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Database: UniProt
Entry: Q16820
LinkDB: Q16820
Original site: Q16820 
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   10-APR-2019, entry version 178.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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
RT   project: 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
RT   human 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
RT   meprinbeta). A 13-amino-acid sequence is required for proteolytic
RT   processing and 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
RP   SPECIFICITY, 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
RT   type I membrane protein protect the C-terminal region from proteolytic
RT   cleavage and diminish its secretion.";
RL   Biochem. J. 369:659-665(2003).
RN   [7]
RP   CLEAVAGE OF GASTRIN, SUBSTRATE SPECIFICITY, AND MUTAGENESIS OF
RP   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
RT   for 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.,
RA   Andrejevic-Blant S., 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
RP   FGF19; 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
RT   astacin metalloprotease family reflected by physiological
RT   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
RT   unexpected 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
RP   ASN-218; ASN-254; ASN-370; ASN-436; ASN-445; ASN-547 AND ASN-592,
RP   DISULFIDE BONDS, COFACTOR, ZINC-BINDING SITES, SUBUNIT, AND
RP   SUBCELLULAR LOCATION.
RX   PubMed=22988105; DOI=10.1073/pnas.1211076109;
RA   Arolas J.L., Broder C., Jefferson T., Guevara T., Sterchi E.E.,
RA   Bode W., 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.,
RA   Gilissen C., del Rosario M., Hoischen A., Scheffer H., de Vries B.B.,
RA   Brunner H.G., 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
CC       the P1' position. Known substrates include: FGF19, VGFA, IL1B,
CC       IL18, procollagen I and III, E-cadherin, KLK7, gastrin, ADAM10,
CC       tenascin-C. The presence of several pro-inflammatory cytokine
CC       among substrates implicate MEP1B in inflammation. It is also
CC       involved in tissue remodeling due to its capability to degrade
CC       extracellular matrix components. {ECO:0000269|PubMed:21693781}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Hydrolysis of proteins, including azocasein, and
CC         peptides. Hydrolysis of 5-His-|-Leu-6, 6-Leu-|-Cys-7, 14-Ala-|-
CC         Leu-15 and 19-Cys-|-Gly-20 bonds in insulin B chain.;
CC         EC=3.4.24.63; 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
CC       subunits, or heterotetramer of two alpha and two beta subunits
CC       formed by non-covalent association of two disulfide-linked
CC       heterodimers (By similarity). Interacts with MBL2 through its
CC       carbohydrate moiety. This interaction may inhibit its catalytic
CC       activity (By similarity). {ECO:0000250}.
CC   -!- INTERACTION:
CC       Self; NbExp=2; IntAct=EBI-968418, EBI-968418;
CC       P14780:MMP9; NbExp=2; IntAct=EBI-968418, EBI-1382326;
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
CC       membrane bound but may also be shed from the surface by ADAM-10
CC       and ADAM-17. {ECO:0000269|PubMed:22988105}.
CC   -!- TISSUE SPECIFICITY: The major site of expression is the brush
CC       border membrane of small intestinal and kidney epithelial cells.
CC       {ECO:0000269|PubMed:12387727}.
CC   -!- PTM: N-glycosylated; contains high mannose and/or complex
CC       biantennary structures.
CC   -!- PTM: O-glycosylation protect the C-terminal region from
CC       proteolytic cleavage and diminish secretion, this seems to be
CC       specific to human. {ECO:0000269|PubMed:10215852,
CC       ECO:0000269|PubMed:12888571, ECO:0000269|PubMed:18478055,
CC       ECO:0000269|PubMed:18786924, ECO:0000269|PubMed:19748582,
CC       ECO:0000269|PubMed:21693781, ECO:0000269|PubMed:22940918}.
CC   -!- PTM: Proteolytically activated by trypsin in the intestinal lumen
CC       and kallikrein-related peptidases in other tissues.
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   UniGene; Hs.194777; -.
DR   PDB; 4GWM; X-ray; 1.85 A; A/B=23-614.
DR   PDB; 4GWN; X-ray; 3.00 A; A=62-614.
DR   PDBsum; 4GWM; -.
DR   PDBsum; 4GWN; -.
DR   ProteinModelPortal; Q16820; -.
DR   SMR; Q16820; -.
DR   BioGrid; 110388; 4.
DR   CORUM; Q16820; -.
DR   DIP; DIP-34900N; -.
DR   IntAct; Q16820; 1.
DR   MINT; Q16820; -.
DR   STRING; 9606.ENSP00000269202; -.
DR   MEROPS; M12.004; -.
DR   TCDB; 8.A.77.2.1; the sheddase (sheddase) family.
DR   iPTMnet; Q16820; -.
DR   PhosphoSitePlus; Q16820; -.
DR   BioMuta; MEP1B; -.
DR   DMDM; 296439304; -.
DR   PaxDb; Q16820; -.
DR   PeptideAtlas; Q16820; -.
DR   PRIDE; Q16820; -.
DR   ProteomicsDB; 61079; -.
DR   Ensembl; ENST00000269202; ENSP00000269202; ENSG00000141434.
DR   GeneID; 4225; -.
DR   KEGG; hsa:4225; -.
DR   UCSC; uc002kxj.5; human.
DR   CTD; 4225; -.
DR   DisGeNET; 4225; -.
DR   EuPathDB; HostDB:ENSG00000141434.11; -.
DR   GeneCards; MEP1B; -.
DR   H-InvDB; HIX0039722; -.
DR   HGNC; HGNC:7020; MEP1B.
DR   HPA; HPA029119; -.
DR   MIM; 600389; gene.
DR   neXtProt; NX_Q16820; -.
DR   OpenTargets; ENSG00000141434; -.
DR   PharmGKB; PA30754; -.
DR   eggNOG; KOG3714; Eukaryota.
DR   eggNOG; ENOG410ZPX7; LUCA.
DR   GeneTree; ENSGT00950000183111; -.
DR   HOGENOM; HOG000043106; -.
DR   HOVERGEN; HBG052457; -.
DR   InParanoid; Q16820; -.
DR   KO; K08606; -.
DR   OMA; WHIRNFT; -.
DR   OrthoDB; 241999at2759; -.
DR   PhylomeDB; Q16820; -.
DR   TreeFam; TF315280; -.
DR   BRENDA; 3.4.24.63; 2681.
DR   SignaLink; Q16820; -.
DR   GeneWiki; MEP1B; -.
DR   GenomeRNAi; 4225; -.
DR   PRO; PR:Q16820; -.
DR   Proteomes; UP000005640; Chromosome 18.
DR   Bgee; ENSG00000141434; Expressed in 93 organ(s), highest expression level in jejunal mucosa.
DR   ExpressionAtlas; Q16820; baseline and differential.
DR   Genevisible; Q16820; HS.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0005887; C:integral component of plasma membrane; IDA:GO_Central.
DR   GO; GO:0017090; C:meprin A complex; 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:1901998; P:toxin transport; IEA:Ensembl.
DR   CDD; cd06263; MAM; 1.
DR   CDD; cd04282; ZnMc_meprin; 1.
DR   Gene3D; 2.60.210.10; -; 1.
DR   Gene3D; 3.40.390.10; -; 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; IPR034302; Meprin_beta.
DR   InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR   InterPro; IPR001506; Peptidase_M12A.
DR   InterPro; IPR006026; Peptidase_Metallo.
DR   InterPro; IPR008974; TRAF-like.
DR   InterPro; IPR034038; ZnMP_meprin.
DR   PANTHER; PTHR44155; PTHR44155; 1.
DR   PANTHER; PTHR44155:SF3; PTHR44155:SF3; 1.
DR   Pfam; PF01400; Astacin; 1.
DR   Pfam; PF00629; MAM; 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; SSF49599; SSF49599; 1.
DR   SUPFAM; SSF49899; SSF49899; 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; Complete proteome;
KW   Direct protein sequencing; Disulfide bond; EGF-like domain;
KW   Glycoprotein; Hydrolase; Inflammatory response; Membrane;
KW   Metal-binding; Metalloprotease; Polymorphism; Protease;
KW   Reference proteome; Secreted; Signal; Transmembrane;
KW   Transmembrane helix; Zinc; Zymogen.
FT   SIGNAL        1     22       {ECO:0000255}.
FT   PROPEP       23     61       {ECO:0000269|PubMed:8262185,
FT                                ECO:0000269|PubMed:9288916}.
FT                                /FTId=PRO_0000028883.
FT   CHAIN        62    701       Meprin A subunit beta.
FT                                /FTId=PRO_0000028884.
FT   TOPO_DOM     23    652       Extracellular. {ECO:0000255}.
FT   TRANSMEM    653    673       Helical. {ECO:0000255}.
FT   TOPO_DOM    674    701       Cytoplasmic. {ECO:0000255}.
FT   DOMAIN       62    256       Peptidase M12A. {ECO:0000255|PROSITE-
FT                                ProRule:PRU01211}.
FT   DOMAIN      260    429       MAM. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00128}.
FT   DOMAIN      430    585       MATH. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00129}.
FT   DOMAIN      604    644       EGF-like. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   REGION      595    607       Required for proteolytic processing.
FT   ACT_SITE    153    153       {ECO:0000255|PROSITE-ProRule:PRU01211}.
FT   METAL       152    152       Zinc; via tele nitrogen; catalytic.
FT                                {ECO:0000244|PDB:4GWM,
FT                                ECO:0000255|PROSITE-ProRule:PRU01211,
FT                                ECO:0000269|PubMed:22988105}.
FT   METAL       156    156       Zinc; via tele nitrogen; catalytic.
FT                                {ECO:0000244|PDB:4GWM,
FT                                ECO:0000255|PROSITE-ProRule:PRU01211,
FT                                ECO:0000269|PubMed:22988105}.
FT   METAL       162    162       Zinc; via tele nitrogen; catalytic.
FT                                {ECO:0000244|PDB:4GWM,
FT                                ECO:0000255|PROSITE-ProRule:PRU01211,
FT                                ECO:0000269|PubMed:22988105}.
FT   SITE        238    238       Mediates preference for acidic residues
FT                                at subsite P1'.
FT   CARBOHYD    218    218       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:22988105}.
FT   CARBOHYD    254    254       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:22988105}.
FT   CARBOHYD    370    370       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:22988105}.
FT   CARBOHYD    421    421       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    436    436       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:22988105}.
FT   CARBOHYD    445    445       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:22988105}.
FT   CARBOHYD    547    547       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:22988105}.
FT   CARBOHYD    592    592       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:22988105}.
FT   CARBOHYD    593    593       O-linked (GalNAc...) serine.
FT                                {ECO:0000255}.
FT   CARBOHYD    594    594       O-linked (GalNAc...) threonine.
FT                                {ECO:0000255}.
FT   CARBOHYD    599    599       O-linked (GalNAc...) threonine.
FT                                {ECO:0000255}.
FT   CARBOHYD    603    603       O-linked (GalNAc...) serine.
FT                                {ECO:0000255}.
FT   DISULFID    103    255       {ECO:0000255|PROSITE-ProRule:PRU01211,
FT                                ECO:0000269|PubMed:22988105}.
FT   DISULFID    124    144       {ECO:0000255|PROSITE-ProRule:PRU01211,
FT                                ECO:0000269|PubMed:22988105}.
FT   DISULFID    265    427       {ECO:0000255|PROSITE-ProRule:PRU00076,
FT                                ECO:0000269|PubMed:22988105}.
FT   DISULFID    273    273       Interchain. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DISULFID    305    305       Interchain. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076,
FT                                ECO:0000269|PubMed:22988105}.
FT   DISULFID    492    492       Interchain. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DISULFID    608    619       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    613    628       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    630    643       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   VARIANT     324    324       T -> A. {ECO:0000269|PubMed:23033978}.
FT                                /FTId=VAR_069387.
FT   VARIANT     326    326       V -> M (in dbSNP:rs9959396).
FT                                /FTId=VAR_057064.
FT   VARIANT     695    695       P -> L (in dbSNP:rs616114).
FT                                {ECO:0000269|PubMed:15489334,
FT                                ECO:0000269|PubMed:9288916}.
FT                                /FTId=VAR_057065.
FT   MUTAGEN     248    248       K->Y: Decreased activity toward gastrin.
FT                                {ECO:0000269|PubMed:12888571}.
FT   MUTAGEN     595    607       Missing: Abolishes secretion.
FT                                {ECO:0000269|PubMed:12387727}.
FT   CONFLICT     71     71       W -> S (in Ref. 4; AA sequence).
FT                                {ECO:0000305}.
FT   CONFLICT     74     74       T -> P (in Ref. 4; AA sequence).
FT                                {ECO:0000305}.
FT   CONFLICT    546    546       S -> P (in Ref. 2; AAU05377 and 3;
FT                                AAI36560/AAI44245). {ECO:0000305}.
FT   CONFLICT    698    698       Missing (in Ref. 1; CAA57107).
FT                                {ECO:0000305}.
FT   TURN         29     32       {ECO:0000244|PDB:4GWM}.
FT   HELIX        37     43       {ECO:0000244|PDB:4GWM}.
FT   TURN         50     52       {ECO:0000244|PDB:4GWM}.
FT   STRAND       63     65       {ECO:0000244|PDB:4GWN}.
FT   HELIX        67     69       {ECO:0000244|PDB:4GWM}.
FT   STRAND       73     79       {ECO:0000244|PDB:4GWM}.
FT   HELIX        85    101       {ECO:0000244|PDB:4GWM}.
FT   STRAND      105    108       {ECO:0000244|PDB:4GWM}.
FT   STRAND      113    119       {ECO:0000244|PDB:4GWM}.
FT   STRAND      122    126       {ECO:0000244|PDB:4GWM}.
FT   STRAND      133    140       {ECO:0000244|PDB:4GWM}.
FT   HELIX       147    158       {ECO:0000244|PDB:4GWM}.
FT   HELIX       163    165       {ECO:0000244|PDB:4GWN}.
FT   HELIX       169    171       {ECO:0000244|PDB:4GWM}.
FT   STRAND      173    175       {ECO:0000244|PDB:4GWM}.
FT   HELIX       177    179       {ECO:0000244|PDB:4GWM}.
FT   HELIX       185    188       {ECO:0000244|PDB:4GWM}.
FT   TURN        193    195       {ECO:0000244|PDB:4GWN}.
FT   TURN        213    216       {ECO:0000244|PDB:4GWM}.
FT   STRAND      217    221       {ECO:0000244|PDB:4GWM}.
FT   STRAND      223    228       {ECO:0000244|PDB:4GWM}.
FT   HELIX       229    231       {ECO:0000244|PDB:4GWM}.
FT   TURN        232    236       {ECO:0000244|PDB:4GWM}.
FT   HELIX       243    252       {ECO:0000244|PDB:4GWM}.
FT   STRAND      259    265       {ECO:0000244|PDB:4GWM}.
FT   HELIX       272    274       {ECO:0000244|PDB:4GWM}.
FT   STRAND      276    278       {ECO:0000244|PDB:4GWM}.
FT   STRAND      280    282       {ECO:0000244|PDB:4GWM}.
FT   STRAND      285    289       {ECO:0000244|PDB:4GWM}.
FT   STRAND      292    294       {ECO:0000244|PDB:4GWN}.
FT   STRAND      299    304       {ECO:0000244|PDB:4GWN}.
FT   STRAND      311    315       {ECO:0000244|PDB:4GWM}.
FT   STRAND      317    319       {ECO:0000244|PDB:4GWM}.
FT   STRAND      324    328       {ECO:0000244|PDB:4GWM}.
FT   STRAND      335    337       {ECO:0000244|PDB:4GWM}.
FT   STRAND      339    347       {ECO:0000244|PDB:4GWM}.
FT   STRAND      354    363       {ECO:0000244|PDB:4GWM}.
FT   STRAND      366    379       {ECO:0000244|PDB:4GWM}.
FT   STRAND      382    384       {ECO:0000244|PDB:4GWM}.
FT   STRAND      386    392       {ECO:0000244|PDB:4GWM}.
FT   STRAND      398    405       {ECO:0000244|PDB:4GWM}.
FT   STRAND      412    425       {ECO:0000244|PDB:4GWM}.
FT   STRAND      429    434       {ECO:0000244|PDB:4GWM}.
FT   HELIX       438    440       {ECO:0000244|PDB:4GWM}.
FT   STRAND      447    449       {ECO:0000244|PDB:4GWM}.
FT   STRAND      460    466       {ECO:0000244|PDB:4GWM}.
FT   STRAND      469    480       {ECO:0000244|PDB:4GWM}.
FT   HELIX       485    487       {ECO:0000244|PDB:4GWM}.
FT   STRAND      494    501       {ECO:0000244|PDB:4GWM}.
FT   HELIX       508    510       {ECO:0000244|PDB:4GWM}.
FT   STRAND      514    519       {ECO:0000244|PDB:4GWM}.
FT   STRAND      527    531       {ECO:0000244|PDB:4GWN}.
FT   HELIX       536    539       {ECO:0000244|PDB:4GWM}.
FT   STRAND      541    544       {ECO:0000244|PDB:4GWM}.
FT   STRAND      550    564       {ECO:0000244|PDB:4GWM}.
FT   HELIX       565    568       {ECO:0000244|PDB:4GWM}.
FT   STRAND      573    575       {ECO:0000244|PDB:4GWM}.
FT   STRAND      578    587       {ECO:0000244|PDB:4GWM}.
FT   HELIX       589    591       {ECO:0000244|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
//
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