Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P30279 (CCND2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
G1/S-specific cyclin-D2
Gene names
Name:CCND2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length289 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Regulatory component of the cyclin D2-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G1/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G1 phase. Hypophosphorylates RB1 in early G1 phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity. Component of the ternary complex, cyclin D2/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex By similarity.

Subunit structure

Interacts with either CDK4 or CDK6 protein kinase to form a serine/threonine kinase holoenzyme complex. The cyclin subunit imparts substrate specificity to the complex. Component of the ternary complex cyclin D/CDK4/CDKN1B required for nuclear translocation and modulation of CDK4-mediated kinase activity. Ref.10

Subcellular location

Nucleus. Cytoplasm. Membrane. Note: Cyclin D-CDK4 complexes accumulate at the nuclear membrane and are then translocated into the nucleus through interaction with KIP/CIP family members By similarity. Ref.10

Post-translational modification

Polyubiquitinated by the SCF(FBXL2) complex, leading to proteasomal degradation.

Sequence similarities

Belongs to the cyclin family. Cyclin D subfamily.

Contains 1 cyclin N-terminal domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CDKN1AP389362EBI-748789,EBI-375077

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 289289G1/S-specific cyclin-D2
PRO_0000080437

Regions

Domain26 – 151126Cyclin N-terminal

Natural variations

Natural variant2681G → R. Ref.5
Corresponds to variant rs3217921 [ dbSNP | Ensembl ].
VAR_018820

Experimental info

Sequence conflict166 – 1672KL → NV in AAA51928. Ref.9
Sequence conflict2241T → H in AAA51928. Ref.9

Sequences

Sequence LengthMass (Da)Tools
P30279 [UniParc].

Last modified April 1, 1993. Version 1.
Checksum: E4E5FEF476D76D90

FASTA28933,067
        10         20         30         40         50         60 
MELLCHEVDP VRRAVRDRNL LRDDRVLQNL LTIEERYLPQ CSYFKCVQKD IQPYMRRMVA 

        70         80         90        100        110        120 
TWMLEVCEEQ KCEEEVFPLA MNYLDRFLAG VPTPKSHLQL LGAVCMFLAS KLKETSPLTA 

       130        140        150        160        170        180 
EKLCIYTDNS IKPQELLEWE LVVLGKLKWN LAAVTPHDFI EHILRKLPQQ REKLSLIRKH 

       190        200        210        220        230        240 
AQTFIALCAT DFKFAMYPPS MIATGSVGAA ICGLQQDEEV SSLTCDALTE LLAKITNTDV 

       250        260        270        280 
DCLKACQEQI EAVLLNSLQQ YRQDQRDGSK SEDELDQAST PTDVRDIDL 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and chromosomal mapping of CCND genes encoding human D-type cyclins."
Xiong Y., Menninger J., Beach D., Ward D.C.
Genomics 13:575-584(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Cyclins D1 and D2 are differentially expressed in human B-lymphoid cell lines."
Palmero I., Holder A., Sinclair A.J., Dickson C., Peters G.
Oncogene 8:1049-1054(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]Miyajima N.
Submitted (MAR-1993) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Bone marrow.
[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 (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]NIEHS SNPs program
Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ARG-268.
[6]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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. expand/collapse author list , 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].
[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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Bone marrow and Uterus.
[9]"Genomic organization, chromosomal localization, and independent expression of human cyclin D genes."
Inaba T., Matsushime H., Valentine M., Roussel M.F., Sherr C.J., Look A.T.
Genomics 13:565-574(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-240.
Tissue: Placenta.
[10]"Migratory localization of cyclin D2-Cdk4 complex suggests a spatial regulation of the G1-S transition."
Wang Z., Xie Y., Zhang L., Zhang H., An X., Wang T., Meng A.
Cell Struct. Funct. 33:171-183(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CDK4, SUBCELLULAR LOCATION.
[11]"F-box protein FBXL2 targets cyclin D2 for ubiquitination and degradation to inhibit leukemic cell proliferation."
Chen B.B., Glasser J.R., Coon T.A., Zou C., Miller H.L., Fenton M., McDyer J.F., Boyiadzis M., Mallampalli R.K.
Blood 119:3132-3141(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION BY SCF(FBXL2).
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M90813 mRNA. Translation: AAA51926.1.
X68452 mRNA. Translation: CAA48493.1.
D13639 mRNA. Translation: BAA02802.1.
BT019847 mRNA. Translation: AAV38650.1.
AF518005 Genomic DNA. Translation: AAM54041.1.
AK291146 mRNA. Translation: BAF83835.1.
CH471116 Genomic DNA. Translation: EAW88851.1.
BC010958 mRNA. Translation: AAH10958.1.
BC089384 mRNA. Translation: AAH89384.1.
M88083 expand/collapse EMBL AC list , M88080, M88081, M88082 Genomic DNA. Translation: AAA51928.1.
PIRA42822.
RefSeqNP_001750.1. NM_001759.3.
UniGeneHs.376071.

3D structure databases

ProteinModelPortalP30279.
SMRP30279. Positions 23-257.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107334. 21 interactions.
DIPDIP-178N.
IntActP30279. 6 interactions.
MINTMINT-1433179.
STRING9606.ENSP00000261254.

Chemistry

ChEMBLCHEMBL2095942.

PTM databases

PhosphoSiteP30279.

Polymorphism databases

DMDM231741.

Proteomic databases

PaxDbP30279.
PRIDEP30279.

Protocols and materials databases

DNASU894.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000261254; ENSP00000261254; ENSG00000118971.
GeneID894.
KEGGhsa:894.
UCSCuc001qmo.3. human.

Organism-specific databases

CTD894.
GeneCardsGC12P004382.
HGNCHGNC:1583. CCND2.
HPAHPA049138.
MIM123833. gene.
neXtProtNX_P30279.
PharmGKBPA26150.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5024.
HOGENOMHOG000008182.
HOVERGENHBG050837.
InParanoidP30279.
KOK10151.
OMALIRKHVQ.
OrthoDBEOG7J447H.
PhylomeDBP30279.
TreeFamTF101004.

Enzyme and pathway databases

ReactomeREACT_115566. Cell Cycle.
SignaLinkP30279.

Gene expression databases

BgeeP30279.
CleanExHS_CCND2.
GenevestigatorP30279.

Family and domain databases

Gene3D1.10.472.10. 2 hits.
InterProIPR013763. Cyclin-like.
IPR014400. Cyclin_A/B/D/E.
IPR004367. Cyclin_C-dom.
IPR015451. Cyclin_D.
IPR006671. Cyclin_N.
[Graphical view]
PANTHERPTHR10177:SF66. PTHR10177:SF66. 1 hit.
PfamPF02984. Cyclin_C. 1 hit.
PF00134. Cyclin_N. 1 hit.
[Graphical view]
PIRSFPIRSF001771. Cyclin_A_B_D_E. 1 hit.
SMARTSM00385. CYCLIN. 1 hit.
[Graphical view]
SUPFAMSSF47954. SSF47954. 2 hits.
PROSITEPS00292. CYCLINS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCCND2. human.
GeneWikiCyclin_D2.
GenomeRNAi894.
NextBio3696.
PROP30279.
SOURCESearch...

Entry information

Entry nameCCND2_HUMAN
AccessionPrimary (citable) accession number: P30279
Secondary accession number(s): A8K531, Q13955, Q5U035
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: April 16, 2014
This is version 140 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM