CCND1
entrez
595
canonical
uniprot
P24385
canonical
ensembl
ENSG00000110092
resolver
ensp
ENSP00000227507
resolver
enst
ENST00000227507
resolver
genesymbol
CCND1
resolver
genesymbol_syn
BCL1
resolver
genesymbol_syn
PRAD1
resolver
hgnc
HGNC:1582
resolver
uniprot
Q6FI00
resolver
uniprot
Q6LEF0
resolver
uniprot_entry
CCND1_HUMAN
resolver
uniprot_entry
Q6FI00_HUMAN
resolver
uniprot_sec
Q6LEF0
resolver
amino_acid_sequence
MEHQLLCCEVETIRRAYPDANLLNDRVLRAMLKAEETCAPSVSYFKCVQKEVLPSMRKIVATWMLEVCEEQKCEEEVFPLAMNYLDRFLSLEPVKKSRLQLLGATCMFVASKMKETIPLTAEKLCIYTDNSIRPEELLQMELLLVNKLKWNLAAMTPHDFIEHFLSKMPEAEENKQIIRKHAQTFVALCATDVKFISNPPSMVAAGSVVAAVQGLNLRSPNNFLSYYRLTRFLSRVIKCDPDCLRACQEQIEALLESSLRQAQQNMDPKAAEEEEEEEEEVDLACTPTDVRDVDI
uniprot
proteins
disease_involvement
DISEASE: Note=A chromosomal aberration involving CCND1 may be a cause of B-lymphocytic malignancy, particularly mantle-cell lymphoma (MCL). Translocation t(11;14)(q13;q32) with immunoglobulin gene regions. Activation of CCND1 may be oncogenic by directly altering progression through the cell cycle. {ECO:0000269|PubMed:1826542, ECO:0000269|PubMed:8204893, ECO:0000269|PubMed:8695815}.; DISEASE: Note=A chromosomal aberration involving CCND1 may be a cause of parathyroid adenomas. Translocation t(11;11)(q13;p15) with the parathyroid hormone (PTH) enhancer. {ECO:0000269|PubMed:1826542}.; DISEASE: Multiple myeloma (MM) [MIM:254500]: A malignant tumor of plasma cells usually arising in the bone marrow and characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria and anemia. Complications of multiple myeloma are bone pain, hypercalcemia, renal failure and spinal cord compression. The aberrant antibodies that are produced lead to impaired humoral immunity and patients have a high prevalence of infection. Amyloidosis may develop in some patients. Multiple myeloma is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. {ECO:0000269|PubMed:8695815}. Note=The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration involving CCND1 is found in multiple myeloma. Translocation t(11;14)(q13;q32) with the IgH locus.
uniprot
proteins
function
FUNCTION: Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition (PubMed:1827756, PubMed:1833066, PubMed:19412162, PubMed:33854235, PubMed:8114739, PubMed:8302605). 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 G(1) phase (PubMed:1827756, PubMed:1833066, PubMed:19412162, PubMed:8114739, PubMed:8302605). Hypophosphorylates RB1 in early G(1) phase (PubMed:1827756, PubMed:1833066, PubMed:19412162, PubMed:8114739, PubMed:8302605). Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals (PubMed:1827756, PubMed:1833066, PubMed:19412162, PubMed:8302605). Also a substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity (PubMed:15241418). Component of the ternary complex, cyclin D1/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex (PubMed:9106657). Exhibits transcriptional corepressor activity with INSM1 on the NEUROD1 and INS promoters in a cell cycle-independent manner (PubMed:16569215, PubMed:18417529). {ECO:0000269|PubMed:15241418, ECO:0000269|PubMed:16569215, ECO:0000269|PubMed:1827756, ECO:0000269|PubMed:1833066, ECO:0000269|PubMed:18417529, ECO:0000269|PubMed:19412162, ECO:0000269|PubMed:33854235, ECO:0000269|PubMed:8114739, ECO:0000269|PubMed:8302605, ECO:0000269|PubMed:9106657}.
uniprot
proteins
mass_dalton
33729
uniprot
proteins
mutagenesis
MUTAGEN 286..288; /note="TPT->ATA: Reduced ubiquitination and subsequent degradation by the proteasome."; /evidence="ECO:0000269|PubMed:10766840"; MUTAGEN 286; /note="T->A: Reduced interaction with the DCX(AMBRA1) complex, and subsequent ubiquitination and degradation by the proteasome. Abolished ubiquitination and subsequent degradation following DNA damage."; /evidence="ECO:0000269|PubMed:19412162, ECO:0000269|PubMed:33854232, ECO:0000269|PubMed:33854235, ECO:0000269|PubMed:33854239"; MUTAGEN 287; /note="P->A,L,S: Reduced interaction with the DCX(AMBRA1) complex, and subsequent ubiquitination and degradation by the proteasome."; /evidence="ECO:0000269|PubMed:33854235
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Thr-286 by MAP kinases is required for ubiquitination and degradation by the DCX(AMBRA1) complex (PubMed:10766840, PubMed:17205132, PubMed:33854232, PubMed:33854235, PubMed:33854239). It also plays an essential role for recognition by the FBXO31 component of SCF (SKP1-cullin-F-box) protein ligase complex following DNA damage (PubMed:19412162). {ECO:0000269|PubMed:10766840, ECO:0000269|PubMed:17205132, ECO:0000269|PubMed:19412162, ECO:0000269|PubMed:33854232, ECO:0000269|PubMed:33854235, ECO:0000269|PubMed:33854239}.; PTM: Ubiquitinated at Lys-269 by the DCX(AMBRA1) complex during the transition from G1 to S cell phase, leading to its degradation: ubiquitination is dependent on Thr-286 phosphorylation (PubMed:33854232, PubMed:33854235, PubMed:33854239). The DCX(AMBRA1) complex represents the major regulator of CCND1 stability during the G1/S transition (PubMed:33854232, PubMed:33854235, PubMed:33854239). Also ubiquitinated by the SCF(FBXO4) and Cul7-RING(FBXW8) ubiquitin-protein ligase complexes (PubMed:17205132). Following DNA damage it is ubiquitinated by the SCF(FBXO31) protein ligase complex (PubMed:19412162, PubMed:29279382). SCF(FBXO31) ubiquitination is dependent on Thr-286 phosphorylation (PubMed:10766840, PubMed:19412162, PubMed:29279382). Ubiquitinated also by UHRF2 apparently in a phosphorylation-independent manner (PubMed:21952639). Ubiquitination leads to its degradation and G1 arrest. Deubiquitinated by USP2; leading to its stabilization (PubMed:19917254). Ubiquitinated by FBXO32 at Lys-58 via 'Lys27'-linked polyubiquitination; leading to its stabilization (PubMed:40307251). {ECO:0000269|PubMed:10766840, ECO:0000269|PubMed:17205132, ECO:0000269|PubMed:19412162, ECO:0000269|PubMed:19917254, ECO:0000269|PubMed:21952639, ECO:0000269|PubMed:29279382, ECO:0000269|PubMed:33854232, ECO:0000269|PubMed:33854235, ECO:0000269|PubMed:33854239, ECO:0000269|PubMed:40307251}.
uniprot
proteins
protein_family
Cyclin D subfamily
uniprot
proteins
protein_family
Cyclin family
uniprot
proteins
pubmed
10766840
uniprot
proteins
pubmed
15241418
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16569215
uniprot
proteins
pubmed
17205132
uniprot
proteins
pubmed
1826542
uniprot
proteins
pubmed
1827756
uniprot
proteins
pubmed
1833066
uniprot
proteins
pubmed
1833629
uniprot
proteins
pubmed
18417529
uniprot
proteins
pubmed
19124461
uniprot
proteins
pubmed
19237565
uniprot
proteins
pubmed
19412162
uniprot
proteins
pubmed
19917254
uniprot
proteins
pubmed
20399237
uniprot
proteins
pubmed
21952639
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
29279382
uniprot
proteins
pubmed
33854232
uniprot
proteins
pubmed
33854235
uniprot
proteins
pubmed
33854239
uniprot
proteins
pubmed
40307251
uniprot
proteins
pubmed
7687458
uniprot
proteins
pubmed
8114739
uniprot
proteins
pubmed
8204893
uniprot
proteins
pubmed
8302605
uniprot
proteins
pubmed
8695815
uniprot
proteins
pubmed
9106657
uniprot
proteins
sequence_length
295
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20399237, ECO:0000269|PubMed:29279382, ECO:0000269|PubMed:40307251, ECO:0000269|PubMed:9106657}. Cytoplasm {ECO:0000269|PubMed:29279382, ECO:0000269|PubMed:9106657}. Nucleus membrane {ECO:0000269|PubMed:9106657}. Note=Cyclin D-CDK4 complexes accumulate at the nuclear membrane and are then translocated to the nucleus through interaction with KIP/CIP family members. {ECO:0000269|PubMed:9106657}.
uniprot
proteins