GP2_HUMAN
ID GP2_HUMAN Reviewed; 537 AA.
AC P55259; A6NFM9; A6NJA8; Q13338; Q9UIF1;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 3.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Pancreatic secretory granule membrane major glycoprotein GP2 {ECO:0000305|PubMed:8666297};
DE AltName: Full=Pancreatic zymogen granule membrane protein GP-2 {ECO:0000305|PubMed:8666297};
DE AltName: Full=ZAP75;
DE Flags: Precursor;
GN Name=GP2 {ECO:0000312|HGNC:HGNC:4441};
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 ALPHA), AND TISSUE SPECIFICITY.
RX PubMed=8666297; DOI=10.1016/0378-1119(96)00065-0;
RA Wong S.M.E., Lowe A.W.;
RT "Sequence of the cDNA encoding human GP-2, the major membrane protein in
RT the secretory granule of the exocrine pancreas.";
RL Gene 171:311-312(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 8-537 (ISOFORMS ALPHA AND 2), SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND DOMAIN.
RX PubMed=10760606; DOI=10.1016/s0167-4781(00)00057-9;
RA Fukuoka S.;
RT "Molecular cloning and sequences of cDNAs encoding alpha (large) and beta
RT (small) isoforms of human pancreatic zymogen granule membrane-associated
RT protein GP2.";
RL Biochim. Biophys. Acta 1491:376-380(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 8-537 (ISOFORM BETA).
RC TISSUE=Pancreas;
RA Fukuoka S.;
RT "Molecular structure of human pancreatic GP2, a major glycoprotein with GPI
RT anchor in the zymogen granule membranes.";
RL Submitted (SEP-1994) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=19907495; DOI=10.1038/nature08529;
RA Hase K., Kawano K., Nochi T., Pontes G.S., Fukuda S., Ebisawa M.,
RA Kadokura K., Tobe T., Fujimura Y., Kawano S., Yabashi A., Waguri S.,
RA Nakato G., Kimura S., Murakami T., Iimura M., Hamura K., Fukuoka S.,
RA Lowe A.W., Itoh K., Kiyono H., Ohno H.;
RT "Uptake through glycoprotein 2 of FimH(+) bacteria by M cells initiates
RT mucosal immune response.";
RL Nature 462:226-230(2009).
CC -!- FUNCTION: Functions as an intestinal M-cell transcytotic receptor
CC specific of type-I-piliated bacteria that participates in the mucosal
CC immune response toward these bacteria. At the apical membrane of M-
CC cells it binds fimH, a protein of the bacteria type I pilus tip.
CC Internalizes bound bacteria, like E.coli and S.typhimurium, from the
CC lumen of the intestine and delivers them, through M-cells, to the
CC underlying organized lymphoid follicles where they are captured by
CC antigen-presenting dendritic cells to elicit a mucosal immune response.
CC {ECO:0000305|PubMed:19907495}.
CC -!- SUBUNIT: Interacts with SYCN. {ECO:0000250|UniProtKB:P19218}.
CC -!- INTERACTION:
CC P55259-4; Q8N5M9: JAGN1; NbExp=3; IntAct=EBI-17746146, EBI-10266796;
CC -!- SUBCELLULAR LOCATION: Zymogen granule membrane
CC {ECO:0000250|UniProtKB:P19218}; Lipid-anchor, GPI-anchor
CC {ECO:0000250|UniProtKB:P19218}. Secreted {ECO:0000269|PubMed:10760606}.
CC Cell membrane {ECO:0000250|UniProtKB:P19218}; Lipid-anchor, GPI-anchor
CC {ECO:0000250|UniProtKB:P19218}. Apical cell membrane
CC {ECO:0000250|UniProtKB:Q9D733}; Lipid-anchor, GPI-anchor
CC {ECO:0000250|UniProtKB:P19218}. Membrane raft
CC {ECO:0000250|UniProtKB:P19218}; Lipid-anchor, GPI-anchor
CC {ECO:0000250|UniProtKB:P19218}. Endosome
CC {ECO:0000250|UniProtKB:Q9D733}. Note=Secreted, after cleavage, in the
CC pancreatic juice. {ECO:0000305|PubMed:10760606}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=P55259-1; Sequence=Displayed;
CC Name=Beta {ECO:0000303|PubMed:10760606};
CC IsoId=P55259-2; Sequence=VSP_006948;
CC Name=Alpha {ECO:0000303|PubMed:10760606};
CC IsoId=P55259-3; Sequence=VSP_035750;
CC Name=2;
CC IsoId=P55259-4; Sequence=VSP_035749;
CC -!- TISSUE SPECIFICITY: Expressed in pancreas (at protein level)
CC (PubMed:8666297, PubMed:10760606). Specifically expressed by M
CC (microfold) cells which are atypical epithelial cells of the intestine
CC (at protein level) (PubMed:19907495). {ECO:0000269|PubMed:10760606,
CC ECO:0000269|PubMed:19907495, ECO:0000269|PubMed:8666297}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:P19218}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-8 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB19240.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; U36221; AAB19240.1; ALT_INIT; mRNA.
DR EMBL; AC106796; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471186; EAW50311.1; -; Genomic_DNA.
DR EMBL; AB035541; BAA88166.1; -; mRNA.
DR EMBL; AB035542; BAA88167.1; -; mRNA.
DR EMBL; D38225; BAA07400.1; -; mRNA.
DR CCDS; CCDS10582.2; -. [P55259-3]
DR CCDS; CCDS42128.1; -. [P55259-1]
DR CCDS; CCDS45432.1; -. [P55259-4]
DR CCDS; CCDS45433.1; -. [P55259-2]
DR PIR; G02091; G02091.
DR RefSeq; NP_001007241.2; NM_001007240.2. [P55259-1]
DR RefSeq; NP_001493.2; NM_001502.3. [P55259-3]
DR PDB; 7P6R; X-ray; 1.90 A; A/B=29-184.
DR PDB; 7P6S; X-ray; 1.35 A; A=29-184.
DR PDB; 7P6T; X-ray; 1.40 A; A=29-184.
DR PDBsum; 7P6R; -.
DR PDBsum; 7P6S; -.
DR PDBsum; 7P6T; -.
DR AlphaFoldDB; P55259; -.
DR SMR; P55259; -.
DR BioGRID; 109075; 4.
DR IntAct; P55259; 3.
DR STRING; 9606.ENSP00000370767; -.
DR GlyConnect; 1593; 4 N-Linked glycans (1 site).
DR GlyGen; P55259; 7 sites, 4 N-linked glycans (1 site).
DR iPTMnet; P55259; -.
DR PhosphoSitePlus; P55259; -.
DR BioMuta; GP2; -.
DR DMDM; 215274153; -.
DR jPOST; P55259; -.
DR MassIVE; P55259; -.
DR PaxDb; P55259; -.
DR PeptideAtlas; P55259; -.
DR PRIDE; P55259; -.
DR ProteomicsDB; 56819; -. [P55259-1]
DR ProteomicsDB; 56820; -. [P55259-2]
DR ProteomicsDB; 56821; -. [P55259-3]
DR ProteomicsDB; 56822; -. [P55259-4]
DR ABCD; P55259; 4 sequenced antibodies.
DR Antibodypedia; 2620; 405 antibodies from 22 providers.
DR DNASU; 2813; -.
DR Ensembl; ENST00000302555.10; ENSP00000304044.6; ENSG00000169347.17. [P55259-3]
DR Ensembl; ENST00000341642.9; ENSP00000343861.5; ENSG00000169347.17. [P55259-4]
DR Ensembl; ENST00000381360.9; ENSP00000370765.5; ENSG00000169347.17. [P55259-2]
DR Ensembl; ENST00000381362.8; ENSP00000370767.4; ENSG00000169347.17. [P55259-1]
DR GeneID; 2813; -.
DR KEGG; hsa:2813; -.
DR MANE-Select; ENST00000302555.10; ENSP00000304044.6; NM_001502.4; NP_001493.2. [P55259-3]
DR UCSC; uc002dgv.4; human. [P55259-1]
DR CTD; 2813; -.
DR DisGeNET; 2813; -.
DR GeneCards; GP2; -.
DR HGNC; HGNC:4441; GP2.
DR HPA; ENSG00000169347; Tissue enriched (pancreas).
DR MIM; 602977; gene.
DR neXtProt; NX_P55259; -.
DR OpenTargets; ENSG00000169347; -.
DR PharmGKB; PA28822; -.
DR VEuPathDB; HostDB:ENSG00000169347; -.
DR eggNOG; ENOG502QT6B; Eukaryota.
DR GeneTree; ENSGT00940000156038; -.
DR HOGENOM; CLU_028679_1_0_1; -.
DR InParanoid; P55259; -.
DR OMA; QGYGNPS; -.
DR PhylomeDB; P55259; -.
DR TreeFam; TF330284; -.
DR PathwayCommons; P55259; -.
DR Reactome; R-HSA-163125; Post-translational modification: synthesis of GPI-anchored proteins.
DR SignaLink; P55259; -.
DR BioGRID-ORCS; 2813; 15 hits in 1063 CRISPR screens.
DR ChiTaRS; GP2; human.
DR GeneWiki; GP2_(gene); -.
DR GenomeRNAi; 2813; -.
DR Pharos; P55259; Tbio.
DR PRO; PR:P55259; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P55259; protein.
DR Bgee; ENSG00000169347; Expressed in body of pancreas and 114 other tissues.
DR ExpressionAtlas; P55259; baseline and differential.
DR Genevisible; P55259; HS.
DR GO; GO:0031362; C:anchored component of external side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0042589; C:zymogen granule membrane; ISS:UniProtKB.
DR GO; GO:0003823; F:antigen binding; IDA:UniProtKB.
DR GO; GO:0005201; F:extracellular matrix structural constituent; IBA:GO_Central.
DR GO; GO:0002412; P:antigen transcytosis by M cells in mucosal-associated lymphoid tissue; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:1990266; P:neutrophil migration; IBA:GO_Central.
DR Gene3D; 2.60.40.4100; -; 1.
DR InterPro; IPR042235; ZP-C.
DR InterPro; IPR001507; ZP_dom.
DR InterPro; IPR017977; ZP_dom_CS.
DR Pfam; PF00100; Zona_pellucida; 1.
DR PRINTS; PR00023; ZPELLUCIDA.
DR SMART; SM00241; ZP; 1.
DR PROSITE; PS00682; ZP_1; 1.
DR PROSITE; PS51034; ZP_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Cytoplasmic vesicle;
KW Disulfide bond; EGF-like domain; Endosome; Glycoprotein; GPI-anchor;
KW Immunity; Innate immunity; Lipoprotein; Membrane; Receptor;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..28
FT /evidence="ECO:0000250|UniProtKB:P25291"
FT CHAIN 29..512
FT /note="Pancreatic secretory granule membrane major
FT glycoprotein GP2"
FT /id="PRO_0000041657"
FT PROPEP 513..537
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000041658"
FT DOMAIN 186..230
FT /note="EGF-like"
FT /evidence="ECO:0000305|PubMed:10760606"
FT DOMAIN 228..484
FT /note="ZP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00375"
FT LIPID 512
FT /note="GPI-anchor amidated asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 65
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 122
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 362
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 190..200
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 194..209
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 211..241
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 229..320
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 261..284
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 401..461
FT /evidence="ECO:0000250|UniProtKB:P07911,
FT ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 422..477
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 466..473
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT VAR_SEQ 31..180
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10760606"
FT /id="VSP_035749"
FT VAR_SEQ 32..178
FT /note="Missing (in isoform Beta)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_006948"
FT VAR_SEQ 179..181
FT /note="Missing (in isoform Alpha)"
FT /evidence="ECO:0000303|PubMed:10760606,
FT ECO:0000303|PubMed:8666297"
FT /id="VSP_035750"
FT CONFLICT 189
FT /note="K -> KK (in Ref. 5; BAA07400)"
FT /evidence="ECO:0000305"
FT CONFLICT 243
FT /note="L -> Q (in Ref. 5; BAA07400)"
FT /evidence="ECO:0000305"
FT CONFLICT 248
FT /note="L -> F (in Ref. 5; BAA07400)"
FT /evidence="ECO:0000305"
FT CONFLICT 505
FT /note="A -> G (in Ref. 5; BAA07400)"
FT /evidence="ECO:0000305"
FT CONFLICT 535..537
FT /note="WLF -> LAV (in Ref. 5; BAA07400)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 537 AA; 59480 MW; 8A6B6A0FC64F50B8 CRC64;
MPHLMERMVG SGLLWLALVS CILTQASAVQ RGYGNPIEAS SYGLDLDCGA PGTPEAHVCF
DPCQNYTLLD EPFRSTENSA GSQGCDKNMS GWYRFVGEGG VRMSETCVQV HRCQTDAPMW
LNGTHPALGD GITNHTACAH WSGNCCFWKT EVLVKACPGG YHVYRLEGTP WCNLRYCTVP
RDPSTVEDKC EKACRPEEEC LALNSTWGCF CRQDLNSSDV HSLQPQLDCG PREIKVKVDK
CLLGGLGLGE EVIAYLRDPN CSSILQTEER NWVSVTSPVQ ASACRNILER NQTHAIYKNT
LSLVNDFIIR DTILNINFQC AYPLDMKVSL QAALQPIVSS LNVSVDGNGE FIVRMALFQD
QNYTNPYEGD AVELSVESVL YVGAILEQGD TSRFNLVLRN CYATPTEDKA DLVKYFIIRN
SCSNQRDSTI HVEENGQSSE SRFSVQMFMF AGHYDLVFLH CEIHLCDSLN EQCQPSCSRS
QVRSEVPAID LARVLDLGPI TRRGAQSPGV MNGTPSTAGF LVAWPMVLLT VLLAWLF
