CCND1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: CCND1_MOUSE
• UniProt AC: P25322
• Protein Name: G1/S-specific cyclin-D1
• Gene Name: Ccnd1
• Organism: Mus musculus (Mouse).
• Sequence Length: 295
• Subcellular Localization: Nucleus . Cytoplasm. Membrane. Cyclin D-CDK4 complexes accumulate at the nuclear membrane and are then translocated into 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 (By similarity)..
• Protein Sequence: MEHQLLCCEVETIRRAYPDTNLLNDRVLRAMLKTEETCAPSVSYFKCVQKEIVPSMRKIVATWMLEVCEEQKCEEEVFPLAMNYLDRFLSLEPLKKSRLQLLGATCMFVASKMKETIPLTAEKLCIYTDNSIRPEELLQMELLLVNKLKWNLAAMTPHDFIEHFLSKMPEADENKQTIRKHAQTFVALCATDVKFISNPPSMVAAGSVVAAMQGLNLGSPNNFLSCYRTTHFLSRVIKCDPDCLRACQEQIEALLESSLRQAQQNVDPKATEEEGEVEEEAGLACTPTDVRDVDI

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
46	Ubiquitination	APSVSYFKCVQKEIV CCCCCHHHHHHHHHH	25.84	19767775
238	Ubiquitination	HFLSRVIKCDPDCLR HHHHHHHCCCHHHHH	29.72	19767775
269	Ubiquitination	AQQNVDPKATEEEGE HHHCCCCCCCCCCCC	64.57	19767775
286	Phosphorylation	EEAGLACTPTDVRDV HHHCCCCCCCCCCCC	24.50	27087446
288	Phosphorylation	AGLACTPTDVRDVDI HCCCCCCCCCCCCCC	29.04	25619855

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
286	T	Phosphorylation	Kinase	DYRK1B	Q9Z188	PSP
286	T	Phosphorylation	Kinase	GSK3A	P49840	PSP
286	T	Phosphorylation	Kinase	GSK3B	Q9WV60	PSP
288	T	Phosphorylation	Kinase	DYR1B	Q9Z188	PhosphoELM
288	T	Phosphorylation	Kinase	GSK3B	Q9WV60	PSP
288	T	Phosphorylation	Kinase	MAP2K3	O09110	GPS
-	K	Ubiquitination	E3 ubiquitin ligase	Fbxo31	Q3TQF0	PMID:22199232
-	K	Ubiquitination	E3 ubiquitin ligase	Fbxo4	Q8CHQ0	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
286	T	Phosphorylation	Phosphorylation at Thr-286 by MAP kinases is required for ubiquitination and degradation following DNA damage.	17081987
286	T	Phosphorylation	SCF-type ubiquitination is dependent on Thr-286 phosphorylation.	17081987
286	T	ubiquitylation	Phosphorylation at Thr-286 by MAP kinases is required for ubiquitination and degradation following DNA damage.	17081987
286	T	ubiquitylation	SCF-type ubiquitination is dependent on Thr-286 phosphorylation.	17081987

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of CCND1_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
MYBB_MOUSE	Mybl2	physical	10645009
CRYAB_MOUSE	Cryab	physical	17081987
CDK4_MOUSE	Cdk4	physical	17081987
CDN1A_MOUSE	Cdkn1a	physical	17081987
CDK4_MOUSE	Cdk4	physical	17699765
CDN1B_MOUSE	Cdkn1b	physical	17699765
CDK4_MOUSE	Cdk4	physical	16102793
CDK6_MOUSE	Cdk6	physical	16102793
CDK4_MOUSE	Cdk4	physical	12588994
HSP7C_MOUSE	Hspa8	physical	12588994
CDN1A_MOUSE	Cdkn1a	physical	12588994
CDK4_MOUSE	Cdk4	physical	23707388
CDK4_MOUSE	Cdk4	physical	16627785
RB_MOUSE	Rb1	physical	9191053

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

Phosphorylation

"Phosphorylation-dependent ubiquitination of cyclin D1 by theSCF(FBX4-alphaB crystallin) complex.";
Lin D.I., Barbash O., Kumar K.G., Weber J.D., Harper J.W.,Klein-Szanto A.J., Rustgi A., Fuchs S.Y., Diehl J.A.;
Mol. Cell 24:355-366(2006).
Cited for: UBIQUITINATION, INTERACTION WITH FBXO4, INTERACTION WITH A UBIQUITINLIGASE COMPLEX CONTAINING CRYAB, SKP1, CUL1 AND FBXO4, MUTAGENESIS OFTHR-286, AND PHOSPHORYLATION AT THR-286.
PubMed: 17081987

Ubiquitylation

"Lysine 269 is essential for cyclin D1 ubiquitylation by theSCF(Fbx4/alphaB-crystallin) ligase and subsequent proteasome-dependentdegradation.";
Barbash O., Egan E., Pontano L.L., Kosak J., Diehl J.A.;
Oncogene 28:4317-4325(2009).
Cited for: UBIQUITINATION AT LYS-269, INTERACTION WITH CDKN1B AND CDK4, SUBUNIT,SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-269 AND THR-286.
PubMed: 19767775