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   24-JAN-2024, entry version 148.
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}.
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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.
DR   RefSeq; XP_011523583.1; XM_011525281.2. [Q8NFT6-3]
DR   AlphaFoldDB; Q8NFT6; -.
DR   SMR; Q8NFT6; -.
DR   BioGRID; 123157; 35.
DR   IntAct; Q8NFT6; 29.
DR   MINT; Q8NFT6; -.
DR   STRING; 9606.ENSP00000323663; -.
DR   GlyGen; Q8NFT6; 1 site, 1 O-linked glycan (1 site).
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; 9606-ENSP00000323663; -.
DR   PeptideAtlas; Q8NFT6; -.
DR   ProteomicsDB; 73350; -. [Q8NFT6-1]
DR   ProteomicsDB; 73351; -. [Q8NFT6-2]
DR   ProteomicsDB; 73352; -. [Q8NFT6-3]
DR   ProteomicsDB; 73353; -. [Q8NFT6-4]
DR   Antibodypedia; 29863; 160 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   AGR; HGNC:17883; -.
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; PASCTCQ; -.
DR   OrthoDB; 5402803at2759; -.
DR   PhylomeDB; Q8NFT6; -.
DR   TreeFam; TF332790; -.
DR   PathwayCommons; Q8NFT6; -.
DR   SignaLink; Q8NFT6; -.
DR   BioGRID-ORCS; 80174; 18 hits in 1153 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 114 other cell types or tissues.
DR   ExpressionAtlas; Q8NFT6; baseline and differential.
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:HPA.
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; DBF zinc finger; 1.
DR   InterPro; IPR006572; Znf_DBF.
DR   InterPro; IPR038545; Znf_DBF_sf.
DR   PANTHER; PTHR15375; ACTIVATOR OF S-PHASE KINASE-RELATED; 1.
DR   PANTHER; PTHR15375:SF24; PROTEIN DBF4 HOMOLOG B; 1.
DR   Pfam; PF07535; zf-DBF; 1.
DR   SMART; SM00586; ZnF_DBF; 1.
DR   PROSITE; PS51265; ZF_DBF4; 1.
DR   Genevisible; Q8NFT6; HS.
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
//