Reviewed, UniProtKB/Swiss-Prot Q14242 (SELPL_HUMAN)

Names and origin

Protein names

Recommended name:
    P-selectin glycoprotein ligand 1
      Short name=PSGL-1
      Short name=Selectin P ligand
Alternative name(s):
    CD_antigen=CD162

Gene names

Name:

SELPLG

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	412 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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.
Subunit structure	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.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Expressed on neutrophils, monocytes and most lymphocytes.
Post-translational modification	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.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat Signal Transmembrane
Ligand	Sialic acid
PTM	Cleavage on pair of basic residues Glycoprotein Phosphoprotein Pyrrolidone carboxylic acid Sulfation
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Cellular component	integral to plasma membrane Ref.2 Traceable author statement. Source: ProtInc membrane fraction Ref.2 Traceable author statement. Source: ProtInc
Molecular function	bacterial binding Traceable author statement. Source: ProtInc receptor binding Ref.2 Non-traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 17

17

Potential

Propeptide

18 – 41

24

PRO_0000022302

Chain

42 – 412

371

P-selectin glycoprotein ligand 1

PRO_0000022303

Regions

Topological domain

18 – 320

303

Extracellular Potential

Transmembrane

321 – 341

21

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

Modified residue

48

1

Sulfotyrosine

Modified residue

51

1

Sulfotyrosine

Modified residue

389

1

Phosphoserine

Modified residue

393

1

Phosphothreonine

Glycosylation

57

1

O-linked (GalNAc...)

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

Natural variations

Natural variant

62

1

M → I: dbSNP rs2228315.

VAR_019156

Natural variant

132 – 141

10

Missing in short form; not an alternative splicing.

VAR_005611

Natural variant

246

1

P → S: dbSNP rs8179142.

VAR_019157

Experimental info

Mutagenesis

44

1

T → A: No effect on L-selectin binding nor neutrophil rolling

Mutagenesis

46 – 52

7

YEYLDYD → FEFLDFE: No sulfation. Almost complete loss of P-selectin binding. No effect on E-selectin binding

Mutagenesis

46 – 51

6

YEYLDY → FEFLDF: No sulfation. Almost complete loss of P-selectin binding. No effect on E-selectin binding

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

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

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

Mutagenesis

57

1

T → A: No E- nor P-selctin binding, and very little neutrophil rolling. Binding of L-selectin reduced by 91%; when associated with F-46; F-48 and F-51

Mutagenesis

320

1

C → A or S: No dimer formation. No effect on P-selectin binding

Sequence conflict

23 – 39

17

Missing in BAC05283. Ref.4

Sequence conflict

50

1

D → E in BAC05283. Ref.4

Sequence conflict

219

1

M → T in BAC05283. Ref.4

Sequence conflict

396

1

P → A in BAC05283. Ref.4

Secondary structure

1

.

.

.

412

Helix Strand Turn

Details...

Turn

51 – 53

3

Sequences

	Sequence		Length	Mass (Da)
	Q14242-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: A92A2A902DC9963A	FASTA	412	43,201
	10 20 30 40 50 60 MPLQLLLLLI LLGPGNSLQL WDTWADEAEK ALGPLLARDR RQATEYEYLD YDFLPETEPP 70 80 90 100 110 120 EMLRNSTDTT PLTGPGTPES TTVEPAARRS TGLDAGGAVT ELTTELANMG NLSTDSAAME 130 140 150 160 170 180 IQTTQPAATE AQTTQPVPTE AQTTPLAATE AQTTRLTATE AQTTPLAATE AQTTPPAATE 190 200 210 220 230 240 AQTTQPTGLE AQTTAPAAME AQTTAPAAME AQTTPPAAME AQTTQTTAME AQTTAPEATE 250 260 270 280 290 300 AQTTQPTATE AQTTPLAAME ALSTEPSATE ALSMEPTTKR GLFIPFSVSS VTHKGIPMAA 310 320 330 340 350 360 SNLSVNYPVG APDHISVKQC LLAILILALV ATIFFVCTVV LAVRLSRKGH MYPVRNYSPT 370 380 390 400 410 EMVCISSLLP DGGEGPSATA NGGLSKAKSP GLTPEPREDR EGDDLTLHSF LP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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: 7541799] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[2]	"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: 7505206] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT 132-GLN--ALA-141 DEL.
[3]	SeattleSNPs program for genomic applications Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ILE-62 AND SER-246.
[4]	"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. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT 132-GLN--ALA-141 DEL. Tissue: Uterus.
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT 132-GLN--ALA-141 DEL. Tissue: Brain.
[6]	"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: 7521878] [Abstract] Cited for: PROTEIN SEQUENCE OF 350-355 AND 390-396, INTERACTION WITH SELP AND SELE, CARBOHYDRATE STRUCTURE, SUBUNIT, SIALIC ACID CONTENT. Tissue: Neutrophil.
[7]	"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: 7585949] [Abstract] Cited for: SULFATION, INTERACTION WITH SELP, MUTAGENESIS OF 46-TYR--ASP-52.
[8]	"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: 7585950] [Abstract] Cited for: SULFATION, INTERACTION WITH SELP, MUTAGENESIS OF TYR-46; TYR-48; TYR-51 AND THR-57.
[9]	"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: 7559387] [Abstract] Cited for: SULFATION, INTERACTION WITH SELP.
[10]	"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: 8702529] [Abstract] Cited for: STRUCTURE OF O-LINKED CARBOHYDRATES.
[11]	"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: 10713099] [Abstract] Cited for: INTERACTION WITH SELP, DISULFIDE BOND AT CYS-320, MUTAGENESIS OF CYS-320.
[12]	"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: 11566773] [Abstract] Cited for: INTERACTION WITH SELE AND SELP, SULFATION, FUNCTION.
[13]	"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: 12403782] [Abstract] Cited for: INTERACTION WITH SELL, FUNCTION, MUTAGENESIS OF THR-44; TYR-48; TYR-51 AND THR-57.
[14]	"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: 12736247] [Abstract] Cited for: INTERACTION WITH SELL, SULFATION, GYCOSYLATION.
[15]	"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: 18196517] [Abstract] Cited for: INTERACTION WITH SNX20.
[16]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-389 AND THR-393, MASS SPECTROMETRY.
[17]	"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: 11081633] [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, GLYCOLYSATION AT THR-57, PYROGLUTAMATE FORMATION AT GLN-42.
[18]	Erratum Somers W.S., Tang J., Shaw G.D., Camphausen R.T. Cell 105:971-971(2001)
+	Additional computationally mapped references.

Web resources

Wikipedia

P-selectin glycoprotein ligand 1 entry

SeattleSNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

U25956 Genomic DNA. Translation: AAA74577.1.
U02297 mRNA. Translation: AAC50061.1.
AY331789 Genomic DNA. Translation: AAP81163.1.
AK098315 mRNA. Translation: BAC05283.1.
BC029782 mRNA. Translation: AAH29782.1.

PIR

A57468.

RefSeq

NP_002997.1.

UniGene

Hs.591014

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1G1S	X-ray	1.90	C/D	42-68	[»]

ModBase

Search...

PTM databases

GlycoSuiteDB

Q14242.

PhosphoSite

Q14242.

Genome annotation databases

Ensembl

ENSG00000110876. Homo sapiens. [Contig view]

GeneID

6404.

KEGG

hsa:6404.

Organism-specific databases

HGNC

HGNC:10722. SELPLG.

HPA

CAB002431.

MIM

600738. gene.

PharmGKB

PA35644.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

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