REG3A_HUMAN
ID REG3A_HUMAN Reviewed; 175 AA.
AC Q06141;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Regenerating islet-derived protein 3-alpha;
DE Short=REG-3-alpha;
DE AltName: Full=Hepatointestinal pancreatic protein;
DE Short=HIP/PAP;
DE AltName: Full=Human proislet peptide;
DE AltName: Full=Pancreatitis-associated protein 1;
DE AltName: Full=Regenerating islet-derived protein III-alpha;
DE Short=Reg III-alpha;
DE Contains:
DE RecName: Full=Regenerating islet-derived protein 3-alpha 16.5 kDa form;
DE Contains:
DE RecName: Full=Regenerating islet-derived protein 3-alpha 15 kDa form;
DE Flags: Precursor;
GN Name=REG3A; Synonyms=HIP, PAP, PAP1;
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].
RC TISSUE=Pancreas, and Small intestine;
RX PubMed=7679928; DOI=10.1016/0167-4781(93)90290-t;
RA Itoh T., Teraoka H.;
RT "Cloning and tissue-specific expression of cDNAs for the human and mouse
RT homologues of rat pancreatitis-associated protein (PAP).";
RL Biochim. Biophys. Acta 1172:184-186(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Pancreas;
RX PubMed=1469087; DOI=10.1172/jci116115;
RA Orelle B., Keim V., Masciotra L., Dagorn J.-C., Iovanna J.-L.;
RT "Human pancreatitis-associated protein. Messenger RNA cloning and
RT expression in pancreatic diseases.";
RL J. Clin. Invest. 90:2284-2291(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=1325291;
RA Lasserre C., Christa L., Simon M.T., Vernier P., Brechot C.;
RT "A novel gene (HIP) activated in human primary liver cancer.";
RL Cancer Res. 52:5089-5095(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Blood;
RX PubMed=8188210; DOI=10.1006/geno.1994.1019;
RA Dusetti N.J., Frigerio J.-M., Fox M.F., Swallow D.M., Dagorn J.-C.,
RA Iovanna J.L.;
RT "Molecular cloning, genomic organization, and chromosomal localization of
RT the human pancreatitis-associated protein (PAP) gene.";
RL Genomics 19:108-114(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8076648; DOI=10.1111/j.1432-1033.1994.tb19991.x;
RA Lasserre C., Simon M.T., Ishikawa H., Diriong S., Nguyen V.C., Christa L.,
RA Vernier P., Brechot C.;
RT "Structural organization and chromosomal localization of a human gene
RT (HIP/PAP) encoding a C-type lectin overexpressed in primary liver cancer.";
RL Eur. J. Biochem. 224:29-38(1994).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
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 [7]
RP PROTEIN SEQUENCE OF N-TERMINUS, AND PROTEOLYTIC PROCESSING.
RX PubMed=19254208; DOI=10.1042/bj20090005;
RA Medveczky P., Szmola R., Sahin-Toth M.;
RT "Proteolytic activation of human pancreatitis-associated protein is
RT required for peptidoglycan binding and bacterial aggregation.";
RL Biochem. J. 420:335-343(2009).
RN [8]
RP FUNCTION, AND MANNAN- AND PEPTIDOGLYCAN-BINDING.
RX PubMed=16931762; DOI=10.1126/science.1127119;
RA Cash H.L., Whitham C.V., Behrendt C.L., Hooper L.V.;
RT "Symbiotic bacteria direct expression of an intestinal bactericidal
RT lectin.";
RL Science 313:1126-1130(2006).
RN [9]
RP TISSUE SPECIFICITY, AND INTERACTION WITH EXTL3.
RX PubMed=22727489; DOI=10.1016/j.immuni.2012.04.010;
RA Lai Y., Li D., Li C., Muehleisen B., Radek K.A., Park H.J., Jiang Z.,
RA Li Z., Lei H., Quan Y., Zhang T., Wu Y., Kotol P., Morizane S., Hata T.R.,
RA Iwatsuki K., Tang C., Gallo R.L.;
RT "The antimicrobial protein REG3A regulates keratinocyte proliferation and
RT differentiation after skin injury.";
RL Immunity 37:74-84(2012).
RN [10]
RP STRUCTURE BY NMR, MOTIF EPN, AND MUTAGENESIS OF GLU-114 AND GLU-118.
RX PubMed=20382864; DOI=10.1073/pnas.0909449107;
RA Lehotzky R.E., Partch C.L., Mukherjee S., Cash H.L., Goldman W.E.,
RA Gardner K.H., Hooper L.V.;
RT "Molecular basis for peptidoglycan recognition by a bactericidal lectin.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:7722-7727(2010).
CC -!- FUNCTION: Bactericidal C-type lectin which acts exclusively against
CC Gram-positive bacteria and mediates bacterial killing by binding to
CC surface-exposed carbohydrate moieties of peptidoglycan. Regulates
CC keratinocyte proliferation and differentiation after skin injury via
CC activation of EXTL3-PI3K-AKT signaling pathway.
CC {ECO:0000269|PubMed:16931762}.
CC -!- SUBUNIT: Interacts with EXTL3. {ECO:0000269|PubMed:22727489}.
CC -!- INTERACTION:
CC Q06141; Q99750: MDFI; NbExp=3; IntAct=EBI-10223932, EBI-724076;
CC Q06141; Q06141: REG3A; NbExp=2; IntAct=EBI-10223932, EBI-10223932;
CC -!- SUBCELLULAR LOCATION: Secreted. Note=Found in the apical region of
CC pancreatic acinar cells.
CC -!- TISSUE SPECIFICITY: Highly expressed in epidermal keratinocytes of
CC psoriasis patients (at protein level). Constitutively expressed in
CC intestine. Low expression is found in healthy pancreas. Overexpressed
CC during the acute phase of pancreatitis and in some patients with
CC chronic pancreatitis. {ECO:0000269|PubMed:1469087,
CC ECO:0000269|PubMed:22727489}.
CC -!- INDUCTION: Appears in pancreatic juice after induction of pancreatic
CC inflammation.
CC -!- DOMAIN: The EPN motif is essential for recognition of the peptidoglycan
CC carbohydrate backbone and for efficient bacterial killing with Glu-114
CC playing a key role in peptidoglycan binding and bactericidal activity.
CC -!- PTM: Proteolytic processing by trypsin removes an inhibitory N-terminal
CC propeptide and is essential for peptidoglycan binding and antibacterial
CC activity. {ECO:0000269|PubMed:19254208}.
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding;
CC Note=Pancreatitis-associated protein 1;
CC URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_hum_Ctlect_256";
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DR EMBL; D13510; BAA02728.1; -; mRNA.
DR EMBL; M84337; AAA36415.1; -; mRNA.
DR EMBL; S51768; AAB24642.1; -; mRNA.
DR EMBL; X68641; CAA48605.1; -; mRNA.
DR EMBL; L15533; AAA60020.1; -; Genomic_DNA.
DR EMBL; BC036776; AAH36776.1; -; mRNA.
DR CCDS; CCDS1965.1; -.
DR PIR; A49616; A49616.
DR RefSeq; NP_002571.1; NM_002580.2.
DR RefSeq; NP_620354.1; NM_138937.2.
DR RefSeq; NP_620355.1; NM_138938.2.
DR PDB; 1UV0; X-ray; 1.78 A; A=27-175.
DR PDB; 2GO0; NMR; -; A=39-175.
DR PDB; 4MTH; X-ray; 1.47 A; A=38-175.
DR PDBsum; 1UV0; -.
DR PDBsum; 2GO0; -.
DR PDBsum; 4MTH; -.
DR AlphaFoldDB; Q06141; -.
DR SMR; Q06141; -.
DR BioGRID; 111103; 15.
DR DIP; DIP-60688N; -.
DR IntAct; Q06141; 4.
DR STRING; 9606.ENSP00000377456; -.
DR MEROPS; I63.002; -.
DR TCDB; 1.C.111.1.2; the regiiiGama (regiiiGama) family.
DR UniLectin; Q06141; -.
DR BioMuta; REG3A; -.
DR DMDM; 464341; -.
DR EPD; Q06141; -.
DR jPOST; Q06141; -.
DR MassIVE; Q06141; -.
DR PaxDb; Q06141; -.
DR PeptideAtlas; Q06141; -.
DR PRIDE; Q06141; -.
DR ProteomicsDB; 58418; -.
DR Antibodypedia; 16859; 544 antibodies from 34 providers.
DR DNASU; 5068; -.
DR Ensembl; ENST00000305165.3; ENSP00000304311.2; ENSG00000172016.16.
DR Ensembl; ENST00000393878.5; ENSP00000377456.1; ENSG00000172016.16.
DR Ensembl; ENST00000409839.7; ENSP00000386630.3; ENSG00000172016.16.
DR GeneID; 5068; -.
DR KEGG; hsa:5068; -.
DR MANE-Select; ENST00000305165.3; ENSP00000304311.2; NM_002580.3; NP_002571.1.
DR CTD; 5068; -.
DR DisGeNET; 5068; -.
DR GeneCards; REG3A; -.
DR HGNC; HGNC:8601; REG3A.
DR HPA; ENSG00000172016; Group enriched (intestine, pancreas).
DR MIM; 167805; gene.
DR neXtProt; NX_Q06141; -.
DR OpenTargets; ENSG00000172016; -.
DR PharmGKB; PA32931; -.
DR VEuPathDB; HostDB:ENSG00000172016; -.
DR eggNOG; KOG4297; Eukaryota.
DR GeneTree; ENSGT00940000162300; -.
DR HOGENOM; CLU_049894_18_0_1; -.
DR InParanoid; Q06141; -.
DR OMA; CYLYVPQ; -.
DR OrthoDB; 1509611at2759; -.
DR PhylomeDB; Q06141; -.
DR PathwayCommons; Q06141; -.
DR Reactome; R-HSA-6803157; Antimicrobial peptides.
DR SignaLink; Q06141; -.
DR BioGRID-ORCS; 5068; 6 hits in 1055 CRISPR screens.
DR ChiTaRS; REG3A; human.
DR EvolutionaryTrace; Q06141; -.
DR GeneWiki; REG3A; -.
DR GenomeRNAi; 5068; -.
DR Pharos; Q06141; Tbio.
DR PRO; PR:Q06141; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q06141; protein.
DR Bgee; ENSG00000172016; Expressed in ileal mucosa and 113 other tissues.
DR ExpressionAtlas; Q06141; baseline and differential.
DR Genevisible; Q06141; HS.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0030246; F:carbohydrate binding; TAS:ProtInc.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0070492; F:oligosaccharide binding; IBA:GO_Central.
DR GO; GO:0042834; F:peptidoglycan binding; IBA:GO_Central.
DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR GO; GO:0006953; P:acute-phase response; IEA:UniProtKB-KW.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IBA:GO_Central.
DR GO; GO:0044278; P:cell wall disruption in another organism; IBA:GO_Central.
DR GO; GO:0007157; P:heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; TAS:ProtInc.
DR GO; GO:0045617; P:negative regulation of keratinocyte differentiation; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:0010838; P:positive regulation of keratinocyte proliferation; ISS:UniProtKB.
DR GO; GO:0090303; P:positive regulation of wound healing; ISS:UniProtKB.
DR GO; GO:0043434; P:response to peptide hormone; IBA:GO_Central.
DR Gene3D; 3.10.100.10; -; 1.
DR InterPro; IPR001304; C-type_lectin-like.
DR InterPro; IPR016186; C-type_lectin-like/link_sf.
DR InterPro; IPR018378; C-type_lectin_CS.
DR InterPro; IPR016187; CTDL_fold.
DR Pfam; PF00059; Lectin_C; 1.
DR SMART; SM00034; CLECT; 1.
DR SUPFAM; SSF56436; SSF56436; 1.
DR PROSITE; PS00615; C_TYPE_LECTIN_1; 1.
DR PROSITE; PS50041; C_TYPE_LECTIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acute phase; Antimicrobial; Direct protein sequencing;
KW Disulfide bond; Inflammatory response; Lectin; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..26
FT /evidence="ECO:0000250"
FT CHAIN 27..175
FT /note="Regenerating islet-derived protein 3-alpha 16.5 kDa
FT form"
FT /id="PRO_0000017429"
FT PROPEP 27..37
FT /evidence="ECO:0000269|PubMed:19254208"
FT /id="PRO_0000422741"
FT CHAIN 38..175
FT /note="Regenerating islet-derived protein 3-alpha 15 kDa
FT form"
FT /id="PRO_0000422742"
FT DOMAIN 47..172
FT /note="C-type lectin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT MOTIF 114..116
FT /note="EPN"
FT DISULFID 40..51
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DISULFID 68..171
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DISULFID 146..163
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT MUTAGEN 114
FT /note="E->Q: Reduces peptidoglycan binding and
FT antibacterial activity."
FT /evidence="ECO:0000269|PubMed:20382864"
FT MUTAGEN 118
FT /note="E->Q: Reduces antibacterial activity but no effect
FT on peptidoglycan binding."
FT /evidence="ECO:0000269|PubMed:20382864"
FT CONFLICT 173..175
FT /note="FTD -> VH (in Ref. 2; AAA36415)"
FT /evidence="ECO:0000305"
FT STRAND 44..47
FT /evidence="ECO:0007829|PDB:4MTH"
FT STRAND 50..59
FT /evidence="ECO:0007829|PDB:4MTH"
FT HELIX 61..68
FT /evidence="ECO:0007829|PDB:4MTH"
FT HELIX 82..92
FT /evidence="ECO:0007829|PDB:4MTH"
FT STRAND 100..107
FT /evidence="ECO:0007829|PDB:4MTH"
FT TURN 109..112
FT /evidence="ECO:0007829|PDB:4MTH"
FT STRAND 114..116
FT /evidence="ECO:0007829|PDB:2GO0"
FT TURN 123..125
FT /evidence="ECO:0007829|PDB:2GO0"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:4MTH"
FT HELIX 137..139
FT /evidence="ECO:0007829|PDB:4MTH"
FT STRAND 140..142
FT /evidence="ECO:0007829|PDB:4MTH"
FT STRAND 145..150
FT /evidence="ECO:0007829|PDB:4MTH"
FT HELIX 151..153
FT /evidence="ECO:0007829|PDB:4MTH"
FT STRAND 157..161
FT /evidence="ECO:0007829|PDB:4MTH"
FT STRAND 167..173
FT /evidence="ECO:0007829|PDB:4MTH"
SQ SEQUENCE 175 AA; 19395 MW; C51149FAC22EB68C CRC64;
MLPPMALPSV SWMLLSCLML LSQVQGEEPQ RELPSARIRC PKGSKAYGSH CYALFLSPKS
WTDADLACQK RPSGNLVSVL SGAEGSFVSS LVKSIGNSYS YVWIGLHDPT QGTEPNGEGW
EWSSSDVMNY FAWERNPSTI SSPGHCASLS RSTAFLRWKD YNCNVRLPYV CKFTD
