Reviewed, UniProtKB/Swiss-Prot Q9UBU7 (DBF4A_HUMAN)

Names and origin

Protein names

Recommended name:
    Protein DBF4 homolog A
Alternative name(s):
    Activator of S phase kinase
    DBF4-type zinc finger-containing protein 1
    Chiffon homolog A

Gene names

Name:	DBF4
Synonyms:	ASK, DBF4A, ZDBF1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	674 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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 phase. The complex CDC7-DBF4A selectively phosphorylates MCM2 subunit at 'Ser-40' and 'Ser-53' and then is involved in regulating the initiation of DNA replication during cell cycle. Ref.1 Ref.2 Ref.10
Subunit structure	Forms a complex with CDC7. Note that CDC7 forms distinct complex either with DBF4A or DBF4B. Such complexes are stable upon replication stress. Interacts with MEN1, MCM2, ORC2L, ORC4L and ORC6L. Ref.1 Ref.2 Ref.10 Ref.9
Subcellular location	Nucleus. Ref.1
Tissue specificity	Highly expressed in testis and thymus. Expressed also in most cancer cells lines. Ref.1
Induction	Induced in G1 phase at low level, increased during G1-S phase and remain high during S and G2-M phase. Ref.1 Ref.2
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.11 Ref.12 Ref.13
Sequence similarities	Contains 2 BRCT domains. Contains 1 DBF4-type zinc finger.

Ontologies

Keywords
Biological process	Cell cycle DNA replication
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Zinc-finger
Ligand	Metal-binding Zinc
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	DNA replication Ref.1 Inferred from Experiment. Source: Reactome G1/S transition of mitotic cell cycle Ref.1 Traceable author statement. Source: ProtInc
Cellular component	nucleoplasm Inferred from Experiment. Source: Reactome
Molecular function	enzyme activator activity Ref.1 Traceable author statement. Source: ProtInc nucleic acid binding Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: IntAct zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
LSM8	O95777	1	EBI-372690,EBI-347779

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9UBU7-1)

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: Q9UBU7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     228-234: LYRPFYL → SPAVHLM
     235-674: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 674	674	Protein DBF4 homolog A		PRO_0000234061
Regions
	Domain	40 – 128	89	BRCT 1
	Domain	154 – 179	26	BRCT 2
	Zinc finger	289 – 337	49	DBF4-type
Amino acid modifications
	Modified residue	354	1	Phosphoserine Ref.13
	Modified residue	359	1	Phosphoserine Ref.12 Ref.13
	Modified residue	381	1	Phosphoserine Ref.11 Ref.12
	Modified residue	535	1	Phosphothreonine Ref.11
	Modified residue	539	1	Phosphoserine Ref.11
Natural variations
	Alternative sequence	228 – 234	7	LYRPFYL → SPAVHLM in isoform 2.		VSP_018203
	Alternative sequence	235 – 674	440	Missing in isoform 2.		VSP_018204
	Natural variant	112	1	Y → N: dbSNP rs1476703.		VAR_052970
	Natural variant	575	1	H → R: dbSNP rs2041049.		VAR_052971
Experimental info
	Sequence conflict	581	1	I → L in EAL24170. Ref.6
	Sequence conflict	584	1	R → Q in EAL24170. Ref.6
	Sequence conflict	619	1	L → P in EAL24170. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 353FEB7E85507E5C	FASTA	674	76,858
	10 20 30 40 50 60 MNSGAMRIHS KGHFQGGIQV KNEKNRPSLK SLKTDNRPEK SKCKPLWGKV FYLDLPSVTI 70 80 90 100 110 120 SEKLQKDIKD LGGRVEEFLS KDISYLISNK KEAKFAQTLG RISPVPSPES AYTAETTSPH 130 140 150 160 170 180 PSHDGSSFKS PDTVCLSRGK LLVEKAIKDH DFIPSNSILS NALSWGVKIL HIDDIRYYIE 190 200 210 220 230 240 QKKKELYLLK KSSTSVRDGG KRVGSGAQKT RTGRLKKPFV KVEDMSQLYR PFYLQLTNMP 250 260 270 280 290 300 FINYSIQKPC SPFDVDKPSS MQKQTQVKLR IQTDGDKYGG TSIQLQLKEK KKKGYCECCL 310 320 330 340 350 360 QKYEDLETHL LSEQHRNFAQ SNQYQVVDDI VSKLVFDFVE YEKDTPKKKR IKYSVGSLSP 370 380 390 400 410 420 VSASVLKKTE QKEKVELQHI SQKDCQEDDT TVKEQNFLYK ETQETEKKLL FISEPIPHPS 430 440 450 460 470 480 NELRGLNEKM SNKCSMLSTA EDDIRQNFTQ LPLHKNKQEC ILDISEHTLS ENDLEELRVD 490 500 510 520 530 540 HYKCNIQASV HVSDFSTDNS GSQPKQKSDT VLFPAKDLKE KDLHSIFTHD SGLITINSSQ 550 560 570 580 590 600 EHLTVQAKAP FHTPPEEPNE CDFKNMDSLP SGKIHRKVKI ILGRNRKENL EPNAEFDKRT 610 620 630 640 650 660 EFITQEENRI CSSPVQSLLD LFQTSEEKSE FLGFTSYTEK SGICNVLDIW EEENSDNLLT 670 AFFSSPSTST FTGF
	Isoform 2. Checksum: 50357B9FCF8472BC	FASTA	234	26,124
	10 20 30 40 50 60 MNSGAMRIHS KGHFQGGIQV KNEKNRPSLK SLKTDNRPEK SKCKPLWGKV FYLDLPSVTI 70 80 90 100 110 120 SEKLQKDIKD LGGRVEEFLS KDISYLISNK KEAKFAQTLG RISPVPSPES AYTAETTSPH 130 140 150 160 170 180 PSHDGSSFKS PDTVCLSRGK LLVEKAIKDH DFIPSNSILS NALSWGVKIL HIDDIRYYIE 190 200 210 220 230 QKKKELYLLK KSSTSVRDGG KRVGSGAQKT RTGRLKKPFV KVEDMSQSPA VHLM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel growth- and cell cycle-regulated protein, ASK, activates human Cdc7-related kinase and is essential for G1/S transition in mammalian cells." Kumagai H., Sato N., Yamada M., Mahony D., Seghezzi W., Lees E., Arai K., Masai H. Mol. Cell. Biol. 19:5083-5095(1999) [PubMed: 10373557] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, INTERACTION WITH CDC7, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION.
[2]	"Mammalian Cdc7-Dbf4 protein kinase complex is essential for initiation of DNA replication." Jiang W., McDonald D., Hope T.J., Hunter T. EMBO J. 18:5703-5713(1999) [PubMed: 10523313] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH CDC7, INDUCTION.
[3]	"Use of a semi-automated yeast two-hybrid system to identify proteins that interact with the human Cdc7 protein." Hollingsworth R. Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Testis.
[5]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed: 12690205] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	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].
[8]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain and Testis.
[9]	"Functional interaction between tumor suppressor menin and activator of S-phase kinase." Schnepp R.W., Hou Z., Wang H., Petersen C., Silva A., Masai H., Hua X. Cancer Res. 64:6791-6796(2004) [PubMed: 15374998] [Abstract] Cited for: INTERACTION WITH MEN1.
[10]	"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: 17062569] [Abstract] Cited for: FUNCTION, INTERACTION WITH CDC7.
[11]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-381; THR-535 AND SER-539, MASS SPECTROMETRY.
[12]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-359 AND SER-381, MASS SPECTROMETRY.
[13]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-354 AND SER-359, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB028069 mRNA. Translation: BAA78326.1. AB028070 mRNA. Translation: BAA78327.1. AF160249 mRNA. Translation: AAD41911.1. AF160876 mRNA. Translation: AAD45357.1. AK292569 mRNA. Translation: BAF85258.1. AC003083 Genomic DNA. Translation: AAS07442.1. AC005164 Genomic DNA. Translation: AAS07418.1. CH236949 Genomic DNA. Translation: EAL24170.1. CH471091 Genomic DNA. Translation: EAW76930.1. BC036045 mRNA. Translation: AAH36045.1. BC047693 mRNA. Translation: AAH47693.1.
IPI	IPI00170805. IPI00744939.
PIR	T02633.
RefSeq	NP_006707.1.
UniGene	Hs.485380
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UBU7. 1 interaction.
PTM databases
PhosphoSite	Q9UBU7.
Proteomic databases
PRIDE	Q9UBU7.
Genome annotation databases
Ensembl	ENSG00000006634. Homo sapiens. [Contig view]
GeneID	10926.
KEGG	hsa:10926.
Organism-specific databases
GeneCards	GC07P087343.
H-InvDB	HIX0006820.
HGNC	HGNC:17364. DBF4.
MIM	604281. gene.
PharmGKB	PA142672016.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q9UBU7.
HOVERGEN	Q9UBU7.
OMA	Q9UBU7. SEEKSEF.
Enzyme and pathway databases
Reactome	REACT_152. Cell Cycle, Mitotic. REACT_1538. Cell Cycle Checkpoints. REACT_383. DNA Replication.
Gene expression databases
ArrayExpress	Q9UBU7.
Bgee	Q9UBU7.
CleanEx	HS_DBF4.
GermOnline	ENSG00000006634. Homo sapiens.
Family and domain databases
InterPro	IPR001357. BRCT. IPR006572. Znf_DBF. [Graphical view]
Pfam	PF07535. zf-DBF. 1 hit. [Graphical view]
SMART	SM00292. BRCT. 1 hit. SM00586. ZnF_DBF. 1 hit. [Graphical view]
PROSITE	PS50172. BRCT. False negative. PS51265. ZF_DBF4. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	41507.
SOURCE	Search...

Entry information

Entry name

DBF4A_HUMAN

Accession

Primary (citable) accession number: Q9UBU7
Secondary accession number(s): A4D1D8 , A8K954, O75226, Q75MS6, Q75N01, Q9Y2M6

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 2, 2006
Last sequence update:	May 1, 2000
Last modified:	June 16, 2009
This is version 64 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)