PGRP1_HUMAN
ID PGRP1_HUMAN Reviewed; 196 AA.
AC O75594; Q4VB36;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Peptidoglycan recognition protein 1;
DE AltName: Full=Peptidoglycan recognition protein short;
DE Short=PGRP-S;
DE Flags: Precursor;
GN Name=PGLYRP1; Synonyms=PGLYRP, PGRP, TNFSF3L;
GN ORFNames=SBBI68, UNQ639/PRO1269;
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], AND TISSUE SPECIFICITY.
RC TISSUE=Bone marrow;
RX PubMed=9707603; DOI=10.1073/pnas.95.17.10078;
RA Kang D., Liu G., Lundstroem A., Gelius E., Steiner H.;
RT "A peptidoglycan recognition protein in innate immunity conserved from
RT insects to humans.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:10078-10082(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Wan T., Zhang W., Cao X.;
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [6]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=11461926; DOI=10.1074/jbc.m105566200;
RA Liu C., Xu Z., Gupta D., Dziarski R.;
RT "Peptidoglycan recognition proteins: a novel family of four human innate
RT immunity pattern recognition molecules.";
RL J. Biol. Chem. 276:34686-34694(2001).
RN [7]
RP FUNCTION, SUBUNIT, GLYCOSYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=16354652; DOI=10.1074/jbc.m511631200;
RA Lu X., Wang M., Qi J., Wang H., Li X., Gupta D., Dziarski R.;
RT "Peptidoglycan recognition proteins are a new class of human bactericidal
RT proteins.";
RL J. Biol. Chem. 281:5895-5907(2006).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 22-196, AND DISULFIDE BONDS.
RX PubMed=15769462; DOI=10.1016/j.jmb.2005.01.070;
RA Guan R., Wang Q., Sundberg E.J., Mariuzza R.A.;
RT "Crystal structure of human peptidoglycan recognition protein S (PGRP-S) at
RT 1.70 A resolution.";
RL J. Mol. Biol. 347:683-691(2005).
RN [9]
RP INTERACTION WITH HSPBP1, AND FUNCTION.
RX PubMed=21247889; DOI=10.1074/jbc.m110.163436;
RA Yashin D.V., Dukhanina E.A., Kabanova O.D., Romanova E.A., Lukyanova T.I.,
RA Tonevitskii A.G., Raynes D.A., Gnuchev N.V., Guerriero V., Georgiev G.P.,
RA Sashchenko L.P.;
RT "The heat shock-binding protein (HspBP1) protects cells against the
RT cytotoxic action of the Tag7-Hsp70 complex.";
RL J. Biol. Chem. 286:10258-10264(2011).
RN [10]
RP FUNCTION, AND INTERACTION WITH TNFRSF1A.
RX PubMed=26183779; DOI=10.1074/jbc.m115.639732;
RA Yashin D.V., Ivanova O.K., Soshnikova N.V., Sheludchenkov A.A.,
RA Romanova E.A., Dukhanina E.A., Tonevitsky A.G., Gnuchev N.V., Gabibov A.G.,
RA Georgiev G.P., Sashchenko L.P.;
RT "Tag7 (PGLYRP1) in Complex with Hsp70 Induces Alternative Cytotoxic
RT Processes in Tumor Cells via TNFR1 Receptor.";
RL J. Biol. Chem. 290:21724-21731(2015).
RN [11]
RP INTERACTION WITH TREM1, AND FUNCTION.
RX PubMed=25595774; DOI=10.4049/jimmunol.1402303;
RA Read C.B., Kuijper J.L., Hjorth S.A., Heipel M.D., Tang X., Fleetwood A.J.,
RA Dantzler J.L., Grell S.N., Kastrup J., Wang C., Brandt C.S., Hansen A.J.,
RA Wagtmann N.R., Xu W., Stennicke V.W.;
RT "Cutting Edge: identification of neutrophil PGLYRP1 as a ligand for TREM-
RT 1.";
RL J. Immunol. 194:1417-1421(2015).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH S100A4.
RX PubMed=26654597; DOI=10.1080/15384101.2015.1104440;
RA Dukhanina E.A., Lukyanova T.I., Romanova E.A., Guerriero V., Gnuchev N.V.,
RA Georgiev G.P., Yashin D.V., Sashchenko L.P.;
RT "A new role for PGRP-S (Tag7) in immune defense: lymphocyte migration is
RT induced by a chemoattractant complex of Tag7 with Mts1.";
RL Cell Cycle 14:3635-3643(2015).
RN [13]
RP FUNCTION.
RX PubMed=29083508; DOI=10.1002/iub.1688;
RA Sharapova T.N., Ivanova O.K., Prasolov V.S., Romanova E.A.,
RA Sashchenko L.P., Yashin D.V.;
RT "Innate immunity protein Tag7 (PGRP-S) activates lymphocytes capable of
RT Fasl-Fas-dependent contact killing of virus-infected cells.";
RL IUBMB Life 69:971-977(2017).
RN [14]
RP FUNCTION.
RX PubMed=28977785; DOI=10.1159/000479382;
RA Sharapova T.N., Ivanova O.K., Soshnikova N.V., Romanova E.A.,
RA Sashchenko L.P., Yashin D.V.;
RT "Innate Immunity Protein Tag7 Induces 3 Distinct Populations of Cytotoxic
RT Cells That Use Different Mechanisms to Exhibit Their Antitumor Activity on
RT Human Leukocyte Antigen-Deficient Cancer Cells.";
RL J. Innate Immun. 9:598-608(2017).
RN [15]
RP FUNCTION, AND INTERACTION WITH S100A4.
RX PubMed=30713770;
RA Sharapova T.N., Romanova E.A., Sashchenko L.P., Yashin D.V.;
RT "Tag7-Mts1 Complex Induces Lymphocytes Migration via CCR5 and CXCR3
RT Receptors.";
RL Acta Naturae 10:115-120(2018).
CC -!- FUNCTION: Innate immunity protein that plays several important
CC functions in antimicrobial and antitumor defense systems. Acts as a
CC pattern receptor that binds to murein peptidoglycans (PGN) of Gram-
CC positive bacteria and thus provides bactericidal activity
CC (PubMed:9707603). Forms an equimolar complex with heat shock protein
CC HSPA1A and induces programmed cell death through apoptosis and
CC necroptosis in tumor cell lines by activating the TNFR1 receptor on the
CC target cell membrane (PubMed:21247889, PubMed:26183779). In addition,
CC acts in complex with the Ca(2+)-binding protein S100A4 as a
CC chemoattractant able to induce lymphocyte movement (PubMed:26654597).
CC Mechanistically, this complex acts as a ligand of the chemotactic
CC receptors CCR5 and CXCR3 which are present on the cells of the immune
CC system (PubMed:30713770). Promotes also the activation of lymphocytes
CC that become able to kill virus-infected cells as well as tumor cells by
CC modulating the spectrum of their target-cell specificity
CC (PubMed:29083508, PubMed:28977785). Induction of cytotoxicity on
CC monocyte surface requires interaction with TREM1 receptor
CC (PubMed:28977785, PubMed:25595774). {ECO:0000269|PubMed:21247889,
CC ECO:0000269|PubMed:25595774, ECO:0000269|PubMed:26183779,
CC ECO:0000269|PubMed:26654597, ECO:0000269|PubMed:28977785,
CC ECO:0000269|PubMed:29083508, ECO:0000269|PubMed:30713770,
CC ECO:0000269|PubMed:9707603}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:16354652,
CC PubMed:15769462). Interacts with HSPA1A; this interaction forms a
CC cytotoxic complex that is released by lymphokine-activated killer cells
CC (By similarity). Interacts with HSPBP1; this interaction blocks the
CC cytotoxic activity of the PGLYRP1-HSPA1A complex (PubMed:21247889).
CC Interacts with TNFRSF1A; this interaction is important for cell death
CC induction (PubMed:26183779). Interacts with S100A4; this complex acts
CC as a chemoattractant that promotes lymphocyte movement
CC (PubMed:26654597, PubMed:30713770). Interacts with TREM1
CC (PubMed:25595774). {ECO:0000250|UniProtKB:O88593,
CC ECO:0000269|PubMed:15769462, ECO:0000269|PubMed:16354652,
CC ECO:0000269|PubMed:21247889, ECO:0000269|PubMed:25595774,
CC ECO:0000269|PubMed:26183779, ECO:0000269|PubMed:26654597,
CC ECO:0000269|PubMed:30713770}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16354652}.
CC Cytoplasmic granule {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Highly expressed in bone marrow. Weak expression
CC found in kidney, liver, small intestine, spleen, thymus, peripheral
CC leukocyte, lung, fetal spleen and neutrophils.
CC {ECO:0000269|PubMed:11461926, ECO:0000269|PubMed:9707603}.
CC -!- PTM: N-glycosylated. N-glycosylation is required for bactericidal
CC activity. {ECO:0000269|PubMed:16354652}.
CC -!- SIMILARITY: Belongs to the N-acetylmuramoyl-L-alanine amidase 2 family.
CC {ECO:0000305}.
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DR EMBL; AF076483; AAC31822.1; -; mRNA.
DR EMBL; AF242517; AAF99598.1; -; mRNA.
DR EMBL; AY358936; AAQ89295.1; -; mRNA.
DR EMBL; AC007785; AAD38243.1; -; Genomic_DNA.
DR EMBL; BC096154; AAH96154.1; -; mRNA.
DR EMBL; BC096155; AAH96155.1; -; mRNA.
DR EMBL; BC096156; AAH96156.1; -; mRNA.
DR EMBL; BC096157; AAH96157.1; -; mRNA.
DR EMBL; BC101845; AAI01846.1; -; mRNA.
DR EMBL; BC101847; AAI01848.1; -; mRNA.
DR CCDS; CCDS12680.1; -.
DR RefSeq; NP_005082.1; NM_005091.2.
DR PDB; 1YCK; X-ray; 1.70 A; A=22-196.
DR PDBsum; 1YCK; -.
DR AlphaFoldDB; O75594; -.
DR SMR; O75594; -.
DR BioGRID; 114474; 4.
DR IntAct; O75594; 4.
DR MINT; O75594; -.
DR STRING; 9606.ENSP00000008938; -.
DR GlyGen; O75594; 1 site.
DR iPTMnet; O75594; -.
DR PhosphoSitePlus; O75594; -.
DR BioMuta; PGLYRP1; -.
DR jPOST; O75594; -.
DR MassIVE; O75594; -.
DR PaxDb; O75594; -.
DR PeptideAtlas; O75594; -.
DR PRIDE; O75594; -.
DR ProteomicsDB; 50104; -.
DR Antibodypedia; 18065; 354 antibodies from 35 providers.
DR DNASU; 8993; -.
DR Ensembl; ENST00000008938.5; ENSP00000008938.3; ENSG00000008438.5.
DR GeneID; 8993; -.
DR KEGG; hsa:8993; -.
DR MANE-Select; ENST00000008938.5; ENSP00000008938.3; NM_005091.3; NP_005082.1.
DR UCSC; uc002pdx.4; human.
DR CTD; 8993; -.
DR DisGeNET; 8993; -.
DR GeneCards; PGLYRP1; -.
DR HGNC; HGNC:8904; PGLYRP1.
DR HPA; ENSG00000008438; Tissue enriched (bone).
DR MIM; 604963; gene.
DR neXtProt; NX_O75594; -.
DR OpenTargets; ENSG00000008438; -.
DR PharmGKB; PA33241; -.
DR VEuPathDB; HostDB:ENSG00000008438; -.
DR eggNOG; ENOG502S2KY; Eukaryota.
DR GeneTree; ENSGT00940000161006; -.
DR HOGENOM; CLU_037559_3_2_1; -.
DR InParanoid; O75594; -.
DR OMA; EIIRTWP; -.
DR OrthoDB; 1110472at2759; -.
DR PhylomeDB; O75594; -.
DR TreeFam; TF323898; -.
DR PathwayCommons; O75594; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-6803157; Antimicrobial peptides.
DR SignaLink; O75594; -.
DR BioGRID-ORCS; 8993; 20 hits in 1066 CRISPR screens.
DR EvolutionaryTrace; O75594; -.
DR GeneWiki; PGLYRP1; -.
DR GenomeRNAi; 8993; -.
DR Pharos; O75594; Tbio.
DR PRO; PR:O75594; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; O75594; protein.
DR Bgee; ENSG00000008438; Expressed in bone marrow and 100 other tissues.
DR Genevisible; O75594; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0097013; C:phagocytic vesicle lumen; TAS:Reactome.
DR GO; GO:0035580; C:specific granule lumen; TAS:Reactome.
DR GO; GO:1904724; C:tertiary granule lumen; TAS:Reactome.
DR GO; GO:0008745; F:N-acetylmuramoyl-L-alanine amidase activity; IEA:InterPro.
DR GO; GO:0042834; F:peptidoglycan binding; IDA:UniProtKB.
DR GO; GO:0016019; F:peptidoglycan immune receptor activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB.
DR GO; GO:0051701; P:biological process involved in interaction with host; IEA:Ensembl.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB.
DR GO; GO:0016045; P:detection of bacterium; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; NAS:UniProtKB.
DR GO; GO:0031640; P:killing of cells of another organism; IDA:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; IEA:Ensembl.
DR GO; GO:0032827; P:negative regulation of natural killer cell differentiation involved in immune response; IEA:Ensembl.
DR GO; GO:0009253; P:peptidoglycan catabolic process; IEA:InterPro.
DR CDD; cd06583; PGRP; 1.
DR Gene3D; 3.40.80.10; -; 1.
DR InterPro; IPR036505; Amidase/PGRP_sf.
DR InterPro; IPR002502; Amidase_domain.
DR InterPro; IPR017331; Peptidoglycan_recognition.
DR InterPro; IPR015510; PGRP.
DR InterPro; IPR006619; PGRP_domain_met/bac.
DR PANTHER; PTHR11022; PTHR11022; 1.
DR Pfam; PF01510; Amidase_2; 1.
DR PIRSF; PIRSF037945; PGRPs; 1.
DR SMART; SM00644; Ami_2; 1.
DR SMART; SM00701; PGRP; 1.
DR SUPFAM; SSF55846; SSF55846; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic; Antimicrobial; Disulfide bond; Glycoprotein;
KW Immunity; Innate immunity; Pyrrolidone carboxylic acid; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..196
FT /note="Peptidoglycan recognition protein 1"
FT /id="PRO_0000023901"
FT DOMAIN 53..180
FT /note="N-acetylmuramoyl-L-alanine amidase"
FT /evidence="ECO:0000255"
FT MOD_RES 22
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000250|UniProtKB:Q8SPP7"
FT CARBOHYD 112
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 30..154
FT /evidence="ECO:0000269|PubMed:15769462"
FT DISULFID 46..91
FT /evidence="ECO:0000269|PubMed:15769462"
FT DISULFID 67..73
FT /evidence="ECO:0000269|PubMed:15769462"
FT VARIANT 34
FT /note="V -> G (in dbSNP:rs34180629)"
FT /id="VAR_050497"
FT HELIX 36..39
FT /evidence="ECO:0007829|PDB:1YCK"
FT STRAND 52..61
FT /evidence="ECO:0007829|PDB:1YCK"
FT HELIX 70..86
FT /evidence="ECO:0007829|PDB:1YCK"
FT STRAND 96..99
FT /evidence="ECO:0007829|PDB:1YCK"
FT STRAND 105..109
FT /evidence="ECO:0007829|PDB:1YCK"
FT TURN 110..112
FT /evidence="ECO:0007829|PDB:1YCK"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:1YCK"
FT TURN 120..122
FT /evidence="ECO:0007829|PDB:1YCK"
FT HELIX 123..125
FT /evidence="ECO:0007829|PDB:1YCK"
FT STRAND 126..133
FT /evidence="ECO:0007829|PDB:1YCK"
FT STRAND 136..138
FT /evidence="ECO:0007829|PDB:1YCK"
FT HELIX 142..157
FT /evidence="ECO:0007829|PDB:1YCK"
FT STRAND 160..169
FT /evidence="ECO:0007829|PDB:1YCK"
FT HELIX 170..172
FT /evidence="ECO:0007829|PDB:1YCK"
FT STRAND 174..176
FT /evidence="ECO:0007829|PDB:1YCK"
FT HELIX 181..187
FT /evidence="ECO:0007829|PDB:1YCK"
SQ SEQUENCE 196 AA; 21731 MW; D954C51440DC27DC CRC64;
MSRRSMLLAW ALPSLLRLGA AQETEDPACC SPIVPRNEWK ALASECAQHL SLPLRYVVVS
HTAGSSCNTP ASCQQQARNV QHYHMKTLGW CDVGYNFLIG EDGLVYEGRG WNFTGAHSGH
LWNPMSIGIS FMGNYMDRVP TPQAIRAAQG LLACGVAQGA LRSNYVLKGH RDVQRTLSPG
NQLYHLIQNW PHYRSP
