Reviewed, UniProtKB/Swiss-Prot P06493 (CDC2_HUMAN)

Names and origin

Protein names

Recommended name:
    Cell division control protein 2 homolog
    EC=2.7.11.22
    EC=2.7.11.23
Alternative name(s):
    p34 protein kinase
    Cyclin-dependent kinase 1
      Short name=CDK1

Gene names

Name:

CDC2

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

General annotation (Comments)

Function	Plays a key role in the control of the eukaryotic cell cycle. It is required in higher cells for entry into S-phase and mitosis. p34 is a component of the kinase complex that phosphorylates the repetitive C-terminus of RNA polymerase II.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate.
Enzyme regulation	Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-161 activates it.
Subunit structure	Forms a stable but non-covalent complex with a regulatory subunit and with a cyclin. Interacts with DLGAP5. Isoform 2 is unable to complex with cyclin B1 and also fails to bind to the CDK inhibitor p21. Interacts with catalytically active CCNB1 and RALBP1 during mitosis to form an endocytotic complex during interphase. Ref.8 Ref.9
Subcellular location	Nucleus By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Cell cycle Cell division Mitosis
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process Inferred from Experiment. Source: Reactome anti-apoptosis Inferred from direct assay. Source: UniProtKB cell division Inferred from electronic annotation. Source: UniProtKB-KW mitosis Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of ubiquitin-protein ligase activity during mitotic cell cycle Inferred from Experiment. Source: Reactome protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro
Cellular component	cytosol Inferred from Experiment. Source: Reactome midbody Inferred from direct assay. Source: UniProtKB nucleoplasm Inferred from Experiment. Source: Reactome spindle microtubule Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW RNA polymerase subunit kinase activity Inferred from electronic annotation. Source: EC cyclin-dependent protein kinase activity Inferred from direct assay. Source: UniProtKB protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AURKB	Q96GD4	1	EBI-444308,EBI-624291
BIRC5	O15392	1	EBI-444308,EBI-518823
Birc6	O88738	1	EBI-444308,EBI-912068	From a different organism.
CCNB1	P14635	1	EBI-444308,EBI-495332
CDC25C	P30307	1	EBI-444308,EBI-974439
FOXO1	Q12778	4	EBI-444308,EBI-1108782
HMGA1	P17096-1	1	EBI-444308,EBI-746854
INCENP	Q9NQS7	1	EBI-444308,EBI-307907
LATS1	O95835	1	EBI-444308,EBI-444209
MYT1	Q01538	1	EBI-444308,EBI-515143
NDE1	Q9NXR1	1	EBI-444308,EBI-941227
NDEL1	Q9GZM8	1	EBI-444308,EBI-928842
PPP1CA	P62136	1	EBI-444308,EBI-357253
PPP1CC	P36873-1	1	EBI-444308,EBI-356289

Alternative products

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

Isoform 1 (identifier: P06493-1)

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: P06493-2)

Also known as: CDC2deltaT;

The sequence of this isoform differs from the canonical sequence as follows:
     107-163: Missing.

Note: Found in breast cancer tissues.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 297

297

Cell division control protein 2 homolog

PRO_0000085724

Regions

Domain

4 – 287

284

Protein kinase

Nucleotide binding

10 – 18

9

ATP By similarity

Sites

Active site

128

1

Proton acceptor By similarity

Binding site

33

1

ATP By similarity

Amino acid modifications

Modified residue

5

1

Phosphothreonine Ref.19

Modified residue

14

1

Phosphothreonine Ref.19 Ref.10 Ref.15 Ref.17 Ref.20

Modified residue

15

1

Phosphotyrosine Ref.19 Ref.10 Ref.15 Ref.17 Ref.20 Ref.11 Ref.12 Ref.14

Modified residue

19

1

Phosphotyrosine Ref.19 Ref.17 Ref.12 Ref.14

Modified residue

39

1

Phosphoserine Ref.19

Modified residue

77

1

Phosphotyrosine Ref.19

Modified residue

160

1

Phosphotyrosine Ref.18

Modified residue

161

1

Phosphothreonine Ref.19 Ref.18 Ref.13 Ref.16

Modified residue

222

1

Phosphothreonine Ref.19

Natural variations

Alternative sequence

107 – 163

57

Missing in isoform 2.

VSP_021375

Secondary structure

1

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297

Helix Strand Turn

Details...

Beta strand

4 – 12

9

Beta strand

14 – 23

10

Turn

24 – 26

3

Beta strand

29 – 36

8

Beta strand

39 – 42

4

Helix

46 – 57

12

Beta strand

66 – 71

6

Beta strand

73 – 81

9

Beta strand

84 – 86

3

Helix

87 – 93

7

Beta strand

94 – 96

3

Helix

102 – 121

20

Beta strand

133 – 136

4

Beta strand

142 – 144

3

Helix

167 – 169

3

Helix

172 – 176

5

Helix

184 – 199

16

Helix

209 – 220

12

Turn

225 – 227

3

Beta strand

234 – 236

3

Helix

249 – 252

4

Turn

253 – 255

3

Helix

258 – 267

10

Turn

272 – 274

3

Helix

278 – 283

6

Helix

285 – 287

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 1, 1988. Version 1. Checksum: 942D79448EFE490A	FASTA	297	34,095
	10 20 30 40 50 60 MEDYTKIEKI GEGTYGVVYK GRHKTTGQVV AMKKIRLESE EEGVPSTAIR EISLLKELRH 70 80 90 100 110 120 PNIVSLQDVL MQDSRLYLIF EFLSMDLKKY LDSIPPGQYM DSSLVKSYLY QILQGIVFCH 130 140 150 160 170 180 SRRVLHRDLK PQNLLIDDKG TIKLADFGLA RAFGIPIRVY THEVVTLWYR SPEVLLGSAR 190 200 210 220 230 240 YSTPVDIWSI GTIFAELATK KPLFHGDSEI DQLFRIFRAL GTPNNEVWPE VESLQDYKNT 250 260 270 280 290 FPKWKPGSLA SHVKNLDENG LDLLSKMLIY DPAKRISGKM ALNHPYFNDL DNQIKKM
	Isoform 2 (CDC2deltaT). Checksum: 50FC3D192024E38C	FASTA	240	27,503
	10 20 30 40 50 60 MEDYTKIEKI GEGTYGVVYK GRHKTTGQVV AMKKIRLESE EEGVPSTAIR EISLLKELRH 70 80 90 100 110 120 PNIVSLQDVL MQDSRLYLIF EFLSMDLKKY LDSIPPGQYM DSSLVKVVTL WYRSPEVLLG 130 140 150 160 170 180 SARYSTPVDI WSIGTIFAEL ATKKPLFHGD SEIDQLFRIF RALGTPNNEV WPEVESLQDY 190 200 210 220 230 240 KNTFPKWKPG SLASHVKNLD ENGLDLLSKM LIYDPAKRIS GKMALNHPYF NDLDNQIKKM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complementation used to clone a human homologue of the fission yeast cell cycle control gene cdc2." Lee M.G., Nurse P. Nature 327:31-35(1987) [PubMed: 3553962] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"T-loop deletion of CDC2 from breast cancer tissues eliminates binding to cyclin B1 and cyclin-dependent kinase inhibitor p21." Ohta T., Okamoto K., Isohashi F., Shibata K., Fukuda M., Yamaguchi S., Xiong Y. Cancer Res. 58:1095-1098(1998) [PubMed: 9515786] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Mammary cancer.
[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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	NIEHS SNPs program Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [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] (ISOFORM 1). Tissue: Skin.
[7]	"Activation of cdc2 protein kinase during mitosis in human cells: cell cycle-dependent phosphorylation and subunit rearrangement." Draetta G., Beach D. Cell 54:17-26(1988) [PubMed: 3289755] [Abstract] Cited for: PHOSPHORYLATION, ASSOCIATION WITH P13.
[8]	"RLIP, an effector of the Ral GTPases, is a platform for Cdk1 to phosphorylate epsin during the switch off of endocytosis in mitosis." Rosse C., L'Hoste S., Offner N., Picard A., Camonis J. J. Biol. Chem. 278:30597-30604(2003) [PubMed: 12775724] [Abstract] Cited for: INTERACTION WITH RALBP1.
[9]	"Fbx7 functions in the SCF complex regulating Cdk1-cyclin B-phosphorylated hepatoma up-regulated protein (HURP) proteolysis by a proline-rich region." Hsu J.-M., Lee Y.-C.G., Yu C.-T.R., Huang C.-Y.F. J. Biol. Chem. 279:32592-32602(2004) [PubMed: 15145941] [Abstract] Cited for: INTERACTION WITH DLGAP5.
[10]	"Global phosphoproteome of HT-29 human colon adenocarcinoma cells." Kim J.-E., Tannenbaum S.R., White F.M. J. Proteome Res. 4:1339-1346(2005) [PubMed: 16083285] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-14 AND TYR-15, MASS SPECTROMETRY.
[11]	"Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules." Zhang Y., Wolf-Yadlin A., Ross P.L., Pappin D.J., Rush J., Lauffenburger D.A., White F.M. Mol. Cell. Proteomics 4:1240-1250(2005) [PubMed: 15951569] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-15, MASS SPECTROMETRY. Tissue: Epithelium.
[12]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-15 AND TYR-19, MASS SPECTROMETRY.
[13]	"Phosphoproteome analysis of the human mitotic spindle." Nousiainen M., Sillje H.H.W., Sauer G., Nigg E.A., Koerner R. Proc. Natl. Acad. Sci. U.S.A. 103:5391-5396(2006) [PubMed: 16565220] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-161, MASS SPECTROMETRY. Tissue: Epithelium.
[14]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-15 AND TYR-19, MASS SPECTROMETRY.
[15]	"Toward a global characterization of the phosphoproteome in prostate cancer cells: identification of phosphoproteins in the LNCaP cell line." Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S. Electrophoresis 28:2027-2034(2007) [PubMed: 17487921] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-14 AND TYR-15, MASS SPECTROMETRY.
[16]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-161, MASS SPECTROMETRY. Tissue: Epithelium.
[17]	"Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry." Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., Keri G., Wehland J., Daub H. Mol. Cell. Proteomics 6:537-547(2007) [PubMed: 17192257] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-14; TYR-15 AND TYR-19, MASS SPECTROMETRY.
[18]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-160 AND THR-161, MASS SPECTROMETRY.
[19]	"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 THR-5; THR-14; TYR-15; TYR-19; SER-39; TYR-77; THR-161 AND THR-222, MASS SPECTROMETRY.
[20]	"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 THR-14 AND TYR-15, MASS SPECTROMETRY.
[21]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

X05360 mRNA. Translation: CAA28963.1.
Y00272 mRNA. Translation: CAA68376.1.
D88357 mRNA. Translation: BAA26001.1.
AK291939 mRNA. Translation: BAF84628.1.
BT007004 mRNA. Translation: AAP35650.1.
AF512554 Genomic DNA. Translation: AAM34793.1.
BC014563 mRNA. Translation: AAH14563.1.

IPI

IPI00026689.
IPI00073536.

PIR

A29539.

RefSeq

NP_001777.1.
NP_203698.1.

UniGene

Hs.334562

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LC9	model	-	A	1-297	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:35N.

IntAct

P06493. 29 interactions.

PTM databases

PhosphoSite

P06493.

2-D gel databases

SWISS-2DPAGE

P06493.

Proteomic databases

PRIDE

P06493.

Genome annotation databases

Ensembl

ENSG00000170312. Homo sapiens. [Contig view]

GeneID

983.

UCSC

uc001jld.1. human.
uc001jlg.1. human.

Organism-specific databases

GeneCards

GC10P062208.

H-InvDB

HIX0008851.

HGNC

HGNC:1722. CDC2.

HPA

CAB003799.
HPA003387.

MIM

116940. gene.

PharmGKB

PA99.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P06493.

Enzyme and pathway databases

BRENDA

2.7.11.22. 247.
2.7.11.23. 247.

Pathway_Interaction_DB

foxm1pathway. FOXM1 transcription factor network.
retinoic_acid_pathway. Retinoic acid receptors-mediated signaling.

Reactome

REACT_152. Cell Cycle, Mitotic.
REACT_1538. Cell Cycle Checkpoints.
REACT_6850. Cdc20:Phospho-APC/C mediated degradation of Cyclin A.

Gene expression databases

ArrayExpress

P06493.

Bgee

P06493.

CleanEx

HS_CDC2.

GermOnline

ENSG00000170312. 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.
IPR002290. Ser_thr_pkinase.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

ProDom

PD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

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

BindingDB

P06493.

NextBio

4122.

SOURCE

Search...

Entry information

Entry name

CDC2_HUMAN

Accession

Primary (citable) accession number: P06493
Secondary accession number(s): A8K7C4, O60764

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1988
Last sequence update:	January 1, 1988
Last modified:	July 7, 2009
This is version 134 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)