P30281 (CCND3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
G1/S-specific cyclin-D3

Gene names

Name:

CCND3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	292 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Regulatory component of the cyclin D3-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G1/S transition. 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 G1 phase. Hypophosphorylates RB1 in early G1 phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity. Component of the ternary complex, cyclin D3/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. Ref.11
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. Interacts with ATF5. Interacts with EIF3K. Component of the ternary complex cyclin D/CDK4/CDKN1B required for nuclear translocation and modulation of CDK4-mediated kinase activity. Can form similar complexes with either CDKN1A or CDKN2A. Ref.10 Ref.11 Ref.12 Ref.13
Subcellular location	Nucleus. Cytoplasm. Membrane. Note: Cyclin D-CDK4 complexes accumulate at the nuclear membrane and are then translocated to the nucleus through interaction with KIP/CIP family members By similarity. Ref.11
Sequence similarities	Belongs to the cyclin family. Cyclin D subfamily. Contains 1 cyclin N-terminal domain.

Ontologies

Keywords
Biological process	Cell cycle Cell division
Cellular component	Cytoplasm Membrane Nucleus
Coding sequence diversity	Polymorphism
Molecular function	Cyclin
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell division Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of cyclin-dependent protein kinase activity Inferred from direct assay. Source: BHF-UCL positive regulation of protein phosphorylation Inferred from direct assay. Source: BHF-UCL
Cellular component	cyclin-dependent protein kinase holoenzyme complex Inferred from direct assay. Source: BHF-UCL cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein kinase binding Inferred from physical interaction. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDK14	O94921	5	EBI-375013,EBI-1043945
CDK4	P11802	6	EBI-375013,EBI-295644
CDK6	Q00534	2	EBI-375013,EBI-295663
CDKN1A	P38936	3	EBI-375013,EBI-375077

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 292

292

G1/S-specific cyclin-D3

PRO_0000080442

Regions

Domain

27 – 152

126

Cyclin N-terminal

Amino acid modifications

Modified residue

263

1

Phosphoserine Ref.14

Modified residue

279

1

Phosphoserine Ref.15

Natural variations

Natural variant

134

1

P → S.
Corresponds to variant rs3218089 [ dbSNP | Ensembl ].

VAR_020412

Natural variant

253

1

E → D.
Corresponds to variant rs33966734 [ dbSNP | Ensembl ].

VAR_033726

Natural variant

259

1

S → A. Ref.1 Ref.3 Ref.5 Ref.7
Corresponds to variant rs1051130 [ dbSNP | Ensembl ].

VAR_014205

Secondary structure

1

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292

Helix Strand Turn

Details...

Helix

25 – 34

10

Helix

35 – 38

4

Turn

45 – 47

3

Turn

49 – 51

3

Helix

54 – 70

17

Helix

77 – 91

15

Helix

96 – 98

3

Turn

99 – 101

3

Helix

105 – 114

10

Helix

123 – 127

5

Turn

128 – 130

3

Helix

134 – 144

11

Helix

157 – 160

4

Helix

161 – 166

6

Turn

172 – 174

3

Helix

175 – 191

17

Helix

193 – 195

3

Helix

200 – 204

5

Helix

224 – 229

6

Helix

237 – 252

16

Sequences

	Sequence		Length	Mass (Da)
	P30281 [UniParc]. Last modified May 15, 2002. Version 2. Checksum: 16E7B1604FEB0029	FASTA	292	32,520
	10 20 30 40 50 60 MELLCCEGTR HAPRAGPDPR LLGDQRVLQS LLRLEERYVP RASYFQCVQR EIKPHMRKML 70 80 90 100 110 120 AYWMLEVCEE QRCEEEVFPL AMNYLDRYLS CVPTRKAQLQ LLGAVCMLLA SKLRETTPLT 130 140 150 160 170 180 IEKLCIYTDH AVSPRQLRDW EVLVLGKLKW DLAAVIAHDF LAFILHRLSL PRDRQALVKK 190 200 210 220 230 240 HAQTFLALCA TDYTFAMYPP SMIATGSIGA AVQGLGACSM SGDELTELLA GITGTEVDCL 250 260 270 280 290 RACQEQIEAA LRESLREASQ TSSSPAPKAP RGSSSQGPSQ TSTPTDVTAI HL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and chromosomal mapping of CCND genes encoding human D-type cyclins." Xiong Y., Menninger J., Beach D., Ward D.C. Genomics 13:575-584(1992) [PubMed: 1386336] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ALA-259.
[2]	"Cloning and characterization of human cyclin D3, a cDNA closely related in sequence to the PRAD1/cyclin D1 proto-oncogene." Motokura T., Keyomarsi K., Kronenberg H.M., Arnold A. J. Biol. Chem. 267:20412-20415(1992) [PubMed: 1383201] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	NIEHS SNPs program Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ALA-259.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Umbilical cord blood.
[5]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-259.
[6]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ALA-259.
[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: Lung.
[9]	"Genomic organization, chromosomal localization, and independent expression of human cyclin D genes." Inaba T., Matsushime H., Valentine M., Roussel M.F., Sherr C.J., Look A.T. Genomics 13:565-574(1992) [PubMed: 1386335] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 52-237. Tissue: Placenta.
[10]	"New functional activities for the p21 family of CDK inhibitors." LaBaer J., Garrett M.D., Stevenson L.F., Slingerland J.M., Sandhu C., Chou H.S., Fattaey A., Harlow E. Genes Dev. 11:847-862(1997) [PubMed: 9106657] [Abstract] Cited for: INTERACTION WITH CDK4 AND CDKN1A.
[11]	"Cyclin D3 interacts with human activating transcription factor 5 and potentiates its transcription activity." Liu W., Sun M., Jiang J., Shen X., Sun Q., Liu W., Shen H., Gu J. Biochem. Biophys. Res. Commun. 321:954-960(2004) [PubMed: 15358120] [Abstract] Cited for: INTERACTION WITH ATF5, FUNCTION, SUBCELLULAR LOCATION.
[12]	"Identification of the p28 subunit of eukaryotic initiation factor 3(eIF3k) as a new interaction partner of cyclin D3." Shen X., Yang Y., Liu W., Sun M., Jiang J., Zong H., Gu J. FEBS Lett. 573:139-146(2004) [PubMed: 15327989] [Abstract] Cited for: INTERACTION WITH EIF3K.
[13]	"Regulated activating Thr172 phosphorylation of cyclin-dependent kinase 4(CDK4): its relationship with cyclins and CDK 'inhibitors'." Bockstaele L., Kooken H., Libert F., Paternot S., Dumont J.E., de Launoit Y., Roger P.P., Coulonval K. Mol. Cell. Biol. 26:5070-5085(2006) [PubMed: 16782892] [Abstract] Cited for: INTERACTION WITH CDK4; CDKN2A AND CDKN1B.
[14]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-263, MASS SPECTROMETRY.
[15]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-279, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M90814 mRNA. Translation: AAA51927.1.
M92287 mRNA. Translation: AAA52137.1.
AF517525 Genomic DNA. Translation: AAM51826.1.
AK315421 mRNA. Translation: BAG37810.1.
CR542246 mRNA. Translation: CAG47042.1.
AL160163 Genomic DNA. Translation: CAI23491.1.
CH471081 Genomic DNA. Translation: EAX04071.1.
BC011616 mRNA. Translation: AAH11616.1.
M88087 , M88084, M88085, M88086 Genomic DNA. Translation: AAA51929.1.

IPI

IPI00025817.

PIR

B42822.

RefSeq

NP_001129489.1. NM_001136017.2.
NP_001129597.1. NM_001136125.1.
NP_001129598.1. NM_001136126.1.
NP_001751.1. NM_001760.3.

UniGene

Hs.534307.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3G33	X-ray	3.00	B/D	1-292	[»]

ProteinModelPortal

P30281.

SMR

P30281. Positions 23-254.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31734N.

IntAct

P30281. 23 interactions.

MINT

MINT-1201666.

STRING

P30281.

PTM databases

PhosphoSite

P30281.

Polymorphism databases

DMDM

20981685.

Proteomic databases

PRIDE

P30281.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000372991; ENSP00000362082; ENSG00000112576.

GeneID

896.

KEGG

hsa:896.

UCSC

uc003orn.1. human.

Organism-specific databases

CTD

896.

GeneCards

GC06M041949.

H-InvDB

HIX0005877.

HGNC

HGNC:1585. CCND3.

HPA

CAB000116.

MIM

123834. gene.

neXtProt

NX_P30281.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG12790.

GeneTree

ENSGT00560000076942.

HOGENOM

HBG713252.

HOVERGEN

HBG050837.

InParanoid

P30281.

OMA

ISGETEC.

OrthoDB

EOG4JWVF1.

PhylomeDB

P30281.

Enzyme and pathway databases

Pathway_Interaction_DB

ar_pathway. Coregulation of Androgen receptor activity.
il2_stat5pathway. IL2 signaling events mediated by STAT5.

Reactome

REACT_152. Cell Cycle, Mitotic.

Gene expression databases

ArrayExpress

P30281.

Bgee

P30281.

CleanEx

HS_CCND3.

Genevestigator

P30281.

GermOnline

ENSG00000112576. Homo sapiens.

Family and domain databases

InterPro

IPR013763. Cyclin-like.
IPR014400. Cyclin_A/B/D/E.
IPR004367. Cyclin_C.
IPR006671. Cyclin_N.
[Graphical view]

Gene3D

G3DSA:1.10.472.10. Cyclin_related. 2 hits.

KO

K10152.

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]

SUPFAM

SSF47954. Cyclin_like. 2 hits.

PROSITE

PS00292. CYCLINS. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

3702.

SOURCE

Search...

Entry information

Entry name

CCND3_HUMAN

Accession

Primary (citable) accession number: P30281
Secondary accession number(s): B2RD63 , Q5T8J0, Q6FG62, Q96F49

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	May 15, 2002
Last modified:	January 25, 2012
This is version 124 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.