PILRA_HUMAN
ID PILRA_HUMAN Reviewed; 303 AA.
AC Q9UKJ1; Q8NHI1;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Paired immunoglobulin-like type 2 receptor alpha;
DE AltName: Full=Cell surface receptor FDF03;
DE AltName: Full=Inhibitory receptor PILR-alpha;
DE Flags: Precursor;
GN Name=PILRA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH PTPN6,
RP GLYCOSYLATION, PHOSPHORYLATION, MUTAGENESIS OF TYR-269, AND VARIANT GLY-78.
RX PubMed=10660620; DOI=10.1074/jbc.275.6.4467;
RA Mousseau D.D., Banville D., L'Abbe D., Bouchard P., Shen S.H.;
RT "PILRalpha, a novel immunoreceptor tyrosine-based inhibitory motif-bearing
RT protein, recruits SHP-1 upon tyrosine phosphorylation and is paired with
RT the truncated counterpart PILRbeta.";
RL J. Biol. Chem. 275:4467-4474(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3 AND 4), FUNCTION, TISSUE
RP SPECIFICITY, INTERACTION WITH PTPN6 AND PTPN11, GLYCOSYLATION,
RP PHOSPHORYLATION, AND VARIANT GLY-78.
RX PubMed=10903717; DOI=10.4049/jimmunol.165.3.1197;
RA Fournier N., Chalus L., Durand I., Garcia E., Pin J.J., Churakova T.,
RA Patel S., Zlot C., Gorman D., Zurawski S., Abrams J., Bates E.E.,
RA Garrone P.;
RT "FDF03, a novel inhibitory receptor of the immunoglobulin superfamily, is
RT expressed by human dendritic and myeloid cells.";
RL J. Immunol. 165:1197-1209(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT GLY-78.
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP INTERACTION WITH HERPES SIMPLEX VIRUS 1 GLYCOPROTEIN B (MICROBIAL
RP INFECTION), AND FUNCTION AS A CORECEPTOR FOR THE VIRUS (MICROBIAL
RP INFECTION).
RX PubMed=18358807; DOI=10.1016/j.cell.2008.01.043;
RA Satoh T., Arii J., Suenaga T., Wang J., Kogure A., Uehori J., Arase N.,
RA Shiratori I., Tanaka S., Kawaguchi Y., Spear P.G., Lanier L.L., Arase H.;
RT "PILRalpha is a herpes simplex virus-1 entry coreceptor that associates
RT with glycoprotein B.";
RL Cell 132:935-944(2008).
RN [6]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-100.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [7]
RP FUNCTION.
RX PubMed=21241660; DOI=10.1016/j.bbrc.2011.01.047;
RA Kogure A., Shiratori I., Wang J., Lanier L.L., Arase H.;
RT "PANP is a novel O-glycosylated PILRalpha ligand expressed in neural
RT tissues.";
RL Biochem. Biophys. Res. Commun. 405:428-433(2011).
CC -!- FUNCTION: Paired receptors consist of highly related activating and
CC inhibitory receptors and are widely involved in the regulation of the
CC immune system. PILRA is thought to act as a cellular signaling
CC inhibitory receptor by recruiting cytoplasmic phosphatases like
CC PTPN6/SHP-1 and PTPN11/SHP-2 via their SH2 domains that block signal
CC transduction through dephosphorylation of signaling molecules. Receptor
CC for PIANP. {ECO:0000269|PubMed:10903717, ECO:0000269|PubMed:21241660}.
CC -!- FUNCTION: (Microbial infection) Acts as an entry co-receptor for herpes
CC simplex virus 1. {ECO:0000269|PubMed:18358807}.
CC -!- SUBUNIT: Monomer. Interacts with PTPN6/SHP-1 and PTPN11/SHP-2 upon
CC tyrosine phosphorylation. {ECO:0000269|PubMed:10660620,
CC ECO:0000269|PubMed:10903717}.
CC -!- SUBUNIT: (Microbial infection) Interacts with herpes simplex virus 1
CC glycoprotein B. {ECO:0000269|PubMed:18358807}.
CC -!- INTERACTION:
CC Q9UKJ1; Q5KU26: COLEC12; NbExp=2; IntAct=EBI-965833, EBI-1104680;
CC Q9UKJ1; Q9NQX5: NPDC1; NbExp=6; IntAct=EBI-965833, EBI-748927;
CC Q9UKJ1; P29350: PTPN6; NbExp=5; IntAct=EBI-965833, EBI-78260;
CC Q9UKJ1; P06436: gB; Xeno; NbExp=3; IntAct=EBI-965833, EBI-1771271;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane {ECO:0000305}; Single-
CC pass type I membrane protein {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane {ECO:0000305}; Single-
CC pass type I membrane protein {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Secreted {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Secreted {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9UKJ1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UKJ1-2; Sequence=VSP_017502;
CC Name=3; Synonyms=FDF03-deltaTM;
CC IsoId=Q9UKJ1-3; Sequence=VSP_017501;
CC Name=4; Synonyms=FDF03-M14;
CC IsoId=Q9UKJ1-4; Sequence=VSP_017500;
CC -!- TISSUE SPECIFICITY: Predominantly detected in hemopoietic tissues and
CC is expressed by monocytes, macrophages, and granulocytes, but not by
CC lymphocytes. Also strongly expressed by dendritic cells (DC);
CC preferentially by CD14+/CD1a- DC derived from CD34+ progenitors. Also
CC expressed by CD11c+ blood and tonsil DC, but not by CD11c- DC
CC precursors. {ECO:0000269|PubMed:10903717}.
CC -!- DOMAIN: Contains 2 copies of a cytoplasmic motif that is referred to as
CC the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is
CC involved in modulation of cellular responses. The phosphorylated ITIM
CC motif can bind the SH2 domain of several SH2-containing phosphatases.
CC PTPN6 seems to bind predominantly to the first ITIM motif.
CC -!- PTM: According to PubMed:10660620, N- and O-glycosylated. According to
CC PubMed:10903717, only N-glycosylated. {ECO:0000269|PubMed:10660620,
CC ECO:0000269|PubMed:10903717, ECO:0000269|PubMed:19159218}.
CC -!- PTM: Phosphorylated on tyrosine residues. {ECO:0000269|PubMed:10660620,
CC ECO:0000269|PubMed:10903717}.
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DR EMBL; AF161080; AAD52964.1; -; mRNA.
DR EMBL; AJ400841; CAC01613.1; -; mRNA.
DR EMBL; AJ400842; CAC01614.1; -; mRNA.
DR EMBL; AJ400843; CAC01615.1; -; mRNA.
DR EMBL; AC005071; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC017812; AAH17812.1; -; mRNA.
DR CCDS; CCDS47660.1; -. [Q9UKJ1-4]
DR CCDS; CCDS5691.1; -. [Q9UKJ1-1]
DR CCDS; CCDS5692.1; -. [Q9UKJ1-3]
DR RefSeq; NP_038467.2; NM_013439.2. [Q9UKJ1-1]
DR RefSeq; NP_840056.1; NM_178272.1. [Q9UKJ1-3]
DR RefSeq; NP_840057.1; NM_178273.1. [Q9UKJ1-4]
DR PDB; 3WUZ; X-ray; 1.30 A; A=32-150.
DR PDB; 3WV0; X-ray; 2.30 A; A/B=32-150.
DR PDB; 4NFB; X-ray; 1.60 A; A=32-150.
DR PDB; 5XO2; X-ray; 2.20 A; A/B=32-150.
DR PDB; 5XOF; X-ray; 1.96 A; A/B/C/D=32-150.
DR PDBsum; 3WUZ; -.
DR PDBsum; 3WV0; -.
DR PDBsum; 4NFB; -.
DR PDBsum; 5XO2; -.
DR PDBsum; 5XOF; -.
DR AlphaFoldDB; Q9UKJ1; -.
DR SMR; Q9UKJ1; -.
DR BioGRID; 119017; 25.
DR IntAct; Q9UKJ1; 13.
DR STRING; 9606.ENSP00000198536; -.
DR UniLectin; Q9UKJ1; -.
DR GlyGen; Q9UKJ1; 2 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q9UKJ1; -.
DR PhosphoSitePlus; Q9UKJ1; -.
DR BioMuta; PILRA; -.
DR DMDM; 296439272; -.
DR jPOST; Q9UKJ1; -.
DR MassIVE; Q9UKJ1; -.
DR PaxDb; Q9UKJ1; -.
DR PeptideAtlas; Q9UKJ1; -.
DR PRIDE; Q9UKJ1; -.
DR ProteomicsDB; 84802; -. [Q9UKJ1-1]
DR ProteomicsDB; 84803; -. [Q9UKJ1-2]
DR ProteomicsDB; 84804; -. [Q9UKJ1-3]
DR ProteomicsDB; 84805; -. [Q9UKJ1-4]
DR Antibodypedia; 30692; 177 antibodies from 24 providers.
DR DNASU; 29992; -.
DR Ensembl; ENST00000198536.7; ENSP00000198536.2; ENSG00000085514.16. [Q9UKJ1-1]
DR Ensembl; ENST00000350573.2; ENSP00000340109.2; ENSG00000085514.16. [Q9UKJ1-3]
DR Ensembl; ENST00000394000.6; ENSP00000377569.2; ENSG00000085514.16. [Q9UKJ1-4]
DR GeneID; 29992; -.
DR KEGG; hsa:29992; -.
DR MANE-Select; ENST00000198536.7; ENSP00000198536.2; NM_013439.3; NP_038467.2.
DR UCSC; uc003uuo.1; human. [Q9UKJ1-1]
DR CTD; 29992; -.
DR DisGeNET; 29992; -.
DR GeneCards; PILRA; -.
DR HGNC; HGNC:20396; PILRA.
DR HPA; ENSG00000085514; Low tissue specificity.
DR MIM; 605341; gene.
DR neXtProt; NX_Q9UKJ1; -.
DR NIAGADS; ENSG00000085514; -.
DR OpenTargets; ENSG00000085514; -.
DR PharmGKB; PA134873007; -.
DR VEuPathDB; HostDB:ENSG00000085514; -.
DR eggNOG; ENOG502SUHR; Eukaryota.
DR GeneTree; ENSGT00940000163799; -.
DR HOGENOM; CLU_070832_0_0_1; -.
DR InParanoid; Q9UKJ1; -.
DR OMA; YFCRVEM; -.
DR OrthoDB; 1325787at2759; -.
DR PhylomeDB; Q9UKJ1; -.
DR TreeFam; TF338478; -.
DR PathwayCommons; Q9UKJ1; -.
DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR SignaLink; Q9UKJ1; -.
DR BioGRID-ORCS; 29992; 25 hits in 1060 CRISPR screens.
DR ChiTaRS; PILRA; human.
DR GenomeRNAi; 29992; -.
DR Pharos; Q9UKJ1; Tbio.
DR PRO; PR:Q9UKJ1; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9UKJ1; protein.
DR Bgee; ENSG00000085514; Expressed in monocyte and 140 other tissues.
DR ExpressionAtlas; Q9UKJ1; baseline and differential.
DR Genevisible; Q9UKJ1; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0042288; F:MHC class I protein binding; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IDA:MGI.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR013106; Ig_V-set.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Glycoprotein;
KW Host-virus interaction; Immunoglobulin domain; Membrane; Phosphoprotein;
KW Receptor; Reference proteome; Secreted; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..303
FT /note="Paired immunoglobulin-like type 2 receptor alpha"
FT /id="PRO_0000226821"
FT TOPO_DOM 20..197
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 198..218
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 219..303
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 32..150
FT /note="Ig-like V-type"
FT REGION 226..296
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 267..272
FT /note="ITIM motif 1"
FT MOTIF 296..301
FT /note="ITIM motif 2"
FT COMPBIAS 231..256
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 271..296
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT VAR_SEQ 152..303
FT /note="AVTTTTQRPSSMTTTWRLSSTTTTTGLRVTQGKRRSDSWHISLETAVGVAVA
FT VTVLGIMILGLICLLRWRRRKGQQRTKATTPAREPFQNTEEPYENIRNEGQNTDPKLNP
FT KDDGIVYASLALSSSTSPRAPPSHRPLKSPQNETLYSVLKA -> GNPSKTQRSHMRIS
FT GMKDKIQIPS (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:10903717"
FT /id="VSP_017500"
FT VAR_SEQ 152..224
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10903717"
FT /id="VSP_017501"
FT VAR_SEQ 264..303
FT /note="DDGIVYASLALSSSTSPRAPPSHRPLKSPQNETLYSVLKA -> LHLTQSTS
FT QPPSPQEPPERDPVLCLKGLTNGQPSQD (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_017502"
FT VARIANT 78
FT /note="R -> G (in dbSNP:rs1859788)"
FT /evidence="ECO:0000269|PubMed:10660620,
FT ECO:0000269|PubMed:10903717, ECO:0000269|PubMed:15489334"
FT /id="VAR_060361"
FT VARIANT 279
FT /note="S -> L (in dbSNP:rs34266222)"
FT /id="VAR_056062"
FT MUTAGEN 269
FT /note="Y->F: Greatly diminishes interaction with PTPN6."
FT /evidence="ECO:0000269|PubMed:10660620"
FT CONFLICT 92
FT /note="D -> E (in Ref. 2; CAC01615)"
FT /evidence="ECO:0000305"
FT CONFLICT 281
FT /note="R -> K (in Ref. 1; AAD52964)"
FT /evidence="ECO:0000305"
FT STRAND 34..36
FT /evidence="ECO:0007829|PDB:3WUZ"
FT STRAND 39..44
FT /evidence="ECO:0007829|PDB:3WUZ"
FT STRAND 49..56
FT /evidence="ECO:0007829|PDB:3WUZ"
FT STRAND 68..77
FT /evidence="ECO:0007829|PDB:3WUZ"
FT STRAND 79..83
FT /evidence="ECO:0007829|PDB:3WUZ"
FT TURN 84..87
FT /evidence="ECO:0007829|PDB:3WUZ"
FT HELIX 91..93
FT /evidence="ECO:0007829|PDB:3WUZ"
FT TURN 94..96
FT /evidence="ECO:0007829|PDB:5XO2"
FT STRAND 97..100
FT /evidence="ECO:0007829|PDB:3WUZ"
FT STRAND 106..112
FT /evidence="ECO:0007829|PDB:3WUZ"
FT HELIX 117..119
FT /evidence="ECO:0007829|PDB:3WUZ"
FT STRAND 121..131
FT /evidence="ECO:0007829|PDB:3WUZ"
FT TURN 132..134
FT /evidence="ECO:0007829|PDB:3WUZ"
FT STRAND 135..140
FT /evidence="ECO:0007829|PDB:3WUZ"
FT STRAND 145..150
FT /evidence="ECO:0007829|PDB:3WUZ"
FT CONFLICT Q9UKJ1-4:168
FT /note="K -> R (in Ref. 2; CAC01615)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 303 AA; 34005 MW; 77BD068C63274A40 CRC64;
MGRPLLLPLL PLLLPPAFLQ PSGSTGSGPS YLYGVTQPKH LSASMGGSVE IPFSFYYPWE
LATAPDVRIS WRRGHFHRQS FYSTRPPSIH KDYVNRLFLN WTEGQKSGFL RISNLQKQDQ
SVYFCRVELD TRSSGRQQWQ SIEGTKLSIT QAVTTTTQRP SSMTTTWRLS STTTTTGLRV
TQGKRRSDSW HISLETAVGV AVAVTVLGIM ILGLICLLRW RRRKGQQRTK ATTPAREPFQ
NTEEPYENIR NEGQNTDPKL NPKDDGIVYA SLALSSSTSP RAPPSHRPLK SPQNETLYSV
LKA
