P-selectin

Details

Name

P-selectin

Synonyms

• CD62 antigen-like family member P
• GMP-140
• GMRP
• Granule membrane protein 140
• GRMP
• LECAM3
• Leukocyte-endothelial cell adhesion molecule 3
• PADGEM
• Platelet activation dependent granule-external membrane protein

Gene Name

SELP

Organism

Humans

Amino acid sequence

>lcl|BSEQ0016331|P-selectin
MANCQIAILYQRFQRVVFGISQLLCFSALISELTNQKEVAAWTYHYSTKAYSWNISRKYC
QNRYTDLVAIQNKNEIDYLNKVLPYYSSYYWIGIRKNNKTWTWVGTKKALTNEAENWADN
EPNNKRNNEDCVEIYIKSPSAPGKWNDEHCLKKKHALCYTASCQDMSCSKQGECLETIGN
YTCSCYPGFYGPECEYVRECGELELPQHVLMNCSHPLGNFSFNSQCSFHCTDGYQVNGPS
KLECLASGIWTNKPPQCLAAQCPPLKIPERGNMTCLHSAKAFQHQSSCSFSCEEGFALVG
PEVVQCTASGVWTAPAPVCKAVQCQHLEAPSEGTMDCVHPLTAFAYGSSCKFECQPGYRV
RGLDMLRCIDSGHWSAPLPTCEAISCEPLESPVHGSMDCSPSLRAFQYDTNCSFRCAEGF
MLRGADIVRCDNLGQWTAPAPVCQALQCQDLPVPNEARVNCSHPFGAFRYQSVCSFTCNE
GLLLVGASVLQCLATGNWNSVPPECQAIPCTPLLSPQNGTMTCVQPLGSSSYKSTCQFIC
DEGYSLSGPERLDCTRSGRWTDSPPMCEAIKCPELFAPEQGSLDCSDTRGEFNVGSTCHF
SCDNGFKLEGPNNVECTTSGRWSATPPTCKGIASLPTPGLQCPALTTPGQGTMYCRHHPG
TFGFNTTCYFGCNAGFTLIGDSTLSCRPSGQWTAVTPACRAVKCSELHVNKPIAMNCSNL
WGNFSYGSICSFHCLEGQLLNGSAQTACQENGHWSTTVPTCQAGPLTIQEALTYFGGAVA
STIGLIMGGTLLALLRKRFRQKDDGKCPLNPHSHLGTYGVFTNAAFDPSP

Number of residues

830

Molecular Weight

90833.105

Theoretical pI

6.64

GO Classification

Functions

fucose binding / glycosphingolipid binding / heparin binding / lipopolysaccharide binding / oligosaccharide binding / sialic acid binding

Processes

blood coagulation / calcium-mediated signaling using intracellular calcium source / cell adhesion / defense response to Gram-negative bacterium / heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules / inflammatory response / leukocyte cell-cell adhesion / leukocyte migration / leukocyte tethering or rolling / platelet activation / platelet degranulation / positive regulation of cell adhesion / positive regulation of leukocyte migration / positive regulation of phosphatidylinositol 3-kinase signaling / positive regulation of platelet activation / regulation of cellular extravasation / regulation of integrin activation / response to lipopolysaccharide / response to organic cyclic compound

Components

cytoplasm / external side of plasma membrane / extracellular space / integral component of plasma membrane / nucleoplasm / plasma membrane / platelet alpha granule membrane / platelet dense granule membrane

General Function

Sialic acid binding

Specific Function

Ca(2+)-dependent receptor for myeloid cells that binds to carbohydrates on neutrophils and monocytes. Mediates the interaction of activated endothelial cells or platelets with leukocytes. The ligand recognized is sialyl-Lewis X. Mediates rapid rolling of leukocyte rolling over vascular surfaces during the initial steps in inflammation through interaction with PSGL1.

Pfam Domain Function

• Sushi (PF00084)
• Lectin_C (PF00059)

Transmembrane Regions

772-795

Cellular Location

Membrane

Gene sequence

>lcl|BSEQ0016332|P-selectin (SELP)
ATGGCCAACTGCCAAATAGCCATCTTGTACCAGAGATTCCAGAGAGTGGTCTTTGGAATT
TCCCAACTCCTTTGCTTCAGTGCCCTGATCTCTGAACTAACAAACCAGAAAGAAGTGGCA
GCATGGACTTATCATTACAGCACAAAAGCATACTCATGGAATATTTCCCGTAAATACTGC
CAGAATCGCTACACAGACTTAGTGGCCATCCAGAATAAAAATGAAATTGATTACCTCAAT
AAGGTCCTACCCTACTACAGCTCCTACTACTGGATTGGGATCCGAAAGAACAATAAGACA
TGGACATGGGTGGGAACCAAAAAGGCTCTCACCAACGAGGCTGAGAACTGGGCTGATAAT
GAACCTAACAACAAAAGGAACAACGAGGACTGCGTGGAGATATACATCAAGAGTCCGTCA
GCCCCTGGCAAGTGGAATGATGAGCACTGCTTGAAGAAAAAGCACGCATTGTGTTACACA
GCCTCCTGCCAGGACATGTCCTGCAGCAAACAAGGAGAGTGCCTCGAGACCATCGGGAAC
TACACCTGCTCCTGTTACCCTGGATTCTATGGGCCAGAATGTGAATACGTGAGAGAGTGT
GGAGAACTTGAGCTCCCTCAACACGTGCTCATGAACTGCAGCCACCCTCTGGGAAACTTC
TCTTTTAACTCGCAGTGCAGCTTCCACTGCACTGACGGGTACCAAGTAAATGGGCCCAGC
AAGCTGGAATGCTTGGCTTCTGGAATCTGGACAAATAAGCCTCCACAGTGTTTAGCTGCC
CAGTGCCCACCCCTGAAGATTCCTGAACGAGGAAACATGACCTGCCTTCATTCTGCAAAA
GCATTCCAGCATCAGTCTAGCTGCAGCTTCAGTTGTGAAGAGGGATTTGCATTAGTTGGA
CCGGAAGTGGTGCAATGCACAGCCTCGGGGGTATGGACAGCCCCAGCCCCAGTGTGTAAA
GCTGTGCAGTGTCAGCACCTGGAAGCCCCCAGTGAAGGAACCATGGACTGTGTTCATCCG
CTCACTGCTTTTGCCTATGGCTCCAGCTGTAAATTTGAGTGCCAGCCCGGCTACAGAGTG
AGGGGCTTGGACATGCTCCGCTGCATTGACTCTGGACACTGGTCTGCACCCTTGCCAACC
TGTGAGGCTATTTCGTGTGAGCCGCTGGAGAGTCCTGTCCACGGAAGCATGGATTGCTCT
CCATCCTTGAGAGCGTTTCAGTATGACACCAACTGTAGCTTCCGCTGTGCTGAAGGTTTC
ATGCTGAGAGGAGCCGATATAGTTCGGTGTGATAACTTGGGACAGTGGACAGCACCAGCC
CCAGTCTGTCAAGCTTTGCAGTGCCAGGATCTCCCAGTTCCAAATGAGGCCCGGGTGAAC
TGCTCCCACCCCTTCGGTGCCTTTAGGTACCAGTCAGTCTGCAGCTTCACCTGCAATGAA
GGCTTGCTCCTGGTGGGAGCAAGTGTGCTACAGTGCTTGGCTACTGGAAACTGGAATTCT
GTTCCTCCAGAATGCCAAGCCATTCCCTGCACACCTTTGCTAAGCCCTCAGAATGGAACA
ATGACCTGTGTTCAACCTCTTGGAAGTTCCAGTTATAAATCCACATGTCAATTCATCTGT
GACGAGGGATATTCTTTGTCTGGACCAGAAAGATTGGATTGTACTCGATCGGGACGCTGG
ACAGACTCCCCACCAATGTGTGAAGCCATCAAGTGCCCAGAACTCTTTGCCCCAGAGCAG
GGCAGCCTGGATTGTTCTGACACTCGTGGAGAATTCAATGTTGGCTCCACCTGCCATTTC
TCTTGTGACAACGGCTTTAAGCTGGAGGGGCCCAATAATGTGGAATGCACAACTTCTGGA
AGATGGTCAGCTACTCCACCAACCTGCAAAGGCATAGCATCACTTCCTACTCCAGGGGTG
CAATGTCCAGCCCTCACCACTCCTGGGCAGGGAACCATGTACTGTAGGCATCATCCGGGA
ACCTTTGGTTTTAATACCACTTGTTACTTTGGCTGCAACGCTGGATTCACACTCATAGGA
GACAGCACTCTCAGCTGCAGACCTTCAGGACAATGGACAGCAGTAACTCCAGCATGCAGA
GCTGTGAAATGCTCAGAACTACATGTTAATAAGCCAATAGCGATGAACTGCTCCAACCTC
TGGGGAAACTTCAGTTATGGATCAATCTGCTCTTTCCATTGTCTAGAGGGCCAGTTACTT
AATGGCTCTGCACAAACAGCATGCCAAGAGAATGGCCACTGGTCAACTACCGTGCCAACC
TGCCAAGCAGGACCATTGACTATCCAGGAAGCCCTGACTTACTTTGGTGGAGCGGTGGCT
TCTACGATAGGTCTGATAATGGGTGGGACGCTCCTGGCTTTGCTAAGAAAGCGTTTCAGA
CAAAAAGATGATGGGAAATGCCCCTTGAATCCTCACAGCCACCTAGGAACATATGGAGTT
TTTACAAACGCTGCATTTGACCCGAGTCCTTAA

Chromosome Location

1

Locus

1q22-q25

External Identifiers

Resource	Link
UniProtKB ID	P16109
UniProtKB Entry Name	LYAM3_HUMAN
GenBank Protein ID	183389
GenBank Gene ID	M60234
GenAtlas ID	SELP
HGNC ID	HGNC:10721

General References

1. Johnston GI, Cook RG, McEver RP: Cloning of GMP-140, a granule membrane protein of platelets and endothelium: sequence similarity to proteins involved in cell adhesion and inflammation. Cell. 1989 Mar 24;56(6):1033-44. [Article]
2. Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, McLaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM, Prigmore E: The DNA sequence and biological annotation of human chromosome 1. Nature. 2006 May 18;441(7091):315-21. [Article]
3. Fujimoto T, Stroud E, Whatley RE, Prescott SM, Muszbek L, Laposata M, McEver RP: P-selectin is acylated with palmitic acid and stearic acid at cysteine 766 through a thioester linkage. J Biol Chem. 1993 May 25;268(15):11394-400. [Article]
4. Sako D, Comess KM, Barone KM, Camphausen RT, Cumming DA, Shaw GD: A sulfated peptide segment at the amino terminus of PSGL-1 is critical for P-selectin binding. Cell. 1995 Oct 20;83(2):323-31. [Article]
5. Pouyani T, Seed B: PSGL-1 recognition of P-selectin is controlled by a tyrosine sulfation consensus at the PSGL-1 amino terminus. Cell. 1995 Oct 20;83(2):333-43. [Article]
6. Wilkins PP, Moore KL, McEver RP, Cummings RD: Tyrosine sulfation of P-selectin glycoprotein ligand-1 is required for high affinity binding to P-selectin. J Biol Chem. 1995 Sep 29;270(39):22677-80. [Article]
7. Florian V, Schluter T, Bohnensack R: A new member of the sorting nexin family interacts with the C-terminus of P-selectin. Biochem Biophys Res Commun. 2001 Mar 9;281(4):1045-50. [Article]
8. Knauth P, Schluter T, Czubayko M, Kirsch C, Florian V, Schreckenberger S, Hahn H, Bohnensack R: Functions of sorting nexin 17 domains and recognition motif for P-selectin trafficking. J Mol Biol. 2005 Apr 8;347(4):813-25. [Article]
9. Lewandrowski U, Moebius J, Walter U, Sickmann A: Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach. Mol Cell Proteomics. 2006 Feb;5(2):226-33. Epub 2005 Oct 31. [Article]
10. Kerr SC, Fieger CB, Snapp KR, Rosen SD: Endoglycan, a member of the CD34 family of sialomucins, is a ligand for the vascular selectins. J Immunol. 2008 Jul 15;181(2):1480-90. [Article]
11. Freedman SJ, Sanford DG, Bachovchin WW, Furie BC, Baleja JD, Furie B: Structure and function of the epidermal growth factor domain of P-selectin. Biochemistry. 1996 Oct 29;35(43):13733-44. [Article]
12. Bajorath J, Stenkamp R, Aruffo A: Knowledge-based model building of proteins: concepts and examples. Protein Sci. 1993 Nov;2(11):1798-810. [Article]
13. Somers WS, Tang J, Shaw GD, Camphausen RT: Insights into the molecular basis of leukocyte tethering and rolling revealed by structures of P- and E-selectin bound to SLe(X) and PSGL-1. Cell. 2000 Oct 27;103(3):467-79. [Article]
14. Herrmann SM, Ricard S, Nicaud V, Mallet C, Evans A, Ruidavets JB, Arveiler D, Luc G, Cambien F: The P-selectin gene is highly polymorphic: reduced frequency of the Pro715 allele carriers in patients with myocardial infarction. Hum Mol Genet. 1998 Aug;7(8):1277-84. [Article]
15. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [Article]
16. Zee RY, Cook NR, Cheng S, Reynolds R, Erlich HA, Lindpaintner K, Ridker PM: Polymorphism in the P-selectin and interleukin-4 genes as determinants of stroke: a population-based, prospective genetic analysis. Hum Mol Genet. 2004 Feb 15;13(4):389-96. Epub 2003 Dec 17. [Article]

Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB01109	Heparin	approved, investigational	unknown	inhibitor	Details
DB03721	N-acetyl-alpha-neuraminic acid	experimental	unknown		Details
DB08813	Nadroparin	approved, investigational	unknown	inhibitor	Details
DB06779	Dalteparin	approved	unknown	inhibitor	Details
DB15271	Crizanlizumab	approved, investigational	yes	inhibitor	Details