CDK4_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: CDK4_MOUSE
• UniProt AC: P30285
• Protein Name: Cyclin-dependent kinase 4
• Gene Name: Cdk4
• Organism: Mus musculus (Mouse).
• Sequence Length: 303
• Subcellular Localization: Cytoplasm. Nucleus. Membrane. Cytoplasmic when non-complexed. Forms a cyclin D-CDK4 complex in the cytoplasm as cells progress through G(1) phase. The complex accumulates on the nuclear membrane and enters the nucleus on transition from G(1) to S pha
• Protein Description: Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes 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 phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex (By similarity)..
• Protein Sequence: MAATRYEPVAEIGVGAYGTVYKARDPHSGHFVALKSVRVPNGGAAGGGLPVSTVREVALLRRLEAFEHPNVVRLMDVCATSRTDRDIKVTLVFEHIDQDLRTYLDKAPPPGLPVETIKDLMRQFLSGLDFLHANCIVHRDLKPENILVTSNGTVKLADFGLARIYSYQMALTPVVVTLWYRAPEVLLQSTYATPVDMWSVGCIFAEMFRRKPLFCGNSEADQLGKIFDLIGLPPEDDWPREVSLPRGAFAPRGPRPVQSVVPEMEESGAQLLLEMLTFNPHKRISAFRALQHSYLHKEESDAE

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
2	Acetylation	------MAATRYEPV ------CCCCCEECC	19.96	-
78	Glutathionylation	VVRLMDVCATSRTDR EEEEEEHHHCCCCCC	2.73	24333276
172	Phosphorylation	YSYQMALTPVVVTLW EEHHHCCCCHHHHHH	12.42	22817900
293	Phosphorylation	AFRALQHSYLHKEES HHHHHHHHHHHHHHH	19.21	25619855
294	Phosphorylation	FRALQHSYLHKEESD HHHHHHHHHHHHHHC	15.65	25619855
300	Phosphorylation	SYLHKEESDAE---- HHHHHHHHCCC----	43.12	27087446

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
172	T	Phosphorylation	Kinase	CDK7	Q03147	PhosphoELM

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
172	T	Phosphorylation	In resting cells, phosphorylation on Thr-172 is prevented by the non-tyrosine-phosphorylated form of CDKN1B (By similarity).	8139570
172	T	Phosphorylation	Phosphorylation at Thr-172 is required for enzymatic activity.	8139570
172	T	Phosphorylation	Thus, in proliferating cells, CDK4 within the complex is phosphorylated on Thr-172 in the T-loop.	8139570

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of CDK4_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
CDN1B_MOUSE	Cdkn1b	physical	11967266
CDN1A_MOUSE	Cdkn1a	physical	11967266
RUNX3_HUMAN	RUNX3	physical	19351720
CCND1_MOUSE	Ccnd1	physical	17699765
CDN1B_MOUSE	Cdkn1b	physical	17699765
RB_MOUSE	Rb1	physical	15158336
CCND2_MOUSE	Ccnd2	physical	9584157
CDN1B_MOUSE	Cdkn1b	physical	8822197
RB_MOUSE	Rb1	physical	8547220
CEBPA_MOUSE	Cebpa	physical	20516642
CCND1_MOUSE	Ccnd1	physical	20516642
PSD10_MOUSE	Psmd10	physical	20516642
CCND3_MOUSE	Ccnd3	physical	11254678
RB_MOUSE	Rb1	physical	11254678
H11_MOUSE	Hist1h1a	physical	12007403
PCNA_MOUSE	Pcna	physical	12970760
CDN1A_MOUSE	Cdkn1a	physical	12970760
CCND1_MOUSE	Ccnd1	physical	12970760
H12_MOUSE	Hist1h1c	physical	12970760
CCND1_MOUSE	Ccnd1	physical	23707388
HS90A_MOUSE	Hsp90aa1	physical	11867521
CDC37_MOUSE	Cdc37	physical	11867521
CCND1_MOUSE	Ccnd1	physical	16331266
H15_MOUSE	Hist1h1b	physical	16627785
MEF2D_HUMAN	MEF2D	physical	25733682

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Phosphorylation

"Regulation of cyclin D-dependent kinase 4 (cdk4) by cdk4-activatingkinase.";
Kato J.-Y., Matsuoka M., Strom D.K., Sherr C.J.;
Mol. Cell. Biol. 14:2713-2721(1994).
Cited for: PHOSPHORYLATION AT THR-172.
PubMed: 8139570