DBF4A_MOUSE
ID DBF4A_MOUSE Reviewed; 663 AA.
AC Q9QZ41; B7ZNS0; Q3TQP4; Q3V1K2; Q6NSQ1; Q9CXF2;
DT 02-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Protein DBF4 homolog A;
DE AltName: Full=MuDBF4;
GN Name=Dbf4; Synonyms=Dbf4a;
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 [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH CDC7 AND
RP MCM2, AND INDUCTION.
RC STRAIN=C57BL/6J; TISSUE=Egg, and Embryo;
RX PubMed=10517317; DOI=10.1007/s004380051078;
RA Lepke M., Puetter V., Staib C., Kneissl M., Berger C., Hoehn K., Nanda I.,
RA Schmid M., Grummt F.;
RT "Identification, characterization and chromosomal localization of the
RT cognate human and murine DBF4 genes.";
RL Mol. Gen. Genet. 262:220-229(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 75-345.
RC STRAIN=C57BL/6J; TISSUE=Liver;
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] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1-287.
RC TISSUE=Brain, and Jaw;
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 INTERACTION WITH MCM2; ORC2; ORC4 AND ORC6.
RX PubMed=12614612; DOI=10.1016/s0022-2836(03)00079-2;
RA Kneissl M., Puetter V., Szalay A.A., Grummt F.;
RT "Interaction and assembly of murine pre-replicative complex proteins in
RT yeast and mouse cells.";
RL J. Mol. Biol. 327:111-128(2003).
CC -!- FUNCTION: Regulatory subunit for CDC7 which activates its kinase
CC activity thereby playing a central role DNA in 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:10517317}.
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 (By similarity).
CC {ECO:0000250|UniProtKB:Q9UBU7, ECO:0000269|PubMed:10517317,
CC ECO:0000269|PubMed:12614612}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9QZ41-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9QZ41-2; Sequence=VSP_018205;
CC Name=3;
CC IsoId=Q9QZ41-3; Sequence=VSP_018206, VSP_018207;
CC -!- INDUCTION: In a cell cycle-dependent manner. Induced at low level
CC through G1. Increased during S phase and decreased at the end of S
CC phase. {ECO:0000269|PubMed:10517317}.
CC -!- PTM: Phosphorylation increases its interaction with PSIP1.
CC {ECO:0000250|UniProtKB:Q9UBU7}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH69983.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
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DR EMBL; AJ003132; CAB56847.1; -; mRNA.
DR EMBL; AK014480; BAB29383.1; -; mRNA.
DR EMBL; AK132403; BAE21148.1; -; mRNA.
DR EMBL; AK163408; BAE37338.1; -; mRNA.
DR EMBL; BC069983; AAH69983.1; ALT_SEQ; mRNA.
DR EMBL; BC145392; AAI45393.1; -; mRNA.
DR CCDS; CCDS19081.1; -. [Q9QZ41-1]
DR CCDS; CCDS57324.1; -. [Q9QZ41-2]
DR RefSeq; NP_001177646.1; NM_001190717.1. [Q9QZ41-2]
DR RefSeq; NP_038754.1; NM_013726.3. [Q9QZ41-1]
DR AlphaFoldDB; Q9QZ41; -.
DR SMR; Q9QZ41; -.
DR STRING; 10090.ENSMUSP00000132906; -.
DR iPTMnet; Q9QZ41; -.
DR PhosphoSitePlus; Q9QZ41; -.
DR PaxDb; Q9QZ41; -.
DR PRIDE; Q9QZ41; -.
DR ProteomicsDB; 277947; -. [Q9QZ41-1]
DR ProteomicsDB; 277948; -. [Q9QZ41-2]
DR ProteomicsDB; 277949; -. [Q9QZ41-3]
DR Antibodypedia; 15373; 240 antibodies from 35 providers.
DR DNASU; 27214; -.
DR Ensembl; ENSMUST00000002368; ENSMUSP00000002368; ENSMUSG00000002297. [Q9QZ41-2]
DR Ensembl; ENSMUST00000171808; ENSMUSP00000132906; ENSMUSG00000002297. [Q9QZ41-1]
DR GeneID; 27214; -.
DR KEGG; mmu:27214; -.
DR UCSC; uc008wkc.2; mouse. [Q9QZ41-1]
DR UCSC; uc008wkd.2; mouse. [Q9QZ41-2]
DR UCSC; uc008wke.2; mouse. [Q9QZ41-3]
DR CTD; 10926; -.
DR MGI; MGI:1351328; Dbf4.
DR VEuPathDB; HostDB:ENSMUSG00000002297; -.
DR eggNOG; KOG4139; Eukaryota.
DR GeneTree; ENSGT00530000063909; -.
DR HOGENOM; CLU_030726_2_0_1; -.
DR InParanoid; Q9QZ41; -.
DR OMA; CECCFVG; -.
DR PhylomeDB; Q9QZ41; -.
DR TreeFam; TF332790; -.
DR Reactome; R-MMU-176187; Activation of ATR in response to replication stress.
DR Reactome; R-MMU-68962; Activation of the pre-replicative complex.
DR BioGRID-ORCS; 27214; 13 hits in 75 CRISPR screens.
DR ChiTaRS; Dbf4; mouse.
DR PRO; PR:Q9QZ41; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q9QZ41; protein.
DR Bgee; ENSMUSG00000002297; Expressed in ureteric bud tip and 195 other tissues.
DR ExpressionAtlas; Q9QZ41; baseline and differential.
DR Genevisible; Q9QZ41; MM.
DR GO; GO:0031431; C:Dbf4-dependent protein kinase complex; IBA:GO_Central.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
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:0004674; F:protein serine/threonine kinase activity; ISA:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
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 GO; GO:0007089; P:traversing start control point of mitotic cell cycle; ISA:MGI.
DR Gene3D; 6.10.250.3410; -; 1.
DR InterPro; IPR001357; BRCT_dom.
DR InterPro; IPR006572; Znf_DBF.
DR InterPro; IPR038545; Znf_DBF_sf.
DR Pfam; PF00533; BRCT; 1.
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 Alternative splicing; Cell cycle; DNA replication; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Zinc; Zinc-finger.
FT CHAIN 1..663
FT /note="Protein DBF4 homolog A"
FT /id="PRO_0000234062"
FT DOMAIN 40..128
FT /note="BRCT 1"
FT DOMAIN 154..179
FT /note="BRCT 2"
FT ZN_FING 288..336
FT /note="DBF4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00600"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 99..131
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 369..480
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 603..627
FT /note="Integrase domain-binding motif 1 (IBM1)"
FT /evidence="ECO:0000250|UniProtKB:Q9UBU7"
FT MOTIF 644..663
FT /note="Integrase domain-binding motif 2 (IBM2)"
FT /evidence="ECO:0000250|UniProtKB:Q9UBU7"
FT COMPBIAS 109..131
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 295
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00600"
FT BINDING 298
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00600"
FT BINDING 308
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00600"
FT BINDING 314
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00600"
FT MOD_RES 311
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBU7"
FT MOD_RES 344
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBU7"
FT MOD_RES 353
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBU7"
FT MOD_RES 358
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBU7"
FT MOD_RES 412
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBU7"
FT MOD_RES 614
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBU7"
FT MOD_RES 656
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBU7"
FT MOD_RES 658
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBU7"
FT VAR_SEQ 212..213
FT /note="TG -> R (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_018205"
FT VAR_SEQ 308..321
FT /note="HLLSEKHRNFAQSN -> VNVIFHLGLVFLKI (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_018206"
FT VAR_SEQ 322..663
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_018207"
SQ SEQUENCE 663 AA; 74176 MW; 72E05CB87C3B1650 CRC64;
MNLETMRIHS KAPLPGGIQD RNEKNRPSLK SLKADNRLEK SKYKPLWGKI FYLDLPSITI
CEKLQKDIKE LGGRVEEFLS KDISYFVSNK KEAKYAQTLG RVSPVPSPES AYTAETTSPH
PSHDGSSFKS QDRVCLSRGK LLAEKAVKDH DFIPANSILS NALSWGVKIL HIDDIRYYIE
QKKKALSALK KSSASGKDAG KKAGPGIQKT RTGRLKKPFL KVEDVNRCYR PFYLQLPSLP
CINYFLQKPC SPFDIEKSSS VQKQAQPKLR INMDGDKCGT PVQLQLKEKR KKGYCECCLQ
KYEDLETHLL SEKHRNFAQS NQYQVVDDIV SQLVFDFVEY GRDTPQKKRI RYSVGSLSSV
SANVLKNTAP KEKPLLEPNF QKDVGESSGH LLKPNSQYEE TQKPEEKHGF ASEPTTYSSA
GLKGCDRKPV SMFNASEPDP EQEYAQLPLR DSTPEHQVTE GRNDGEQRVD PAPGVSQSCG
QVSHLSTESN LPQPQLAADI TQLSAKDLQE KGFHVVIGHA SDLVALNTSK EQLTMKARTP
PCSPQEPHEC DTENMENLPC GKIQRKVRML LGQQKANAEP SAELDKKRTE YLPAHEDRTC
GSPVQSLLDL FQTSEEKSEF LGFTGYTENS GICDVLDIWE EENSSTLLST FFSSPSTSAF
VGF
