Q8NFT6 (DBF4B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein DBF4 homolog B

Alternative name(s):
Activator of S phase kinase-like protein 1
Short name=ASK-like protein 1
Chiffon homolog B
Dbf4-related factor 1

Gene names

Name:	DBF4B
Synonyms:	ASKL1, DRF1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	615 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Regulatory subunit for CDC7 which activates its kinase activity thereby playing a central role in DNA replication and cell proliferation. Required for progression of S and M phases. The complex CDC7-DBF4B selectively phosphorylates MCM2 subunit at 'Ser-40' and then is involved in regulating the initiation of DNA replication during cell cycle. Ref.1 Ref.6 Ref.7
Subunit structure	Forms a complex with CDC7. Note that CDC7 forms distinct complex either with DBF4/DBF4A or DBF4B. Such complexes are stable upon replication stress.
Subcellular location	Nucleus. Note: Predominantly found in soluble fraction but not in the chromatin-bound fraction. Ref.1 Ref.6
Tissue specificity	Widely expressed. Highly expressed in testis. Ref.1
Developmental stage	Increases as cells enter in S phase through G2/M phase. The protein has a short half-life (at protein level). Ref.1 Ref.6
Post-translational modification	Phosphorylated. Ref.1
Sequence similarities	Contains 1 BRCT domain. Contains 1 DBF4-type zinc finger.

Ontologies

Keywords
Biological process	Cell cycle
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Zinc-finger
Ligand	Metal-binding Zinc
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	aggresome Inferred from direct assay. Source: HPA nucleus Inferred from direct assay. Source: HPA
Molecular_function	nucleic acid binding Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8NFT6-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8NFT6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     425-431: VSATTLL → HRPCRLP
     432-615: Missing.

Isoform 3 (identifier: Q8NFT6-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-186: Missing.
     397-615: VTQGRAAGQQ...HCGFLAVDSG → GIPEQDGTVD...GSSQGQAAPD

Note: No experimental confirmation available.

Isoform 4 (identifier: Q8NFT6-4)

The sequence of this isoform differs from the canonical sequence as follows:
     157-170: GSISGGGSGGSSSL → VSWGKMGQSRWSPA
     171-615: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 615	615	Protein DBF4 homolog B		PRO_0000317553
Regions
	Domain	43 – 133	91	BRCT
	Zinc finger	294 – 343	50	DBF4-type
Natural variations
	Alternative sequence	1 – 186	186	Missing in isoform 3.		VSP_031014
	Alternative sequence	157 – 170	14	GSISG…GSSSL → VSWGKMGQSRWSPA in isoform 4.		VSP_031015
	Alternative sequence	171 – 615	445	Missing in isoform 4.		VSP_031016
	Alternative sequence	397 – 615	219	VTQGR…AVDSG → GIPEQDGTVDSTQAPAERAG TGEVPGPIASCQDLGVSVDV FVDPPGIPVSRSPACQCLLP SSGFMELSSGPDLALFGHKR KVQFPSGSAKKRVGASWPQA SFFVPIAPNPCGTRTTSGKR LPSLPLTGHESRLLASLQPL CHSQTCLSLPDPFPWQPTDR PAEFWATQPSWLGKGWPPGP EDSECTATGPVSQEAGQLLS CPTAPGWPSAPLYSATSVQP SGAPVESRSTSLLQPLPASA GASCSRCLWAPQPLQVPCLP VSQPWSQPQPQPQPHAGREL LLRVPKVLGSSQGQAAPD in isoform 3.		VSP_031017
	Alternative sequence	425 – 431	7	VSATTLL → HRPCRLP in isoform 2.		VSP_031018
	Alternative sequence	432 – 615	184	Missing in isoform 2.		VSP_031019
Experimental info
	Sequence conflict	207	1	K → R in AAL75985. Ref.2
	Sequence conflict	352	1	G → D in AAL75985. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: 02C1F957B60415A4	FASTA	615	67,243
	10 20 30 40 50 60 MSEPGKGDDC LELESSMAES RLRAPDLGVS RCLGKCQKNS PGARKHPFSG KSFYLDLPAG 70 80 90 100 110 120 KNLQFLTGAI QQLGGVIEGF LSKEVSYIVS SRREVKAESS GKSHRGCPSP SPSEVRVETS 130 140 150 160 170 180 AMVDPKGSHP RPSRKPVDSV PLSRGKELLQ KAIRNQGSIS GGGSGGSSSL LTNARSWGVR 190 200 210 220 230 240 ILHVDEMMMH VQQLSLASLC VKKQQPKKPE GTCPAAESRT RKVARLKAPF LKIEDESRKF 250 260 270 280 290 300 RPFHHQFKSF PEISFLGPKD ASPFEAPTTL GSMHHTRESK DGEPSPRSAA HTMPRRKKGY 310 320 330 340 350 360 CECCQEAFEE LHVHLQSAQH RSFALEAHLY AEVDRIIAQL SHSFADIPFQ AGLPRWSGSP 370 380 390 400 410 420 ASDCDPLCPE TLHPHQPSHP RAASPRIRKE DSCQASVTQG RAAGQQRWTE SLDGVMGPPA 430 440 450 460 470 480 SHTCVSATTL LPALPKGSRE QGCLCPCPAS FTQSHLVTSL ALLPGEWSPA EDMPLHPSQE 490 500 510 520 530 540 NSFAPADIPV KGPLLFPEAR PWLMSARCWV RPFPFVTWGC LIPHDTTPLH EEVSPCPCLR 550 560 570 580 590 600 LGYLYLLLTQ SLWCRVRVPS LSTAGPIPRT SHPCTLAFPS YLNDHDLGHL CQAKPQGWNT 610 PQPFLHCGFL AVDSG
	Isoform 2 [UniParc]. Checksum: 7E16C13BC9413B46	FASTA	431	47,177
	10 20 30 40 50 60 MSEPGKGDDC LELESSMAES RLRAPDLGVS RCLGKCQKNS PGARKHPFSG KSFYLDLPAG 70 80 90 100 110 120 KNLQFLTGAI QQLGGVIEGF LSKEVSYIVS SRREVKAESS GKSHRGCPSP SPSEVRVETS 130 140 150 160 170 180 AMVDPKGSHP RPSRKPVDSV PLSRGKELLQ KAIRNQGSIS GGGSGGSSSL LTNARSWGVR 190 200 210 220 230 240 ILHVDEMMMH VQQLSLASLC VKKQQPKKPE GTCPAAESRT RKVARLKAPF LKIEDESRKF 250 260 270 280 290 300 RPFHHQFKSF PEISFLGPKD ASPFEAPTTL GSMHHTRESK DGEPSPRSAA HTMPRRKKGY 310 320 330 340 350 360 CECCQEAFEE LHVHLQSAQH RSFALEAHLY AEVDRIIAQL SHSFADIPFQ AGLPRWSGSP 370 380 390 400 410 420 ASDCDPLCPE TLHPHQPSHP RAASPRIRKE DSCQASVTQG RAAGQQRWTE SLDGVMGPPA 430 SHTCHRPCRL P
	Isoform 3 [UniParc]. Checksum: AE51A015F4ACD22E	FASTA	508	54,741
	10 20 30 40 50 60 MMMHVQQLSL ASLCVKKQQP KKPEGTCPAA ESRTRKVARL KAPFLKIEDE SRKFRPFHHQ 70 80 90 100 110 120 FKSFPEISFL GPKDASPFEA PTTLGSMHHT RESKDGEPSP RSAAHTMPRR KKGYCECCQE 130 140 150 160 170 180 AFEELHVHLQ SAQHRSFALE AHLYAEVDRI IAQLSHSFAD IPFQAGLPRW SGSPASDCDP 190 200 210 220 230 240 LCPETLHPHQ PSHPRAASPR IRKEDSCQAS GIPEQDGTVD STQAPAERAG TGEVPGPIAS 250 260 270 280 290 300 CQDLGVSVDV FVDPPGIPVS RSPACQCLLP SSGFMELSSG PDLALFGHKR KVQFPSGSAK 310 320 330 340 350 360 KRVGASWPQA SFFVPIAPNP CGTRTTSGKR LPSLPLTGHE SRLLASLQPL CHSQTCLSLP 370 380 390 400 410 420 DPFPWQPTDR PAEFWATQPS WLGKGWPPGP EDSECTATGP VSQEAGQLLS CPTAPGWPSA 430 440 450 460 470 480 PLYSATSVQP SGAPVESRST SLLQPLPASA GASCSRCLWA PQPLQVPCLP VSQPWSQPQP 490 500 QPQPHAGREL LLRVPKVLGS SQGQAAPD
	Isoform 4 [UniParc]. Checksum: C93EE702A59B282E	FASTA	170	18,392
	10 20 30 40 50 60 MSEPGKGDDC LELESSMAES RLRAPDLGVS RCLGKCQKNS PGARKHPFSG KSFYLDLPAG 70 80 90 100 110 120 KNLQFLTGAI QQLGGVIEGF LSKEVSYIVS SRREVKAESS GKSHRGCPSP SPSEVRVETS 130 140 150 160 170 AMVDPKGSHP RPSRKPVDSV PLSRGKELLQ KAIRNQVSWG KMGQSRWSPA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Drf1, a novel regulatory subunit for human Cdc7 kinase." Montagnoli A., Bosotti R., Villa F., Rialland M., Brotherton D., Mercurio C., Berthelsen J., Santocanale C. EMBO J. 21:3171-3181(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INTERACTION WITH CDC7.
[2]	Shannon M. Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Lung.
[6]	"A second human Dbf4/ASK-related protein, Drf1/ASKL1, is required for efficient progression of S and M phases." Yoshizawa-Sugata N., Ishii A., Taniyama C., Matsui E., Arai K., Masai H. J. Biol. Chem. 280:13062-13070(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, INTERACTION WITH CDC7.
[7]	"Cdc7 is an active kinase in human cancer cells undergoing replication stress." Tenca P., Brotherton D., Montagnoli A., Rainoldi S., Albanese C., Santocanale C. J. Biol. Chem. 282:208-215(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CDC7.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF448801 mRNA. Translation: AAM73808.1. AF465820 mRNA. Translation: AAL75985.1. AK023149 mRNA. Translation: BAB14431.1. CH471178 Genomic DNA. Translation: EAW51581.1. CH471178 Genomic DNA. Translation: EAW51584.1. CH471178 Genomic DNA. Translation: EAW51587.1. CH471178 Genomic DNA. Translation: EAW51582.1. CH471178 Genomic DNA. Translation: EAW51586.1. BC016158 mRNA. Translation: AAH16158.1.
IPI	IPI00152878. IPI00168899. IPI00303912. IPI00790777.
RefSeq	NP_079380.2. NM_025104.3. NP_663696.1. NM_145663.2.
UniGene	Hs.369998.
3D structure databases
ProteinModelPortal	Q8NFT6.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8NFT6. 2 interactions.
MINT	MINT-1477188.
STRING	9606.ENSP00000323663.
PTM databases
PhosphoSite	Q8NFT6.
Polymorphism databases
DMDM	74715595.
Proteomic databases
PaxDb	Q8NFT6.
PRIDE	Q8NFT6.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000315005; ENSP00000323663; ENSG00000161692. ENST00000393547; ENSP00000377178; ENSG00000161692.
GeneID	80174.
KEGG	hsa:80174.
UCSC	uc002ihd.2. human. uc002ihe.3. human. uc002ihf.3. human. uc010wjc.2. human.
Organism-specific databases
CTD	80174.
GeneCards	GC17P042785.
HGNC	HGNC:17883. DBF4B.
HPA	HPA048465.
MIM	611661. gene.
neXtProt	NX_Q8NFT6.
PharmGKB	PA143485447.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG314450.
HOGENOM	HOG000112166.
InParanoid	Q8NFT6.
OMA	PRTSHPC.
OrthoDB	EOG4QRH3M.
PhylomeDB	Q8NFT6.
Gene expression databases
ArrayExpress	Q8NFT6.
Bgee	Q8NFT6.
CleanEx	HS_DBF4B.
Genevestigator	Q8NFT6.
Family and domain databases
InterPro	IPR006572. Znf_DBF. [Graphical view]
Pfam	PF07535. zf-DBF. 1 hit. [Graphical view]
SMART	SM00586. ZnF_DBF. 1 hit. [Graphical view]
PROSITE	PS50172. BRCT. False negative. PS51265. ZF_DBF4. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	80174.
NextBio	70499.
SOURCE	Search...

Entry information

Entry name

DBF4B_HUMAN

Accession

Primary (citable) accession number: Q8NFT6
Secondary accession number(s): D3DX56 , Q8TEX0, Q96B19, Q9H912

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 5, 2008
Last sequence update:	October 1, 2002
Last modified:	May 1, 2013
This is version 76 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.