PGRP4_HUMAN
ID PGRP4_HUMAN Reviewed; 373 AA.
AC Q96LB8; A8K838; Q3B822; Q3B823; Q5SY63; Q5SY64; Q9HD75;
DT 28-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 2.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Peptidoglycan recognition protein 4;
DE AltName: Full=Peptidoglycan recognition protein I-beta;
DE Short=PGLYRPIbeta;
DE Short=PGRP-I-beta;
DE AltName: Full=Peptidoglycan recognition protein intermediate beta;
DE Flags: Precursor;
GN Name=PGLYRP4; Synonyms=PGRPIB; ORFNames=SBBI67;
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), TISSUE SPECIFICITY, AND VARIANTS
RP LEU-13 AND VAL-192.
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 [MRNA] (ISOFORM 2), AND VARIANTS LEU-3 AND ILE-213.
RA Zhang W., Wan T., Cao X.;
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS LEU-13 AND VAL-192.
RC TISSUE=Esophagus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS LEU-3;
RP LEU-13; VAL-192 AND ILE-213.
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, SUBUNIT, GLYCOSYLATION, INDUCTION, SUBCELLULAR LOCATION, 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 [7]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 210-373 IN COMPLEX WITH
RP PEPTIDOGLYCAN-PEPTIDE, SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=17502600; DOI=10.1073/pnas.0701453104;
RA Cho S., Wang Q., Swaminathan C.P., Hesek D., Lee M., Boons G.-J.,
RA Mobashery S., Mariuzza R.A.;
RT "Structural insights into the bactericidal mechanism of human peptidoglycan
RT recognition proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:8761-8766(2007).
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: Homodimer; disulfide-linked. Heterodimer with PGLYRP3;
CC disulfide-linked. {ECO:0000269|PubMed:16354652,
CC ECO:0000269|PubMed:17502600}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16354652}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96LB8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96LB8-2; Sequence=VSP_024388;
CC -!- TISSUE SPECIFICITY: Detected in skin epidermis, eccrine sweat glands
CC and ducts, mucous cells in the submandibular salivary gland, mucous
CC cells in the throat, ciliary body epithelial cells of the eye, small
CC intestine, colon, stomach and in mature epithelial cells of the tongue
CC (at protein level). High expression in skin and esophagus. Expressed
CC also to a much lesser extent in the tonsils and thymus.
CC {ECO:0000269|PubMed:11461926, 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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF99599.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AY035377; AAK72485.1; -; mRNA.
DR EMBL; AF242518; AAF99599.1; ALT_FRAME; mRNA.
DR EMBL; AK292203; BAF84892.1; -; mRNA.
DR EMBL; AL591704; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC142636; AAI42637.1; -; mRNA.
DR EMBL; BC107157; AAI07158.1; -; mRNA.
DR EMBL; BC107158; AAI07159.1; -; mRNA.
DR CCDS; CCDS30871.1; -. [Q96LB8-1]
DR RefSeq; NP_065126.2; NM_020393.3. [Q96LB8-1]
DR RefSeq; XP_011508091.1; XM_011509789.2. [Q96LB8-1]
DR RefSeq; XP_011508092.1; XM_011509790.1. [Q96LB8-1]
DR RefSeq; XP_011508093.1; XM_011509791.2. [Q96LB8-2]
DR PDB; 2EAV; X-ray; 2.20 A; A/B=209-373.
DR PDB; 2EAX; X-ray; 2.10 A; A/B/C=209-373.
DR PDBsum; 2EAV; -.
DR PDBsum; 2EAX; -.
DR AlphaFoldDB; Q96LB8; -.
DR SMR; Q96LB8; -.
DR BioGRID; 121379; 1.
DR STRING; 9606.ENSP00000352672; -.
DR GlyGen; Q96LB8; 5 sites.
DR iPTMnet; Q96LB8; -.
DR PhosphoSitePlus; Q96LB8; -.
DR BioMuta; PGLYRP4; -.
DR DMDM; 143811439; -.
DR MassIVE; Q96LB8; -.
DR PaxDb; Q96LB8; -.
DR PeptideAtlas; Q96LB8; -.
DR PRIDE; Q96LB8; -.
DR Antibodypedia; 34122; 181 antibodies from 26 providers.
DR DNASU; 57115; -.
DR Ensembl; ENST00000359650.10; ENSP00000352672.5; ENSG00000163218.15. [Q96LB8-1]
DR Ensembl; ENST00000368739.3; ENSP00000357728.3; ENSG00000163218.15. [Q96LB8-2]
DR GeneID; 57115; -.
DR KEGG; hsa:57115; -.
DR MANE-Select; ENST00000359650.10; ENSP00000352672.5; NM_020393.4; NP_065126.2.
DR UCSC; uc001fbo.4; human. [Q96LB8-1]
DR CTD; 57115; -.
DR DisGeNET; 57115; -.
DR GeneCards; PGLYRP4; -.
DR HGNC; HGNC:30015; PGLYRP4.
DR HPA; ENSG00000163218; Group enriched (cervix, esophagus, skin, vagina).
DR MIM; 608198; gene.
DR neXtProt; NX_Q96LB8; -.
DR OpenTargets; ENSG00000163218; -.
DR PharmGKB; PA134902492; -.
DR VEuPathDB; HostDB:ENSG00000163218; -.
DR eggNOG; ENOG502S2KY; Eukaryota.
DR GeneTree; ENSGT00940000162349; -.
DR HOGENOM; CLU_037559_1_0_1; -.
DR InParanoid; Q96LB8; -.
DR OMA; AREAHCP; -.
DR OrthoDB; 1110472at2759; -.
DR PhylomeDB; Q96LB8; -.
DR TreeFam; TF323898; -.
DR PathwayCommons; Q96LB8; -.
DR Reactome; R-HSA-6803157; Antimicrobial peptides.
DR SignaLink; Q96LB8; -.
DR BioGRID-ORCS; 57115; 10 hits in 1067 CRISPR screens.
DR ChiTaRS; PGLYRP4; human.
DR EvolutionaryTrace; Q96LB8; -.
DR GenomeRNAi; 57115; -.
DR Pharos; Q96LB8; Tbio.
DR PRO; PR:Q96LB8; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q96LB8; protein.
DR Bgee; ENSG00000163218; Expressed in lower esophagus mucosa and 63 other tissues.
DR Genevisible; Q96LB8; HS.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
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: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: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; Alternative splicing; Antibiotic; Antimicrobial;
KW Disulfide bond; Glycoprotein; Immunity; Innate immunity;
KW Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..373
FT /note="Peptidoglycan recognition protein 4"
FT /id="PRO_0000023924"
FT DOMAIN 74..212
FT /note="N-acetylmuramoyl-L-alanine amidase 1"
FT /evidence="ECO:0000255"
FT DOMAIN 235..358
FT /note="N-acetylmuramoyl-L-alanine amidase 2"
FT /evidence="ECO:0000255"
FT REGION 293..302
FT /note="Interaction with murein"
FT REGION 353..354
FT /note="Interaction with murein"
FT BINDING 263
FT /ligand="peptidoglycan"
FT /ligand_id="ChEBI:CHEBI:8005"
FT BINDING 274
FT /ligand="peptidoglycan"
FT /ligand_id="ChEBI:CHEBI:8005"
FT CARBOHYD 22
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 39
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 109
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 145
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 247
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 210..332
FT /evidence="ECO:0000269|PubMed:17502600"
FT DISULFID 226..270
FT /evidence="ECO:0000269|PubMed:17502600"
FT DISULFID 246..252
FT /evidence="ECO:0000269|PubMed:17502600"
FT VAR_SEQ 47..50
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_024388"
FT VARIANT 3
FT /note="P -> L (in dbSNP:rs12096209)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.2"
FT /id="VAR_050503"
FT VARIANT 13
FT /note="I -> L (in dbSNP:rs3006458)"
FT /evidence="ECO:0000269|PubMed:11461926,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334"
FT /id="VAR_033283"
FT VARIANT 92
FT /note="Q -> R (in dbSNP:rs3006453)"
FT /id="VAR_031586"
FT VARIANT 192
FT /note="G -> V (in dbSNP:rs3006448)"
FT /evidence="ECO:0000269|PubMed:11461926,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334"
FT /id="VAR_031587"
FT VARIANT 213
FT /note="V -> I (in dbSNP:rs12063091)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.2"
FT /id="VAR_031588"
FT VARIANT 301
FT /note="D -> N (in dbSNP:rs35347202)"
FT /id="VAR_031589"
FT STRAND 212..214
FT /evidence="ECO:0007829|PDB:2EAX"
FT HELIX 216..219
FT /evidence="ECO:0007829|PDB:2EAX"
FT STRAND 231..240
FT /evidence="ECO:0007829|PDB:2EAX"
FT HELIX 249..265
FT /evidence="ECO:0007829|PDB:2EAX"
FT STRAND 275..278
FT /evidence="ECO:0007829|PDB:2EAX"
FT STRAND 284..288
FT /evidence="ECO:0007829|PDB:2EAX"
FT STRAND 290..292
FT /evidence="ECO:0007829|PDB:2EAX"
FT TURN 298..300
FT /evidence="ECO:0007829|PDB:2EAX"
FT HELIX 301..303
FT /evidence="ECO:0007829|PDB:2EAX"
FT STRAND 304..311
FT /evidence="ECO:0007829|PDB:2EAX"
FT STRAND 314..316
FT /evidence="ECO:0007829|PDB:2EAX"
FT HELIX 320..335
FT /evidence="ECO:0007829|PDB:2EAX"
FT STRAND 338..347
FT /evidence="ECO:0007829|PDB:2EAX"
FT HELIX 348..351
FT /evidence="ECO:0007829|PDB:2EAX"
FT STRAND 352..354
FT /evidence="ECO:0007829|PDB:2EAX"
FT HELIX 359..365
FT /evidence="ECO:0007829|PDB:2EAX"
SQ SEQUENCE 373 AA; 40620 MW; 8E882E1FF608F6F3 CRC64;
MLPWLLVFSA LGIQAWGDSS WNKTQAKQVS EGLQYLFENI SQLTEKGLPT DVSTTVSRKA
WGAEAVGCSI QLTTPVNVLV IHHVPGLECH DQTVCSQRLR ELQAHHVHNN SGCDVAYNFL
VGDDGRVYEG VGWNIQGVHT QGYNNISLGF AFFGTKKGHS PSPAALSAME NLITYAVQKG
HLSSSYVQPL LGKGENCLAP RQKTSLKKAC PGVVPRSVWG ARETHCPRMT LPAKYGIIIH
TAGRTCNISD ECRLLVRDIQ SFYIDRLKSC DIGYNFLVGQ DGAIYEGVGW NVQGSSTPGY
DDIALGITFM GTFTGIPPNA AALEAAQDLI QCAMVKGYLT PNYLLVGHSD VARTLSPGQA
LYNIISTWPH FKH
