CCND2_HUMAN
ID CCND2_HUMAN Reviewed; 289 AA.
AC P30279; A8K531; Q13955; Q5U035;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=G1/S-specific cyclin-D2 {ECO:0000303|PubMed:1386336};
GN Name=CCND2 {ECO:0000303|PubMed:1386336, ECO:0000312|HGNC:HGNC:1583};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1386336; DOI=10.1016/0888-7543(92)90127-e;
RA Xiong Y., Menninger J., Beach D., Ward D.C.;
RT "Molecular cloning and chromosomal mapping of CCND genes encoding human D-
RT type cyclins.";
RL Genomics 13:575-584(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8455931;
RA Palmero I., Holder A., Sinclair A.J., Dickson C., Peters G.;
RT "Cyclins D1 and D2 are differentially expressed in human B-lymphoid cell
RT lines.";
RL Oncogene 8:1049-1054(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow;
RA Miyajima N.;
RL Submitted (MAR-1993) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARG-268.
RG NIEHS SNPs program;
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-240.
RC TISSUE=Placenta;
RX PubMed=1386335; DOI=10.1016/0888-7543(92)90126-d;
RA Inaba T., Matsushime H., Valentine M., Roussel M.F., Sherr C.J., Look A.T.;
RT "Genomic organization, chromosomal localization, and independent expression
RT of human cyclin D genes.";
RL Genomics 13:565-574(1992).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 105-140 (ISOFORM 2).
RC TISSUE=Glioblastoma;
RG The Cancer Genome Anatomy Project (CGAP) at the National Cancer Institute;
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP FUNCTION, AND INTERACTION WITH CDK6.
RX PubMed=8114739; DOI=10.1128/mcb.14.3.2077-2086.1994;
RA Meyerson M., Harlow E.;
RT "Identification of G1 kinase activity for cdk6, a novel cyclin D partner.";
RL Mol. Cell. Biol. 14:2077-2086(1994).
RN [13]
RP FUNCTION, INTERACTION WITH CDK4, AND SUBCELLULAR LOCATION.
RX PubMed=18827403; DOI=10.1247/csf.08019;
RA Wang Z., Xie Y., Zhang L., Zhang H., An X., Wang T., Meng A.;
RT "Migratory localization of cyclin D2-Cdk4 complex suggests a spatial
RT regulation of the G1-S transition.";
RL Cell Struct. Funct. 33:171-183(2008).
RN [14]
RP SUBCELLULAR LOCATION (ISOFORM 2), AND ALTERNATIVE SPLICING.
RX PubMed=17873913; DOI=10.1038/sj.onc.1210750;
RA Denicourt C., Legault P., McNabb F.A., Rassart E.;
RT "Human and mouse cyclin D2 splice variants: transforming activity and
RT subcellular localization.";
RL Oncogene 27:1253-1262(2008).
RN [15]
RP UBIQUITINATION BY SCF(FBXL2).
RX PubMed=22323446; DOI=10.1182/blood-2011-06-358911;
RA Chen B.B., Glasser J.R., Coon T.A., Zou C., Miller H.L., Fenton M.,
RA McDyer J.F., Boyiadzis M., Mallampalli R.K.;
RT "F-box protein FBXL2 targets cyclin D2 for ubiquitination and degradation
RT to inhibit leukemic cell proliferation.";
RL Blood 119:3132-3141(2012).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-271, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [17]
RP INVOLVEMENT IN MPPH3, AND VARIANTS MPPH3 ASN-280; ALA-280; ARG-281; LEU-281
RP AND GLY-284.
RX PubMed=24705253; DOI=10.1038/ng.2948;
RG FORGE Canada Consortium;
RA Mirzaa G.M., Parry D.A., Fry A.E., Giamanco K.A., Schwartzentruber J.,
RA Vanstone M., Logan C.V., Roberts N., Johnson C.A., Singh S.,
RA Kholmanskikh S.S., Adams C., Hodge R.D., Hevner R.F., Bonthron D.T.,
RA Braun K.P., Faivre L., Riviere J.B., St-Onge J., Gripp K.W., Mancini G.M.,
RA Pang K., Sweeney E., van Esch H., Verbeek N., Wieczorek D., Steinraths M.,
RA Majewski J., Boycott K.M., Pilz D.T., Ross M.E., Dobyns W.B.,
RA Sheridan E.G.;
RT "De novo CCND2 mutations leading to stabilization of cyclin D2 cause
RT megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome.";
RL Nat. Genet. 46:510-515(2014).
RN [18]
RP UBIQUITINATION.
RX PubMed=33854235; DOI=10.1038/s41586-021-03445-y;
RA Simoneschi D., Rona G., Zhou N., Jeong Y.T., Jiang S., Milletti G.,
RA Arbini A.A., O'Sullivan A., Wang A.A., Nithikasem S., Keegan S., Siu Y.,
RA Cianfanelli V., Maiani E., Nazio F., Cecconi F., Boccalatte F., Fenyoe D.,
RA Jones D.R., Busino L., Pagano M.;
RT "CRL4AMBRA1 is a master regulator of D-type cyclins.";
RL Nature 592:789-793(2021).
RN [19]
RP UBIQUITINATION.
RX PubMed=33854239; DOI=10.1038/s41586-021-03474-7;
RA Chaikovsky A.C., Li C., Jeng E.E., Loebell S., Lee M.C., Murray C.W.,
RA Cheng R., Demeter J., Swaney D.L., Chen S.H., Newton B.W., Johnson J.R.,
RA Drainas A.P., Shue Y.T., Seoane J.A., Srinivasan P., He A., Yoshida A.,
RA Hipkins S.Q., McCrea E., Poltorack C.D., Krogan N.J., Diehl J.A., Kong C.,
RA Jackson P.K., Curtis C., Petrov D.A., Bassik M.C., Winslow M.M., Sage J.;
RT "The AMBRA1 E3 ligase adaptor regulates the stability of cyclin D.";
RL Nature 592:794-798(2021).
CC -!- FUNCTION: Regulatory component of the cyclin D2-CDK4 (DC) complex that
CC phosphorylates and inhibits members of the retinoblastoma (RB) protein
CC family including RB1 and regulates the cell-cycle during G(1)/S
CC transition (PubMed:8114739, PubMed:18827403). Phosphorylation of RB1
CC allows dissociation of the transcription factor E2F from the RB/E2F
CC complex and the subsequent transcription of E2F target genes which are
CC responsible for the progression through the G(1) phase (PubMed:8114739,
CC PubMed:18827403). Hypophosphorylates RB1 in early G(1) phase
CC (PubMed:8114739, PubMed:18827403). Cyclin D-CDK4 complexes are major
CC integrators of various mitogenenic and antimitogenic signals
CC (PubMed:8114739, PubMed:18827403). {ECO:0000269|PubMed:18827403,
CC ECO:0000269|PubMed:8114739}.
CC -!- SUBUNIT: Interacts with either CDK4 or CDK6 protein kinase to form a
CC serine/threonine kinase holoenzyme complex (PubMed:8114739,
CC PubMed:18827403). The cyclin subunit imparts substrate specificity to
CC the complex (PubMed:8114739, PubMed:18827403).
CC {ECO:0000269|PubMed:18827403, ECO:0000269|PubMed:8114739}.
CC -!- INTERACTION:
CC P30279; P11802: CDK4; NbExp=15; IntAct=EBI-748789, EBI-295644;
CC P30279; Q00535: CDK5; NbExp=16; IntAct=EBI-748789, EBI-1041567;
CC P30279; P38936: CDKN1A; NbExp=17; IntAct=EBI-748789, EBI-375077;
CC P30279; P46527: CDKN1B; NbExp=6; IntAct=EBI-748789, EBI-519280;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:18827403}. Cytoplasm
CC {ECO:0000269|PubMed:18827403}. Nucleus membrane
CC {ECO:0000269|PubMed:18827403}. Note=Cyclin D-CDK4 complexes accumulate
CC at the nuclear membrane and are then translocated into the nucleus
CC through interaction with KIP/CIP family members.
CC {ECO:0000269|PubMed:18827403}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000269|PubMed:17873913}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P30279-1; Sequence=Displayed;
CC Name=2; Synonyms=Truncated;
CC IsoId=P30279-2; Sequence=VSP_057295, VSP_057296;
CC -!- PTM: Phosphorylation at Thr-280 by MAP kinases is required for
CC ubiquitination and degradation by the DCX(AMBRA1) complex.
CC {ECO:0000250|UniProtKB:P24385}.
CC -!- PTM: Ubiquitinated by the DCX(AMBRA1) complex during the transition
CC from G1 to S cell phase, leading to its degradation: ubiquitination is
CC dependent on Thr-280 phosphorylation (PubMed:33854235,
CC PubMed:33854239). The DCX(AMBRA1) complex represents the major
CC regulator of CCND2 stability during the G1/S transition
CC (PubMed:33854235, PubMed:33854239). Polyubiquitinated by the SCF(FBXL2)
CC complex, leading to proteasomal degradation (PubMed:22323446).
CC {ECO:0000269|PubMed:22323446, ECO:0000269|PubMed:33854235,
CC ECO:0000269|PubMed:33854239}.
CC -!- DISEASE: Megalencephaly-polymicrogyria-polydactyly-hydrocephalus
CC syndrome 3 (MPPH3) [MIM:615938]: A syndrome characterized by
CC megalencephaly, ventriculomegaly that may lead to hydrocephalus, and
CC polymicrogyria; polydactyly may also be seen. There is considerable
CC phenotypic similarity between this disorder and the megalencephaly-
CC capillary malformation syndrome. {ECO:0000269|PubMed:24705253}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- MISCELLANEOUS: [Isoform 2]: Acts as proto-oncogene. Retains ability to
CC bind CDK4, but unable to catalyze efficiently RB phosphorylation and
CC inactivation. {ECO:0000269|PubMed:17873913}.
CC -!- SIMILARITY: Belongs to the cyclin family. Cyclin D subfamily.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/ccnd2/";
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DR EMBL; M90813; AAA51926.1; -; mRNA.
DR EMBL; X68452; CAA48493.1; -; mRNA.
DR EMBL; D13639; BAA02802.1; -; mRNA.
DR EMBL; BT019847; AAV38650.1; -; mRNA.
DR EMBL; AF518005; AAM54041.1; -; Genomic_DNA.
DR EMBL; AK291146; BAF83835.1; -; mRNA.
DR EMBL; AC006122; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471116; EAW88851.1; -; Genomic_DNA.
DR EMBL; BC010958; AAH10958.1; -; mRNA.
DR EMBL; BC089384; AAH89384.1; -; mRNA.
DR EMBL; M88083; AAA51928.1; -; Genomic_DNA.
DR EMBL; M88080; AAA51928.1; JOINED; Genomic_DNA.
DR EMBL; M88081; AAA51928.1; JOINED; Genomic_DNA.
DR EMBL; M88082; AAA51928.1; JOINED; Genomic_DNA.
DR EMBL; AI146555; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS8524.1; -. [P30279-1]
DR PIR; A42822; A42822.
DR RefSeq; NP_001750.1; NM_001759.3. [P30279-1]
DR PDB; 6EI2; X-ray; 1.61 A; C=114-123.
DR PDBsum; 6EI2; -.
DR AlphaFoldDB; P30279; -.
DR SMR; P30279; -.
DR BioGRID; 107334; 146.
DR ComplexPortal; CPX-2011; Cyclin D2-CDK4 complex.
DR CORUM; P30279; -.
DR DIP; DIP-178N; -.
DR IntAct; P30279; 11.
DR MINT; P30279; -.
DR STRING; 9606.ENSP00000261254; -.
DR BindingDB; P30279; -.
DR ChEMBL; CHEMBL2095942; -.
DR ChEMBL; CHEMBL3301385; -.
DR ChEMBL; CHEMBL3301386; -.
DR iPTMnet; P30279; -.
DR PhosphoSitePlus; P30279; -.
DR BioMuta; CCND2; -.
DR DMDM; 231741; -.
DR EPD; P30279; -.
DR jPOST; P30279; -.
DR MassIVE; P30279; -.
DR MaxQB; P30279; -.
DR PaxDb; P30279; -.
DR PeptideAtlas; P30279; -.
DR PRIDE; P30279; -.
DR ProteomicsDB; 54647; -. [P30279-1]
DR Antibodypedia; 10540; 839 antibodies from 38 providers.
DR DNASU; 894; -.
DR Ensembl; ENST00000261254.8; ENSP00000261254.3; ENSG00000118971.9. [P30279-1]
DR Ensembl; ENST00000676279.1; ENSP00000502597.1; ENSG00000118971.9. [P30279-1]
DR Ensembl; ENST00000676411.1; ENSP00000502654.1; ENSG00000118971.9. [P30279-1]
DR GeneID; 894; -.
DR KEGG; hsa:894; -.
DR MANE-Select; ENST00000261254.8; ENSP00000261254.3; NM_001759.4; NP_001750.1.
DR UCSC; uc001qmo.4; human. [P30279-1]
DR CTD; 894; -.
DR DisGeNET; 894; -.
DR GeneCards; CCND2; -.
DR GeneReviews; CCND2; -.
DR HGNC; HGNC:1583; CCND2.
DR HPA; ENSG00000118971; Low tissue specificity.
DR MalaCards; CCND2; -.
DR MIM; 123833; gene.
DR MIM; 615938; phenotype.
DR neXtProt; NX_P30279; -.
DR OpenTargets; ENSG00000118971; -.
DR Orphanet; 83473; Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome.
DR PharmGKB; PA26150; -.
DR VEuPathDB; HostDB:ENSG00000118971; -.
DR eggNOG; KOG0656; Eukaryota.
DR GeneTree; ENSGT00940000155180; -.
DR HOGENOM; CLU_052190_0_0_1; -.
DR InParanoid; P30279; -.
DR OMA; CLEMDTN; -.
DR OrthoDB; 1234739at2759; -.
DR PhylomeDB; P30279; -.
DR TreeFam; TF101004; -.
DR PathwayCommons; P30279; -.
DR Reactome; R-HSA-69231; Cyclin D associated events in G1.
DR Reactome; R-HSA-8934593; Regulation of RUNX1 Expression and Activity.
DR Reactome; R-HSA-9661069; Defective binding of RB1 mutants to E2F1,(E2F2, E2F3).
DR Reactome; R-HSA-9754119; Drug-mediated inhibition of CDK4/CDK6 activity.
DR SignaLink; P30279; -.
DR SIGNOR; P30279; -.
DR BioGRID-ORCS; 894; 50 hits in 1100 CRISPR screens.
DR ChiTaRS; CCND2; human.
DR GeneWiki; Cyclin_D2; -.
DR GenomeRNAi; 894; -.
DR Pharos; P30279; Tbio.
DR PRO; PR:P30279; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P30279; protein.
DR Bgee; ENSG00000118971; Expressed in adrenal tissue and 203 other tissues.
DR ExpressionAtlas; P30279; baseline and differential.
DR Genevisible; P30279; HS.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0097129; C:cyclin D2-CDK4 complex; IPI:ComplexPortal.
DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016538; F:cyclin-dependent protein serine/threonine kinase regulator activity; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; IPI:BHF-UCL.
DR GO; GO:0008344; P:adult locomotory behavior; IEA:Ensembl.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0071481; P:cellular response to X-ray; IEA:Ensembl.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IC:ComplexPortal.
DR GO; GO:0007616; P:long-term memory; IEA:Ensembl.
DR GO; GO:0044772; P:mitotic cell cycle phase transition; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:BHF-UCL.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:BHF-UCL.
DR GO; GO:0045737; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity; IDA:BHF-UCL.
DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; IMP:BHF-UCL.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:BHF-UCL.
DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; IBA:GO_Central.
DR CDD; cd00043; CYCLIN; 1.
DR InterPro; IPR039361; Cyclin.
DR InterPro; IPR013763; Cyclin-like.
DR InterPro; IPR036915; Cyclin-like_sf.
DR InterPro; IPR004367; Cyclin_C-dom.
DR InterPro; IPR015451; Cyclin_D.
DR InterPro; IPR006671; Cyclin_N.
DR PANTHER; PTHR10177; PTHR10177; 1.
DR PANTHER; PTHR10177:SF66; PTHR10177:SF66; 1.
DR Pfam; PF02984; Cyclin_C; 1.
DR Pfam; PF00134; Cyclin_N; 1.
DR SMART; SM00385; CYCLIN; 1.
DR SMART; SM01332; Cyclin_C; 1.
DR SUPFAM; SSF47954; SSF47954; 2.
DR PROSITE; PS00292; CYCLINS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell cycle; Cell division; Cyclin;
KW Cytoplasm; Disease variant; Membrane; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..289
FT /note="G1/S-specific cyclin-D2"
FT /id="PRO_0000080437"
FT DOMAIN 26..151
FT /note="Cyclin N-terminal"
FT REGION 264..289
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 265..289
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 271
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 280
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P30280"
FT VAR_SEQ 138..209
FT /note="EWELVVLGKLKWNLAAVTPHDFIEHILRKLPQQREKLSLIRKHAQTFIALCA
FT TDFKFAMYPPSMIATGSVGA -> VMTGPFLPSFLRFPLSPGQQYAFYHHCQSKFLGSR
FT MTPPIEFTHLWAIAHLIGNHCLFFVCSYYVPRLRAQH (in isoform 2)"
FT /evidence="ECO:0000303|Ref.11"
FT /id="VSP_057295"
FT VAR_SEQ 210..289
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.11"
FT /id="VSP_057296"
FT VARIANT 268
FT /note="G -> R (in dbSNP:rs3217921)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_018820"
FT VARIANT 280
FT /note="T -> A (in MPPH3; dbSNP:rs587777618)"
FT /evidence="ECO:0000269|PubMed:24705253"
FT /id="VAR_072370"
FT VARIANT 280
FT /note="T -> N (in MPPH3; dbSNP:rs587777620)"
FT /evidence="ECO:0000269|PubMed:24705253"
FT /id="VAR_072371"
FT VARIANT 281
FT /note="P -> L (in MPPH3; dbSNP:rs587777622)"
FT /evidence="ECO:0000269|PubMed:24705253"
FT /id="VAR_072372"
FT VARIANT 281
FT /note="P -> R (in MPPH3; dbSNP:rs587777622)"
FT /evidence="ECO:0000269|PubMed:24705253"
FT /id="VAR_072373"
FT VARIANT 284
FT /note="V -> G (in MPPH3; dbSNP:rs777786993)"
FT /evidence="ECO:0000269|PubMed:24705253"
FT /id="VAR_072374"
FT CONFLICT 166..167
FT /note="KL -> NV (in Ref. 10; AAA51928)"
FT /evidence="ECO:0000305"
FT CONFLICT 224
FT /note="T -> H (in Ref. 10; AAA51928)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 289 AA; 33067 MW; E4E5FEF476D76D90 CRC64;
MELLCHEVDP VRRAVRDRNL LRDDRVLQNL LTIEERYLPQ CSYFKCVQKD IQPYMRRMVA
TWMLEVCEEQ KCEEEVFPLA MNYLDRFLAG VPTPKSHLQL LGAVCMFLAS KLKETSPLTA
EKLCIYTDNS IKPQELLEWE LVVLGKLKWN LAAVTPHDFI EHILRKLPQQ REKLSLIRKH
AQTFIALCAT DFKFAMYPPS MIATGSVGAA ICGLQQDEEV SSLTCDALTE LLAKITNTDV
DCLKACQEQI EAVLLNSLQQ YRQDQRDGSK SEDELDQAST PTDVRDIDL
