Human Gene CCNA2 (ENST00000618014.1) Description and Page Index
  Description: Essential for the control of the cell cycle at the G1/S (start) and the G2/M (mitosis) transitions. (from UniProt P20248)
RefSeq Summary (NM_001237): The protein encoded by this gene belongs to the highly conserved cyclin family, whose members function as regulators of the cell cycle. This protein binds and activates cyclin-dependent kinase 2 and thus promotes transition through G1/S and G2/M. [provided by RefSeq, Aug 2016]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: SRR1163657.111004.1, SRR1163658.202233.1 [ECO:0000332] RNAseq introns :: mixed/partial sample support SAMEA1965299, SAMEA1966682 [ECO:0000350] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000274026.10/ ENSP00000274026.5 RefSeq Select criteria :: based on single protein-coding transcript ##RefSeq-Attributes-END##
Gencode Transcript: ENST00000618014.1
Gencode Gene: ENSG00000145386.10
Transcript (Including UTRs)
   Position: hg38 chr4:121,816,445-121,823,933 Size: 7,489 Total Exon Count: 8 Strand: -
Coding Region
   Position: hg38 chr4:121,817,638-121,823,628 Size: 5,991 Coding Exon Count: 8 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr4:121,816,445-121,823,933)mRNA (may differ from genome)Protein (432 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
LynxMGIneXtProtPubMedReactomeStanford SOURCE

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Cyclin-A2; Short=Cyclin-A;
FUNCTION: Essential for the control of the cell cycle at the G1/S (start) and the G2/M (mitosis) transitions.
SUBUNIT: 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.
INTERACTION: P24941:CDK2; NbExp=16; IntAct=EBI-457097, EBI-375096; P38936:CDKN1A; NbExp=2; IntAct=EBI-457097, EBI-375077; P46527:CDKN1B; NbExp=12; IntAct=EBI-457097, EBI-519280; Q96PU4:UHRF2; NbExp=2; IntAct=EBI-457097, EBI-625304;
SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Cytoplasmic when associated with SCAPER.
DEVELOPMENTAL STAGE: Accumulates steadily during G2 and is abruptly destroyed at mitosis.
PTM: 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).
SIMILARITY: Belongs to the cyclin family. Cyclin AB subfamily.

-  MalaCards Disease Associations
  MalaCards Gene Search: CCNA2
Diseases sorted by gene-association score: splenic diffuse red pulp small b-cell lymphoma (19), lung clear cell carcinoma (18), valproate embryopathy, susceptibility to (8), testicular cancer (7), myxofibrosarcoma (6), retinoblastoma (6), phyllode tumor (4), lung cancer (4), breast cancer (2), hepatocellular carcinoma (2), colorectal cancer (2)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 48.82 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 139.37 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -143.20305-0.470 Picture PostScript Text
3' UTR -276.101193-0.231 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR013763 - Cyclin-like
IPR014400 - Cyclin_A/B/D/E
IPR004367 - Cyclin_C
IPR006671 - Cyclin_N

Pfam Domains:
PF02984 - Cyclin, C-terminal domain
PF00134 - Cyclin, N-terminal domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help

- X-ray

- X-ray

- X-ray MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
1GY3 - X-ray MuPIT 1H1P - X-ray 1H1Q - X-ray
1H1R - X-ray 1H1S - X-ray 1H24 - X-ray
1H25 - X-ray 1H26 - X-ray 1H27 - X-ray
1H28 - X-ray 1JST - X-ray 1JSU - X-ray
1OGU - X-ray 1OI9 - X-ray 1OIU - X-ray
1OIY - X-ray 1OKV - X-ray MuPIT 1OKW - X-ray MuPIT
1OL1 - X-ray MuPIT 1OL2 - X-ray MuPIT 1P5E - X-ray MuPIT
1PKD - X-ray MuPIT 1QMZ - X-ray 1URC - X-ray MuPIT
1VYW - X-ray MuPIT 2BKZ - X-ray MuPIT 2BPM - X-ray MuPIT
2C4G - X-ray MuPIT 2C5N - X-ray MuPIT 2C5O - X-ray MuPIT
2C5V - X-ray MuPIT 2C5X - X-ray MuPIT 2C6T - X-ray MuPIT
2CCH - X-ray 2CCI - X-ray 2CJM - X-ray MuPIT
2I40 - X-ray MuPIT 2IW6 - X-ray MuPIT 2IW8 - X-ray MuPIT
2IW9 - X-ray MuPIT 2UUE - X-ray MuPIT 2UZB - X-ray MuPIT
2UZD - X-ray MuPIT 2UZE - X-ray MuPIT 2UZL - X-ray MuPIT
2V22 - X-ray MuPIT 2WEV - X-ray MuPIT 2WFY - X-ray MuPIT
2WHB - X-ray MuPIT 2WIH - X-ray MuPIT 2WIP - X-ray MuPIT
2WMA - X-ray 2WMB - X-ray 2WPA - X-ray MuPIT
2WXV - X-ray MuPIT 2X1N - X-ray MuPIT 3EID - X-ray MuPIT
3EJ1 - X-ray MuPIT 3EOC - X-ray 3F5X - X-ray MuPIT

ModBase Predicted Comparative 3D Structure on P20248
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
Protein SequenceProtein Sequence    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding
GO:0019901 protein kinase binding
GO:0019904 protein domain specific binding
GO:0097472 cyclin-dependent protein kinase activity

Biological Process:
GO:0000086 G2/M transition of mitotic cell cycle
GO:0007049 cell cycle
GO:0007265 Ras protein signal transduction
GO:0016032 viral process
GO:0016572 histone phosphorylation
GO:0016579 protein deubiquitination
GO:0031100 animal organ regeneration
GO:0032355 response to estradiol
GO:0033762 response to glucagon
GO:0036120 cellular response to platelet-derived growth factor stimulus
GO:0044320 cellular response to leptin stimulus
GO:0044843 cell cycle G1/S phase transition
GO:0045893 positive regulation of transcription, DNA-templated
GO:0048146 positive regulation of fibroblast proliferation
GO:0051301 cell division
GO:0051726 regulation of cell cycle
GO:0071314 cellular response to cocaine
GO:0071373 cellular response to luteinizing hormone stimulus
GO:0071392 cellular response to estradiol stimulus
GO:0071407 cellular response to organic cyclic compound
GO:0071456 cellular response to hypoxia
GO:0071732 cellular response to nitric oxide
GO:0090102 cochlea development
GO:1990314 cellular response to insulin-like growth factor stimulus

Cellular Component:
GO:0000307 cyclin-dependent protein kinase holoenzyme complex
GO:0001939 female pronucleus
GO:0001940 male pronucleus
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0097124 cyclin A2-CDK2 complex

-  Descriptions from all associated GenBank mRNAs
  JD346034 - Sequence 327058 from Patent EP1572962.
BC104783 - Homo sapiens cyclin A2, mRNA (cDNA clone MGC:132443 IMAGE:8143786), complete cds.
BC104787 - Homo sapiens cyclin A2, mRNA (cDNA clone MGC:132447 IMAGE:8143790), complete cds.
A32139 - H.sapiens cyclin A gene.
X51688 - Human mRNA for cyclin A.
JD263155 - Sequence 244179 from Patent EP1572962.
AK291931 - Homo sapiens cDNA FLJ77347 complete cds, highly similar to Homo sapiens cyclin A2 (CCNA2), mRNA.
KJ896552 - Synthetic construct Homo sapiens clone ccsbBroadEn_05946 CCNA2-like gene, encodes complete protein.
CR407692 - Homo sapiens full open reading frame cDNA clone RZPDo834E053D for gene CCNA2, cyclin A2 complete cds, without stopcodon.
JD024072 - Sequence 5096 from Patent EP1572962.
JD029727 - Sequence 10751 from Patent EP1572962.
JD487909 - Sequence 468933 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04110 - Cell cycle
hsa04914 - Progesterone-mediated oocyte maturation

Reactome (by CSHL, EBI, and GO)

Protein P20248 (Reactome details) participates in the following event(s):

R-HSA-170084 Formation of Cyclin A:Cdc2 complexes
R-HSA-174054 Formation of Cyclin A:Cdk2 complexes
R-HSA-69756 Phosphorylation of proteins involved in G2/M transition by active Cyclin A2:Cdc2 complexes
R-HSA-5697009 USP37:RUVLB1:PSMC5 deubiquitinates CCNA1,CCNA2
R-HSA-174164 Phosphorylation of Cyclin A:Cdk2 at Tyr 15
R-HSA-187934 Inactivation of Cyclin A:Cdk2 complexes by p27/p21
R-HSA-187949 CAK-mediated phosphorylation of Cyclin A:Cdk2
R-HSA-174110 Cdc25A mediated dephosphorylation of Cyclin A:phospho-Cdk2
R-HSA-174273 Translocation of Cyclin A:Cdk2 complexes to the nucleus
R-HSA-170087 CAK-mediated phosphorylation of Cyclin A:Cdc2 complexes
R-HSA-170088 Translocation of Cyclin A:phospho-Cdc2 (Thr 14) to the nucleus
R-HSA-170156 Wee1-mediated phosphorylation of Cyclin A:phospho-Cdc2 complexes
R-HSA-170158 Dephosphorylation of nuclear Cyclin A:phospho-Cdc2 complexes
R-HSA-187937 Association of Cyclin A:phospho-Cdk2(Thr 160) with E2F1/E2F3
R-HSA-188371 Association of Cyclin A:Cdk2 with Cdh1
R-HSA-3788708 CDKN1A (p21) prevents association of Cyclin A:Cdk2 with Cdh1
R-HSA-5684081 MRN complex binds CDK2 and RBBP8
R-HSA-5684096 CDK2 phosphorylates RBBP8
R-HSA-170116 Myt-1 mediated phosphorylation of Cyclin A:Cdc2
R-HSA-174171 Association of Cyclin A with the APC/C
R-HSA-187916 Cyclin A:Cdk2 mediated phosphorylation of p27/p21
R-HSA-187959 Phosphorylation of E2F1/E2F3 by Cyclin A:phosph-Cdk2(Thr 160)
R-HSA-174079 Phosphorylation of Cdh1 by Cyclin A:Cdk2
R-HSA-3788705 CDKN1A (p21) prevents phosphorylation of Cdh1 by Cyclin A:Cdk2
R-HSA-68944 Orc1 is phosphorylated by cyclin A/CDK2
R-HSA-187948 Phosphorylation of proteins involved in the G1/S transition by Cyclin A:Cdk2
R-HSA-6805109 CDK2 phosphorylates TP53
R-HSA-1363303 p130 (RBL2) in complex with E2F4/5:DP1/2 binds to cyclin E/A:CDK2
R-HSA-1363306 p130 (RBL2) binds Cyclin E/A:CDK2
R-HSA-1363311 p107 (RBL1) in complex with E2F4:DP1/2 binds to cyclin E/A:CDK2
R-HSA-1363314 p107 (RBL1) binds CyclinE/A:CDK2
R-HSA-174104 Ubiquitination of Cyclin A by APC/C:Cdc20 complex
R-HSA-6793661 (CDK1,CDK2):CCNA phosphorylates MDM2 at T218
R-HSA-187520 Cyclin E/A:Cdk2-mediated phosphorylation of p27/p21
R-HSA-187552 Binding of phospho-p27/p21:Cdk2:Cyclin E/A to the SCF(Skp2):Cks1 complex
R-HSA-69005 Cdc6 protein is phosphorylated by CDK
R-HSA-4088024 CCNA:CDK1/2 complexes and CCNB1:CDK1 complexes phosphorylate FOXM1
R-HSA-187575 Ubiquitination of phospho-p27/p21
R-HSA-1362300 Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1
R-HSA-1538133 G0 and Early G1
R-HSA-69273 Cyclin A/B1/B2 associated events during G2/M transition
R-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry
R-HSA-170145 Phosphorylation of proteins involved in the G2/M transition by Cyclin A:Cdc2 complexes
R-HSA-5689880 Ub-specific processing proteases
R-HSA-69563 p53-Dependent G1 DNA Damage Response
R-HSA-2559586 DNA Damage/Telomere Stress Induced Senescence
R-HSA-6804116 TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest
R-HSA-68911 G2 Phase
R-HSA-176408 Regulation of APC/C activators between G1/S and early anaphase
R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP)
R-HSA-5693607 Processing of DNA double-strand break ends
R-HSA-453279 Mitotic G1-G1/S phases
R-HSA-69275 G2/M Transition
R-HSA-69242 S Phase
R-HSA-174184 Cdc20:Phospho-APC/C mediated degradation of Cyclin A
R-HSA-5688426 Deubiquitination
R-HSA-69580 p53-Dependent G1/S DNA damage checkpoint
R-HSA-2559583 Cellular Senescence
R-HSA-6791312 TP53 Regulates Transcription of Cell Cycle Genes
R-HSA-187577 SCF(Skp2)-mediated degradation of p27/p21
R-HSA-453274 Mitotic G2-G2/M phases
R-HSA-174143 APC/C-mediated degradation of cell cycle proteins
R-HSA-5693567 HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)
R-HSA-68949 Orc1 removal from chromatin
R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation
R-HSA-69278 Cell Cycle (Mitotic)
R-HSA-179419 APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint
R-HSA-597592 Post-translational protein modification
R-HSA-69615 G1/S DNA Damage Checkpoints
R-HSA-2262752 Cellular responses to stress
R-HSA-3700989 Transcriptional Regulation by TP53
R-HSA-6804757 Regulation of TP53 Degradation
R-HSA-69202 Cyclin E associated events during G1/S transition
R-HSA-69017 CDK-mediated phosphorylation and removal of Cdc6
R-HSA-453276 Regulation of mitotic cell cycle
R-HSA-5693538 Homology Directed Repair
R-HSA-69052 Switching of origins to a post-replicative state
R-HSA-5633007 Regulation of TP53 Activity
R-HSA-1640170 Cell Cycle
R-HSA-176409 APC/C:Cdc20 mediated degradation of mitotic proteins
R-HSA-392499 Metabolism of proteins
R-HSA-69620 Cell Cycle Checkpoints
R-HSA-8953897 Cellular responses to external stimuli
R-HSA-212436 Generic Transcription Pathway
R-HSA-6806003 Regulation of TP53 Expression and Degradation
R-HSA-69206 G1/S Transition
R-HSA-5693532 DNA Double-Strand Break Repair
R-HSA-69239 Synthesis of DNA
R-HSA-176814 Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-73894 DNA Repair
R-HSA-69306 DNA Replication
R-HSA-74160 Gene expression (Transcription)

-  Other Names for This Gene
  Alternate Gene Symbols: A8K7B6, AK291931, CCN1, CCNA, CCNA2_HUMAN, P20248, Q2M3U6, Q4W5P4, Q6LER8, uc062zje.1
UCSC ID: uc062zje.1
RefSeq Accession: NM_001237
Protein: P20248 (aka CCNA2_HUMAN or CGA2_HUMAN)
CCDS: CCDS3723.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.