DBF4A_HUMAN
ID DBF4A_HUMAN Reviewed; 674 AA.
AC Q9UBU7; A4D1D8; A8K954; O75226; Q75MS6; Q75N01; Q9Y2M6;
DT 02-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Protein DBF4 homolog A;
DE AltName: Full=Activator of S phase kinase;
DE AltName: Full=Chiffon homolog A;
DE AltName: Full=DBF4-type zinc finger-containing protein 1;
GN Name=DBF4; Synonyms=ASK, DBF4A, ZDBF1;
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] (ISOFORMS 1 AND 2), FUNCTION, INTERACTION WITH
RP CDC7, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=10373557; DOI=10.1128/mcb.19.7.5083;
RA Kumagai H., Sato N., Yamada M., Mahony D., Seghezzi W., Lees E., Arai K.,
RA Masai H.;
RT "A novel growth- and cell cycle-regulated protein, ASK, activates human
RT Cdc7-related kinase and is essential for G1/S transition in mammalian
RT cells.";
RL Mol. Cell. Biol. 19:5083-5095(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH CDC7,
RP AND INDUCTION.
RX PubMed=10523313; DOI=10.1093/emboj/18.20.5703;
RA Jiang W., McDonald D., Hope T.J., Hunter T.;
RT "Mammalian Cdc7-Dbf4 protein kinase complex is essential for initiation of
RT DNA replication.";
RL EMBO J. 18:5703-5713(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Hollingsworth R.;
RT "Use of a semi-automated yeast two-hybrid system to identify proteins that
RT interact with the human Cdc7 protein.";
RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Testis;
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 [9]
RP INTERACTION WITH MEN1.
RX PubMed=15374998; DOI=10.1158/0008-5472.can-04-0724;
RA Schnepp R.W., Hou Z., Wang H., Petersen C., Silva A., Masai H., Hua X.;
RT "Functional interaction between tumor suppressor menin and activator of S-
RT phase kinase.";
RL Cancer Res. 64:6791-6796(2004).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [11]
RP FUNCTION, AND INTERACTION WITH CDC7.
RX PubMed=17062569; DOI=10.1074/jbc.m604457200;
RA Tenca P., Brotherton D., Montagnoli A., Rainoldi S., Albanese C.,
RA Santocanale C.;
RT "Cdc7 is an active kinase in human cancer cells undergoing replication
RT stress.";
RL J. Biol. Chem. 282:208-215(2007).
RN [12]
RP IDENTIFICATION BY 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 [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-354 AND SER-359, AND
RP 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 [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-273; THR-345; SER-381 AND
RP SER-413, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-359, AND IDENTIFICATION BY
RP 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 [18]
RP IDENTIFICATION BY 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 [19]
RP IDENTIFICATION BY 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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-273; SER-312; THR-345;
RP SER-359; SER-381; SER-413; SER-508 AND THR-553, AND IDENTIFICATION BY MASS
RP 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 PHOSPHORYLATION AT SER-625; SER-667 AND SER-669, INTERACTION WITH PSIP1,
RP DOMAIN IBM MOTIF, AND MUTAGENESIS OF SER-625; PHE-631; PHE-634; SER-667 AND
RP SER-669.
RX PubMed=29997176; DOI=10.1073/pnas.1803909115;
RA Sharma S., Cermakova K., De Rijck J., Demeulemeester J., Fabry M.,
RA El Ashkar S., Van Belle S., Lepsik M., Tesina P., Duchoslav V., Novak P.,
RA Hubalek M., Srb P., Christ F., Rezacova P., Hodges H.C., Debyser Z.,
RA Veverka V.;
RT "Affinity switching of the LEDGF/p75 IBD interactome is governed by kinase-
RT dependent phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:E7053-E7062(2018).
CC -!- FUNCTION: Regulatory subunit for CDC7 which activates its kinase
CC activity thereby playing a central role in DNA replication and cell
CC proliferation. Required for progression of S phase. The complex CDC7-
CC DBF4A selectively phosphorylates MCM2 subunit at 'Ser-40' and 'Ser-53'
CC and then is involved in regulating the initiation of DNA replication
CC during cell cycle. {ECO:0000269|PubMed:10373557,
CC ECO:0000269|PubMed:10523313, ECO:0000269|PubMed:17062569}.
CC -!- SUBUNIT: Forms a complex with CDC7. Note that CDC7 forms distinct
CC complex either with DBF4A or DBF4B. Such complexes are stable upon
CC replication stress. Interacts with MEN1, MCM2, ORC2, ORC4 and ORC6.
CC Interacts (via IBM motifs) with PSIP1 (via IBD domain); phosphorylation
CC increases its affinity for PSIP1 (PubMed:29997176).
CC {ECO:0000269|PubMed:10373557, ECO:0000269|PubMed:10523313,
CC ECO:0000269|PubMed:15374998, ECO:0000269|PubMed:17062569,
CC ECO:0000269|PubMed:29997176}.
CC -!- INTERACTION:
CC Q9UBU7; Q13867: BLMH; NbExp=3; IntAct=EBI-372690, EBI-718504;
CC Q9UBU7; O00311: CDC7; NbExp=8; IntAct=EBI-372690, EBI-374980;
CC Q9UBU7; P36544: CHRNA7; NbExp=3; IntAct=EBI-372690, EBI-79333;
CC Q9UBU7; P14136: GFAP; NbExp=3; IntAct=EBI-372690, EBI-744302;
CC Q9UBU7; P10809: HSPD1; NbExp=3; IntAct=EBI-372690, EBI-352528;
CC Q9UBU7; I6L9F6: NEFL; NbExp=3; IntAct=EBI-372690, EBI-10178578;
CC Q9UBU7; O60260-5: PRKN; NbExp=3; IntAct=EBI-372690, EBI-21251460;
CC Q9UBU7-1; O00311: CDC7; NbExp=3; IntAct=EBI-16017435, EBI-374980;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10373557}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UBU7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UBU7-2; Sequence=VSP_018203, VSP_018204;
CC -!- TISSUE SPECIFICITY: Highly expressed in testis and thymus. Expressed
CC also in most cancer cells lines. {ECO:0000269|PubMed:10373557}.
CC -!- INDUCTION: Induced in G1 phase at low level, increased during G1-S
CC phase and remain high during S and G2-M phase.
CC {ECO:0000269|PubMed:10373557, ECO:0000269|PubMed:10523313}.
CC -!- PTM: Phosphorylation increases its interaction with PSIP1.
CC {ECO:0000269|PubMed:29997176}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB028069; BAA78326.1; -; mRNA.
DR EMBL; AB028070; BAA78327.1; -; mRNA.
DR EMBL; AF160249; AAD41911.1; -; mRNA.
DR EMBL; AF160876; AAD45357.1; -; mRNA.
DR EMBL; AK292569; BAF85258.1; -; mRNA.
DR EMBL; AC003083; AAS07442.1; -; Genomic_DNA.
DR EMBL; AC005164; AAS07418.1; -; Genomic_DNA.
DR EMBL; CH236949; EAL24170.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76930.1; -; Genomic_DNA.
DR EMBL; BC036045; AAH36045.1; -; mRNA.
DR EMBL; BC047693; AAH47693.1; -; mRNA.
DR CCDS; CCDS5611.1; -. [Q9UBU7-1]
DR PIR; T02633; T02633.
DR RefSeq; NP_001304989.1; NM_001318060.1.
DR RefSeq; NP_001304990.1; NM_001318061.1.
DR RefSeq; NP_001304991.1; NM_001318062.1.
DR RefSeq; NP_006707.1; NM_006716.3. [Q9UBU7-1]
DR PDB; 4F99; X-ray; 2.33 A; B=210-350.
DR PDB; 4F9A; X-ray; 2.17 A; B/D=210-350.
DR PDB; 4F9B; X-ray; 2.50 A; B/D=210-350.
DR PDB; 4F9C; X-ray; 2.08 A; B=210-350.
DR PDB; 6YA6; X-ray; 1.44 A; B=210-350.
DR PDB; 6YA7; X-ray; 1.67 A; B=210-350.
DR PDB; 6YA8; X-ray; 1.79 A; B=210-350.
DR PDBsum; 4F99; -.
DR PDBsum; 4F9A; -.
DR PDBsum; 4F9B; -.
DR PDBsum; 4F9C; -.
DR PDBsum; 6YA6; -.
DR PDBsum; 6YA7; -.
DR PDBsum; 6YA8; -.
DR AlphaFoldDB; Q9UBU7; -.
DR SMR; Q9UBU7; -.
DR BioGRID; 116129; 36.
DR CORUM; Q9UBU7; -.
DR DIP; DIP-31205N; -.
DR IntAct; Q9UBU7; 14.
DR MINT; Q9UBU7; -.
DR STRING; 9606.ENSP00000265728; -.
DR BindingDB; Q9UBU7; -.
DR ChEMBL; CHEMBL4483; -.
DR iPTMnet; Q9UBU7; -.
DR PhosphoSitePlus; Q9UBU7; -.
DR BioMuta; DBF4; -.
DR DMDM; 74753231; -.
DR EPD; Q9UBU7; -.
DR jPOST; Q9UBU7; -.
DR MassIVE; Q9UBU7; -.
DR MaxQB; Q9UBU7; -.
DR PaxDb; Q9UBU7; -.
DR PeptideAtlas; Q9UBU7; -.
DR PRIDE; Q9UBU7; -.
DR ProteomicsDB; 84071; -. [Q9UBU7-1]
DR ProteomicsDB; 84072; -. [Q9UBU7-2]
DR Antibodypedia; 15373; 240 antibodies from 35 providers.
DR DNASU; 10926; -.
DR Ensembl; ENST00000265728.6; ENSP00000265728.1; ENSG00000006634.8. [Q9UBU7-1]
DR Ensembl; ENST00000413643.5; ENSP00000414083.1; ENSG00000006634.8. [Q9UBU7-2]
DR GeneID; 10926; -.
DR KEGG; hsa:10926; -.
DR MANE-Select; ENST00000265728.6; ENSP00000265728.1; NM_006716.4; NP_006707.1.
DR UCSC; uc003ujf.1; human. [Q9UBU7-1]
DR CTD; 10926; -.
DR DisGeNET; 10926; -.
DR GeneCards; DBF4; -.
DR HGNC; HGNC:17364; DBF4.
DR HPA; ENSG00000006634; Tissue enriched (testis).
DR MIM; 604281; gene.
DR neXtProt; NX_Q9UBU7; -.
DR OpenTargets; ENSG00000006634; -.
DR PharmGKB; PA142672016; -.
DR VEuPathDB; HostDB:ENSG00000006634; -.
DR eggNOG; KOG4139; Eukaryota.
DR GeneTree; ENSGT00530000063909; -.
DR HOGENOM; CLU_030726_2_0_1; -.
DR InParanoid; Q9UBU7; -.
DR OMA; KQNMELC; -.
DR OrthoDB; 615385at2759; -.
DR PhylomeDB; Q9UBU7; -.
DR TreeFam; TF332790; -.
DR PathwayCommons; Q9UBU7; -.
DR Reactome; R-HSA-176187; Activation of ATR in response to replication stress.
DR Reactome; R-HSA-68962; Activation of the pre-replicative complex.
DR SignaLink; Q9UBU7; -.
DR SIGNOR; Q9UBU7; -.
DR BioGRID-ORCS; 10926; 499 hits in 1049 CRISPR screens.
DR ChiTaRS; DBF4; human.
DR GeneWiki; DBF4; -.
DR GenomeRNAi; 10926; -.
DR Pharos; Q9UBU7; Tbio.
DR PRO; PR:Q9UBU7; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9UBU7; protein.
DR Bgee; ENSG00000006634; Expressed in ventricular zone and 146 other tissues.
DR ExpressionAtlas; Q9UBU7; baseline and differential.
DR Genevisible; Q9UBU7; HS.
DR GO; GO:0031431; C:Dbf4-dependent protein kinase complex; IBA:GO_Central.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0008047; F:enzyme activator activity; TAS:ProtInc.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006260; P:DNA replication; TAS:ProtInc.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; TAS:ProtInc.
DR GO; GO:0010571; P:positive regulation of nuclear cell cycle DNA replication; IBA:GO_Central.
DR GO; GO:1901987; P:regulation of cell cycle phase transition; IBA:GO_Central.
DR Gene3D; 6.10.250.3410; -; 1.
DR InterPro; IPR006572; Znf_DBF.
DR InterPro; IPR038545; Znf_DBF_sf.
DR Pfam; PF07535; zf-DBF; 1.
DR SMART; SM00586; ZnF_DBF; 1.
DR PROSITE; PS51265; ZF_DBF4; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell cycle; DNA replication;
KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat; Zinc;
KW Zinc-finger.
FT CHAIN 1..674
FT /note="Protein DBF4 homolog A"
FT /id="PRO_0000234061"
FT DOMAIN 40..128
FT /note="BRCT 1"
FT DOMAIN 154..179
FT /note="BRCT 2"
FT ZN_FING 289..337
FT /note="DBF4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00600"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 100..131
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 614..638
FT /note="Integrase domain-binding motif 1 (IBM1)"
FT /evidence="ECO:0000269|PubMed:29997176"
FT MOTIF 655..674
FT /note="Integrase domain-binding motif 2 (IBM2)"
FT /evidence="ECO:0000269|PubMed:29997176"
FT COMPBIAS 26..40
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 109..131
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 296
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00600"
FT BINDING 299
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00600"
FT BINDING 309
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00600"
FT BINDING 315
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00600"
FT MOD_RES 273
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 312
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 345
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 354
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 359
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 381
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 413
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 508
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 553
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 625
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:29997176"
FT MOD_RES 667
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:29997176"
FT MOD_RES 669
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:29997176"
FT VAR_SEQ 228..234
FT /note="LYRPFYL -> SPAVHLM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10373557"
FT /id="VSP_018203"
FT VAR_SEQ 235..674
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10373557"
FT /id="VSP_018204"
FT VARIANT 112
FT /note="Y -> N (in dbSNP:rs1476703)"
FT /id="VAR_052970"
FT VARIANT 575
FT /note="H -> R (in dbSNP:rs2041049)"
FT /id="VAR_052971"
FT MUTAGEN 625
FT /note="S->D: Phosphomimetic mutant. Increased interaction
FT with PSIP1."
FT /evidence="ECO:0000269|PubMed:29997176"
FT MUTAGEN 631
FT /note="F->A: Loss of interaction with PSIP1; when
FT associated with A-634."
FT /evidence="ECO:0000269|PubMed:29997176"
FT MUTAGEN 634
FT /note="F->A: Loss of interaction with PSIP1; when
FT associated with A-631."
FT /evidence="ECO:0000269|PubMed:29997176"
FT MUTAGEN 667
FT /note="S->D: Phosphomimetic mutant. Increased interaction
FT with PSIP1; when associated with D-669."
FT /evidence="ECO:0000269|PubMed:29997176"
FT MUTAGEN 669
FT /note="S->D: Phosphomimetic mutant. Increased interaction
FT with PSIP1; when associated with D-667."
FT /evidence="ECO:0000269|PubMed:29997176"
FT CONFLICT 581
FT /note="I -> L (in Ref. 6; EAL24170)"
FT /evidence="ECO:0000305"
FT CONFLICT 584
FT /note="R -> Q (in Ref. 6; EAL24170)"
FT /evidence="ECO:0000305"
FT CONFLICT 619
FT /note="L -> P (in Ref. 6; EAL24170)"
FT /evidence="ECO:0000305"
FT STRAND 217..224
FT /evidence="ECO:0007829|PDB:6YA6"
FT STRAND 227..229
FT /evidence="ECO:0007829|PDB:4F9B"
FT STRAND 232..235
FT /evidence="ECO:0007829|PDB:6YA6"
FT STRAND 244..246
FT /evidence="ECO:0007829|PDB:6YA6"
FT STRAND 294..296
FT /evidence="ECO:0007829|PDB:6YA6"
FT TURN 297..300
FT /evidence="ECO:0007829|PDB:6YA6"
FT STRAND 301..304
FT /evidence="ECO:0007829|PDB:6YA6"
FT HELIX 306..309
FT /evidence="ECO:0007829|PDB:6YA6"
FT HELIX 313..319
FT /evidence="ECO:0007829|PDB:6YA6"
FT HELIX 322..324
FT /evidence="ECO:0007829|PDB:6YA7"
FT HELIX 325..331
FT /evidence="ECO:0007829|PDB:6YA6"
SQ SEQUENCE 674 AA; 76858 MW; 353FEB7E85507E5C CRC64;
MNSGAMRIHS KGHFQGGIQV KNEKNRPSLK SLKTDNRPEK SKCKPLWGKV FYLDLPSVTI
SEKLQKDIKD LGGRVEEFLS KDISYLISNK KEAKFAQTLG RISPVPSPES AYTAETTSPH
PSHDGSSFKS PDTVCLSRGK LLVEKAIKDH DFIPSNSILS NALSWGVKIL HIDDIRYYIE
QKKKELYLLK KSSTSVRDGG KRVGSGAQKT RTGRLKKPFV KVEDMSQLYR PFYLQLTNMP
FINYSIQKPC SPFDVDKPSS MQKQTQVKLR IQTDGDKYGG TSIQLQLKEK KKKGYCECCL
QKYEDLETHL LSEQHRNFAQ SNQYQVVDDI VSKLVFDFVE YEKDTPKKKR IKYSVGSLSP
VSASVLKKTE QKEKVELQHI SQKDCQEDDT TVKEQNFLYK ETQETEKKLL FISEPIPHPS
NELRGLNEKM SNKCSMLSTA EDDIRQNFTQ LPLHKNKQEC ILDISEHTLS ENDLEELRVD
HYKCNIQASV HVSDFSTDNS GSQPKQKSDT VLFPAKDLKE KDLHSIFTHD SGLITINSSQ
EHLTVQAKAP FHTPPEEPNE CDFKNMDSLP SGKIHRKVKI ILGRNRKENL EPNAEFDKRT
EFITQEENRI CSSPVQSLLD LFQTSEEKSE FLGFTSYTEK SGICNVLDIW EEENSDNLLT
AFFSSPSTST FTGF
