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

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Reviewed, UniProtKB/Swiss-Prot P24385 (CCND1_HUMAN)

Last modified June 16, 2009. Version 108. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    G1/S-specific cyclin-D1
Alternative name(s):
    PRAD1 oncogene
    BCL-1 oncogene

Gene names

Name:	CCND1
Synonyms:	BCL1, PRAD1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	295 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Essential for the control of the cell cycle at the G1/S (start) transition.
Subunit structure	Interacts with the CDK4 and CDK6 protein kinases to form a serine/threonine kinase holoenzyme complex. The cyclin subunit imparts substrate specificity to the complex. Ref.10
Post-translational modification	Phosphorylation at Thr-286 by MAP kinases is required for ubiquitination and degradation following DNA damage. It probably plays an essential role for recognition by the FBXO31 component of SCF (SKP1-cullin-F-box) protein ligase complex. Following DNA damage it is ubiquitinated by some SCF (SKP1-cullin-F-box) protein ligase complex containing FBXO31. Ubiquitination leads to its degradation and G1 arrest.
Involvement in disease	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. A chromosomal aberration involving CCND1 may be a cause of parathyroid adenomas [MIM:168461]. Translocation t(11;11)(q13;p15) with the parathyroid hormone (PTH) enhancer. A chromosomal aberration involving CCND1 may be a cause of multiple myeloma [MIM:254500]. Translocation t(11;14)(q13;q32) with the IgH locus.
Sequence similarities	Belongs to the cyclin family. Cyclin D subfamily.

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Ontologies

Keywords
Biological process	Cell cycle Cell division DNA damage
Coding sequence diversity	Chromosomal rearrangement
Disease	Proto-oncogene
Molecular function	Cyclin
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure
Gene Ontology (GO)
Biological process	G1 DNA damage checkpoint Ref.13 Inferred from direct assay. Source: UniProtKB G1/S transition of mitotic cell cycle Ref.13 Inferred from direct assay. Source: UniProtKB cell division Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of cyclin-dependent protein kinase activity Inferred from direct assay. Source: UniProtKB positive regulation of protein amino acid phosphorylation Inferred from direct assay. Source: UniProtKB response to UV-A Inferred from direct assay. Source: UniProtKB
Cellular component	cyclin-dependent protein kinase holoenzyme complex Inferred from direct assay. Source: UniProtKB cytosol Inferred from Experiment. Source: Reactome nucleoplasm Inferred from Experiment. Source: Reactome
Molecular function	protein kinase binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct
BRCA1	P38398	2	EBI-375001,EBI-349905
CDK4	P11802	6	EBI-375001,EBI-295644
CDK6	Q00534	1	EBI-375001,EBI-295663
CDKN1A	P38936	2	EBI-375001,EBI-375077
CDKN1B	P46527	2	EBI-375001,EBI-519280
MCM10	Q7L590	1	EBI-375001,EBI-374912
ORC4L	O43929	1	EBI-375001,EBI-374889
PPP1CB	P62140	1	EBI-375001,EBI-352350
PPP1CC	P36873-1	1	EBI-375001,EBI-356289

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 295

295

G1/S-specific cyclin-D1

PRO_0000080430

Amino acid modifications

Modified residue

226

Phosphotyrosine Ref.12

Modified residue

286

Phosphothreonine

Experimental info

Mutagenesis

286

T → A: Abolishes ubiquitination and subsequent degradation following DNA damage.

Sequence conflict

130

N → G in AAA52136. Ref.3

Sequence conflict

168 – 169

MP → IA in M74092. Ref.2

Sequence conflict

188

L → S in AAA52136. Ref.3

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Sequences

Sequence

Length

Mass (Da)

Tools

P24385-1 [UniParc].

Last modified March 1, 1992. Version 1.
Checksum: 3CC00C9905F58D3A
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FASTA

295

33,729

        10         20         30         40         50         60 
MEHQLLCCEV ETIRRAYPDA NLLNDRVLRA MLKAEETCAP SVSYFKCVQK EVLPSMRKIV 

        70         80         90        100        110        120 
ATWMLEVCEE QKCEEEVFPL AMNYLDRFLS LEPVKKSRLQ LLGATCMFVA SKMKETIPLT 

       130        140        150        160        170        180 
AEKLCIYTDN SIRPEELLQM ELLLVNKLKW NLAAMTPHDF IEHFLSKMPE AEENKQIIRK 

       190        200        210        220        230        240 
HAQTFVALCA TDVKFISNPP SMVAAGSVVA AVQGLNLRSP NNFLSYYRLT RFLSRVIKCD 

       250        260        270        280        290 
PDCLRACQEQ IEALLESSLR QAQQNMDPKA AEEEEEEEEE VDLACTPTDV RDVDI

« Hide

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel cyclin encoded by a bcl1-linked candidate oncogene." Motokura T., Bloom T., Kim H.G., Jueppner H., Ruderman J.V., Kronenberg H.M., Arnold A. Nature 350:512-515(1991) [PubMed: 1826542] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Isolation of three novel human cyclins by rescue of G1 cyclin (Cln) function in yeast." Lew D.J., Dulic V., Reed S.I. Cell 66:1197-1206(1991) [PubMed: 1833066] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Human D-type cyclin." Xiong Y., Connolly T., Futcher B., Beach D. Cell 65:691-699(1991) [PubMed: 1827756] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Characterization of a candidate bcl-1 gene." Withers D.A., Harvey R.C., Faust J.B., Melnyk O., Carey K., Meeker T.C. Mol. Cell. Biol. 11:4846-4853(1991) [PubMed: 1833629] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"Rearrangement of CCND1 (BCL1/PRAD1) 3' untranslated region in mantle-cell lymphomas and t(11q13)-associated leukemias." Rimokh R., Berger F., Bastard C., Klein B., French M., Archimbaud E., Rouault J.-P., Santa Lucia B., Duret L., Vuillaume M. Blood 83:3689-3696(1994) [PubMed: 8204893] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	"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 (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	NIEHS SNPs program Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Placenta.
[9]	"The PRAD1/cyclin D1 proto-oncogene: genomic organization, 5' DNA sequence, and sequence of a tumor-specific rearrangement breakpoint." Motokura T., Arnold A. Genes Chromosomes Cancer 7:89-95(1993) [PubMed: 7687458] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-66. Tissue: Placenta.
[10]	"CDK6 (PLSTIRE) and CDK4 (PSK-J3) are a distinct subset of the cyclin-dependent kinases that associate with cyclin D1." Bates S., Bonetta L., McAllan D., Parry D., Holder A., Dickson C., Peters G. Oncogene 9:71-79(1994) [PubMed: 8302605] [Abstract] Cited for: INTERACTION WITH CDK4 AND CDK6.
[11]	"Dysregulation of cyclin D1 by translocation into an IgH gamma switch region in two multiple myeloma cell lines." Chesi M., Bergsagel P.L., Brents L.A., Smith C.M., Gerhard D.S., Kuehl W.M. Blood 88:674-681(1996) [PubMed: 8695815] [Abstract] Cited for: INVOLVEMENT IN MULTIPLE MYELOMA.
[12]	"Tyrosine phosphorylated Par3 regulates epithelial tight junction assembly promoted by EGFR signaling." Wang Y., Du D., Fang L., Yang G., Zhang C., Zeng R., Ullrich A., Lottspeich F., Chen Z. EMBO J. 25:5058-5070(2006) [PubMed: 17053785] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-226, MASS SPECTROMETRY.
[13]	"F-box protein FBXO31 mediates cyclin D1 degradation to induce G1 arrest after DNA damage." Santra M.K., Wajapeyee N., Green M.R. Nature 0:0-0(2009) [PubMed: 19412162] [Abstract] Cited for: PHOSPHORYLATION AT THR-286, UBIQUITINATION, MUTAGENESIS OF THR-286.
+	Additional computationally mapped references.

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Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

SHMPD

The Singapore human mutation and polymorphism database

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Cross-references

Sequence databases

X59798 mRNA. Translation: CAA42470.1.
M74092 mRNA. No translation available.
M64349 mRNA. Translation: AAA52136.1.
M73554 mRNA. Translation: AAA58392.1.
Z23022 mRNA. Translation: CAA80558.1.
BT019845 mRNA. Translation: AAV38648.1.
AF511593 Genomic DNA. Translation: AAM34300.2.
BC000076 mRNA. Translation: AAH00076.1.
BC001501 mRNA. Translation: AAH01501.1.
BC014078 mRNA. Translation: AAH14078.1.
BC023620 mRNA. Translation: AAH23620.1.
BC025302 mRNA. Translation: AAH25302.1.
L09054 Genomic DNA. Translation: AAA36481.1.

IPI

IPI00028098.

PIR

A38977.

RefSeq

NP_444284.1.

UniGene

Hs.523852

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2W96	X-ray	2.30	A	1-271	[»]
2W99	X-ray	2.80	A	1-271	[»]
2W9F	X-ray	2.85	A	1-271	[»]
2W9Z	X-ray	2.45	A	16-271	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:123N.

IntAct

P24385. 10 interactions.

PTM databases

PhosphoSite

P24385.

Proteomic databases

PRIDE

P24385.

Genome annotation databases

Ensembl

ENSG00000110092. Homo sapiens. [Contig view]

GeneID

595.

KEGG

hsa:595.

Organism-specific databases

GeneCards

GC11P069165.

H-InvDB

HIX0009889.

HGNC

HGNC:1582. CCND1.

HPA

CAB000024.

MIM

168461. gene.
254500. phenotype.

Orphanet

67038. Leukemia, B-cell lymphocytic, chronic.

PharmGKB

PA75.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P24385.

HOVERGEN

P24385.

OMA

P24385. LCCEVET.

Enzyme and pathway databases

Pathway_Interaction_DB

wnt_canonical_pathway. Canonical Wnt signaling pathway.
ar_pathway. Coregulation of Androgen receptor activity.
foxm1pathway. FOXM1 transcription factor network.
trkrpathway. Neurotrophic factor-mediated Trk receptor signaling.
ps1pathway. Presenilin action in Notch and Wnt signaling.
telomerasepathway. Regulation of Telomerase.
p38gammadeltapathway. Signaling mediated by p38-gamma and p38-delta.
pi3kplctrkpathway. Trk receptor signaling mediated by PI3K and PLC-gamma.

Reactome

REACT_152. Cell Cycle, Mitotic.

Gene expression databases

ArrayExpress

P24385.

Bgee

P24385.

CleanEx

HS_CCND1.

GermOnline

ENSG00000110092. Homo sapiens.

Family and domain databases

InterPro

IPR015451. CycD.
IPR006670. Cyclin.
IPR014400. Cyclin_A_B_D_E.
IPR004367. Cyclin_C.
IPR006671. Cyclin_N.
IPR013763. Cyclin_related.
[Graphical view]

Gene3D

G3DSA:1.10.472.10. Cyclin_related. 1 hit.

PANTHER

PTHR10177:SF12. CycD. 1 hit.

Pfam

PF02984. Cyclin_C. 1 hit.
PF00134. Cyclin_N. 1 hit.
[Graphical view]

PIRSF

PIRSF001771. Cyclin_A_B_D_E. 1 hit.

SMART

SM00385. CYCLIN. 1 hit.
[Graphical view]

PROSITE

PS00292. CYCLINS. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB01169. Arsenic trioxide.

NextBio

2419.

SOURCE

Search...

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Entry information

Entry name

CCND1_HUMAN

Accession

Primary (citable) accession number: P24385
Secondary accession number(s): Q6LEF0

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 1992
Last sequence update:	March 1, 1992
Last modified:	June 16, 2009
This is version 108 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Amino acid modifications

Experimental info

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents