dbPTM

CCND1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	CCND1_HUMAN
UniProt AC	P24385
Protein Name	G1/S-specific cyclin-D1
Gene Name	CCND1
Organism	Homo sapiens (Human).
Sequence Length	295
Subcellular Localization	Nucleus . Cytoplasm . Membrane . Cyclin D-CDK4 complexes accumulate at the nuclear membrane and are then translocated to the nucleus through interaction with KIP/CIP family members..
Protein 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. 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. Hypophosphorylates RB1 in early G(1) 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 D1/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. Exhibits transcriptional corepressor activity with INSM1 on the NEUROD1 and INS promoters in a cell cycle-independent manner..
Protein Sequence	MEHQLLCCEVETIRRAYPDANLLNDRVLRAMLKAEETCAPSVSYFKCVQKEVLPSMRKIVATWMLEVCEEQKCEEEVFPLAMNYLDRFLSLEPVKKSRLQLLGATCMFVASKMKETIPLTAEKLCIYTDNSIRPEELLQMELLLVNKLKWNLAAMTPHDFIEHFLSKMPEAEENKQIIRKHAQTFVALCATDVKFISNPPSMVAAGSVVAAVQGLNLRSPNNFLSYYRLTRFLSRVIKCDPDCLRACQEQIEALLESSLRQAQQNMDPKAAEEEEEEEEEVDLACTPTDVRDVDI

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
33	Sumoylation	RVLRAMLKAEETCAP HHHHHHHHHHHHCCC	40.44	-
33	Ubiquitination	RVLRAMLKAEETCAP HHHHHHHHHHHHCCC	40.44	-
37	Phosphorylation	AMLKAEETCAPSVSY HHHHHHHHCCCCCCH	12.89	30177828
41	Phosphorylation	AEETCAPSVSYFKCV HHHHCCCCCCHHHHH	12.74	28355574
43	Phosphorylation	ETCAPSVSYFKCVQK HHCCCCCCHHHHHHH	29.23	30108239
44	Phosphorylation	TCAPSVSYFKCVQKE HCCCCCCHHHHHHHH	12.61	30177828
46	Methylation	APSVSYFKCVQKEVL CCCCCHHHHHHHHHH	25.84	-
46	Ubiquitination	APSVSYFKCVQKEVL CCCCCHHHHHHHHHH	25.84	-
50	Ubiquitination	SYFKCVQKEVLPSMR CHHHHHHHHHHHHHH	29.41	-
90	Phosphorylation	NYLDRFLSLEPVKKS HHHHHHHCCCCCCHH	28.16	22817900
95	Ubiquitination	FLSLEPVKKSRLQLL HHCCCCCCHHHHHHH	56.60	21906983
96	Ubiquitination	LSLEPVKKSRLQLLG HCCCCCCHHHHHHHH	40.83	-
111	Phosphorylation	ATCMFVASKMKETIP HHHHHHHHHCCCCCC	28.16	-
112	Ubiquitination	TCMFVASKMKETIPL HHHHHHHHCCCCCCC	44.23	-
114	Ubiquitination	MFVASKMKETIPLTA HHHHHHCCCCCCCCH	56.28	21906983
131	Phosphorylation	LCIYTDNSIRPEELL HHHCCCCCCCHHHHH	23.84	-
149	Ubiquitination	LLLVNKLKWNLAAMT HHHHHHHHHHHHHCC	35.33	-
167	Ubiquitination	FIEHFLSKMPEAEEN HHHHHHHCCCHHHHH	61.70	21906983
175	Ubiquitination	MPEAEENKQIIRKHA CCHHHHHHHHHHHHH	46.27	21906983
180	Ubiquitination	ENKQIIRKHAQTFVA HHHHHHHHHHHHHHH	32.65	-
197	Phosphorylation	ATDVKFISNPPSMVA HCCCHHHCCCHHHHH	46.55	22817900
219	Phosphorylation	VQGLNLRSPNNFLSY HHCCCCCCCCCHHHH	34.84	24719451
226	Phosphorylation	SPNNFLSYYRLTRFL CCCCHHHHHHHHHHH	8.51	17053785
234	Phosphorylation	YRLTRFLSRVIKCDP HHHHHHHHHHHCCCH	23.07	22817900
238	Ubiquitination	RFLSRVIKCDPDCLR HHHHHHHCCCHHHHH	29.72	21906983
257	Phosphorylation	QIEALLESSLRQAQQ HHHHHHHHHHHHHHH	34.34	28450419
258	Phosphorylation	IEALLESSLRQAQQN HHHHHHHHHHHHHHH	20.42	28450419
269	Ubiquitination	AQQNMDPKAAEEEEE HHHHCCHHHHHHHHH	56.83	1976777
286	Phosphorylation	EEVDLACTPTDVRDV HHCCCCCCCCCCCCC	24.50	10766840
288	Phosphorylation	VDLACTPTDVRDVDI CCCCCCCCCCCCCCC	29.04	10766840

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
90	S	Phosphorylation	Kinase	PRKACA	P17612	GPS
90	S	Phosphorylation	Kinase	PKA-FAMILY	-	GPS
90	S	Phosphorylation	Kinase	PKA_GROUP	-	PhosphoELM
197	S	Phosphorylation	Kinase	PRKACA	P17612	GPS
197	S	Phosphorylation	Kinase	PKA-FAMILY	-	GPS
197	S	Phosphorylation	Kinase	PKA_GROUP	-	PhosphoELM
234	S	Phosphorylation	Kinase	PRKACA	P17612	GPS
234	S	Phosphorylation	Kinase	PKA-FAMILY	-	GPS
234	S	Phosphorylation	Kinase	PKA_GROUP	-	PhosphoELM
286	T	Phosphorylation	Kinase	DYRK1A	Q13627	PSP
286	T	Phosphorylation	Kinase	GSK3B	P49841	PSP
286	T	Phosphorylation	Kinase	CHUK	O15111	GPS
286	T	Phosphorylation	Kinase	GSK-FAMILY	-	GPS
286	T	Phosphorylation	Kinase	IKK-FAMILY	-	GPS
286	T	Phosphorylation	Kinase	GSK-3_GROUP	-	PhosphoELM
288	T	Phosphorylation	Kinase	DYRK1B	Q9Y463	PSP
-	K	Ubiquitination	E3 ubiquitin ligase	FBXW8	Q8N3Y1	PMID:17205132
-	K	Ubiquitination	E3 ubiquitin ligase	UHRF2	Q96PU4	PMID:21952639
-	K	Ubiquitination	E3 ubiquitin ligase	BTRC	Q9Y297	PMID:24658274
-	K	Ubiquitination	E3 ubiquitin ligase	FBXO4	Q9UKT5	PMID:17081987
-	K	Ubiquitination	E3 ubiquitin ligase	FBXO31	Q5XUX0	PMID:20664978
-	K	Ubiquitination	E3 ubiquitin ligase	HACE1	Q8IYU2	PMID:17694067
-	K	Ubiquitination	E3 ubiquitin ligase	SKP2	Q13309	PMID:11439327

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
286	T	Phosphorylation	10766840
Phosphorylation at Thr-286 by MAP kinases is required for ubiquitination and degradation following DNA damage.
286	T	Phosphorylation	10766840
SCF-type ubiquitination is dependent on Thr-286 phosphorylation (By similarity).
286	T	ubiquitylation	10766840
Phosphorylation at Thr-286 by MAP kinases is required for ubiquitination and degradation following DNA damage.
286	T	ubiquitylation	10766840
SCF-type ubiquitination is dependent on Thr-286 phosphorylation (By similarity).

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of CCND1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
ANDR_HUMAN	AR	physical	15558026
HDAC3_HUMAN	HDAC3	physical	15558026
THB_HUMAN	THRB	physical	12048199
HDAC3_HUMAN	HDAC3	physical	12048199
CDK4_HUMAN	CDK4	physical	10580009
TAF1_HUMAN	TAF1	physical	9926939
TAF1_HUMAN	TAF1	physical	11126356
RB_HUMAN	RB1	physical	11126356
ESR1_HUMAN	ESR1	physical	9039267
STAT3_HUMAN	STAT3	physical	11279133
TSC2_HUMAN	TSC2	physical	16357142
RFC1_HUMAN	RFC1	physical	10353443
ANDR_HUMAN	AR	physical	10344732
PCNA_HUMAN	PCNA	physical	7908906
MYBB_MOUSE	Mybl2	physical	10645009
XPO1_HUMAN	XPO1	physical	12529437
CDK4_HUMAN	CDK4	physical	9837900
CDN1A_HUMAN	CDKN1A	physical	8657154
PCNA_HUMAN	PCNA	physical	8101826
CDN1B_HUMAN	CDKN1B	physical	15695403
CDN1A_HUMAN	CDKN1A	physical	15695403
INSM1_HUMAN	INSM1	physical	16569215
HSP7C_HUMAN	HSPA8	physical	18537972
CDK4_HUMAN	CDK4	physical	18537972
ESR1_HUMAN	ESR1	physical	16061635
HDAC1_HUMAN	HDAC1	physical	15713663
HDAC3_HUMAN	HDAC3	physical	15713663
STAT3_HUMAN	STAT3	physical	15659654
RB_HUMAN	RB1	physical	11593423
RB_HUMAN	RB1	physical	15485920
HDAC1_HUMAN	HDAC1	physical	20484017
HDAC3_HUMAN	HDAC3	physical	20484017
BRCA1_HUMAN	BRCA1	physical	17334399
CDK4_HUMAN	CDK4	physical	17205132
SKP1_HUMAN	SKP1	physical	17205132
CUL1_HUMAN	CUL1	physical	17205132
CUL7_HUMAN	CUL7	physical	17205132
FBX4_HUMAN	FBXO4	physical	17081987
SKP1_HUMAN	SKP1	physical	17081987
CUL1_HUMAN	CUL1	physical	17081987
FBX31_HUMAN	FBXO31	physical	19412162
CDN1A_HUMAN	CDKN1A	physical	17556661
UBP2_HUMAN	USP2	physical	19917254
UHRF2_HUMAN	UHRF2	physical	21952639
CDK1_HUMAN	CDK1	physical	7903056
PCNA_HUMAN	PCNA	physical	7903056
MCM7_HUMAN	MCM7	physical	12519773
MCM2_HUMAN	MCM2	physical	12519773
MCM3_HUMAN	MCM3	physical	12519773
MCM6_HUMAN	MCM6	physical	12519773
CDK4_HUMAN	CDK4	physical	12519773
ITLN1_HUMAN	ITLN1	genetic	22647378
CDK2_HUMAN	CDK2	physical	9178893
CDK4_HUMAN	CDK4	physical	9178893
CDK6_HUMAN	CDK6	physical	9178893
RB_HUMAN	RB1	physical	9178893
RB_HUMAN	RB1	physical	8647086
RB_HUMAN	RB1	physical	8867812
CDN1B_HUMAN	CDKN1B	physical	8978686
CDK4_HUMAN	CDK4	physical	8978686
CDN1B_HUMAN	CDKN1B	physical	19556892
CCND1_HUMAN	CCND1	physical	11940657
CDK4_HUMAN	CDK4	physical	12036906
CDN1B_HUMAN	CDKN1B	physical	12036906
CDK4_HUMAN	CDK4	physical	17420273
CDK6_HUMAN	CDK6	physical	17420273
CDN2A_HUMAN	CDKN2A	physical	17420273
ARF_HUMAN	CDKN2A	physical	17420273
CDN1A_HUMAN	CDKN1A	physical	17420273
FBXW8_HUMAN	FBXW8	physical	18650423
FBW1A_HUMAN	BTRC	physical	18650423
CUL1_HUMAN	CUL1	physical	18650423
RB_HUMAN	RB1	physical	10491434
UBF1_HUMAN	UBTF	physical	10202152
RB_HUMAN	RB1	physical	9190208
CDN1A_HUMAN	CDKN1A	physical	8756624
RB_HUMAN	RB1	physical	9003781
RB_HUMAN	RB1	physical	8662825
CDK4_HUMAN	CDK4	physical	8662825
ORC4_HUMAN	ORC4	physical	15232106
MCM10_HUMAN	MCM10	physical	15232106
CDK4_HUMAN	CDK4	physical	15232106
CDN1A_HUMAN	CDKN1A	physical	15232106
CDK6_HUMAN	CDK6	physical	15232106
RB_HUMAN	RB1	physical	12676926
P73_HUMAN	TP73	physical	12676926
CDN1B_HUMAN	CDKN1B	physical	17053782
RB_HUMAN	RB1	physical	9139732
CDK4_HUMAN	CDK4	physical	23718855
CDN1B_HUMAN	CDKN1B	physical	17254966
RB_HUMAN	RB1	physical	10486249
BRNP1_HUMAN	BRINP1	physical	21988832
CDN1A_HUMAN	CDKN1A	physical	21988832
LIPL_HUMAN	LPL	physical	21988832
RABE1_HUMAN	RABEP1	physical	21988832
RPA2_HUMAN	POLR1B	physical	21988832
FBX4_HUMAN	FBXO4	physical	24019069
CDK4_HUMAN	CDK4	physical	25416956
CDN1A_HUMAN	CDKN1A	physical	25416956
CDN1B_HUMAN	CDKN1B	physical	25416956
EP300_HUMAN	EP300	physical	15951563
BCAS3_HUMAN	BCAS3	physical	25640309
CAD13_HUMAN	CDH13	physical	25640309
KLK7_HUMAN	KLK7	physical	25640309
KLK9_HUMAN	KLK9	physical	25640309
ADT2_HUMAN	SLC25A5	physical	26496610
AT2B1_HUMAN	ATP2B1	physical	26496610
BTD_HUMAN	BTD	physical	26496610
CDK1_HUMAN	CDK1	physical	26496610
CDN1B_HUMAN	CDKN1B	physical	26496610
CDN2A_HUMAN	CDKN2A	physical	26496610
ARF_HUMAN	CDKN2A	physical	26496610
REV3L_HUMAN	REV3L	physical	26496610
CDK4_HUMAN	CDK4	physical	19767775
CDN1B_HUMAN	CDKN1B	physical	19767775
PSMD7_HUMAN	PSMD7	physical	19767775
CDK4_HUMAN	CDK4	physical	26203195
CDN1A_HUMAN	CDKN1A	physical	26203195
CDN1A_HUMAN	CDKN1A	physical	23007395
CDK4_HUMAN	CDK4	physical	23007395
CDK4_HUMAN	CDK4	physical	11160398
CDK6_HUMAN	CDK6	physical	11160398
CDC27_HUMAN	CDC27	physical	20439707
DTBP1_HUMAN	DTNBP1	physical	27130439
CDK4_HUMAN	CDK4	physical	27130439
CDN1B_HUMAN	CDKN1B	physical	28514442
CDN1C_HUMAN	CDKN1C	physical	28514442
CDN1A_HUMAN	CDKN1A	physical	28514442
CDN2C_HUMAN	CDKN2C	physical	28514442
TRHY_HUMAN	TCHH	physical	28514442
CDK5_HUMAN	CDK5	physical	28514442
CDK2_HUMAN	CDK2	physical	28514442
TSR3_HUMAN	TSR3	physical	28514442
CDK1_HUMAN	CDK1	physical	28514442
CDK4_HUMAN	CDK4	physical	28514442
CDK4_HUMAN	CDK4	physical	29142209
FBX4_HUMAN	FBXO4	physical	29142209

Drug and Disease Associations

Kegg Disease
H00006	Hairy-cell leukemia
H00010	Multiple myeloma
H00016	Oral cancer
H00017	Esophageal cancer
H00031	Breast cancer
H00047	Gallbladder cancer
H00055	Laryngeal cancer
H00559	von Hippel-Lindau syndrome
OMIM 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.
254500
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
DB01169	Arsenic trioxide

Regulatory Network of CCND1_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"F-box protein FBXO31 mediates cyclin D1 degradation to induce G1arrest after DNA damage."; Santra M.K., Wajapeyee N., Green M.R.; Nature 459:722-725(2009). Cited for: PHOSPHORYLATION AT THR-286, UBIQUITINATION, AND MUTAGENESIS OFTHR-286.	19412162 [Abstract]
"Tyrosine phosphorylated Par3 regulates epithelial tight junctionassembly 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). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-226, AND MASSSPECTROMETRY.	17053785 [Abstract]

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