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P30279

- CCND2_HUMAN

UniProt

P30279 - CCND2_HUMAN

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Protein

G1/S-specific cyclin-D2

Gene

CCND2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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).By similarity

GO - Molecular functioni

  1. protein kinase binding Source: BHF-UCL

GO - Biological processi

  1. cell cycle Source: UniProtKB-KW
  2. cell division Source: UniProtKB-KW
  3. positive regulation of cyclin-dependent protein serine/threonine kinase activity Source: BHF-UCL
  4. positive regulation of protein phosphorylation Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Cyclin

Keywords - Biological processi

Cell cycle, Cell division

Enzyme and pathway databases

ReactomeiREACT_821. Cyclin D associated events in G1.
SignaLinkiP30279.

Names & Taxonomyi

Protein namesi
Recommended name:
G1/S-specific cyclin-D2
Gene namesi
Name:CCND2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 12

Organism-specific databases

HGNCiHGNC:1583. CCND2.

Subcellular locationi

Nucleus 1 Publication. Cytoplasm 1 Publication. Membrane 1 Publication
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

GO - Cellular componenti

  1. chromatin Source: UniProtKB
  2. cyclin-dependent protein kinase holoenzyme complex Source: UniProtKB
  3. cytosol Source: UniProtKB
  4. nuclear membrane Source: UniProtKB
  5. nucleolus Source: UniProtKB
  6. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Organism-specific databases

Orphaneti83473. Megalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalus.
PharmGKBiPA26150.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 289289G1/S-specific cyclin-D2PRO_0000080437Add
BLAST

Post-translational modificationi

Polyubiquitinated by the SCF(FBXL2) complex, leading to proteasomal degradation.1 Publication

Keywords - PTMi

Ubl conjugation

Proteomic databases

MaxQBiP30279.
PaxDbiP30279.
PRIDEiP30279.

PTM databases

PhosphoSiteiP30279.

Expressioni

Gene expression databases

BgeeiP30279.
CleanExiHS_CCND2.
GenevestigatoriP30279.

Organism-specific databases

HPAiHPA049138.

Interactioni

Subunit structurei

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.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
CDKN1AP389363EBI-748789,EBI-375077

Protein-protein interaction databases

BioGridi107334. 23 interactions.
DIPiDIP-178N.
IntActiP30279. 6 interactions.
MINTiMINT-1433179.
STRINGi9606.ENSP00000261254.

Structurei

3D structure databases

ProteinModelPortaliP30279.
SMRiP30279. Positions 23-257.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini26 – 151126Cyclin N-terminalAdd
BLAST

Sequence similaritiesi

Belongs to the cyclin family. Cyclin D subfamily.Curated
Contains 1 cyclin N-terminal domain.Curated

Phylogenomic databases

eggNOGiCOG5024.
GeneTreeiENSGT00760000118939.
HOGENOMiHOG000008182.
HOVERGENiHBG050837.
InParanoidiP30279.
KOiK10151.
OMAiLIRKHVQ.
OrthoDBiEOG7J447H.
PhylomeDBiP30279.
TreeFamiTF101004.

Family and domain databases

Gene3Di1.10.472.10. 2 hits.
InterProiIPR013763. Cyclin-like.
IPR014400. Cyclin_A/B/D/E/F.
IPR004367. Cyclin_C-dom.
IPR015451. Cyclin_D.
IPR006671. Cyclin_N.
[Graphical view]
PANTHERiPTHR10177:SF66. PTHR10177:SF66. 1 hit.
PfamiPF02984. Cyclin_C. 1 hit.
PF00134. Cyclin_N. 1 hit.
[Graphical view]
PIRSFiPIRSF001771. Cyclin_A_B_D_E. 1 hit.
SMARTiSM00385. CYCLIN. 1 hit.
[Graphical view]
SUPFAMiSSF47954. SSF47954. 2 hits.
PROSITEiPS00292. CYCLINS. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P30279 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MELLCHEVDP VRRAVRDRNL LRDDRVLQNL LTIEERYLPQ CSYFKCVQKD
60 70 80 90 100
IQPYMRRMVA TWMLEVCEEQ KCEEEVFPLA MNYLDRFLAG VPTPKSHLQL
110 120 130 140 150
LGAVCMFLAS KLKETSPLTA EKLCIYTDNS IKPQELLEWE LVVLGKLKWN
160 170 180 190 200
LAAVTPHDFI EHILRKLPQQ REKLSLIRKH AQTFIALCAT DFKFAMYPPS
210 220 230 240 250
MIATGSVGAA ICGLQQDEEV SSLTCDALTE LLAKITNTDV DCLKACQEQI
260 270 280
EAVLLNSLQQ YRQDQRDGSK SEDELDQAST PTDVRDIDL
Length:289
Mass (Da):33,067
Last modified:April 1, 1993 - v1
Checksum:iE4E5FEF476D76D90
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti166 – 1672KL → NV in AAA51928. (PubMed:1386335)Curated
Sequence conflicti224 – 2241T → H in AAA51928. (PubMed:1386335)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti268 – 2681G → R.1 Publication
Corresponds to variant rs3217921 [ dbSNP | Ensembl ].
VAR_018820

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS8524.1.
PIRiA42822.
RefSeqiNP_001750.1. NM_001759.3.
UniGeneiHs.376071.

Genome annotation databases

EnsembliENST00000261254; ENSP00000261254; ENSG00000118971.
GeneIDi894.
KEGGihsa:894.
UCSCiuc001qmo.3. human.

Polymorphism databases

DMDMi231741.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS8524.1.
PIRi A42822.
RefSeqi NP_001750.1. NM_001759.3.
UniGenei Hs.376071.

3D structure databases

ProteinModelPortali P30279.
SMRi P30279. Positions 23-257.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 107334. 23 interactions.
DIPi DIP-178N.
IntActi P30279. 6 interactions.
MINTi MINT-1433179.
STRINGi 9606.ENSP00000261254.

Chemistry

ChEMBLi CHEMBL2095942.

PTM databases

PhosphoSitei P30279.

Polymorphism databases

DMDMi 231741.

Proteomic databases

MaxQBi P30279.
PaxDbi P30279.
PRIDEi P30279.

Protocols and materials databases

DNASUi 894.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000261254 ; ENSP00000261254 ; ENSG00000118971 .
GeneIDi 894.
KEGGi hsa:894.
UCSCi uc001qmo.3. human.

Organism-specific databases

CTDi 894.
GeneCardsi GC12P004382.
HGNCi HGNC:1583. CCND2.
HPAi HPA049138.
MIMi 123833. gene.
neXtProti NX_P30279.
Orphaneti 83473. Megalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalus.
PharmGKBi PA26150.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG5024.
GeneTreei ENSGT00760000118939.
HOGENOMi HOG000008182.
HOVERGENi HBG050837.
InParanoidi P30279.
KOi K10151.
OMAi LIRKHVQ.
OrthoDBi EOG7J447H.
PhylomeDBi P30279.
TreeFami TF101004.

Enzyme and pathway databases

Reactomei REACT_821. Cyclin D associated events in G1.
SignaLinki P30279.

Miscellaneous databases

ChiTaRSi CCND2. human.
GeneWikii Cyclin_D2.
GenomeRNAii 894.
NextBioi 3696.
PROi P30279.
SOURCEi Search...

Gene expression databases

Bgeei P30279.
CleanExi HS_CCND2.
Genevestigatori P30279.

Family and domain databases

Gene3Di 1.10.472.10. 2 hits.
InterProi IPR013763. Cyclin-like.
IPR014400. Cyclin_A/B/D/E/F.
IPR004367. Cyclin_C-dom.
IPR015451. Cyclin_D.
IPR006671. Cyclin_N.
[Graphical view ]
PANTHERi PTHR10177:SF66. PTHR10177:SF66. 1 hit.
Pfami PF02984. Cyclin_C. 1 hit.
PF00134. Cyclin_N. 1 hit.
[Graphical view ]
PIRSFi PIRSF001771. Cyclin_A_B_D_E. 1 hit.
SMARTi SM00385. CYCLIN. 1 hit.
[Graphical view ]
SUPFAMi SSF47954. SSF47954. 2 hits.
PROSITEi PS00292. CYCLINS. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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).

Entry informationi

Entry nameiCCND2_HUMAN
AccessioniPrimary (citable) accession number: P30279
Secondary accession number(s): A8K531, Q13955, Q5U035
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: October 29, 2014
This is version 146 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3