O00311 (CDC7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [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	574 AA.
Sequence status	Complete.
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.9
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	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA replication Traceable author statement. Source: Reactome G1/S transition of mitotic cell cycle Traceable author statement. Source: Reactome M/G1 transition of mitotic cell cycle Traceable author statement. Source: Reactome cell cycle checkpoint Traceable author statement. Source: Reactome cell division Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of cell proliferation Inferred from mutant phenotype PubMed 17102137. Source: HGNC regulation of S phase Inferred from mutant phenotype PubMed 17102137. Source: HGNC
Cellular_component	cytoplasm Inferred from direct assay Ref.1. Source: HGNC nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW kinase activity Inferred from direct assay Ref.1. Source: HGNC metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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

27

1

Phosphoserine Ref.12

Natural variations

Natural variant

23

1

Q → P. Ref.4
Corresponds to variant rs13447459 [ dbSNP | Ensembl ].

VAR_019255

Natural variant

99

1

I → V. Ref.4
Corresponds to variant rs13447492 [ dbSNP | Ensembl ].

VAR_019256

Natural variant

112

1

G → W. Ref.4
Corresponds to variant rs13447493 [ dbSNP | Ensembl ].

VAR_019257

Natural variant

162

1

F → L. Ref.4 Ref.13
Corresponds to variant rs13447503 [ dbSNP | Ensembl ].

VAR_019258

Natural variant

208

1

I → M. Ref.13
Corresponds to variant rs34979509 [ dbSNP | Ensembl ].

VAR_040403

Natural variant

209

1

E → D. Ref.13
Corresponds to variant rs56327502 [ dbSNP | Ensembl ].

VAR_040404

Natural variant

441

1

K → R. Ref.4 Ref.13
Corresponds to variant rs13447539 [ dbSNP | Ensembl ].

VAR_019259

Natural variant

472

1

T → I. Ref.13
Corresponds to variant rs56381770 [ dbSNP | Ensembl ].

VAR_040405

Natural variant

498

1

S → A. Ref.13
Corresponds to variant rs35055915 [ dbSNP | Ensembl ].

VAR_040406

Experimental info

Sequence conflict

89

1

L → V in AAB97512. Ref.3

Secondary structure

1

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574

Helix Strand Turn

Details...

Helix

42 – 50

9

Helix

52 – 56

5

Beta strand

59 – 66

8

Beta strand

68 – 79

12

Beta strand

84 – 92

9

Helix

98 – 110

13

Beta strand

121 – 126

6

Beta strand

129 – 135

7

Helix

142 – 146

5

Helix

151 – 170

20

Helix

180 – 182

3

Beta strand

183 – 186

4

Turn

187 – 190

4

Beta strand

191 – 194

4

Helix

209 – 213

5

Turn

217 – 219

3

Helix

377 – 379

3

Helix

382 – 385

4

Helix

394 – 409

16

Beta strand

412 – 415

4

Helix

420 – 431

12

Helix

433 – 442

10

Beta strand

445 – 451

7

Helix

458 – 465

8

Helix

540 – 549

10

Turn

554 – 556

3

Helix

560 – 564

5

Helix

567 – 569

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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	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].
[7]	"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].
[8]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DBF4.
[9]	"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: FUNCTION, INTERACTION WITH DBF4B.
[10]	"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: INTERACTION WITH DBF4B.
[11]	"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: INTERACTION WITH DBF4 AND DBF4B.
[12]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, MASS SPECTROMETRY.
[13]	"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] [Europe PMC] [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

EMBL
GenBank
DDBJ

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.
CH471097 Genomic DNA. Translation: EAW73114.1.
CH471097 Genomic DNA. Translation: EAW73115.1.
BC110526 mRNA. Translation: AAI10527.1.
BC110527 mRNA. Translation: AAI10528.1.
BC111044 mRNA. Translation: AAI11045.1.

IPI

IPI00448121.

RefSeq

NP_001127891.1. NM_001134419.1.
NP_001127892.1. NM_001134420.1.
NP_003494.1. NM_003503.3.

UniGene

Hs.533573.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4F99	X-ray	2.33	A	37-574	[»]
4F9A	X-ray	2.17	A/C	37-574	[»]
4F9B	X-ray	2.50	A/C	37-574	[»]
4F9C	X-ray	2.08	A	37-574	[»]

ProteinModelPortal

O00311.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31728N.

IntAct

O00311. 12 interactions.

MINT

MINT-1201209.

STRING

9606.ENSP00000234626.

PTM databases

PhosphoSite

O00311.

Proteomic databases

PaxDb

O00311.

PRIDE

O00311.

Protocols and materials databases

DNASU

8317.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000234626; ENSP00000234626; ENSG00000097046.
ENST00000428239; ENSP00000393139; ENSG00000097046.

GeneID

8317.

KEGG

hsa:8317.

UCSC

uc001doe.3. human.

Organism-specific databases

CTD

8317.

GeneCards

GC01P091966.

HGNC

HGNC:1745. CDC7.

HPA

CAB002669.

MIM

603311. gene.

neXtProt

NX_O00311.

PharmGKB

PA26272.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG250270.

HOGENOM

HOG000193450.

HOVERGEN

HBG003991.

InParanoid

O00311.

KO

K02214.

OMA

STKVMNS.

OrthoDB

EOG4W6NW3.

PhylomeDB

O00311.

Enzyme and pathway databases

BRENDA

2.7.11.1. 2681.

Reactome

REACT_115566. Cell Cycle.
REACT_21300. Mitotic M-M/G1 phases.
REACT_383. DNA Replication.

Gene expression databases

ArrayExpress

O00311.

Bgee

O00311.

CleanEx

HS_CDC7.

Genevestigator

O00311.

GermOnline

ENSG00000097046. Homo sapiens.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Pfam

PF00069. Pkinase. 2 hits.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

O00311.

ChEMBL

CHEMBL5443.

GenomeRNAi

8317.

NextBio

31147.

SOURCE

Search...

Entry information

Entry name

CDC7_HUMAN

Accession

Primary (citable) accession number: O00311
Secondary accession number(s): D3DT31, O00558, Q5T5U5

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 11, 2001
Last sequence update:	July 1, 1997
Last modified:	May 1, 2013
This is version 132 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.