Q14242 (SELPL_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified April 3, 2013. Version 118. History...
Names and origin
|Protein names||Recommended name:|
P-selectin glycoprotein ligand 1
Selectin P ligand
|Organism||Homo sapiens (Human) [Reference proteome]|
|Taxonomic identifier||9606 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo|
|Sequence length||412 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
A SLe(x)-type glycan, which through high affinity, calcium-dependent interactions with E-, P- and L-selectins, mediates rapid rolling of leukocytes over vascular surfaces during the initial steps in inflammation. PSGL1 is critical for the initial leukocyte capture. Ref.13 Ref.15
Homodimer; disulfide-linked. Interaction with P-, E- and L-selectins, through their lectin/EGF domains, is required for promoting recruitment and rolling of leukocytes. These interactions require sialyl Lewis X glycan modification but there is a differing dependence for tyrosine sulfations. Sulfation on Tyr-51 of PSGL1 is most important for high affinity L-selectin/SELL binding while P-selectin/SELP requires sulfation on Tyr-48. E-selectin/SELE binds with much lower affinity and requires the sLe(x) epitope, but apparantly not tyrosine sulfation. Dimerization appears not to be required for P-selectin/SELP binding. Interacts with SNX20. Interacts with MSN and SYK; mediates the activation of SYK by SELPLG. Ref.7 Ref.8 Ref.9 Ref.10 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17
Expressed on neutrophils, monocytes and most lymphocytes.
Displays complex, core-2, sialylated and fucosylated O-linked oligosaccharides, at least some of which appear to contain poly-N-acetyllactosamine with varying degrees of substitution. Mainly disialylated or neutral forms of the core-2 tetrasaccharide, Galbeta1-->4GlcNAcbeta1-->6(Galbeta1-->3)GalNAcOH. The GlcN:GalN ratio is approximately 2:1 and the Man:Fuc ratio 3:5. Contains about 14% fucose with alpha-1,3 linkage present in two forms: One species is a disialylated, monofucosylated glycan, and the other, a monosialylated, trifucosylated glycan with a polylactosamine backbone. The fucosylated forms carry the Lewis antigen and are important for interaction with selectins and for functioning in leukocyte rolling. The modification containing the sialyl Lewis X glycan is on Thr-57. No sulfated O-glycans. Some N-glycosylation.
Sulfation, in conjunction with the SLe(x)-containing glycan, is necessary for P- and L-selectin binding. High affinity P-selectin binding has a preferred requirement for the isomer sulfated on both Tyr-48 and Tyr-51, whereas L-selectin binding requires predominantly sulfation on Tyr-51 with sulfation on Tyr-48 playing only a minor role. These sulfations play an important role in L- and P-selectin-mediated neutrophil recruitment, and leukocyte rolling.
|Biological process||Cell adhesion|
|Coding sequence diversity||Alternative splicing|
|PTM||Cleavage on pair of basic residues|
Pyrrolidone carboxylic acid
Direct protein sequencing
|Gene Ontology (GO)|
Traceable author statement. Source: Reactomecell adhesioncellular response to interleukin-6leukocyte adhesive activation
Inferred from sequence or structural similarity. Source: UniProtKBleukocyte tethering or rolling
Inferred from electronic annotation. Source: InterPro
|Cellular_component||integral to plasma membrane|
|Molecular_function||bacterial cell surface bindingreceptor binding|
|Complete GO annotation...|
|This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]|
|Isoform 1 (identifier: Q14242-1) |
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
|Isoform 2 (identifier: Q14242-2) |
The sequence of this isoform differs from the canonical sequence as follows:
1-1: M → MAVGASGLEGDKMAGAM
|Note: No experimental confirmation available.|
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Signal peptide||1 – 17||17||Potential|
|Propeptide||18 – 41||24||PRO_0000022302|
|Chain||42 – 412||371||P-selectin glycoprotein ligand 1||PRO_0000022303|
|Topological domain||18 – 320||303||Extracellular Potential|
|Transmembrane||321 – 341||21||Helical; Potential|
|Topological domain||342 – 412||71||Cytoplasmic Potential|
|Repeat||122 – 131||10||1|
|Repeat||132 – 141||10||2|
|Repeat||142 – 151||10||3|
|Repeat||162 – 171||10||4|
|Repeat||182 – 191||10||5|
|Repeat||192 – 201||10||6|
|Repeat||202 – 211||10||7|
|Repeat||212 – 221||10||8|
|Repeat||222 – 231||10||9|
|Repeat||232 – 241||10||10|
|Repeat||242 – 251||10||11|
|Repeat||252 – 261||10||12|
|Region||122 – 261||140||12 X 10 AA tandem repeats|
Amino acid modifications
|Modified residue||42||1||Pyrrolidone carboxylic acid|
|Modified residue||46||1||Sulfotyrosine Ref.19|
|Modified residue||48||1||Sulfotyrosine Ref.19|
|Modified residue||51||1||Sulfotyrosine Ref.19|
|Glycosylation||57||1||O-linked (GalNAc...) Ref.19|
|Glycosylation||65||1||N-linked (GlcNAc...) Potential|
|Glycosylation||111||1||N-linked (GlcNAc...) Potential|
|Glycosylation||302||1||N-linked (GlcNAc...) Potential|
|Disulfide bond||320||Interchain Ref.12|
|Alternative sequence||1||1||M → MAVGASGLEGDKMAGAM in isoform 2.||VSP_044827|
|Natural variant||62||1||M → I. Ref.3 Ref.4|
Corresponds to variant rs2228315 [ dbSNP | Ensembl ].
|Natural variant||132 – 141||10||Missing in short form; not an alternative splicing. |
Corresponds to variant rs63748999 [ dbSNP | Ensembl ].
|Natural variant||246||1||P → S. Ref.4|
Corresponds to variant rs8179142 [ dbSNP | Ensembl ].
|Mutagenesis||44||1||T → A: No effect on L-selectin binding nor neutrophil rolling. Ref.15|
|Mutagenesis||46 – 52||7||YEYLDYD → FEFLDFE: No sulfation. Almost complete loss of P-selectin binding. No effect on E-selectin binding. Ref.8 Ref.9|
|Mutagenesis||46 – 51||6||YEYLDY → FEFLDF: No sulfation. Almost complete loss of P-selectin binding. No effect on E-selectin binding. Ref.9 Ref.15|
|Mutagenesis||46||1||Y → F: Binding L-selectin reduced by 20%, neutrophil recruitment reduced by 30%, and lymphocyte rolling reduced by 32%; when associated with F-48. Binding L-selectin reduced by 86%, neutrophil recruitment reduced by 75%, and lymphocyte rolling reduced by 69%; when associated with F-51. Binding L-selectin reduced by 89%, and neutrophil recruitment reduced by 90%; when associated with F-48 and F-51. Binding of L-selectin reduced by 91%; when associated with F-48; F-51 and A-57. Ref.9|
|Mutagenesis||48||1||Y → F: Binding L-selectin reduced by 20%, neutrophil recruitment reduced by 30%, and lymphocyte rolling reduced by 32%; when associated with F-46. Binding L-lectin reduced by 31%, neutrophil recruitment reduced by 52%, and lymphocyte rolling reduced by 52%; when associated with F-51. Binding L-selectin reduced by 89%, and neutrophil recruitment reduced by 90%; when associated with F-46 and F-51. Binding of L-selectin reduced by 91%; when associated with F-46; F-51 and A-57. Ref.9 Ref.15|
|Mutagenesis||51||1||Y → F: Binding L-selectin reduced by 86%, neutrophil recruitment reduced by 75% and, lymphocyte rolling reduced by 69%; when associated with F-46. Binding L-selectin reduced by 31%, neutrophil recruitment reduced by 52%, and lymphocyte rolling reduced by 52%; when associated with F-48; Binding L-selectin reduced by 89%, and neutrophil recruitment reduced by 90%; when associated with F-46 and F-48. Binding of L-selectin reduced by 91%; when associated with F-46; F-48 and A-57. Ref.9 Ref.15|
|Mutagenesis||57||1||T → A: No E- nor P-selectin binding, and very little neutrophil rolling. Binding of L-selectin reduced by 91%; when associated with F-46; F-48 and F-51. Ref.9 Ref.15|
|Mutagenesis||320||1||C → A or S: No dimer formation. No effect on P-selectin binding. Ref.12|
|Sequence conflict||23 – 39||17||Missing in BAC05283. Ref.3|
|Sequence conflict||50||1||D → E in BAC05283. Ref.3|
|Sequence conflict||219||1||M → T in BAC05283. Ref.3|
|Sequence conflict||222||1||Q → R in BAH12863. Ref.3|
|Sequence conflict||396||1||P → A in BAC05283. Ref.3|
Helix Strand Turn
|Turn||51 – 53||3|
|||"Genomic organization and chromosomal localization of the gene encoding human P-selectin glycoprotein ligand."|
Veldman G.M., Bean K.M., Cumming D.A., Eddy R.L., Sait S.N.J., Shows T.B.
J. Biol. Chem. 270:16470-16475(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
|||"Expression cloning of a functional glycoprotein ligand for P-selectin."|
Sako D., Chang X.J., Barone K.M., Vachino G., White H.M., Shaw G., Veldman G.M., Bean K.M., Ahern T.J., Furie B., Cumming D.A., Larsen G.R.
Cell 75:1179-1186(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT 132-GLN--ALA-141 DEL.
|||"Complete sequencing and characterization of 21,243 full-length human cDNAs."|
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANTS ILE-62 AND 132-GLN--ALA-141 DEL.
|||SeattleSNPs variation discovery resource|
Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ILE-62 AND SER-246.
|||"The finished DNA sequence of human chromosome 12."|
Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. Gibbs R.A.
Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
|||"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."|
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT 132-GLN--ALA-141 DEL.
|||"The P-selectin glycoprotein ligand from human neutrophils displays sialylated, fucosylated, O-linked poly-N-acetyllactosamine."|
Moore K.L., Eaton S.F., Lyons D.E., Lichenstein H.S., Cummings R.D., McEver R.P.
J. Biol. Chem. 269:23318-23327(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 350-355 AND 390-396, INTERACTION WITH SELP AND SELE, STRUCTURE OF CARBOHYDRATE, SUBUNIT, SIALIC ACID CONTENT.
|||"A sulfated peptide segment at the amino terminus of PSGL-1 is critical for P-selectin binding."|
Sako D., Comess K.M., Barone K.M., Camphausen R.T., Cumming D.A., Shaw G.D.
Cell 83:323-331(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: SULFATION, INTERACTION WITH SELP, MUTAGENESIS OF 46-TYR--ASP-52.
|||"PSGL-1 recognition of P-selectin is controlled by a tyrosine sulfation consensus at the PSGL-1 amino terminus."|
Pouyani T., Seed B.
Cell 83:333-343(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: SULFATION, INTERACTION WITH SELP, MUTAGENESIS OF TYR-46; TYR-48; TYR-51 AND THR-57.
|||"Tyrosine sulfation of P-selectin glycoprotein ligand-1 is required for high affinity binding to P-selectin."|
Wilkins P.P., Moore K.L., McEver R.P., Cummings R.D.
J. Biol. Chem. 270:22677-22680(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: SULFATION, INTERACTION WITH SELP.
|||"Structures of the O-glycans on P-selectin glycoprotein ligand-1 from HL-60 cells."|
Wilkins P.P., McEver R.P., Cummings R.D.
J. Biol. Chem. 271:18732-18742(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE OF O-LINKED CARBOHYDRATES.
|||"Noncovalent association of P-selectin glycoprotein ligand-1 and minimal determinants for binding to P-selectin."|
Epperson T.K., Patel K.D., McEver R.P., Cummings R.D.
J. Biol. Chem. 275:7839-7853(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SELP, DISULFIDE BOND AT CYS-320, MUTAGENESIS OF CYS-320.
|||"Tyrosine sulfation enhances but is not required for PSGL-1 rolling adhesion on P-selectin."|
Rodgers S.D., Camphausen R.T., Hammer D.A.
Biophys. J. 81:2001-2009(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SELE AND SELP, SULFATION, FUNCTION.
|||"ITAM-based interaction of ERM proteins with Syk mediates signaling by the leukocyte adhesion receptor PSGL-1."|
Urzainqui A., Serrador J.M., Viedma F., Yanez-Mo M., Rodriguez A., Corbi A.L., Alonso-Lebrero J.L., Luque A., Deckert M., Vazquez J., Sanchez-Madrid F.
Immunity 17:401-412(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MSN AND SYK.
|||"Molecular basis of leukocyte rolling on PSGL-1. Predominant role of core-2 O-glycans and of tyrosine sulfate residue 51."|
Bernimoulin M.P., Zeng X.-L., Abbal C., Giraud S., Martinez M., Michielin O., Schapira M., Spertini O.
J. Biol. Chem. 278:37-47(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SELL, FUNCTION, MUTAGENESIS OF THR-44; TYR-48; TYR-51 AND THR-57.
|||"Model glycosulfopeptides from P-selectin glycoprotein ligand-1 require tyrosine sulfation and a core 2-branched O-glycan to bind to L-selectin."|
Leppaenen A., Yago T., Otto V.I., McEver R.P., Cummings R.D.
J. Biol. Chem. 278:26391-26400(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SELL, SULFATION, GLYCOSYLATION.
|||"SLIC-1/sorting nexin 20: a novel sorting nexin that directs subcellular distribution of PSGL-1."|
Schaff U.Y., Shih H.H., Lorenz M., Sako D., Kriz R., Milarski K., Bates B., Tchernychev B., Shaw G.D., Simon S.I.
Eur. J. Immunol. 38:550-564(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SNX20.
|||"A quantitative atlas of mitotic phosphorylation."|
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
|||"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."|
Somers W.S., Tang J., Shaw G.D., Camphausen R.T.
Cell 103:467-479(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 42-68 IN COMPLEX WITH SELE AND SELP LECTIN/EGF DOMAINS, SULFATION AT TYR-46; TYR-48 AND TYR-51, GLYCOSYLATION AT THR-57, PYROGLUTAMATE FORMATION AT GLN-42.
Somers W.S., Tang J., Shaw G.D., Camphausen R.T.
|+||Additional computationally mapped references.|
|U25956 Genomic DNA. Translation: AAA74577.1.|
U02297 mRNA. Translation: AAC50061.1.
AK098315 mRNA. Translation: BAC05283.1.
AK290395 mRNA. Translation: BAF83084.1.
AK298738 mRNA. Translation: BAG60885.1.
AK298742 mRNA. Translation: BAH12863.1.
AY331789 Genomic DNA. Translation: AAP81163.1.
AC007569 Genomic DNA. No translation available.
AC008119 Genomic DNA. No translation available.
BC029782 mRNA. Translation: AAH29782.1.
|RefSeq||NP_001193538.1. NM_001206609.1. |
3D structure databases
Protein-protein interaction databases
|IntAct||Q14242. 6 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENST00000228463; ENSP00000228463; ENSG00000110876. |
ENST00000388962; ENSP00000373614; ENSG00000110876.
ENST00000550948; ENSP00000447752; ENSG00000110876.
|UCSC||uc001tni.3. human. |
|HGNC||HGNC:10722. SELPLG. |
|MIM||600738. gene. |
Enzyme and pathway databases
|Pathway_Interaction_DB||amb2_neutrophils_pathway. amb2 Integrin signaling. |
|Reactome||REACT_604. Hemostasis. |
Gene expression databases
|GermOnline||ENSG00000110876. Homo sapiens. |
Family and domain databases
|InterPro||IPR026195. PSGL-1. |
|PANTHER||PTHR17384. PTHR17384. 1 hit. |
|Accession||Primary (citable) accession number: Q14242|
Secondary accession number(s): A8K2Y0 Q8N7J7
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
|Disclaimer||Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.|
|Human cell differentiation molecules|
CD nomenclature of surface proteins of human leucocytes and list of entries
|Human chromosome 12|
Human chromosome 12: entries, gene names and cross-references to MIM
|Human entries with polymorphisms or disease mutations|
List of human entries with polymorphisms or disease mutations
|Human polymorphisms and disease mutations|
Index of human polymorphisms and disease mutations
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
Index of Protein Data Bank (PDB) cross-references