CTLA4_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: CTLA4_HUMAN
• UniProt AC: P16410
• Protein Name: Cytotoxic T-lymphocyte protein 4
• Gene Name: CTLA4
• Organism: Homo sapiens (Human).
• Sequence Length: 223
• Subcellular Localization: Cell membrane ; Single-pass type I membrane protein . Exists primarily an intracellular antigen whose surface expression is tightly regulated by restricted trafficking to the cell surface and rapid internalisation; .
• Protein Description: Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of their cognate stimulatory coreceptor CD28..
• Protein Sequence: MACLGFQRHKAQLNLATRTWPCTLLFFLLFIPVFCKAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDFLLWILAAVSSGLFFYSFLLTAVSLSKMLKKRSPLTTGVYVKMPPTEPECEKQFQPYFIPIN

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
55	Phosphorylation	ASSRGIASFVCEYAS HCCCCCEEEEEECCC	19.11	20049867
60	Phosphorylation	IASFVCEYASPGKAT CEEEEEECCCCCCCC	13.78	20049867
113	N-linked_Glycosylation	TSSGNQVNLTIQGLR CCCCCEEEEEECCCC	23.00	UniProtKB CARBOHYD
145	N-linked_Glycosylation	PYYLGIGNGTQIYVI CEEEEECCCCEEEEE	48.71	16002699
198	Phosphorylation	KKRSPLTTGVYVKMP HHCCCCCCEEEEECC	32.12	29978859
201	Phosphorylation	SPLTTGVYVKMPPTE CCCCCEEEEECCCCC	8.83	9973379
218	Phosphorylation	CEKQFQPYFIPIN-- HHHHCCCCEEECC--	11.89	11970985

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
201	Y	Phosphorylation	Kinase	JAK2	O60674	Uniprot
201	Y	Phosphorylation	Kinase	TXK	P42681	Uniprot
201	Y	Phosphorylation	Kinase	ZAP70	P43403	GPS
218	Y	Phosphorylation	Kinase	ZAP70	P43403	GPS

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of CTLA4_HUMAN !!

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of CTLA4_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
CD80_HUMAN	CD80	physical	7545666
CD86_HUMAN	CD86	physical	11279501
CTLA4_HUMAN	CTLA4	physical	11279502
FYN_HUMAN	FYN	physical	9712716
LCK_HUMAN	LCK	physical	9712716
LYN_HUMAN	LYN	physical	9712716
2A5A_HUMAN	PPP2R5A	physical	11994459
AP2M1_HUMAN	AP2M1	physical	9200449
JAK2_HUMAN	JAK2	physical	10842319
CD86_HUMAN	CD86	physical	21982860
CD80_HUMAN	CD80	physical	21982860
AP2M1_HUMAN	AP2M1	physical	9812899

Drug and Disease Associations

• Kegg Disease
• H00081: Hashimoto's thyroiditis
• H00082: Graves' disease
• H00083: Allograft rejection
• H00408: Type I diabetes mellitus
• OMIM Disease
• 152700: Systemic lupus erythematosus (SLE)
• : Note=Genetic variations in CTLA4 may influence susceptibility to Graves disease, an autoimmune disorder associated with overactivity of the thyroid gland and hyperthyroidism.
• 601388:
• 609755: Celiac disease 3 (CELIAC3)
• 616100: Autoimmune lymphoproliferative syndrome 5 (ALPS5)
• Kegg Drug
• D03222: Belatacept (USAN/INN); Nulojix (TN)
• D04603: Ipilimumab (USAN/INN); Yervoy (TN)
• D06657: Tremelimumab (USAN/INN); CP 675206
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

N-linked Glycosylation

"Rigid-body ligand recognition drives cytotoxic T-lymphocyte antigen 4(CTLA-4) receptor triggering.";
Yu C., Sonnen A.F., George R., Dessailly B.H., Stagg L.J., Evans E.J.,Orengo C.A., Stuart D.I., Ladbury J.E., Ikemizu S., Gilbert R.J.,Davis S.J.;
J. Biol. Chem. 286:6685-6696(2011).
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 36-161, GLYCOSYLATION ATASN-113, SUBUNIT, AND DISULFIDE BONDS.
PubMed: 21156796

"Hierarchical regulation of CTLA-4 dimer-based lattice formation andits biological relevance for T cell inactivation.";
Darlington P.J., Kirchhof M.G., Criado G., Sondhi J., Madrenas J.;
J. Immunol. 175:996-1004(2005).
Cited for: GLYCOSYLATION AT ASN-113 AND ASN-145.
PubMed: 16002699

Phosphorylation

"Resting lymphocyte kinase (Rlk/Txk) phosphorylates the YVKM motif andregulates PI 3-kinase binding to T-cell antigen CTLA-4.";
Schneider H., Schwartzberg P.L., Rudd C.E.;
Biochem. Biophys. Res. Commun. 252:14-19(1998).
Cited for: PHOSPHORYLATION AT TYR-201.
PubMed: 9813138

"Tyrosine phosphorylation controls internalization of CTLA-4 byregulating its interaction with clathrin-associated adaptor complexAP-2.";
Shiratori T., Miyatake S., Ohno H., Nakaseko C., Isono K.,Bonifacino J.S., Saito T.;
Immunity 6:583-589(1997).
Cited for: PHOSPHORYLATION AT TYR-201.
PubMed: 9175836