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P30279

- CCND2_HUMAN

UniProt

P30279 - CCND2_HUMAN

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
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    • History
      Entry version 145 (01 Oct 2014)
      Sequence version 1 (01 Apr 1993)
      Previous versions | rss
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    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 binding Source: IntAct
    2. 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

    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

    Keywords - Cellular componenti

    Cytoplasm, Membrane, Nucleus

    Pathology & Biotechi

    Organism-specific databases

    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. 21 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.
    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.

    P30279-1 [UniParc]FASTAAdd to Basket

    « Hide

    MELLCHEVDP VRRAVRDRNL LRDDRVLQNL LTIEERYLPQ CSYFKCVQKD    50
    IQPYMRRMVA TWMLEVCEEQ KCEEEVFPLA MNYLDRFLAG VPTPKSHLQL 100
    LGAVCMFLAS KLKETSPLTA EKLCIYTDNS IKPQELLEWE LVVLGKLKWN 150
    LAAVTPHDFI EHILRKLPQQ REKLSLIRKH AQTFIALCAT DFKFAMYPPS 200
    MIATGSVGAA ICGLQQDEEV SSLTCDALTE LLAKITNTDV DCLKACQEQI 250
    EAVLLNSLQQ YRQDQRDGSK SEDELDQAST PTDVRDIDL 289
    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. 21 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.
    PharmGKBi PA26150.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5024.
    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

    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 1, 2014
    This is version 145 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