15983387"
FT MUTAGEN 1187
FT /note="S->A: Weakly affects the RAD9A interaction after MMS
FT exposure."
FT /evidence="ECO:0000269|PubMed:15983387"
FT MUTAGEN 1430
FT /note="C->G: Abolishes RB1 binding. Abolishes RB1 binding;
FT when associated with K-1432. Weakly detected after methyl
FT methane-sulfonate (MMS) treatment. Expression detected
FT after MMS treatment; when associated with K-1432. Weakly
FT affects the RAD9A interaction after MMS exposure. No effect
FT on the RAD9A interaction after MMS exposure; when
FT associated with K-1432. Resists to DNA damage after MMS
FT exposure; when associated with K-1432."
FT /evidence="ECO:0000269|PubMed:15983387"
FT MUTAGEN 1432
FT /note="E->K: Abolishes RB1 binding; when associated with G-
FT 1430. Expression detected after methyl methane-sulfonate
FT (MMS) treatment; when associated with G-1430. No effect on
FT the RAD9A interaction after MMS exposure; when associated
FT with G-1430. Resists to DNA damage after MMS exposure; when
FT associated with G-1430."
FT /evidence="ECO:0000269|PubMed:15983387"
FT CONFLICT 95
FT /note="N -> D (in Ref. 4; CAH10412)"
FT /evidence="ECO:0000305"
FT CONFLICT 465
FT /note="T -> A (in Ref. 4; CAH10412)"
FT /evidence="ECO:0000305"
FT CONFLICT 475
FT /note="N -> D (in Ref. 6; BAB14248)"
FT /evidence="ECO:0000305"
FT CONFLICT 612
FT /note="I -> T (in Ref. 4; CAH10412)"
FT /evidence="ECO:0000305"
FT CONFLICT 1203
FT /note="K -> S (in Ref. 6; BAB14248)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1844 AA; 207570 MW; A09A3C76CFC77BD1 CRC64;
MVGVLAMAAA AAPPPVKDCE IEPCKKRKKD DDTSTCKTIT KYLSPLGKTR DRVFAPPKPS
NILDYFRKTS PTNEKTQLGK ECKIKSPESV PVDSNKDCTT PLEMFSNVEF KKKRKRVNLS
HQLNNIKTEN EAPIEISSDD SKEDYSLNND FVESSTSVLR YKKQVEVLAE NIQDTKSQPN
TMTSLQNSKK VNPKQGTTKN DFKKLRKRKC RDVVDLSESL PLAEELNLLK KDGKDTKQME
NTTSHANSRD NVTEAAQLND SIITVSYEEF LKSHKENKVE EIPDSTMSIC VPSETVDEIV
KSGYISESEN SEISQQVRFK TVTVLAQVHP IPPKKTGKIP RIFLKQKQFE MENSLSDPEN
EQTVQKRKSN VVIQEEELEL AVLEAGSSEA VKPKCTLEER QQFMKAFRQP ASDALKNGVK
KSSDKQKDLN EKCLYEVGRD DNSKKIMENS GIQMVSKNGN LQLHTDKGSF LKEKNKKLKK
KNKKTLDTGA IPGKNREGNT QKKETTFFLK EKQYQNRMSL RQRKTEFFKS STLFNNESLV
YEDIANDDLL KVSSLCNNNK LSRKTSIPVK DIKLTQSKAE SEASLLNVST PKSTRRSGRI
SSTPTTETIR GIDSDDVQDN SQLKASTQKA ANLSEKHSLY TAELITVPFD SESPIRMKFT
RISTPKKSKK KSNKRSEKSE ATDGGFTSQI RKASNTSKNI SKAKQLIEKA KALHISRSKV
TEEIAIPLRR SSRHQTLPER KKLSETEDSV IIIDSSPTAL KHPEKNQKKL QCLNDVLGKK
LNTSTKNVPG KMKVAPLFLV RKAQKAADPV PSFDESSQDT SEKSQDCDVQ CKAKRDFLMS
GLPDLLKRQI AKKAAALDVY NAVSTSFQRV VHVQQKDDGC CLWHLKPPSC PLLTKFKELN
TKVIDLSKCG IALGEFSTLN SKLKSGNSAA VFMRTRKEFT EEVRNLLLEE IRWSNPEFSL
KKYFPLLLKK QIEHQVLSSE CHSKQELEAD VSHKETKRKL VEAENSKSKR KKPNEYSKNL
EKTNRKSEEL SKRNNSSGIK LDSSKDSGTE DMLWTEKYQP QTASELIGNE LAIKKLHSWL
KDWKRRAELE ERQNLKGKRD EKHEDFSGGI DFKGSSDDEE ESRLCNTVLI TGPTGVGKTA
AVYACAQELG FKIFEVNASS QRSGRQILSQ LKEATQSHQV DKQGVNSQKP CFFNSYYIGK
SPKKISSPKK VVTSPRKVPP PSPKSSGPKR ALPPKTLANY FKVSPKPKNN EEIGMLLENN
KGIKNSFEQK QITQTKSTNA TNSNVKDVGA EEPSRKNATS LILFEEVDVI FDEDAGFLNA
IKTFMATTKR PVILTTSDPT FSLMFDGCFE EIKFSTPSLL NVASYLQMIC LTENFRTDVK
DFVTLLTANT CDIRKSILYL QFWIRSGGGV LEERPLTLYR GNSRNVQLVC SEHGLDNKIY
PKNTKKKRVD LPKCDSGCAE TLFGLKNIFS PSEDLFSFLK HKITMKEEWH KFIQLLTEFQ
MRNVDFLYSN LEFILPLPVD TIPETKNFCG PSVTVDASAA TKSMNCLARK HSEREQPLKK
SQKKKQKKTL VILDDSDLFD TDLDFPDQSI SLSSVSSSSN AEESKTGDEE SKARDKGNNP
ETKKSIPCPP KTTAGKKCSA LVSHCLNSLS EFMDNMSFLD ALLTDVREQN KYGRNDFSWT
NGKVTSGLCD EFSLESNDGW TSQSSGELKA AAEALSFTKC SSAISKALET LNSCKKLGRD
PTNDLTFYVS QKRNNVYFSQ SAANLDNAWK RISVIKSVFS SRSLLYVGNR QASIIEYLPT
LRNICKTEKL KEQGKSKRRF LHYFEGIHLD IPKETVNTLA ADFP
