P20248 (CCNA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cyclin-A2
Short name=Cyclin-A

Gene names

Name:	CCNA2
Synonyms:	CCN1, CCNA

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	432 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Essential for the control of the cell cycle at the G1/S (start) and the G2/M (mitosis) transitions.
Subunit structure	Interacts with the CDK1 and CDK2 protein kinases to form a serine/threonine kinase holoenzyme complex. The cyclin subunit imparts substrate specificity to the complex. When associated with CDK2 (but not with CDK1), interacts with SCAPER. Ref.9
Subcellular location	Nucleus. Cytoplasm. Note: Cytoplasmic when associated with SCAPER. Ref.9
Developmental stage	Accumulates steadily during G2 and is abruptly destroyed at mitosis.
Post-translational modification	Polyubiquitinated via 'Lys-11'-linked ubiquitin by the anaphase-promoting complex (APC/C), leading to its degradation by the proteasome. Deubiquitinated and stabilized by USP37 enables entry into S phase By similarity.
Sequence similarities	Belongs to the cyclin family. Cyclin AB subfamily.

Ontologies

Keywords
Biological process	Cell cycle Cell division Mitosis
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Molecular function	Cyclin
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	Ras protein signal transduction Inferred from expression pattern. Source: BHF-UCL cell division Inferred from electronic annotation. Source: UniProtKB-KW mitosis Inferred from electronic annotation. Source: UniProtKB-KW mitotic cell cycle G2/M transition DNA damage checkpoint Traceable author statement. Source: ProtInc regulation of cyclin-dependent protein kinase activity Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleoplasm Traceable author statement. Source: Reactome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDK2	P24941	16	EBI-457097,EBI-375096
CDKN1A	P38936	2	EBI-457097,EBI-375077
CDKN1B	P46527	12	EBI-457097,EBI-519280

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 432

432

Cyclin-A2

PRO_0000080338

Amino acid modifications

Modified residue

5

1

Phosphoserine Ref.10

Modified residue

55

1

Phosphoserine Ref.10

Natural variations

Natural variant

163

1

I → V. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.7 Ref.8
Corresponds to variant rs769242 [ dbSNP | Ensembl ].

VAR_018819

Experimental info

Sequence conflict

156

1

H → R in CAG28620. Ref.3

Secondary structure

1

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432

Helix Strand Turn

Details...

Helix

176 – 178

3

Helix

179 – 193

15

Turn

197 – 202

6

Helix

208 – 225

18

Helix

229 – 242

14

Helix

250 – 252

3

Helix

253 – 268

16

Beta strand

269 – 271

3

Helix

275 – 280

6

Turn

281 – 284

4

Helix

288 – 302

15

Helix

311 – 319

9

Helix

327 – 340

14

Helix

344 – 347

4

Helix

352 – 368

17

Helix

374 – 380

7

Helix

384 – 399

16

Helix

401 – 403

3

Helix

408 – 412

5

Helix

416 – 418

3

Helix

421 – 423

3

Sequences

	Sequence		Length	Mass (Da)
	P20248 [UniParc]. Last modified November 2, 2010. Version 2. Checksum: 97763A2897DD35F4	FASTA	432	48,551
	10 20 30 40 50 60 MLGNSAPGPA TREAGSALLA LQQTALQEDQ ENINPEKAAP VQQPRTRAAL AVLKSGNPRG 70 80 90 100 110 120 LAQQQRPKTR RVAPLKDLPV NDEHVTVPPW KANSKQPAFT IHVDEAEKEA QKKPAESQKI 130 140 150 160 170 180 EREDALAFNS AISLPGPRKP LVPLDYPMDG SFESPHTMDM SIILEDEKPV SVNEVPDYHE 190 200 210 220 230 240 DIHTYLREME VKCKPKVGYM KKQPDITNSM RAILVDWLVE VGEEYKLQNE TLHLAVNYID 250 260 270 280 290 300 RFLSSMSVLR GKLQLVGTAA MLLASKFEEI YPPEVAEFVY ITDDTYTKKQ VLRMEHLVLK 310 320 330 340 350 360 VLTFDLAAPT VNQFLTQYFL HQQPANCKVE SLAMFLGELS LIDADPYLKY LPSVIAGAAF 370 380 390 400 410 420 HLALYTVTGQ SWPESLIRKT GYTLESLKPC LMDLHQTYLK APQHAQQSIR EKYKNSKYHG 430 VSLLNPPETL NL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Hepatitis B virus integration in a cyclin A gene in a hepatocellular carcinoma." Wang J., Chenivesse X., Henglein B., Brechot C. Nature 343:555-557(1990) [PubMed: 1967822] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-163.
[2]	"Structure and cell cycle-regulated transcription of the human cyclin A gene." Henglein B., Chenivesse X., Wang D., Eick D., Brechot C. Proc. Natl. Acad. Sci. U.S.A. 91:5490-5494(1994) [PubMed: 8202514] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT VAL-163.
[3]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-163.
[4]	NIEHS SNPs program Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT VAL-163.
[5]	"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], VARIANT VAL-163.
[6]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [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], VARIANT VAL-163.
[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], VARIANT VAL-163. Tissue: Brain.
[9]	"SCAPER, a novel cyclin A-interacting protein that regulates cell cycle progression." Tsang W.Y., Wang L., Chen Z., Sanchez I., Dynlacht B.D. J. Cell Biol. 178:621-633(2007) [PubMed: 17698606] [Abstract] Cited for: INTERACTION WITH SCAPER, SUBCELLULAR LOCATION.
[10]	"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: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-5 AND SER-55, MASS SPECTROMETRY.
[11]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]	"Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and promote S phase entry." Huang X., Summers M.K., Pham V., Lill J.R., Liu J., Lee G., Kirkpatrick D.S., Jackson P.K., Fang G., Dixit V.M. Mol. Cell 42:511-523(2011) [PubMed: 21596315] [Abstract] Cited for: UBIQUITINATION, DEUBIQUITINATION BY USP37.
[13]	"Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex." Jeffrey P.D., Russo A.A., Polyak K., Gibbs E., Hurwitz J., Massague J., Pavletich N.P. Nature 376:313-320(1995) [PubMed: 7630397] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 173-432 COMPLEXED WITH CDK2.
[14]	"Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex." Russo A.A., Jeffrey P.D., Patten A.K., Massague J., Pavletich N.P. Nature 382:325-331(1996) [PubMed: 8684460] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 173-432 IN CDK2/KIP1 COMPLEX.
[15]	"Structural basis of cyclin-dependent kinase activation by phosphorylation." Russo A.A., Jeffrey P.D., Pavletich N.P. Nat. Struct. Biol. 3:696-700(1996) [PubMed: 8756328] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 173-432 COMPLEXED WITH CDK2.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X51688 mRNA. Translation: CAA35986.1.
X68303 Genomic DNA. Translation: CAA48375.1.
CR407692 mRNA. Translation: CAG28620.1.
AF518006 Genomic DNA. Translation: AAM54042.1.
AK291931 mRNA. Translation: BAF84620.1.
AC079341 Genomic DNA. Translation: AAY40969.1.
CH471056 Genomic DNA. Translation: EAX05246.1.
BC104783 mRNA. Translation: AAI04784.1.
BC104787 mRNA. Translation: AAI04788.1.

IPI

IPI00022865.

PIR

S08277.

RefSeq

NP_001228.1. NM_001237.3.

UniGene

Hs.58974.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1E9H	X-ray	2.50	B/D	175-432	[»]
1FIN	X-ray	2.30	B/D	173-432	[»]
1FVV	X-ray	2.80	B/D	173-432	[»]
1GY3	X-ray	2.70	B/D	175-432	[»]
1H1P	X-ray	2.10	B/D	175-432	[»]
1H1Q	X-ray	2.50	B/D	175-432	[»]
1H1R	X-ray	2.00	B/D	175-432	[»]
1H1S	X-ray	2.00	B/D	175-432	[»]
1H24	X-ray	2.50	B/D	174-432	[»]
1H25	X-ray	2.50	B/D	174-432	[»]
1H26	X-ray	2.24	B/D	174-432	[»]
1H27	X-ray	2.20	B/D	174-432	[»]
1H28	X-ray	2.80	B/D	174-432	[»]
1JST	X-ray	2.60	B/D	175-432	[»]
1JSU	X-ray	2.30	B	173-432	[»]
1OGU	X-ray	2.60	B/D	174-432	[»]
1OI9	X-ray	2.10	B/D	174-432	[»]
1OIU	X-ray	2.00	B/D	174-432	[»]
1OIY	X-ray	2.40	B/D	174-432	[»]
1OKV	X-ray	2.40	B/D	173-432	[»]
1OKW	X-ray	2.50	B/D	173-432	[»]
1OL1	X-ray	2.90	B/D	173-432	[»]
1OL2	X-ray	2.60	B/D	173-432	[»]
1P5E	X-ray	2.22	B/D	175-432	[»]
1PKD	X-ray	2.30	B/D	175-432	[»]
1QMZ	X-ray	2.20	B/D	174-432	[»]
1URC	X-ray	2.60	B/D	173-432	[»]
1VYW	X-ray	2.30	B/D	173-432	[»]
2BKZ	X-ray	2.60	B/D	173-432	[»]
2BPM	X-ray	2.40	B/D	174-432	[»]
2C4G	X-ray	2.70	B/D	173-432	[»]
2C5N	X-ray	2.10	B/D	174-432	[»]
2C5O	X-ray	2.10	B/D	173-432	[»]
2C5V	X-ray	2.90	B/D	174-432	[»]
2C5X	X-ray	2.90	B/D	174-432	[»]
2C6T	X-ray	2.61	B/D	175-432	[»]
2CCH	X-ray	1.70	B/D	173-432	[»]
2CCI	X-ray	2.70	B/D	175-432	[»]
2CJM	X-ray	2.30	B/D	175-432	[»]
2I40	X-ray	2.80	B/D	173-432	[»]
2IW6	X-ray	2.30	B/D	174-432	[»]
2IW8	X-ray	2.30	B/D	174-432	[»]
2IW9	X-ray	2.00	B/D	174-432	[»]
2UUE	X-ray	2.06	B/D	174-432	[»]
2UZB	X-ray	2.70	B/D	175-432	[»]
2UZD	X-ray	2.72	B/D	175-432	[»]
2UZE	X-ray	2.40	B/D	175-432	[»]
2UZL	X-ray	2.40	B/D	175-432	[»]
2V22	X-ray	2.60	B/D	174-432	[»]
2WEV	X-ray	2.30	B/D	173-432	[»]
2WFY	X-ray	2.53	B/D	173-432	[»]
2WHB	X-ray	2.90	B/D	173-432	[»]
2WIH	X-ray	2.50	B/D	173-432	[»]
2WIP	X-ray	2.80	B/D	173-432	[»]
2WMA	X-ray	2.80	B/D	174-432	[»]
2WMB	X-ray	2.60	B/D	174-432	[»]
2WPA	X-ray	2.51	B/D	173-432	[»]
2WXV	X-ray	2.60	B/D	173-432	[»]
2X1N	X-ray	2.75	B/D	172-432	[»]
3EID	X-ray	3.15	B/D	173-432	[»]
3EJ1	X-ray	3.22	B/D	173-432	[»]
3EOC	X-ray	3.20	B/D	173-432	[»]
3F5X	X-ray	2.40	B/D	177-432	[»]

ProteinModelPortal

P20248.

SMR

P20248. Positions 173-432.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-638N.

IntAct

P20248. 11 interactions.

MINT

MINT-141826.

STRING

P20248.

PTM databases

PhosphoSite

P20248.

Polymorphism databases

DMDM

311033358.

Proteomic databases

PRIDE

P20248.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000274026; ENSP00000274026; ENSG00000145386.

GeneID

890.

KEGG

hsa:890.

UCSC

uc003iec.2. human.

Organism-specific databases

CTD

890.

GeneCards

GC04M122737.

H-InvDB

HIX0200677.

HGNC

HGNC:1578. CCNA2.

HPA

CAB000114.
HPA020626.

MIM

123835. gene.

neXtProt

NX_P20248.

PharmGKB

PA94.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG16130.

GeneTree

ENSGT00560000076692.

HOGENOM

HBG750484.

HOVERGEN

HBG106244.

InParanoid

P20248.

OMA

PANCKVE.

OrthoDB

EOG41RPV4.

PhylomeDB

P20248.

Enzyme and pathway databases

Pathway_Interaction_DB

il2_stat5pathway. IL2 signaling events mediated by STAT5.
prlsignalingeventspathway. Signaling events mediated by PRL.

Reactome

REACT_152. Cell Cycle, Mitotic.
REACT_383. DNA Replication.
REACT_6850. Cdc20:Phospho-APC/C mediated degradation of Cyclin A.

Gene expression databases

ArrayExpress

P20248.

Bgee

P20248.

CleanEx

HS_CCNA2.

Genevestigator

P20248.

GermOnline

ENSG00000145386. Homo sapiens.

Family and domain databases

InterPro

IPR013763. Cyclin-like.
IPR014400. Cyclin_A/B/D/E.
IPR004367. Cyclin_C.
IPR006671. Cyclin_N.
[Graphical view]

Gene3D

G3DSA:1.10.472.10. Cyclin_related. 2 hits.

KO

K06627.

Pfam

PF02984. Cyclin_C. 1 hit.
PF00134. Cyclin_N. 1 hit.
[Graphical view]

PIRSF

PIRSF001771. Cyclin_A_B_D_E. 1 hit.

SMART

SM00385. CYCLIN. 2 hits.
[Graphical view]

SUPFAM

SSF47954. Cyclin_like. 2 hits.

PROSITE

PS00292. CYCLINS. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

3682.

PMAP-CutDB

P20248.

SOURCE

Search...

Entry information

Entry name

CCNA2_HUMAN

Accession

Primary (citable) accession number: P20248
Secondary accession number(s): A8K7B6 , Q2M3U6, Q4W5P4, Q6LER8

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	November 2, 2010
Last modified:	January 25, 2012
This is version 127 of the entry and version 2 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.