DBF4B_HUMAN
ID DBF4B_HUMAN Reviewed; 615 AA.
AC Q8NFT6; D3DX56; Q8TEX0; Q96B19; Q9H912;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Protein DBF4 homolog B;
DE AltName: Full=Activator of S phase kinase-like protein 1;
DE Short=ASK-like protein 1;
DE AltName: Full=Chiffon homolog B;
DE AltName: Full=Dbf4-related factor 1;
GN Name=DBF4B; Synonyms=ASKL1, DRF1;
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), FUNCTION, SUBCELLULAR LOCATION,
RP PHOSPHORYLATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND INTERACTION
RP WITH CDC7.
RX PubMed=12065429; DOI=10.1093/emboj/cdf290;
RA Montagnoli A., Bosotti R., Villa F., Rialland M., Brotherton D.,
RA Mercurio C., Berthelsen J., Santocanale C.;
RT "Drf1, a novel regulatory subunit for human Cdc7 kinase.";
RL EMBO J. 21:3171-3181(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RA Shannon M.;
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
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 [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Lung;
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 FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND INTERACTION WITH
RP CDC7.
RX PubMed=15668232; DOI=10.1074/jbc.m411653200;
RA Yoshizawa-Sugata N., Ishii A., Taniyama C., Matsui E., Arai K., Masai H.;
RT "A second human Dbf4/ASK-related protein, Drf1/ASKL1, is required for
RT efficient progression of S and M phases.";
RL J. Biol. Chem. 280:13062-13070(2005).
RN [7]
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).
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 and M phases. The complex
CC CDC7-DBF4B selectively phosphorylates MCM2 subunit at 'Ser-40' and then
CC is involved in regulating the initiation of DNA replication during cell
CC cycle. {ECO:0000269|PubMed:12065429, ECO:0000269|PubMed:15668232,
CC ECO:0000269|PubMed:17062569}.
CC -!- SUBUNIT: Forms a complex with CDC7. Note that CDC7 forms distinct
CC complex either with DBF4/DBF4A or DBF4B. Such complexes are stable upon
CC replication stress.
CC -!- INTERACTION:
CC Q8NFT6; P25791: LMO2; NbExp=3; IntAct=EBI-749662, EBI-739696;
CC Q8NFT6-2; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-12205861, EBI-3867333;
CC Q8NFT6-2; P55040: GEM; NbExp=3; IntAct=EBI-12205861, EBI-744104;
CC Q8NFT6-2; Q96MH2: HEXIM2; NbExp=3; IntAct=EBI-12205861, EBI-5460660;
CC Q8NFT6-2; Q99750: MDFI; NbExp=3; IntAct=EBI-12205861, EBI-724076;
CC Q8NFT6-2; Q92824-2: PCSK5; NbExp=3; IntAct=EBI-12205861, EBI-11956269;
CC Q8NFT6-2; Q9HAT0: ROPN1; NbExp=6; IntAct=EBI-12205861, EBI-1378139;
CC Q8NFT6-2; Q96ES7: SGF29; NbExp=3; IntAct=EBI-12205861, EBI-743117;
CC Q8NFT6-2; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-12205861, EBI-5235340;
CC Q8NFT6-2; P14373: TRIM27; NbExp=3; IntAct=EBI-12205861, EBI-719493;
CC Q8NFT6-2; Q8N720: ZNF655; NbExp=3; IntAct=EBI-12205861, EBI-625509;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12065429,
CC ECO:0000269|PubMed:15668232}. Note=Predominantly found in soluble
CC fraction but not in the chromatin-bound fraction.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q8NFT6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NFT6-2; Sequence=VSP_031018, VSP_031019;
CC Name=3;
CC IsoId=Q8NFT6-3; Sequence=VSP_031014, VSP_031017;
CC Name=4;
CC IsoId=Q8NFT6-4; Sequence=VSP_031015, VSP_031016;
CC -!- TISSUE SPECIFICITY: Widely expressed. Highly expressed in testis.
CC {ECO:0000269|PubMed:12065429}.
CC -!- DEVELOPMENTAL STAGE: Increases as cells enter in S phase through G2/M
CC phase. The protein has a short half-life (at protein level).
CC {ECO:0000269|PubMed:12065429, ECO:0000269|PubMed:15668232}.
CC -!- PTM: Phosphorylated. {ECO:0000269|PubMed:12065429}.
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; AF448801; AAM73808.1; -; mRNA.
DR EMBL; AF465820; AAL75985.1; -; mRNA.
DR EMBL; AK023149; BAB14431.1; -; mRNA.
DR EMBL; CH471178; EAW51581.1; -; Genomic_DNA.
DR EMBL; CH471178; EAW51584.1; -; Genomic_DNA.
DR EMBL; CH471178; EAW51587.1; -; Genomic_DNA.
DR EMBL; CH471178; EAW51582.1; -; Genomic_DNA.
DR EMBL; CH471178; EAW51586.1; -; Genomic_DNA.
DR EMBL; BC016158; AAH16158.1; -; mRNA.
DR CCDS; CCDS11485.1; -. [Q8NFT6-1]
DR CCDS; CCDS45706.2; -. [Q8NFT6-2]
DR RefSeq; NP_079380.2; NM_025104.3. [Q8NFT6-2]
DR RefSeq; NP_663696.1; NM_145663.2. [Q8NFT6-1]
DR RefSeq; XP_006722165.1; XM_006722102.3. [Q8NFT6-3]
DR RefSeq; XP_011523583.1; XM_011525281.2. [Q8NFT6-3]
DR AlphaFoldDB; Q8NFT6; -.
DR SMR; Q8NFT6; -.
DR BioGRID; 123157; 34.
DR IntAct; Q8NFT6; 29.
DR MINT; Q8NFT6; -.
DR STRING; 9606.ENSP00000323663; -.
DR iPTMnet; Q8NFT6; -.
DR PhosphoSitePlus; Q8NFT6; -.
DR BioMuta; DBF4B; -.
DR DMDM; 74715595; -.
DR EPD; Q8NFT6; -.
DR jPOST; Q8NFT6; -.
DR MassIVE; Q8NFT6; -.
DR MaxQB; Q8NFT6; -.
DR PaxDb; Q8NFT6; -.
DR PeptideAtlas; Q8NFT6; -.
DR PRIDE; Q8NFT6; -.
DR Antibodypedia; 29863; 143 antibodies from 22 providers.
DR DNASU; 80174; -.
DR Ensembl; ENST00000315005.8; ENSP00000323663.3; ENSG00000161692.18. [Q8NFT6-1]
DR Ensembl; ENST00000393547.6; ENSP00000377178.2; ENSG00000161692.18. [Q8NFT6-2]
DR GeneID; 80174; -.
DR KEGG; hsa:80174; -.
DR MANE-Select; ENST00000315005.8; ENSP00000323663.3; NM_145663.3; NP_663696.1.
DR UCSC; uc002ihf.4; human. [Q8NFT6-1]
DR CTD; 80174; -.
DR DisGeNET; 80174; -.
DR GeneCards; DBF4B; -.
DR HGNC; HGNC:17883; DBF4B.
DR HPA; ENSG00000161692; Low tissue specificity.
DR MIM; 611661; gene.
DR neXtProt; NX_Q8NFT6; -.
DR OpenTargets; ENSG00000161692; -.
DR PharmGKB; PA143485447; -.
DR VEuPathDB; HostDB:ENSG00000161692; -.
DR eggNOG; KOG4139; Eukaryota.
DR GeneTree; ENSGT00530000063909; -.
DR HOGENOM; CLU_030726_1_1_1; -.
DR InParanoid; Q8NFT6; -.
DR OMA; ANPKGSH; -.
DR OrthoDB; 615385at2759; -.
DR PhylomeDB; Q8NFT6; -.
DR TreeFam; TF332790; -.
DR PathwayCommons; Q8NFT6; -.
DR SignaLink; Q8NFT6; -.
DR BioGRID-ORCS; 80174; 13 hits in 1075 CRISPR screens.
DR ChiTaRS; DBF4B; human.
DR GenomeRNAi; 80174; -.
DR Pharos; Q8NFT6; Tbio.
DR PRO; PR:Q8NFT6; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q8NFT6; protein.
DR Bgee; ENSG00000161692; Expressed in right testis and 112 other tissues.
DR ExpressionAtlas; Q8NFT6; baseline and differential.
DR Genevisible; Q8NFT6; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031431; C:Dbf4-dependent protein kinase complex; IBA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0030295; F:protein kinase activator activity; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
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:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0010571; P:positive regulation of nuclear cell cycle DNA replication; IMP:UniProtKB.
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 Alternative splicing; Cell cycle; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Zinc; Zinc-finger.
FT CHAIN 1..615
FT /note="Protein DBF4 homolog B"
FT /id="PRO_0000317553"
FT DOMAIN 43..133
FT /note="BRCT"
FT ZN_FING 294..343
FT /note="DBF4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00600"
FT REGION 93..141
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 264..293
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 371..407
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 391..406
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 301
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00600"
FT BINDING 304
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 BINDING 320
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00600"
FT VAR_SEQ 1..186
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_031014"
FT VAR_SEQ 157..170
FT /note="GSISGGGSGGSSSL -> VSWGKMGQSRWSPA (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_031015"
FT VAR_SEQ 171..615
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_031016"
FT VAR_SEQ 397..615
FT /note="VTQGRAAGQQRWTESLDGVMGPPASHTCVSATTLLPALPKGSREQGCLCPCP
FT ASFTQSHLVTSLALLPGEWSPAEDMPLHPSQENSFAPADIPVKGPLLFPEARPWLMSAR
FT CWVRPFPFVTWGCLIPHDTTPLHEEVSPCPCLRLGYLYLLLTQSLWCRVRVPSLSTAGP
FT IPRTSHPCTLAFPSYLNDHDLGHLCQAKPQGWNTPQPFLHCGFLAVDSG -> GIPEQD
FT GTVDSTQAPAERAGTGEVPGPIASCQDLGVSVDVFVDPPGIPVSRSPACQCLLPSSGFM
FT ELSSGPDLALFGHKRKVQFPSGSAKKRVGASWPQASFFVPIAPNPCGTRTTSGKRLPSL
FT PLTGHESRLLASLQPLCHSQTCLSLPDPFPWQPTDRPAEFWATQPSWLGKGWPPGPEDS
FT ECTATGPVSQEAGQLLSCPTAPGWPSAPLYSATSVQPSGAPVESRSTSLLQPLPASAGA
FT SCSRCLWAPQPLQVPCLPVSQPWSQPQPQPQPHAGRELLLRVPKVLGSSQGQAAPD
FT (in isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_031017"
FT VAR_SEQ 425..431
FT /note="VSATTLL -> HRPCRLP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_031018"
FT VAR_SEQ 432..615
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_031019"
FT CONFLICT 207
FT /note="K -> R (in Ref. 2; AAL75985)"
FT /evidence="ECO:0000305"
FT CONFLICT 352
FT /note="G -> D (in Ref. 2; AAL75985)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 615 AA; 67243 MW; 02C1F957B60415A4 CRC64;
MSEPGKGDDC LELESSMAES RLRAPDLGVS RCLGKCQKNS PGARKHPFSG KSFYLDLPAG
KNLQFLTGAI QQLGGVIEGF LSKEVSYIVS SRREVKAESS GKSHRGCPSP SPSEVRVETS
AMVDPKGSHP RPSRKPVDSV PLSRGKELLQ KAIRNQGSIS GGGSGGSSSL LTNARSWGVR
ILHVDEMMMH VQQLSLASLC VKKQQPKKPE GTCPAAESRT RKVARLKAPF LKIEDESRKF
RPFHHQFKSF PEISFLGPKD ASPFEAPTTL GSMHHTRESK DGEPSPRSAA HTMPRRKKGY
CECCQEAFEE LHVHLQSAQH RSFALEAHLY AEVDRIIAQL SHSFADIPFQ AGLPRWSGSP
ASDCDPLCPE TLHPHQPSHP RAASPRIRKE DSCQASVTQG RAAGQQRWTE SLDGVMGPPA
SHTCVSATTL LPALPKGSRE QGCLCPCPAS FTQSHLVTSL ALLPGEWSPA EDMPLHPSQE
NSFAPADIPV KGPLLFPEAR PWLMSARCWV RPFPFVTWGC LIPHDTTPLH EEVSPCPCLR
LGYLYLLLTQ SLWCRVRVPS LSTAGPIPRT SHPCTLAFPS YLNDHDLGHL CQAKPQGWNT
PQPFLHCGFL AVDSG
