ID MEP1B_HUMAN Reviewed; 701 AA.
AC Q16820; B7ZM35; B9EGL6; Q670J1;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 27-MAR-2024, entry version 205.
DE RecName: Full=Meprin A subunit beta;
DE EC=3.4.24.63;
DE AltName: Full=Endopeptidase-2;
DE AltName: Full=Meprin B;
DE AltName: Full=N-benzoyl-L-tyrosyl-P-amino-benzoic acid hydrolase subunit beta;
DE AltName: Full=PABA peptide hydrolase;
DE AltName: Full=PPH beta;
DE Flags: Precursor;
GN Name=MEP1B;
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], PROTEIN SEQUENCE OF 62-105, AND VARIANT
RP LEU-695.
RC TISSUE=Intestine;
RX PubMed=9288916; DOI=10.1111/j.1432-1033.1997.00920.x;
RA Eldering J.A., Gruenberg J., Hahn D., Croes H.J., Fransen J.A.,
RA Sterchi E.E.;
RT "Polarised expression of human intestinal N-benzoyl-L-tyrosyl-p-
RT aminobenzoic acid hydrolase (human meprin) alpha and beta subunits in
RT Madin-Darby canine kidney cells.";
RL Eur. J. Biochem. 247:920-932(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Small intestine;
RA Haun R.S.;
RT "Expression of human meprin beta.";
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-695.
RC TISSUE=Testis;
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 PROTEIN SEQUENCE OF 62-79.
RC TISSUE=Small intestine mucosa;
RX PubMed=8262185; DOI=10.1016/0014-5793(93)80421-p;
RA Dumermuth E., Eldering J.A., Gruenberg J., Jiang W., Sterchi E.E.;
RT "Cloning of the PABA peptide hydrolase alpha subunit (PPH alpha) from human
RT small intestine and its expression in COS-1 cells.";
RL FEBS Lett. 335:367-375(1993).
RN [5]
RP SUBCELLULAR LOCATION, AND PROTEOLYTIC PROCESSING.
RX PubMed=10215852; DOI=10.1046/j.1432-1327.1999.00268.x;
RA Pischitzis A., Hahn D., Leuenberger B., Sterchi E.E.;
RT "N-Benzoyl-L-tyrosyl-p-aminobenzoic acid hydrolase beta (human meprinbeta).
RT A 13-amino-acid sequence is required for proteolytic processing and
RT subsequent secretion.";
RL Eur. J. Biochem. 261:421-429(1999).
RN [6]
RP GLYCOSYLATION AT SER-593; THR-594; THR-599 AND SER-603, TISSUE SPECIFICITY,
RP AND MUTAGENESIS OF 595-GLN--LEU-607.
RX PubMed=12387727; DOI=10.1042/bj20021398;
RA Leuenberger B., Hahn D., Pischitzis A., Hansen M.K., Sterchi E.E.;
RT "Human meprin beta: O-linked glycans in the intervening region of the type
RT I membrane protein protect the C-terminal region from proteolytic cleavage
RT and diminish its secretion.";
RL Biochem. J. 369:659-665(2003).
RN [7]
RP CLEAVAGE OF GASTRIN, SUBSTRATE SPECIFICITY, AND MUTAGENESIS OF LYS-248.
RX PubMed=12888571; DOI=10.1074/jbc.m303718200;
RA Villa J.P., Bertenshaw G.P., Bond J.S.;
RT "Critical amino acids in the active site of meprin metalloproteinases for
RT substrate and peptide bond specificity.";
RL J. Biol. Chem. 278:42545-42550(2003).
RN [8]
RP CLEAVAGE OF IL18.
RX PubMed=18786924; DOI=10.1074/jbc.m802814200;
RA Banerjee S., Bond J.S.;
RT "Prointerleukin-18 is activated by meprin beta in vitro and in vivo in
RT intestinal inflammation.";
RL J. Biol. Chem. 283:31371-31377(2008).
RN [9]
RP CLEAVAGE OF E-CADHERIN.
RX PubMed=18478055; DOI=10.1371/journal.pone.0002153;
RA Huguenin M., Muller E.J., Trachsel-Rosmann S., Oneda B., Ambort D.,
RA Sterchi E.E., Lottaz D.;
RT "The metalloprotease meprinbeta processes E-cadherin and weakens
RT intercellular adhesion.";
RL PLoS ONE 3:E2153-E2153(2008).
RN [10]
RP ACTIVITY REGULATION.
RX PubMed=20806899; DOI=10.1021/bi1004238;
RA Hedrich J., Lottaz D., Meyer K., Yiallouros I., Jahnen-Dechent W.,
RA Stocker W., Becker-Pauly C.;
RT "Fetuin-A and cystatin C are endogenous inhibitors of human meprin
RT metalloproteases.";
RL Biochemistry 49:8599-8607(2010).
RN [11]
RP CLEAVAGE OF TNC.
RX PubMed=19748582; DOI=10.1016/j.matbio.2009.08.007;
RA Ambort D., Brellier F., Becker-Pauly C., Stocker W., Andrejevic-Blant S.,
RA Chiquet M., Sterchi E.E.;
RT "Specific processing of tenascin-C by the metalloprotease meprinbeta
RT neutralizes its inhibition of cell spreading.";
RL Matrix Biol. 29:31-42(2010).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, AND CLEAVAGE OF FGF19;
RP KLK7 AND VGFA.
RX PubMed=21693781; DOI=10.1074/mcp.m111.009233;
RA Becker-Pauly C., Barre O., Schilling O., Auf dem Keller U., Ohler A.,
RA Broder C., Schutte A., Kappelhoff R., Stocker W., Overall C.M.;
RT "Proteomic analyses reveal an acidic prime side specificity for the astacin
RT metalloprotease family reflected by physiological substrates.";
RL Mol. Cell. Proteomics 10:M111.009233.01-M111.009233.19(2011).
RN [13]
RP CLEAVAGE OF ADAM10, AND ACTIVITY REGULATION.
RX PubMed=22940918; DOI=10.1007/s00018-012-1106-2;
RA Jefferson T., Auf dem Keller U., Bellac C., Metz V.V., Broder C.,
RA Hedrich J., Ohler A., Maier W., Magdolen V., Sterchi E., Bond J.S.,
RA Jayakumar A., Traupe H., Chalaris A., Rose-John S., Pietrzik C.U.,
RA Postina R., Overall C.M., Becker-Pauly C.;
RT "The substrate degradome of meprin metalloproteases reveals an unexpected
RT proteolytic link between meprin beta and ADAM10.";
RL Cell. Mol. Life Sci. 70:309-333(2013).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 25-614, GLYCOSYLATION AT ASN-218;
RP ASN-254; ASN-370; ASN-436; ASN-445; ASN-547 AND ASN-592, DISULFIDE BONDS,
RP COFACTOR, ZINC-BINDING SITES, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=22988105; DOI=10.1073/pnas.1211076109;
RA Arolas J.L., Broder C., Jefferson T., Guevara T., Sterchi E.E., Bode W.,
RA Stocker W., Becker-Pauly C., Gomis-Ruth F.X.;
RT "Structural basis for the sheddase function of human meprin beta
RT metalloproteinase at the plasma membrane.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:16131-16136(2012).
RN [15]
RP VARIANT ALA-324.
RX PubMed=23033978; DOI=10.1056/nejmoa1206524;
RA de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G.,
RA Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P., Gilissen C.,
RA del Rosario M., Hoischen A., Scheffer H., de Vries B.B., Brunner H.G.,
RA Veltman J.A., Vissers L.E.;
RT "Diagnostic exome sequencing in persons with severe intellectual
RT disability.";
RL N. Engl. J. Med. 367:1921-1929(2012).
CC -!- FUNCTION: Membrane metallopeptidase that sheds many membrane-bound
CC proteins. Exhibits a strong preference for acidic amino acids at the
CC P1' position. Known substrates include: FGF19, VGFA, IL1B, IL18,
CC procollagen I and III, E-cadherin, KLK7, gastrin, ADAM10, tenascin-C.
CC The presence of several pro-inflammatory cytokine among substrates
CC implicate MEP1B in inflammation. It is also involved in tissue
CC remodeling due to its capability to degrade extracellular matrix
CC components. {ECO:0000269|PubMed:21693781}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of proteins, including azocasein, and peptides.
CC Hydrolysis of 5-His-|-Leu-6, 6-Leu-|-Cys-7, 14-Ala-|-Leu-15 and 19-
CC Cys-|-Gly-20 bonds in insulin B chain.; EC=3.4.24.63;
CC Evidence={ECO:0000269|PubMed:21693781};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU01211,
CC ECO:0000269|PubMed:22988105};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000255|PROSITE-
CC ProRule:PRU01211, ECO:0000269|PubMed:22988105};
CC -!- ACTIVITY REGULATION: Strongly inhibited by fetuin-A/AHSG.
CC {ECO:0000269|PubMed:20806899, ECO:0000269|PubMed:22940918}.
CC -!- SUBUNIT: Homotetramer consisting of disulfide-linked beta subunits, or
CC heterotetramer of two alpha and two beta subunits formed by non-
CC covalent association of two disulfide-linked heterodimers (By
CC similarity). Interacts with MBL2 through its carbohydrate moiety. This
CC interaction may inhibit its catalytic activity (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC Q16820; Q16820: MEP1B; NbExp=3; IntAct=EBI-968418, EBI-968418;
CC Q16820; P14780: MMP9; NbExp=2; IntAct=EBI-968418, EBI-1382326;
CC Q16820; P19075: TSPAN8; NbExp=4; IntAct=EBI-968418, EBI-4289938;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22988105};
CC Single-pass type I membrane protein. Secreted
CC {ECO:0000269|PubMed:10215852}. Note=Homodimers are essentially membrane
CC bound but may also be shed from the surface by ADAM-10 and ADAM-17.
CC {ECO:0000269|PubMed:22988105}.
CC -!- TISSUE SPECIFICITY: The major site of expression is the brush border
CC membrane of small intestinal and kidney epithelial cells.
CC {ECO:0000269|PubMed:12387727}.
CC -!- PTM: N-glycosylated; contains high mannose and/or complex biantennary
CC structures.
CC -!- PTM: O-glycosylation protect the C-terminal region from proteolytic
CC cleavage and diminish secretion, this seems to be specific to human.
CC {ECO:0000269|PubMed:10215852, ECO:0000269|PubMed:12888571,
CC ECO:0000269|PubMed:18478055, ECO:0000269|PubMed:18786924,
CC ECO:0000269|PubMed:19748582, ECO:0000269|PubMed:21693781,
CC ECO:0000269|PubMed:22940918}.
CC -!- PTM: Proteolytically activated by trypsin in the intestinal lumen and
CC kallikrein-related peptidases in other tissues.
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DR EMBL; X81333; CAA57107.1; -; mRNA.
DR EMBL; AY695931; AAU05377.1; -; mRNA.
DR EMBL; BC136559; AAI36560.1; -; mRNA.
DR EMBL; BC144244; AAI44245.1; -; mRNA.
DR CCDS; CCDS45846.1; -.
DR PIR; S49383; HYHUMB.
DR RefSeq; NP_001295100.1; NM_001308171.1.
DR RefSeq; NP_005916.2; NM_005925.2.
DR PDB; 4GWM; X-ray; 1.85 A; A/B=23-614.
DR PDB; 4GWN; X-ray; 3.00 A; A=62-614.
DR PDB; 7AQ1; X-ray; 2.41 A; A/B=62-595.
DR PDB; 7AUW; X-ray; 2.80 A; A/C=62-608.
DR PDBsum; 4GWM; -.
DR PDBsum; 4GWN; -.
DR PDBsum; 7AQ1; -.
DR PDBsum; 7AUW; -.
DR AlphaFoldDB; Q16820; -.
DR SMR; Q16820; -.
DR BioGRID; 110388; 5.
DR CORUM; Q16820; -.
DR DIP; DIP-34900N; -.
DR IntAct; Q16820; 39.
DR MINT; Q16820; -.
DR STRING; 9606.ENSP00000269202; -.
DR BindingDB; Q16820; -.
DR ChEMBL; CHEMBL4105879; -.
DR MEROPS; M12.004; -.
DR TCDB; 8.A.77.2.1; the sheddase (sheddase) family.
DR GlyCosmos; Q16820; 12 sites, No reported glycans.
DR GlyGen; Q16820; 12 sites.
DR iPTMnet; Q16820; -.
DR PhosphoSitePlus; Q16820; -.
DR BioMuta; MEP1B; -.
DR DMDM; 296439304; -.
DR MassIVE; Q16820; -.
DR PaxDb; 9606-ENSP00000269202; -.
DR PeptideAtlas; Q16820; -.
DR ProteomicsDB; 61079; -.
DR Antibodypedia; 22196; 89 antibodies from 19 providers.
DR DNASU; 4225; -.
DR Ensembl; ENST00000269202.11; ENSP00000269202.6; ENSG00000141434.12.
DR GeneID; 4225; -.
DR KEGG; hsa:4225; -.
DR MANE-Select; ENST00000269202.11; ENSP00000269202.6; NM_005925.3; NP_005916.2.
DR UCSC; uc002kxj.5; human.
DR AGR; HGNC:7020; -.
DR CTD; 4225; -.
DR DisGeNET; 4225; -.
DR GeneCards; MEP1B; -.
DR HGNC; HGNC:7020; MEP1B.
DR HPA; ENSG00000141434; Tissue enriched (intestine).
DR MIM; 600389; gene.
DR neXtProt; NX_Q16820; -.
DR OpenTargets; ENSG00000141434; -.
DR PharmGKB; PA30754; -.
DR VEuPathDB; HostDB:ENSG00000141434; -.
DR eggNOG; KOG3714; Eukaryota.
DR GeneTree; ENSGT00950000183111; -.
DR InParanoid; Q16820; -.
DR OMA; VYCTRKR; -.
DR OrthoDB; 2876645at2759; -.
DR PhylomeDB; Q16820; -.
DR TreeFam; TF315280; -.
DR BRENDA; 3.4.24.18; 2681.
DR BRENDA; 3.4.24.63; 2681.
DR PathwayCommons; Q16820; -.
DR SignaLink; Q16820; -.
DR SIGNOR; Q16820; -.
DR BioGRID-ORCS; 4225; 13 hits in 1144 CRISPR screens.
DR GeneWiki; MEP1B; -.
DR GenomeRNAi; 4225; -.
DR Pharos; Q16820; Tchem.
DR PRO; PR:Q16820; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q16820; Protein.
DR Bgee; ENSG00000141434; Expressed in jejunal mucosa and 102 other cell types or tissues.
DR ExpressionAtlas; Q16820; baseline and differential.
DR Genevisible; Q16820; HS.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0017090; C:meprin A complex; IDA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd00054; EGF_CA; 1.
DR CDD; cd06263; MAM; 1.
DR CDD; cd04282; ZnMc_meprin; 1.
DR Gene3D; 2.60.120.200; -; 1.
DR Gene3D; 3.40.390.10; Collagenase (Catalytic Domain); 1.
DR Gene3D; 2.10.25.10; Laminin; 1.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000998; MAM_dom.
DR InterPro; IPR002083; MATH/TRAF_dom.
DR InterPro; IPR008294; Meprin.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR001506; Peptidase_M12A.
DR InterPro; IPR006026; Peptidase_Metallo.
DR InterPro; IPR008974; TRAF-like.
DR InterPro; IPR049342; TRAF_MEP1_MATH_dom.
DR InterPro; IPR034038; ZnMP_meprin.
DR PANTHER; PTHR10127; DISCOIDIN, CUB, EGF, LAMININ , AND ZINC METALLOPROTEASE DOMAIN CONTAINING; 1.
DR PANTHER; PTHR10127:SF814; MEPRIN A SUBUNIT BETA; 1.
DR Pfam; PF01400; Astacin; 1.
DR Pfam; PF00629; MAM; 1.
DR Pfam; PF21355; TRAF-mep_MATH; 1.
DR PIRSF; PIRSF001196; Meprin; 1.
DR PRINTS; PR00480; ASTACIN.
DR PRINTS; PR00020; MAMDOMAIN.
DR SMART; SM00137; MAM; 1.
DR SMART; SM00061; MATH; 1.
DR SMART; SM00235; ZnMc; 1.
DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 1.
DR SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1.
DR SUPFAM; SSF49599; TRAF domain-like; 1.
DR PROSITE; PS51864; ASTACIN; 1.
DR PROSITE; PS50026; EGF_3; 1.
DR PROSITE; PS00740; MAM_1; 1.
DR PROSITE; PS50060; MAM_2; 1.
DR PROSITE; PS50144; MATH; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Direct protein sequencing; Disulfide bond;
KW EGF-like domain; Glycoprotein; Hydrolase; Inflammatory response; Membrane;
KW Metal-binding; Metalloprotease; Protease; Reference proteome; Secreted;
KW Signal; Transmembrane; Transmembrane helix; Zinc; Zymogen.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT PROPEP 23..61
FT /evidence="ECO:0000269|PubMed:8262185,
FT ECO:0000269|PubMed:9288916"
FT /id="PRO_0000028883"
FT CHAIN 62..701
FT /note="Meprin A subunit beta"
FT /id="PRO_0000028884"
FT TOPO_DOM 23..652
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 653..673
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 674..701
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 62..256
FT /note="Peptidase M12A"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT DOMAIN 260..429
FT /note="MAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00128"
FT DOMAIN 430..585
FT /note="MATH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00129"
FT DOMAIN 604..644
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 595..607
FT /note="Required for proteolytic processing"
FT ACT_SITE 153
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT BINDING 152
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211,
FT ECO:0000269|PubMed:22988105, ECO:0007744|PDB:4GWM"
FT BINDING 156
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211,
FT ECO:0000269|PubMed:22988105, ECO:0007744|PDB:4GWM"
FT BINDING 162
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211,
FT ECO:0000269|PubMed:22988105, ECO:0007744|PDB:4GWM"
FT SITE 238
FT /note="Mediates preference for acidic residues at subsite
FT P1'"
FT CARBOHYD 218
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22988105"
FT CARBOHYD 254
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22988105"
FT CARBOHYD 370
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22988105"
FT CARBOHYD 421
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 436
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22988105"
FT CARBOHYD 445
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22988105"
FT CARBOHYD 547
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22988105"
FT CARBOHYD 592
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22988105"
FT CARBOHYD 593
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 594
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 599
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 603
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT DISULFID 103..255
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211,
FT ECO:0000269|PubMed:22988105"
FT DISULFID 124..144
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211,
FT ECO:0000269|PubMed:22988105"
FT DISULFID 265..427
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:22988105"
FT DISULFID 273
FT /note="Interchain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 305
FT /note="Interchain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:22988105"
FT DISULFID 492
FT /note="Interchain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 608..619
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 613..628
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 630..643
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT VARIANT 324
FT /note="T -> A"
FT /evidence="ECO:0000269|PubMed:23033978"
FT /id="VAR_069387"
FT VARIANT 326
FT /note="V -> M (in dbSNP:rs9959396)"
FT /id="VAR_057064"
FT VARIANT 695
FT /note="P -> L (in dbSNP:rs616114)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:9288916"
FT /id="VAR_057065"
FT MUTAGEN 248
FT /note="K->Y: Decreased activity toward gastrin."
FT /evidence="ECO:0000269|PubMed:12888571"
FT MUTAGEN 595..607
FT /note="Missing: Abolishes secretion."
FT /evidence="ECO:0000269|PubMed:12387727"
FT CONFLICT 71
FT /note="W -> S (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 74
FT /note="T -> P (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 546
FT /note="S -> P (in Ref. 2; AAU05377 and 3; AAI36560/
FT AAI44245)"
FT /evidence="ECO:0000305"
FT CONFLICT 698
FT /note="Missing (in Ref. 1; CAA57107)"
FT /evidence="ECO:0000305"
FT TURN 29..32
FT /evidence="ECO:0007829|PDB:4GWM"
FT HELIX 37..43
FT /evidence="ECO:0007829|PDB:4GWM"
FT TURN 50..52
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 63..65
FT /evidence="ECO:0007829|PDB:4GWN"
FT HELIX 67..69
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 73..79
FT /evidence="ECO:0007829|PDB:4GWM"
FT HELIX 85..101
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 105..108
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 113..119
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 122..126
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 133..140
FT /evidence="ECO:0007829|PDB:4GWM"
FT HELIX 147..158
FT /evidence="ECO:0007829|PDB:4GWM"
FT HELIX 163..165
FT /evidence="ECO:0007829|PDB:7AQ1"
FT HELIX 169..171
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 173..175
FT /evidence="ECO:0007829|PDB:4GWM"
FT HELIX 177..179
FT /evidence="ECO:0007829|PDB:4GWM"
FT HELIX 185..188
FT /evidence="ECO:0007829|PDB:4GWM"
FT TURN 193..195
FT /evidence="ECO:0007829|PDB:7AQ1"
FT TURN 213..216
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 217..221
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 223..228
FT /evidence="ECO:0007829|PDB:4GWM"
FT HELIX 229..231
FT /evidence="ECO:0007829|PDB:4GWM"
FT TURN 232..236
FT /evidence="ECO:0007829|PDB:4GWM"
FT HELIX 243..252
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 259..265
FT /evidence="ECO:0007829|PDB:4GWM"
FT HELIX 272..274
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 276..278
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 280..282
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 285..289
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 292..294
FT /evidence="ECO:0007829|PDB:7AUW"
FT STRAND 299..301
FT /evidence="ECO:0007829|PDB:7AQ1"
FT STRAND 311..315
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 317..319
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 324..328
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 335..337
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 339..347
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 354..363
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 366..379
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 382..384
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 386..392
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 398..405
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 412..425
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 429..434
FT /evidence="ECO:0007829|PDB:4GWM"
FT HELIX 438..440
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 447..449
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 460..466
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 469..480
FT /evidence="ECO:0007829|PDB:4GWM"
FT HELIX 485..487
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 494..501
FT /evidence="ECO:0007829|PDB:4GWM"
FT HELIX 508..510
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 514..519
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 527..531
FT /evidence="ECO:0007829|PDB:4GWN"
FT HELIX 536..539
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 541..544
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 550..564
FT /evidence="ECO:0007829|PDB:4GWM"
FT HELIX 565..568
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 573..575
FT /evidence="ECO:0007829|PDB:4GWM"
FT STRAND 578..587
FT /evidence="ECO:0007829|PDB:4GWM"
FT HELIX 589..591
FT /evidence="ECO:0007829|PDB:4GWM"
SQ SEQUENCE 701 AA; 79571 MW; 4733DBF018A4F3CD CRC64;
MDLWNLSWFL FLDALLVISG LATPENFDVD GGMDQDIFDI NEGLGLDLFE GDIRLDRAQI
RNSIIGEKYR WPHTIPYVLE DSLEMNAKGV ILNAFERYRL KTCIDFKPWA GETNYISVFK
GSGCWSSVGN RRVGKQELSI GANCDRIATV QHEFLHALGF WHEQSRSDRD DYVRIMWDRI
LSGREHNFNT YSDDISDSLN VPYDYTSVMH YSKTAFQNGT EPTIVTRISD FEDVIGQRMD
FSDSDLLKLN QLYNCSSSLS FMDSCSFELE NVCGMIQSSG DNADWQRVSQ VPRGPESDHS
NMGQCQGSGF FMHFDSSSVN VGATAVLESR TLYPKRGFQC LQFYLYNSGS ESDQLNIYIR
EYSADNVDGN LTLVEEIKEI PTGSWQLYHV TLKVTKKFRV VFEGRKGSGA SLGGLSIDDI
NLSETRCPHH IWHIRNFTQF IGSPNGTLYS PPFYSSKGYA FQIYLNLAHV TNAGIYFHLI
SGANDDQLQW PCPWQQATMT LLDQNPDIRQ RMSNQRSITT DPFMTTDNGN YFWDRPSKVG
TVALFSNGTQ FRRGGGYGTS AFITHERLKS RDFIKGDDVY ILLTVEDISH LNSTQIQLTP
APSVQDLCSK TTCKNDGVCT VRDGKAECRC QSGEDWWYMG ERCEKRGSTR DTIVIAVSST
VAVFALMLII TLVSVYCTRK KYRERMSSNR PNLTPQNQHA F
//
