dbPTM

S1PR1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	S1PR1_HUMAN
UniProt AC	P21453
Protein Name	Sphingosine 1-phosphate receptor 1
Gene Name	S1PR1
Organism	Homo sapiens (Human).
Sequence Length	382
Subcellular Localization	Cell membrane Multi-pass membrane protein. Endosome. Membrane raft. Recruited to caveolin-enriched plasma membrane microdomains in response to oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine. Ligand binding leads to receptor internal
Protein Description	G-protein coupled receptor for the bioactive lysosphingolipid sphingosine 1-phosphate (S1P) that seems to be coupled to the G(i) subclass of heteromeric G proteins. Signaling leads to the activation of RAC1, SRC, PTK2/FAK1 and MAP kinases. Plays an important role in cell migration, probably via its role in the reorganization of the actin cytoskeleton and the formation of lamellipodia in response to stimuli that increase the activity of the sphingosine kinase SPHK1. Required for normal chemotaxis toward sphingosine 1-phosphate. Required for normal embryonic heart development and normal cardiac morphogenesis. Plays an important role in the regulation of sprouting angiogenesis and vascular maturation. Inhibits sprouting angiogenesis to prevent excessive sprouting during blood vessel development. Required for normal egress of mature T-cells from the thymus into the blood stream and into peripheral lymphoid organs. Plays a role in the migration of osteoclast precursor cells, the regulation of bone mineralization and bone homeostasis (By similarity). Plays a role in responses to oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine by pulmonary endothelial cells and in the protection against ventilator-induced lung injury..
Protein Sequence	MGPTSVPLVKAHRSSVSDYVNYDIIVRHYNYTGKLNISADKENSIKLTSVVFILICCFIILENIFVLLTIWKTKKFHRPMYYFIGNLALSDLLAGVAYTANLLLSGATTYKLTPAQWFLREGSMFVALSASVFSLLAIAIERYITMLKMKLHNGSNNFRLFLLISACWVISLILGGLPIMGWNCISALSSCSTVLPLYHKHYILFCTTVFTLLLLSIVILYCRIYSLVRTRSRRLTFRKNISKASRSSEKSLALLKTVIIVLSVFIACWAPLFILLLLDVGCKVKTCDILFRAEYFLVLAVLNSGTNPIIYTLTNKEMRRAFIRIMSCCKCPSGDSAGKFKRPIIAGMEFSRSKSDNSSHPQKDEGDNPETIMSSGNVNSSS

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
4	O-linked_Glycosylation	----MGPTSVPLVKA ----CCCCCCCCCCC	36.31	55828475
5	O-linked_Glycosylation	---MGPTSVPLVKAH ---CCCCCCCCCCCC	25.52	55828481
10	Acetylation	PTSVPLVKAHRSSVS CCCCCCCCCCCCCHH	46.27	-
14	O-linked_Glycosylation	PLVKAHRSSVSDYVN CCCCCCCCCHHHHCC	25.81	OGP
30	N-linked_Glycosylation	DIIVRHYNYTGKLNI EEEEEECCCCCCEEE	23.05	12087059
30	N-linked_Glycosylation	DIIVRHYNYTGKLNI EEEEEECCCCCCEEE	23.05	12087059
36	N-linked_Glycosylation	YNYTGKLNISADKEN CCCCCCEEECCCCCC	29.65	UniProtKB CARBOHYD
129	Phosphorylation	GSMFVALSASVFSLL CCHHHHHHHHHHHHH	14.57	22210691
131	Phosphorylation	MFVALSASVFSLLAI HHHHHHHHHHHHHHH	21.96	22210691
143	Phosphorylation	LAIAIERYITMLKMK HHHHHHHHHHHHHHH	6.48	-
236	Phosphorylation	RTRSRRLTFRKNISK HHHHHHHHHHHHHHH	21.41	11583630
328	S-palmitoylation	AFIRIMSCCKCPSGD HHHHHHHCCCCCCCC	1.10	19619245
329	S-palmitoylation	FIRIMSCCKCPSGDS HHHHHHCCCCCCCCC	3.89	19619245
330	Acetylation	IRIMSCCKCPSGDSA HHHHHCCCCCCCCCC	54.21	7427797
331	S-palmitoylation	RIMSCCKCPSGDSAG HHHHCCCCCCCCCCC	1.70	19619245
341	Ubiquitination	GDSAGKFKRPIIAGM CCCCCCCCCCEEECC	61.83	-
351	Phosphorylation	IIAGMEFSRSKSDNS EEECCEECCCCCCCC	23.49	30266825
353	Phosphorylation	AGMEFSRSKSDNSSH ECCEECCCCCCCCCC	35.00	23403867
355	Phosphorylation	MEFSRSKSDNSSHPQ CEECCCCCCCCCCCC	43.18	23403867
358	Phosphorylation	SRSKSDNSSHPQKDE CCCCCCCCCCCCCCC	34.71	26471730
359	Phosphorylation	RSKSDNSSHPQKDEG CCCCCCCCCCCCCCC	45.50	23403867

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
236	T	Phosphorylation	Kinase	AKT1	P31749	Uniprot
236	T	Phosphorylation	Kinase	AKT-FAMILY	-	GPS
236	T	Phosphorylation	Kinase	PKB_GROUP	-	PhosphoELM

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
236	T	Phosphorylation		11583630
S1P-induced endothelial cell migration requires the PKB/AKT1-mediated phosphorylation of the third intracellular loop at the Thr-236 residue.

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
4	O-linked Glycosylation	13 (9)	R ⇒ S;G;C	rs41287280	Lymphocyte counts	27863252
5	O-linked Glycosylation	13 (8)	R ⇒ S;G;C	rs41287280	Lymphocyte counts	27863252

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
5HT1A_HUMAN	HTR1A	physical	11854302
PGFRB_HUMAN	PDGFRB	physical	12480944
GNAI3_HUMAN	GNAI3	physical	8626678
GNAI1_HUMAN	GNAI1	physical	8626678
TRIP6_HUMAN	TRIP6	physical	19293149
WWP2_HUMAN	WWP2	physical	21555855
PPAL_HUMAN	ACP2	physical	28514442
AT2B3_HUMAN	ATP2B3	physical	28514442
HXK3_HUMAN	HK3	physical	28514442
SRC_HUMAN	SRC	physical	28514442
GLP3L_HUMAN	GOLPH3L	physical	28514442
GNAQ_HUMAN	GNAQ	physical	28514442
AT12A_HUMAN	ATP12A	physical	28514442
CD47_HUMAN	CD47	physical	28514442
ARL10_HUMAN	ARL10	physical	28514442
GBG5_HUMAN	GNG5	physical	28514442
RASH_HUMAN	HRAS	physical	28514442
RAP2A_HUMAN	RAP2A	physical	28514442
LMBR1_HUMAN	LMBR1	physical	28514442
TTYH3_HUMAN	TTYH3	physical	28514442
GNA13_HUMAN	GNA13	physical	28514442
AT1A3_HUMAN	ATP1A3	physical	28514442
GRIN1_HUMAN	GPRIN1	physical	28514442
POTEF_HUMAN	POTEF	physical	28514442

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
There are no disease associations of PTM sites.
Kegg Drug
D04187	Fingolimod hydrochloride (JAN/USAN); Gilenya (TN)
D10001	Fingolimod (INN); Gilenya (TN)
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of S1PR1_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Akt-mediated phosphorylation of the G protein-coupled receptor EDG-1is required for endothelial cell chemotaxis."; Lee M.-J., Thangada S., Paik J.-H., Sapkota G.P., Ancellin N.,Chae S.-S., Wu M., Morales-Ruiz M., Sessa W.C., Alessi D.R., Hla T.; Mol. Cell 8:693-704(2001). Cited for: PHOSPHORYLATION AT THR-236, AND MUTAGENESIS OF THR-236.	11583630 [Abstract]

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