P30279 (CCND2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
G1/S-specific cyclin-D2

Gene names

Name:

CCND2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	289 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Cell cycle Cell division
Cellular component	Cytoplasm Membrane Nucleus
Coding sequence diversity	Polymorphism
Molecular function	Cyclin
PTM	Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW cell division Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of cyclin-dependent protein kinase activity Inferred from direct assay PubMed 8114739. Source: BHF-UCL
Cellular_component	chromatin Inferred from direct assay Ref.10. Source: UniProtKB cyclin-dependent protein kinase holoenzyme complex Inferred from direct assay Ref.10. Source: UniProtKB cytosol Inferred from direct assay Ref.10. Source: UniProtKB nuclear membrane Inferred from direct assay Ref.10. Source: UniProtKB nucleolus Inferred from direct assay Ref.10. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 289	289	G1/S-specific cyclin-D2		PRO_0000080437
Regions
	Domain	26 – 151	126	Cyclin N-terminal
Natural variations
	Natural variant	268	1	G → R. Ref.5 Corresponds to variant rs3217921 [ dbSNP | Ensembl ].		VAR_018820
Experimental info
	Sequence conflict	166 – 167	2	KL → NV in AAA51928. Ref.9
	Sequence conflict	224	1	T → H in AAA51928. Ref.9

Sequences

	Sequence		Length	Mass (Da)
	P30279 [UniParc]. Last modified April 1, 1993. Version 1. Checksum: E4E5FEF476D76D90	FASTA	289	33,067
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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

NIEHS-SNPs

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 , M88080, M88081, M88082 Genomic DNA. Translation: AAA51928.1.
IPI	IPI00025810.
PIR	A42822.
RefSeq	NP_001750.1. NM_001759.3.
UniGene	Hs.376071.
3D structure databases
ProteinModelPortal	P30279.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-178N.
IntAct	P30279. 5 interactions.
MINT	MINT-1433179.
STRING	9606.ENSP00000261254.
PTM databases
PhosphoSite	P30279.
Polymorphism databases
DMDM	231741.
Proteomic databases
PaxDb	P30279.
PRIDE	P30279.
Protocols and materials databases
DNASU	894.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000261254; ENSP00000261254; ENSG00000118971.
GeneID	894.
KEGG	hsa:894.
UCSC	uc001qmo.3. human.
Organism-specific databases
CTD	894.
GeneCards	GC12P004382.
HGNC	HGNC:1583. CCND2.
HPA	HPA049138.
MIM	123833. gene.
neXtProt	NX_P30279.
PharmGKB	PA26150.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5024.
HOGENOM	HOG000008182.
HOVERGEN	HBG050837.
InParanoid	P30279.
KO	K10151.
OMA	MELLCLE.
OrthoDB	EOG4JWVF1.
PhylomeDB	P30279.
Enzyme and pathway databases
Pathway_Interaction_DB	il2_stat5pathway. IL2 signaling events mediated by STAT5.
Reactome	REACT_115566. Cell Cycle.
Gene expression databases
Bgee	P30279.
CleanEx	HS_CCND2.
Genevestigator	P30279.
GermOnline	ENSG00000118971. Homo sapiens.
Family and domain databases
Gene3D	1.10.472.10. 2 hits.
InterPro	IPR013763. Cyclin-like. IPR014400. Cyclin_A/B/D/E. IPR004367. Cyclin_C-dom. IPR006671. Cyclin_N. [Graphical view]
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. 1 hit. [Graphical view]
SUPFAM	SSF47954. Cyclin_like. 2 hits.
PROSITE	PS00292. CYCLINS. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL3613.
ChiTaRS	CCND2. human.
GenomeRNAi	894.
NextBio	3696.
SOURCE	Search...

Entry information

Entry name

CCND2_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 130 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.