P78396 (CCNA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cyclin-A1

Gene names

Name:

CCNA1

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

General annotation (Comments)

Function	May be involved in the control of the cell cycle at the G1/S (start) and G2/M (mitosis) transitions. May primarily function in the control of the germline meiotic cell cycle and additionally in the control of mitotic cell cycle in some somatic cells. Ref.7
Subunit structure	Interacts with the CDK2 and the CDC2 protein kinases to form a serine/threonine kinase holoenzyme complex. The cyclin subunit imparts substrate specificity to the complex. Does not bind CDK4 and CDK5 (in vitro). The cyclin A1-CDK2 complex interacts with transcription factor E2F-1 and RB proteins. Found in a complex with CDK2, CABLES1 and CCNE1 By similarity. Interacts with INCA1 and KLHDC9. Ref.8
Subcellular location	Nucleus By similarity.
Tissue specificity	Very high levels in testis and very low levels in brain. Also found in myeloid Leukemia cell lines.
Developmental stage	Expression increases in early G1 phase and reaches highest levels during the S and G2/M phases.
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.
Sequence similarities	Belongs to the cyclin family. Cyclin AB subfamily.

Ontologies

Keywords
Biological process	Cell cycle Cell division Mitosis
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Molecular function	Cyclin
PTM	Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	G2/M transition of mitotic cell cycle Traceable author statement. Source: Reactome cell division Inferred from electronic annotation. Source: UniProtKB-KW male meiosis I Traceable author statement. Source: ProtInc mitosis Inferred from electronic annotation. Source: UniProtKB-KW regulation of cyclin-dependent protein kinase activity Inferred from electronic annotation. Source: InterPro regulation of transcription involved in G1/S phase of mitotic cell cycle Traceable author statement. Source: Reactome spermatogenesis Traceable author statement. Source: ProtInc
Cellular component	cytosol Traceable author statement. Source: ProtInc microtubule cytoskeleton Inferred from direct assay. Source: LIFEdb nucleoplasm Traceable author statement. Source: Reactome
Molecular function	protein kinase binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDKN1A	P38936	2	EBI-375065,EBI-375077

Alternative products

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

Isoform 1 (identifier: P78396-1)

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: P78396-2)

The sequence of this isoform differs from the canonical sequence as follows:
     38-38: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 465	465	Cyclin-A1		PRO_0000080333
Regions
	Compositional bias	388 – 391	4	Poly-Ala
Natural variations
	Alternative sequence	38	1	Missing in isoform 2.		VSP_034392
Experimental info
	Sequence conflict	43 – 47	5	EAMHC → SS in AAV38384. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: C9C023EEA1CF036D	FASTA	465	52,358
	10 20 30 40 50 60 METGFPAIMY PGSFIGGWGE EYLSWEGPGL PDFVFQQQPV ESEAMHCSNP KSGVVLATVA 70 80 90 100 110 120 RGPDACQILT RAPLGQDPPQ RTVLGLLTAN GQYRRTCGQG ITRIRCYSGS ENAFPPAGKK 130 140 150 160 170 180 ALPDCGVQEP PKQGFDIYMD ELEQGDRDSC SVREGMAFED VYEVDTGTLK SDLHFLLDFN 190 200 210 220 230 240 TVSPMLVDSS LLSQSEDISS LGTDVINVTE YAEEIYQYLR EAEIRHRPKA HYMKKQPDIT 250 260 270 280 290 300 EGMRTILVDW LVEVGEEYKL RAETLYLAVN FLDRFLSCMS VLRGKLQLVG TAAMLLASKY 310 320 330 340 350 360 EEIYPPEVDE FVYITDDTYT KRQLLKMEHL LLKVLAFDLT VPTTNQFLLQ YLRRQGVCVR 370 380 390 400 410 420 TENLAKYVAE LSLLEADPFL KYLPSLIAAA AFCLANYTVN KHFWPETLAA FTGYSLSEIV 430 440 450 460 PCLSELHKAY LDIPHRPQQA IREKYKASKY LCVSLMEPPA VLLLQ
	Isoform 2 [UniParc]. Checksum: E67C6E6D741B7D73	FASTA	464	52,230
	10 20 30 40 50 60 METGFPAIMY PGSFIGGWGE EYLSWEGPGL PDFVFQQPVE SEAMHCSNPK SGVVLATVAR 70 80 90 100 110 120 GPDACQILTR APLGQDPPQR TVLGLLTANG QYRRTCGQGI TRIRCYSGSE NAFPPAGKKA 130 140 150 160 170 180 LPDCGVQEPP KQGFDIYMDE LEQGDRDSCS VREGMAFEDV YEVDTGTLKS DLHFLLDFNT 190 200 210 220 230 240 VSPMLVDSSL LSQSEDISSL GTDVINVTEY AEEIYQYLRE AEIRHRPKAH YMKKQPDITE 250 260 270 280 290 300 GMRTILVDWL VEVGEEYKLR AETLYLAVNF LDRFLSCMSV LRGKLQLVGT AAMLLASKYE 310 320 330 340 350 360 EIYPPEVDEF VYITDDTYTK RQLLKMEHLL LKVLAFDLTV PTTNQFLLQY LRRQGVCVRT 370 380 390 400 410 420 ENLAKYVAEL SLLEADPFLK YLPSLIAAAA FCLANYTVNK HFWPETLAAF TGYSLSEIVP 430 440 450 460 CLSELHKAYL DIPHRPQQAI REKYKASKYL CVSLMEPPAV LLLQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of a second human cyclin A that is highly expressed in testis and in several leukemic cell lines." Yang R., Morosetti R., Koeffler H.P. Cancer Res. 57:913-920(1997) [PubMed: 9041194] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Myeloid.
[2]	"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 (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed: 15057823] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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 2). Tissue: Brain.
[6]	"The human testes cyclin A1 disrupts growth and DNA damage response of a yeast replication mutant." Perkins E.L., Wood V.J., Sterling J.F., Hashem V.I., Resnick M.A. Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 55-465. Tissue: Testis.
[7]	"Functions of cyclin A1 in the cell cycle and its interactions with transcription factor E2F-1 and the Rb family of proteins." Yang R., Mueller C., Huynh V., Fung Y.K., Yee A.S., Koeffler H.P. Mol. Cell. Biol. 19:2400-2407(1999) [PubMed: 10022926] [Abstract] Cited for: FUNCTION.
[8]	"Identification of interaction partners and substrates of the cyclin A1-CDK2 complex." Diederichs S., Baeumer N., Ji P., Metzelder S.K., Idos G.E., Cauvet T., Wang W., Moeller M., Pierschalski S., Gromoll J., Schrader M.G., Koeffler H.P., Berdel W.E., Serve H., Mueller-Tidow C. J. Biol. Chem. 279:33727-33741(2004) [PubMed: 15159402] [Abstract] Cited for: INTERACTION WITH INCA1 AND KLHDC9.
[9]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U66838 mRNA. Translation: AAB49754.1. BT019577 mRNA. Translation: AAV38384.1. AL359767 Genomic DNA. Translation: CAI12728.1. CH471075 Genomic DNA. Translation: EAX08565.1. CH471075 Genomic DNA. Translation: EAX08566.1. BC036346 mRNA. Translation: AAH36346.1. U97680 mRNA. Translation: AAB60863.1.
IPI	IPI00019284. IPI00879390.
RefSeq	NP_001104515.1. NM_001111045.1. NP_001104516.1. NM_001111046.1. NP_001104517.1. NM_001111047.1. NP_003905.1. NM_003914.3.
UniGene	Hs.417050.
3D structure databases
ProteinModelPortal	P78396.
SMR	P78396. Positions 214-464.
ModBase	Search...
Protein-protein interaction databases
IntAct	P78396. 7 interactions.
MINT	MINT-104479.
STRING	P78396.
Polymorphism databases
DMDM	8134359.
Proteomic databases
PRIDE	P78396.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000255465; ENSP00000255465; ENSG00000133101.
GeneID	8900.
KEGG	hsa:8900.
UCSC	uc001uvr.2. human. uc001uvs.2. human.
Organism-specific databases
CTD	8900.
GeneCards	GC13P037005.
H-InvDB	HIX0026562.
HGNC	HGNC:1577. CCNA1.
MIM	604036. gene.
neXtProt	NX_P78396.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG12692.
HOGENOM	HBG750484.
HOVERGEN	HBG106244.
InParanoid	P78396.
OMA	AEIRHRP.
OrthoDB	EOG4D7Z5P.
PhylomeDB	P78396.
Enzyme and pathway databases
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	P78396.
Bgee	P78396.
CleanEx	HS_CCNA1.
Genevestigator	P78396.
GermOnline	ENSG00000133101. 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	33435.
SOURCE	Search...

Entry information

Entry name

CCNA1_HUMAN

Accession

Primary (citable) accession number: P78396
Secondary accession number(s): Q5T3V0, Q5U0G2, Q8IY91

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	May 1, 1997
Last modified:	January 25, 2012
This is version 105 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.