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 29-SEP-2021, entry version 205. 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=15; 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/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 SMR; P30279; -. DR BioGRID; 107334; 139. 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; 820 antibodies. DR DNASU; 894; -. DR Ensembl; ENST00000261254; ENSP00000261254; ENSG00000118971. [P30279-1] DR Ensembl; ENST00000676279; ENSP00000502597; ENSG00000118971. [P30279-1] DR Ensembl; ENST00000676411; ENSP00000502654; ENSG00000118971. [P30279-1] DR GeneID; 894; -. DR KEGG; hsa:894; -. 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 SignaLink; P30279; -. DR SIGNOR; P30279; -. DR BioGRID-ORCS; 894; 46 hits in 1035 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 amniotic fluid and 254 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; IEA:Ensembl. 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: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 //