Reviewed, UniProtKB/Swiss-Prot O00311 (CDC7_HUMAN)

Names and origin

Protein names

Recommended name:
    Cell division cycle 7-related protein kinase
      Short name=CDC7-related kinase
      Short name=HsCdc7
      Short name=huCdc7
    EC=2.7.11.1

Gene names

Name:	CDC7
Synonyms:	CDC7L1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	574 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Seems to phosphorylate critical substrates that regulate the G1/S phase transition and/or DNA replication. Can phosphorylates MCM2 and MCM3. Ref.8
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium.
Subunit structure	Forms a complex with either DBF4/DBF4A or DBF4B, leading to the activation of the kinase activity.
Subcellular location	Nucleus.
Sequence similarities	Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CDC7 subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Cell cycle Cell division
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	DNA replication Inferred from Experiment. Source: Reactome G1/S transition of mitotic cell cycle Ref.3 Traceable author statement. Source: ProtInc cell division Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of cell proliferation Inferred from mutant phenotype. Source: HGNC protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro regulation of S phase Inferred from mutant phenotype. Source: HGNC
Cellular component	cytoplasm Ref.1 Inferred from direct assay. Source: HGNC nucleoplasm Inferred from Experiment. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDK4	P11802	1	EBI-374980,EBI-295644
CDKN1A	P38936	1	EBI-374980,EBI-375077
CDKN2A	P42771	1	EBI-374980,EBI-375053
MCM10	Q7L590	1	EBI-374980,EBI-374912
MCM3	P25205	1	EBI-374980,EBI-355153
ORC5L	O43913	1	EBI-374980,EBI-374928
ORC6L	Q9Y5N6	1	EBI-374980,EBI-374840

Alternative products

This entry describes 1 isoform produced by alternative splicing. [Select]

Note: A number of isoforms may be produced.

Isoform 1 (identifier: O00311-1)

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.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 574	574	Cell division cycle 7-related protein kinase		PRO_0000085763
Regions
	Domain	58 – 574	517	Protein kinase
	Nucleotide binding	64 – 72	9	ATP By similarity
Sites
	Active site	177	1	Proton acceptor By similarity
	Binding site	90	1	ATP By similarity
Amino acid modifications
	Modified residue	16	1	Phosphoserine Ref.11
	Modified residue	27	1	Phosphoserine Ref.11
Natural variations
	Natural variant	23	1	Q → P: dbSNP rs13447459. Ref.4		VAR_019255
	Natural variant	99	1	I → V: dbSNP rs13447492. Ref.4		VAR_019256
	Natural variant	112	1	G → W: dbSNP rs13447493. Ref.4		VAR_019257
	Natural variant	162	1	F → L: dbSNP rs13447503. Ref.4 Ref.12		VAR_019258
	Natural variant	208	1	I → M Ref.12		VAR_040403
	Natural variant	209	1	E → D Ref.12		VAR_040404
	Natural variant	441	1	K → R: dbSNP rs13447539. Ref.4 Ref.12		VAR_019259
	Natural variant	472	1	T → I Ref.12		VAR_040405
	Natural variant	498	1	S → A Ref.12		VAR_040406
Experimental info
	Sequence conflict	89	1	L → V in AAB97512. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: 90D549BEE20AE583	FASTA	574	63,888
	10 20 30 40 50 60 MEASLGIQMD EPMAFSPQRD RFQAEGSLKK NEQNFKLAGV KKDIEKLYEA VPQLSNVFKI 70 80 90 100 110 120 EDKIGEGTFS SVYLATAQLQ VGPEEKIALK HLIPTSHPIR IAAELQCLTV AGGQDNVMGV 130 140 150 160 170 180 KYCFRKNDHV VIAMPYLEHE SFLDILNSLS FQEVREYMLN LFKALKRIHQ FGIVHRDVKP 190 200 210 220 230 240 SNFLYNRRLK KYALVDFGLA QGTHDTKIEL LKFVQSEAQQ ERCSQNKSHI ITGNKIPLSG 250 260 270 280 290 300 PVPKELDQQS TTKASVKRPY TNAQIQIKQG KDGKEGSVGL SVQRSVFGER NFNIHSSISH 310 320 330 340 350 360 ESPAVKLMKQ SKTVDVLSRK LATKKKAIST KVMNSAVMRK TASSCPASLT CDCYATDKVC 370 380 390 400 410 420 SICLSRRQQV APRAGTPGFR APEVLTKCPN QTTAIDMWSA GVIFLSLLSG RYPFYKASDD 430 440 450 460 470 480 LTALAQIMTI RGSRETIQAA KTFGKSILCS KEVPAQDLRK LCERLRGMDS STPKLTSDIQ 490 500 510 520 530 540 GHASHQPAIS EKTDHKASCL VQTPPGQYSG NSFKKGDSNS CEHCFDEYNT NLEGWNEVPD 550 560 570 EAYDLLDKLL DLNPASRITA EEALLHPFFK DMSL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human and Xenopus cDNAs encoding budding yeast Cdc7-related kinases: in vitro phosphorylation of MCM subunits by a putative human homologue of Cdc7." Sato N., Arai K., Masai H. EMBO J. 16:4340-4351(1997) [PubMed: 9250678] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver and Testis.
[2]	"A human homolog of the yeast CDC7 gene is overexpressed in some tumors and transformed cell lines." Hess G.F., Drong R.F., Weiland K.L., Slightom J.L., Sclafani R.A., Hollingsworth R.E. Gene 211:133-140(1998) [PubMed: 9573348] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Identification and characterization of a human protein kinase related to budding yeast Cdc7p." Jiang W., Hunter T. Proc. Natl. Acad. Sci. U.S.A. 94:14320-14325(1997) [PubMed: 9405610] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION.
[4]	NIEHS SNPs program Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS PRO-23; VAL-99; TRP-112; LEU-162 AND ARG-441.
[5]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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].
[7]	"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: INTERACTION WITH DBF4.
[8]	"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: 12065429] [Abstract] Cited for: FUNCTION, INTERACTION WITH DBF4B.
[9]	"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: 15668232] [Abstract] Cited for: INTERACTION WITH DBF4B.
[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: INTERACTION WITH DBF4 AND DBF4B.
[11]	"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-16 AND SER-27, MASS SPECTROMETRY.
[12]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-162; MET-208; ASP-209; ARG-441; ILE-472 AND ALA-498.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB003698 mRNA. Translation: BAA19962.1. AF015592 mRNA. Translation: AAC52080.1. AF005209 mRNA. Translation: AAB97512.1. AY585721 Genomic DNA. Translation: AAS79323.1. AL355871 Genomic DNA. Translation: CAI14446.1. BC110526 mRNA. Translation: AAI10527.1. BC110527 mRNA. Translation: AAI10528.1. BC111044 mRNA. Translation: AAI11045.1.
IPI	IPI00448121.
RefSeq	NP_001127891.1. NP_001127892.1. NP_003494.1.
UniGene	Hs.533573
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	O00311. 7 interactions.
PTM databases
PhosphoSite	O00311.
Proteomic databases
PRIDE	O00311.
Genome annotation databases
Ensembl	ENSG00000097046. Homo sapiens. [Contig view]
GeneID	8317.
KEGG	hsa:8317.
UCSC	uc001doe.1. human.
Organism-specific databases
GeneCards	GC01P091678.
H-InvDB	HIX0028491.
HGNC	HGNC:1745. CDC7.
HPA	CAB002669.
MIM	603311. gene.
PharmGKB	PA134879457.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O00311.
HOVERGEN	O00311.
OMA	O00311. ICLSRRQ.
Enzyme and pathway databases
BRENDA	2.7.11.1. 247.
Reactome	REACT_152. Cell Cycle, Mitotic. REACT_1538. Cell Cycle Checkpoints. REACT_383. DNA Replication.
Gene expression databases
ArrayExpress	O00311.
Bgee	O00311.
CleanEx	HS_CDC7.
GermOnline	ENSG00000097046. Homo sapiens.
Family and domain databases
InterPro	IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
ProDom	PD000001. Prot_kinase. 3 hits. [Graphical view] [Entries sharing at least one domain]
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	31147.
SOURCE	Search...

Entry information

Entry name

CDC7_HUMAN

Accession

Primary (citable) accession number: O00311
Secondary accession number(s): O00558, Q5T5U5

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 11, 2001
Last sequence update:	July 1, 1997
Last modified:	July 7, 2009
This is version 91 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)