G1/S-specific cyclin-D1 - Homo sapiens

G1/S-specific cyclin-D1 (Homo sapiens)

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Subcellular Location Biology & Function Disease Associations Interactions Cross-References

General Information

Protein Information
Protein Name	G1/S-specific cyclin-D1
Accession Code	P24385
Gene	CCND1
Organism	Homo sapiens \| Human (Taxonomy: 9606)
Part of Reference Proteome?	Yes
Sequence (Length: 295)
MEHQLLCCEVETIRRAYPDANLLNDRVLRAMLKAEETCAPSVSYFKCVQKEVLPSMRKIVATWMLEVCEEQKCEEEVFPL AMNYLDRFLSLEPVKKSRLQLLGATCMFVASKMKETIPLTAEKLCIYTDNSIRPEELLQMELLLVNKLKWNLAAMTPHDF IEHFLSKMPEAEENKQIIRKHAQTFVALCATDVKFISNPPSMVAAGSVVAAVQGLNLRSPNNFLSYYRLTRFLSRVIKCD PDCLRACQEQIEALLESSLRQAQQNMDPKAAEEEEEEEEEVDLACTPTDVRDVDI

Structure Viewer (PDB: 6P8E)

Subcellular Location

Description
Nucleus {Experimental EvidencePubMed:20399237, Experimental EvidencePubMed:9106657}. Cytoplasm {Experimental EvidencePubMed:9106657}. Nucleus membrane {Experimental EvidencePubMed: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. {Experimental EvidencePubMed:9106657}.
Position in the Nuclear Envelope
Location	Location ID	Description
Nuclear Envelope	SL-0178	The nuclear envelope is a membrane system which surrounds the nucleoplasm of eukaryotic cells. It is composed of the nuclear lamina, nuclear pore complexes and two nuclear membranes. The space between the two membranes is called the nuclear intermembrane space.
Nuclear Membrane	SL-0182	The membrane surrounding the nucleus. This term is used when it is not known if the protein is found in or associated with the inner or outer nuclear membrane.
Membrane Topology
Topology	Source	Annotation Type
Unknown	UniProt	Sequence Analysis
Assigned Ontology terms

Cellular Component	Bicellular Tight Junction (GO:0005923) Cyclin D1-CDK4 Complex (GO:0097128) Cyclin-Dependent Protein Kinase Holoenzyme Complex (GO:0000307) Cytoplasm (GO:0005737) Cytosol (GO:0005829) Nuclear Membrane (GO:0031965) Nucleoplasm (GO:0005654) Nucleus (GO:0005634) Transcription Repressor Complex (GO:0017053)

Biology & Function

Description
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:1833066, PubMed:1827756, PubMed:8114739, PubMed:8302605, PubMed:19412162, PubMed:33854235). 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:1833066, PubMed:1827756, PubMed:8114739, PubMed:8302605, PubMed:19412162). Hypophosphorylates RB1 in early G(1) phase (PubMed:1833066, PubMed:1827756, PubMed:8114739, PubMed:8302605, PubMed:19412162). Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals (PubMed:1833066, PubMed:1827756, PubMed:8302605, PubMed:19412162). 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). {Experimental EvidencePubMed:15241418, Experimental EvidencePubMed:16569215, Experimental EvidencePubMed:1827756, Experimental EvidencePubMed:1833066, Experimental EvidencePubMed:18417529, Experimental EvidencePubMed:19412162, Experimental EvidencePubMed:33854235, Experimental EvidencePubMed:8114739, Experimental EvidencePubMed:8302605, Experimental EvidencePubMed:9106657}.
Assigned Ontology terms

Biological Process	Cell Division (GO:0051301) Cellular Response To DNA Damage Stimulus (GO:0006974) Endoplasmic Reticulum Unfolded Protein Response (GO:0030968) Fat Cell Differentiation (GO:0045444) G1/S Transition Of Mitotic Cell Cycle (GO:0000082) Lactation (GO:0007595) Leydig Cell Differentiation (GO:0033327) Liver Regeneration (GO:0097421) Mammary Gland Alveolus Development (GO:0060749) Mammary Gland Epithelial Cell Proliferation (GO:0033598) Mitotic Cell Cycle Phase Transition (GO:0044772) Mitotic G1 DNA Damage Checkpoint Signaling (GO:0031571) Negative Regulation Of Epithelial Cell Differentiation (GO:0030857) Negative Regulation Of Neuron Apoptotic Process (GO:0043524) Negative Regulation Of Transcription By RNA Polymerase II (GO:0000122) Neuron Differentiation (GO:0030182) Positive Regulation Of Cyclin-Dependent Protein Serine/Threonine Kinase Activity (GO:0045737) Positive Regulation Of G1/S Transition Of Mitotic Cell Cycle (GO:1900087) Positive Regulation Of G2/M Transition Of Mitotic Cell Cycle (GO:0010971) Positive Regulation Of Mammary Gland Epithelial Cell Proliferation (GO:0033601) Positive Regulation Of Protein Phosphorylation (GO:0001934) Protein Phosphorylation (GO:0006468) Re-Entry Into Mitotic Cell Cycle (GO:0000320) Regulation Of Cyclin-Dependent Protein Serine/Threonine Kinase Activity (GO:0000079) Response To Calcium Ion (GO:0051592) Response To Corticosterone (GO:0051412) Response To Estradiol (GO:0032355) Response To Estrogen (GO:0043627) Response To Ethanol (GO:0045471) Response To Iron Ion (GO:0010039) Response To Leptin (GO:0044321) Response To Magnesium Ion (GO:0032026) Response To Organonitrogen Compound (GO:0010243) Response To UV-A (GO:0070141) Response To Vitamin E (GO:0033197) Response To X-Ray (GO:0010165) Response To Xenobiotic Stimulus (GO:0009410) Wnt Signaling Pathway (GO:0016055)
Molecular Function	Cyclin-Dependent Protein Serine/Threonine Kinase Regulator Activity (GO:0016538) Enzyme Binding (GO:0019899) Histone Deacetylase Binding (GO:0042826) Proline-Rich Region Binding (GO:0070064) Protein Kinase Activity (GO:0004672) Protein Kinase Binding (GO:0019901) Protein-Containing Complex Binding (GO:0044877) Transcription Corepressor Activity (GO:0003714)

Disease associations

Description
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. {Experimental EvidencePubMed:1826542, Experimental EvidencePubMed:8204893, Experimental EvidencePubMed:8695815}. 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. {Experimental EvidencePubMed:1826542}. 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. {Experimental EvidencePubMed: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.
Database Associations
OMIM	168461 254500
DisGeNET	595

Protein-Protein Interactions

Interactions with Nuclear Envelope proteins (3 interactors)

Partner (NucEnvDB)		IntAct	Confidence score
P11802	Cyclin-dependent kinase 4	EBI-375341	0.98
P30285	Cyclin-dependent kinase 4	EBI-6988572	0.40
P59595	Nucleoprotein	EBI-25746873	0.58
Interactions with other proteins (67 interactors)

Partner (UniProt)		IntAct	Confidence score
O43929	Origin recognition complex subunit 4	EBI-375191	0.44
Q7L590	Protein MCM10 homolog (HsMCM10)	EBI-375236	0.44
P38936	Cyclin-dependent kinase inhibitor 1 (CDK-interacting protein 1) (Melanoma differentiation-associated protein 6) (MDA-6) (p21)	EBI-375359	0.96
Q00534	Cyclin-dependent kinase 6 (EC 2.7.11.22) (Cell division protein kinase 6) (Serine/threonine-protein kinase PLSTIRE)	EBI-375368	0.73
P46527	Cyclin-dependent kinase inhibitor 1B (Cyclin-dependent kinase inhibitor p27) (p27Kip1)	EBI-519440	0.86
P36873	Serine/threonine-protein phosphatase PP1-gamma catalytic subunit (PP-1G) (EC 3.1.3.16) (Protein phosphatase 1C catalytic subunit)	EBI-1207106	0.00
P62140	Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PP-1B) (PPP1CD) (EC 3.1.3.16) (EC 3.1.3.53)	EBI-1207225	0.00
P24941	Cyclin-dependent kinase 2 (EC 2.7.11.22) (Cell division protein kinase 2) (p33 protein kinase)	EBI-1245713	0.74
P38398	Breast cancer type 1 susceptibility protein (EC 2.3.2.27) (RING finger protein 53) (RING-type E3 ubiquitin transferase BRCA1)	EBI-1381572	0.46
Q9BQA1	Methylosome protein 50 (MEP-50) (Androgen receptor cofactor p44) (WD repeat-containing protein 77) (p44/Mep50)	EBI-2940933	0.35
O60477	BMP/retinoic acid-inducible neural-specific protein 1 (Deleted in bladder cancer protein 1)	EBI-3904862	0.37
P06858	Lipoprotein lipase (LPL) (EC 3.1.1.34) (Phospholipase A1) (EC 3.1.1.32)	EBI-3905646	0.37
Q9H9Y6	DNA-directed RNA polymerase I subunit RPA2 (RNA polymerase I subunit 2) (EC 2.7.7.6) (DNA-directed RNA polymerase I 135 kDa polypeptide) (RPA135)	EBI-3912891	0.37
Q15276	Rab GTPase-binding effector protein 1 (Rabaptin-4) (Rabaptin-5) (Rabaptin-5alpha) (Renal carcinoma antigen NY-REN-17)	EBI-3927352	0.37
Q61193	Ral guanine nucleotide dissociation stimulator-like 2 (RalGDS-like 2) (RalGDS-like factor) (Ras-associated protein RAB2L)	EBI-3956268	0.40
P11233	Ras-related protein Ral-A (EC 3.6.5.2)	EBI-3956368	0.27
Q62796	RalA-binding protein 1 (RalBP1) (Cytocentrin) (Dinitrophenyl S-glutathione ATPase) (DNP-SG ATPase) (EC 7.6.2.2, EC 7.6.2.3) (Ral-interacting protein 1)	EBI-3958451	0.40
O15211	Ral guanine nucleotide dissociation stimulator-like 2 (RalGDS-like 2) (RalGDS-like factor) (Ras-associated protein RAB2L)	EBI-3970188	0.44
P06400	Retinoblastoma-associated protein (p105-Rb) (p110-RB1) (pRb) (Rb) (pp110)	EBI-4479659	0.73
Q96PU4	E3 ubiquitin-protein ligase UHRF2 (EC 2.3.2.27) (Np95/ICBP90-like RING finger protein) (Np95-like RING finger protein) (Nuclear protein 97) (Nuclear zinc finger protein Np97) (RING finger protein 107) (RING-type E3 ubiquitin transferase UHRF2) (Ubiquitin-like PHD and RING finger domain-containing protein 2) (Ubiquitin-like-containing PHD and RING finger domains protein 2)	EBI-6051700	0.60
P51668	Ubiquitin-conjugating enzyme E2 D1 (EC 2.3.2.23) ((E3-independent) E2 ubiquitin-conjugating enzyme D1) (EC 2.3.2.24) (E2 ubiquitin-conjugating enzyme D1) (Stimulator of Fe transport) (SFT) (UBC4/5 homolog) (UbcH5) (Ubiquitin carrier protein D1) (Ubiquitin-conjugating enzyme E2(17)KB 1) (Ubiquitin-conjugating enzyme E2-17 kDa 1) (Ubiquitin-protein ligase D1)	EBI-6051865	0.44
Q29504	Ubiquitin-like modifier-activating enzyme 1 (EC 6.2.1.45) (Ubiquitin-activating enzyme E1)	EBI-6051865	0.44
O95273	Cyclin-D1-binding protein 1 (Grap2 and cyclin-D-interacting protein) (Human homolog of Maid)	EBI-7803086	0.40
P11142	Heat shock cognate 71 kDa protein (EC 3.6.4.10) (Heat shock 70 kDa protein 8) (Lipopolysaccharide-associated protein 1) (LAP-1) (LPS-associated protein 1)	EBI-6557805	0.40
P49841	Glycogen synthase kinase-3 beta (GSK-3 beta) (EC 2.7.11.26) (Serine/threonine-protein kinase GSK3B) (EC 2.7.11.1)	EBI-6594575	0.27
Q13761	Runt-related transcription factor 3 (Acute myeloid leukemia 2 protein) (Core-binding factor subunit alpha-3) (CBF-alpha-3) (Oncogene AML-2) (Polyomavirus enhancer-binding protein 2 alpha C subunit) (PEA2-alpha C) (PEBP2-alpha C) (SL3-3 enhancer factor 1 alpha C subunit) (SL3/AKV core-binding factor alpha C subunit)	EBI-8874899	0.46
Q9BU70	tRNA (adenine(37)-N6)-methyltransferase (EC 2.1.1.-) (tRNA methyltransferase O)	EBI-8996209	0.37
Q5T7W7	Thiosulfate sulfurtransferase/rhodanese-like domain-containing protein 2 (Rhodanese domain-containing protein 2)	EBI-8996222	0.37
O60729	Dual specificity protein phosphatase CDC14B (EC 3.1.3.16) (EC 3.1.3.48) (CDC14 cell division cycle 14 homolog B)	EBI-8996235	0.37
P49336	Cyclin-dependent kinase 8 (EC 2.7.11.22) (EC 2.7.11.23) (Cell division protein kinase 8) (Mediator complex subunit CDK8) (Mediator of RNA polymerase II transcription subunit CDK8) (Protein kinase K35)	EBI-8996248	0.37
P17936	Insulin-like growth factor-binding protein 3 (IBP-3) (IGF-binding protein 3) (IGFBP-3)	EBI-8996274	0.37
Q00597	Fanconi anemia group C protein (Protein FACC)	EBI-8996261	0.37
Q15797	Mothers against decapentaplegic homolog 1 (MAD homolog 1) (Mothers against DPP homolog 1) (JV4-1) (Mad-related protein 1) (SMAD family member 1) (SMAD 1) (Smad1) (hSMAD1) (Transforming growth factor-beta-signaling protein 1) (BSP-1)	EBI-8996300	0.37
Q96LZ3	Calcineurin subunit B type 2 (Calcineurin B-like protein) (CBLP) (Calcineurin BII) (CNBII) (PPP3R1-like) (Protein phosphatase 2B regulatory subunit 2) (Protein phosphatase 3 regulatory subunit B beta isoform)	EBI-8996287	0.37
Q9BYX2	TBC1 domain family member 2A (Armus) (Prostate antigen recognized and identified by SEREX 1) (PARIS-1)	EBI-8996313	0.37
Q8NHU6	Tudor domain-containing protein 7 (PCTAIRE2-binding protein) (Tudor repeat associator with PCTAIRE-2) (Trap)	EBI-8996326	0.37
Q9Y2H8	Zinc finger protein 510	EBI-8996339	0.37
Q9H6U6	BCAS3 microtubule associated cell migration factor (Breast carcinoma-amplified sequence 3) (GAOB1)	EBI-9066887	0.37
P55290	Cadherin-13 (Heart cadherin) (H-cadherin) (P105) (Truncated cadherin) (T-cad) (T-cadherin)	EBI-9066900	0.37
P49862	Kallikrein-7 (hK7) (EC 3.4.21.117) (Serine protease 6) (Stratum corneum chymotryptic enzyme) (hSCCE)	EBI-9066913	0.37
Q9UKQ9	Kallikrein-9 (EC 3.4.21.-) (Kallikrein-like protein 3) (KLK-L3)	EBI-9066926	0.37
P42771	Cyclin-dependent kinase inhibitor 2A (Cyclin-dependent kinase 4 inhibitor A) (CDK4I) (Multiple tumor suppressor 1) (MTS-1) (p16-INK4a) (p16-INK4) (p16INK4A)	EBI-9691857	0.49
Q96TE0	Cyclin-dependent kinase inhibitor 1B (Cyclin-dependent kinase inhibitor p27) (p27Kip1)	EBI-10201598	0.56
P20020	Plasma membrane calcium-transporting ATPase 1 (EC 7.2.2.10) (Plasma membrane calcium ATPase isoform 1) (PMCA1) (Plasma membrane calcium pump isoform 1)	EBI-11132222	0.35
P05141	ADP/ATP translocase 2 (ADP,ATP carrier protein 2) (ADP,ATP carrier protein, fibroblast isoform) (Adenine nucleotide translocator 2) (ANT 2) (Solute carrier family 25 member 5) [Cleaved into: ADP/ATP translocase 2, N-terminally processed]	EBI-11132222	0.35
P43251	Biotinidase (Biotinase) (EC 3.5.1.12)	EBI-11132222	0.35
P06493	Cyclin-dependent kinase 1 (CDK1) (EC 2.7.11.22) (EC 2.7.11.23) (Cell division control protein 2 homolog) (Cell division protein kinase 1) (p34 protein kinase)	EBI-11132222	0.53
O60673	DNA polymerase zeta catalytic subunit (EC 2.7.7.7) (Protein reversionless 3-like) (REV3-like) (hREV3)	EBI-11132222	0.35
Q5VK71	A-kinase anchor protein 8 (AKAP-8) (A-kinase anchor protein 95 kDa) (AKAP 95)	EBI-11602009	0.40
O43823	A-kinase anchor protein 8 (AKAP-8) (A-kinase anchor protein 95 kDa) (AKAP 95)	EBI-11602073	0.40
P49815	Tuberin (Tuberous sclerosis 2 protein)	EBI-11687054	0.40
Q9UJK0	18S rRNA aminocarboxypropyltransferase (EC 2.5.1.-) (20S S rRNA accumulation protein 3 homolog) (HsTsr3)	EBI-21832810	0.35
Q07283	Trichohyalin	EBI-21832810	0.35
Q00535	Cyclin-dependent kinase 5 (EC 2.7.11.1) (Cell division protein kinase 5) (Cyclin-dependent-like kinase 5) (Serine/threonine-protein kinase PSSALRE) (Tau protein kinase II catalytic subunit) (TPKII catalytic subunit)	EBI-21832810	0.35
P49918	Cyclin-dependent kinase inhibitor 1C (Cyclin-dependent kinase inhibitor p57) (p57Kip2)	EBI-21832810	0.35
P42773	Cyclin-dependent kinase 4 inhibitor C (Cyclin-dependent kinase 6 inhibitor) (p18-INK4c) (p18-INK6)	EBI-21832810	0.35
P10275	Androgen receptor (Dihydrotestosterone receptor) (Nuclear receptor subfamily 3 group C member 4)	EBI-15566960	0.54
O15379	Histone deacetylase 3 (HD3) (EC 3.5.1.98) (Protein deacetylase HDAC3) (EC 3.5.1.-) (Protein deacylase HDAC3) (EC 3.5.1.-) (RPD3-2) (SMAP45)	EBI-15567015	0.54
Q16656	Nuclear respiratory factor 1 (NRF-1) (Alpha palindromic-binding protein) (Alpha-pal)	EBI-15593340	0.51
Q5XUX0	F-box only protein 31	EBI-15777409	0.58
P30260	Cell division cycle protein 27 homolog (Anaphase-promoting complex subunit 3) (APC3) (CDC27 homolog) (CDC27Hs) (H-NUC)	EBI-15851991	0.50
P12830	Cadherin-1 (CAM 120/80) (Epithelial cadherin) (E-cadherin) (Uvomorulin) (CD antigen CD324) [Cleaved into: E-Cad/CTF1; E-Cad/CTF2; E-Cad/CTF3]	EBI-15852068	0.40
Q02224	Centromere-associated protein E (Centromere protein E) (CENP-E) (Kinesin-7) (Kinesin-related protein CENPE)	EBI-16716754	0.35
O95239	Chromosome-associated kinesin KIF4A (Chromokinesin-A)	EBI-16716754	0.35
O94880	PHD finger protein 14	EBI-16716754	0.35
Q9UH17	DNA dC->dU-editing enzyme APOBEC-3B (A3B) (EC 3.5.4.38) (Phorbolin-1-related protein) (Phorbolin-2/3)	EBI-25296686	0.27
P12004	Proliferating cell nuclear antigen (PCNA) (Cyclin)	EBI-26956397	0.44

Cross-References

Database	Links
UNIPROT	P24385 Q6LEF0
PDB	2W96 2W99 2W9F 2W9Z 5VZU 6P8E 6P8F 6P8G 6P8H
Pfam	PF02984 PF00134
PROSITE	PS00292
OMIM	168461 254500
DisGeNET	595

G1/S-specific cyclin-D1 (Homo sapiens)

General Information

Protein Information

Structure Viewer (PDB: 6P8E)

Subcellular Location

Description Show

Position in the Nuclear Envelope

Membrane Topology

Assigned Ontology terms

Biology & Function

Description Hide

Assigned Ontology terms

Disease associations

Description

Database Associations

Protein-Protein Interactions

Interactions with Nuclear Envelope proteins (3 interactors)

Interactions with other proteins (67 interactors)

Cross-References

Database

Links

Description

Description