PGRP3_HUMAN
ID PGRP3_HUMAN Reviewed; 341 AA.
AC Q96LB9; A1A4U8; Q5SY65;
DT 28-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Peptidoglycan recognition protein 3;
DE AltName: Full=Peptidoglycan recognition protein I-alpha;
DE Short=PGLYRPIalpha;
DE Short=PGRP-I-alpha;
DE AltName: Full=Peptidoglycan recognition protein intermediate alpha;
DE Flags: Precursor;
GN Name=PGLYRP3; Synonyms=PGRPIA;
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.
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-126.
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 [4]
RP FUNCTION, SUBUNIT, GLYCOSYLATION, SUBCELLULAR LOCATION, INDUCTION, AND
RP TISSUE SPECIFICITY.
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 [5]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 177-341, AND SUBUNIT.
RX PubMed=15140887; DOI=10.1074/jbc.m404920200;
RA Guan R., Malchiodi E.L., Wang Q., Schuck P., Mariuzza R.A.;
RT "Crystal structure of the C-terminal peptidoglycan-binding domain of human
RT peptidoglycan recognition protein Ialpha.";
RL J. Biol. Chem. 279:31873-31882(2004).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 177-341 IN COMPLEX WITH MUREIN
RP FRAGMENT.
RX PubMed=15572450; DOI=10.1073/pnas.0407856101;
RA Guan R., Roychowdhury A., Ember B., Kumar S., Boons G.-J., Mariuzza R.A.;
RT "Structural basis for peptidoglycan binding by peptidoglycan recognition
RT proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:17168-17173(2004).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 177-341 IN COMPLEX WITH MUREIN
RP FRAGMENT.
RX PubMed=16641493; DOI=10.1110/ps.062077606;
RA Guan R., Brown P.H., Swaminathan C.P., Roychowdhury A., Boons G.-J.,
RA Mariuzza R.A.;
RT "Crystal structure of human peptidoglycan recognition protein I alpha bound
RT to a muramyl pentapeptide from Gram-positive bacteria.";
RL Protein Sci. 15:1199-1206(2006).
CC -!- FUNCTION: Pattern receptor that binds to murein peptidoglycans (PGN) of
CC Gram-positive bacteria. Has bactericidal activity towards Gram-positive
CC bacteria. May kill Gram-positive bacteria by interfering with
CC peptidoglycan biosynthesis. Binds also to Gram-negative bacteria, and
CC has bacteriostatic activity towards Gram-negative bacteria. Plays a
CC role in innate immunity. {ECO:0000269|PubMed:16354652}.
CC -!- SUBUNIT: Monomer. Homodimer; disulfide-linked. Heterodimer with
CC PGLYRP4; disulfide-linked. {ECO:0000269|PubMed:15140887,
CC ECO:0000269|PubMed:15572450, ECO:0000269|PubMed:16354652,
CC ECO:0000269|PubMed:16641493}.
CC -!- INTERACTION:
CC Q96LB9; P48643: CCT5; NbExp=3; IntAct=EBI-12339509, EBI-355710;
CC Q96LB9; Q9UHD4: CIDEB; NbExp=3; IntAct=EBI-12339509, EBI-7062247;
CC Q96LB9; P07339: CTSD; NbExp=3; IntAct=EBI-12339509, EBI-2115097;
CC Q96LB9; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-12339509, EBI-18304435;
CC Q96LB9; P28799: GRN; NbExp=3; IntAct=EBI-12339509, EBI-747754;
CC Q96LB9; Q9BPX1: HSD17B14; NbExp=3; IntAct=EBI-12339509, EBI-742664;
CC Q96LB9; P04792: HSPB1; NbExp=3; IntAct=EBI-12339509, EBI-352682;
CC Q96LB9; O60333-2: KIF1B; NbExp=3; IntAct=EBI-12339509, EBI-10975473;
CC Q96LB9; O76011: KRT34; NbExp=3; IntAct=EBI-12339509, EBI-1047093;
CC Q96LB9; P07196: NEFL; NbExp=3; IntAct=EBI-12339509, EBI-475646;
CC Q96LB9; O60260-5: PRKN; NbExp=3; IntAct=EBI-12339509, EBI-21251460;
CC Q96LB9; P60891: PRPS1; NbExp=3; IntAct=EBI-12339509, EBI-749195;
CC Q96LB9; O76024: WFS1; NbExp=3; IntAct=EBI-12339509, EBI-720609;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16354652}.
CC -!- TISSUE SPECIFICITY: Detected in skin epidermis, eccrine sweat glands
CC and ducts, ciliary body epithelial cells of the eye, in small
CC intestine, colon, stomach and in mature epithelial cells of the tongue
CC (at protein level). Highly expressed in skin and esophagus, expressed
CC also in tonsils and thymus and to a much lesser extent in the stomach,
CC descending colon, rectum and brain. {ECO:0000269|PubMed:11461926,
CC ECO:0000269|PubMed:16354652}.
CC -!- INDUCTION: Up-regulated by exposure to Gram-positive and Gram-negative
CC bacteria. {ECO:0000269|PubMed:16354652}.
CC -!- PTM: N-glycosylated. {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; AY035376; AAK72484.1; -; mRNA.
DR EMBL; AL591704; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL161636; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC069741; AAH69741.1; -; mRNA.
DR EMBL; BC069798; AAH69798.1; -; mRNA.
DR EMBL; BC069801; AAH69801.1; -; mRNA.
DR EMBL; BC128114; AAI28115.1; -; mRNA.
DR EMBL; BC128115; AAI28116.1; -; mRNA.
DR CCDS; CCDS1035.1; -.
DR RefSeq; NP_443123.1; NM_052891.2.
DR RefSeq; XP_011507421.1; XM_011509119.1.
DR PDB; 1SK3; X-ray; 2.80 A; A=177-341.
DR PDB; 1SK4; X-ray; 1.65 A; A=179-341.
DR PDB; 1TWQ; X-ray; 2.30 A; A=177-341.
DR PDB; 2APH; X-ray; 2.10 A; A/B=177-341.
DR PDBsum; 1SK3; -.
DR PDBsum; 1SK4; -.
DR PDBsum; 1TWQ; -.
DR PDBsum; 2APH; -.
DR AlphaFoldDB; Q96LB9; -.
DR SMR; Q96LB9; -.
DR BioGRID; 125341; 16.
DR IntAct; Q96LB9; 15.
DR STRING; 9606.ENSP00000290722; -.
DR DrugBank; DB04736; 2-ACETAMIDO-2-DEOXY-BETA-D-GLUCOPYRANOSE(BETA1-4)-2-ACETAMIDO-1,6-ANHYDRO-3-O-[(R)-1-CARBOXYETHYL]-2-DEOXY-BETA-D-GLUCOPYRANOSE-L-ALANYL-GAMMA-D-GLUTAMYL-MESO-DIAMINOPIMELYL-D-ALANINE.
DR GlyGen; Q96LB9; 1 site.
DR iPTMnet; Q96LB9; -.
DR PhosphoSitePlus; Q96LB9; -.
DR BioMuta; PGLYRP3; -.
DR DMDM; 38604974; -.
DR MassIVE; Q96LB9; -.
DR PaxDb; Q96LB9; -.
DR PeptideAtlas; Q96LB9; -.
DR PRIDE; Q96LB9; -.
DR Antibodypedia; 34121; 72 antibodies from 25 providers.
DR DNASU; 114771; -.
DR Ensembl; ENST00000290722.1; ENSP00000290722.1; ENSG00000159527.4.
DR Ensembl; ENST00000683862.1; ENSP00000507327.1; ENSG00000159527.4.
DR GeneID; 114771; -.
DR KEGG; hsa:114771; -.
DR MANE-Select; ENST00000683862.1; ENSP00000507327.1; NM_052891.3; NP_443123.1.
DR UCSC; uc001fbn.1; human.
DR CTD; 114771; -.
DR DisGeNET; 114771; -.
DR GeneCards; PGLYRP3; -.
DR HGNC; HGNC:30014; PGLYRP3.
DR HPA; ENSG00000159527; Group enriched (esophagus, skin, vagina).
DR MIM; 608197; gene.
DR neXtProt; NX_Q96LB9; -.
DR OpenTargets; ENSG00000159527; -.
DR PharmGKB; PA134861692; -.
DR VEuPathDB; HostDB:ENSG00000159527; -.
DR eggNOG; ENOG502S2KY; Eukaryota.
DR GeneTree; ENSGT00940000162657; -.
DR HOGENOM; CLU_037559_1_0_1; -.
DR InParanoid; Q96LB9; -.
DR OMA; WHIQGSH; -.
DR OrthoDB; 1110472at2759; -.
DR PhylomeDB; Q96LB9; -.
DR TreeFam; TF323898; -.
DR PathwayCommons; Q96LB9; -.
DR Reactome; R-HSA-6803157; Antimicrobial peptides.
DR SignaLink; Q96LB9; -.
DR BioGRID-ORCS; 114771; 10 hits in 1080 CRISPR screens.
DR EvolutionaryTrace; Q96LB9; -.
DR GenomeRNAi; 114771; -.
DR Pharos; Q96LB9; Tbio.
DR PRO; PR:Q96LB9; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q96LB9; protein.
DR Bgee; ENSG00000159527; Expressed in lower esophagus mucosa and 50 other tissues.
DR Genevisible; Q96LB9; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0016020; C:membrane; NAS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
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:0046982; F:protein heterodimerization activity; IPI: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: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; 2.
DR Gene3D; 3.40.80.10; -; 2.
DR InterPro; IPR036505; Amidase/PGRP_sf.
DR InterPro; IPR002502; Amidase_domain.
DR InterPro; IPR015510; PGRP.
DR InterPro; IPR006619; PGRP_domain_met/bac.
DR PANTHER; PTHR11022; PTHR11022; 1.
DR Pfam; PF01510; Amidase_2; 2.
DR SMART; SM00644; Ami_2; 2.
DR SMART; SM00701; PGRP; 2.
DR SUPFAM; SSF55846; SSF55846; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic; Antimicrobial; Disulfide bond; Glycoprotein;
KW Immunity; Innate immunity; Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..341
FT /note="Peptidoglycan recognition protein 3"
FT /id="PRO_0000023923"
FT DOMAIN 77..179
FT /note="N-acetylmuramoyl-L-alanine amidase 1"
FT /evidence="ECO:0000255"
FT DOMAIN 200..325
FT /note="N-acetylmuramoyl-L-alanine amidase 2"
FT /evidence="ECO:0000255"
FT REGION 264..269
FT /note="Interaction with murein"
FT BINDING 231
FT /ligand="peptidoglycan"
FT /ligand_id="ChEBI:CHEBI:8005"
FT BINDING 235
FT /ligand="peptidoglycan"
FT /ligand_id="ChEBI:CHEBI:8005"
FT BINDING 242
FT /ligand="peptidoglycan"
FT /ligand_id="ChEBI:CHEBI:8005"
FT CARBOHYD 113
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 178..300
FT DISULFID 194..238
FT DISULFID 214..220
FT VARIANT 35
FT /note="A -> T (in dbSNP:rs55991125)"
FT /id="VAR_061515"
FT VARIANT 126
FT /note="G -> S (in dbSNP:rs843971)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_024561"
FT HELIX 184..187
FT /evidence="ECO:0007829|PDB:1SK4"
FT STRAND 199..208
FT /evidence="ECO:0007829|PDB:1SK4"
FT HELIX 217..233
FT /evidence="ECO:0007829|PDB:1SK4"
FT STRAND 243..246
FT /evidence="ECO:0007829|PDB:1SK4"
FT STRAND 252..256
FT /evidence="ECO:0007829|PDB:1SK4"
FT STRAND 258..260
FT /evidence="ECO:0007829|PDB:2APH"
FT STRAND 263..265
FT /evidence="ECO:0007829|PDB:1SK3"
FT TURN 269..271
FT /evidence="ECO:0007829|PDB:1SK4"
FT STRAND 272..279
FT /evidence="ECO:0007829|PDB:1SK4"
FT STRAND 282..284
FT /evidence="ECO:0007829|PDB:1SK4"
FT HELIX 288..303
FT /evidence="ECO:0007829|PDB:1SK4"
FT STRAND 306..315
FT /evidence="ECO:0007829|PDB:1SK4"
FT HELIX 316..318
FT /evidence="ECO:0007829|PDB:1SK4"
FT STRAND 320..322
FT /evidence="ECO:0007829|PDB:2APH"
FT HELIX 328..333
FT /evidence="ECO:0007829|PDB:1SK4"
FT TURN 337..340
FT /evidence="ECO:0007829|PDB:1SK4"
SQ SEQUENCE 341 AA; 37611 MW; 8ADD5AA97B632076 CRC64;
MGTLPWLLAF FILGLQAWDT PTIVSRKEWG ARPLACRALL TLPVAYIITD QLPGMQCQQQ
SVCSQMLRGL QSHSVYTIGW CDVAYNFLVG DDGRVYEGVG WNIQGLHTQG YNNISLGIAF
FGNKIGSSPS PAALSAAEGL ISYAIQKGHL SPRYIQPLLL KEETCLDPQH PVMPRKVCPN
IIKRSAWEAR ETHCPKMNLP AKYVIIIHTA GTSCTVSTDC QTVVRNIQSF HMDTRNFCDI
GYHFLVGQDG GVYEGVGWHI QGSHTYGFND IALGIAFIGY FVEKPPNAAA LEAAQDLIQC
AVVEGYLTPN YLLMGHSDVV NILSPGQALY NIISTWPHFK H
