AMYP_HUMAN
ID AMYP_HUMAN Reviewed; 511 AA.
AC P04746; B9EJG1; Q9UBH3;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 2.
DT 03-AUG-2022, entry version 220.
DE RecName: Full=Pancreatic alpha-amylase;
DE Short=PA;
DE EC=3.2.1.1 {ECO:0000269|PubMed:10091666, ECO:0000269|PubMed:10769135, ECO:0000269|PubMed:11772019, ECO:0000269|PubMed:11914097};
DE AltName: Full=1,4-alpha-D-glucan glucanohydrolase;
DE Flags: Precursor;
GN Name=AMY2A;
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 [GENOMIC DNA].
RX PubMed=6610603; DOI=10.1016/0378-1119(84)90265-8;
RA Nakamura Y., Ogawa M., Nishide T., Emi M., Kosaki G., Himeno S.,
RA Matsubara K.;
RT "Corrected sequences of cDNAs for human salivary and pancreatic alpha-
RT amylases.";
RL Gene 28:263-270(1984).
RN [2]
RP ERRATUM OF PUBMED:6610603, AND SEQUENCE REVISION.
RA Nakamura Y., Ogawa M., Nishide T., Emi M., Kosaki G., Himeno S.,
RA Matsubara K.;
RL Gene 50:371-372(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Pancreas;
RX PubMed=2450054; DOI=10.1016/0378-1119(87)90213-7;
RA Horii A., Emi M., Tomita N., Nishide T., Ogawa M., Mori T., Matsubara K.;
RT "Primary structure of human pancreatic alpha-amylase gene: its comparison
RT with human salivary alpha-amylase gene.";
RL Gene 60:57-64(1987).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Pancreas;
RX PubMed=6336237;
RA Wise R.J., Karn R.C., Larsen S.H., Hodes M.E., Gardell S.J., Rutter W.J.;
RT "A complementary DNA sequence that predicts a human pancreatic amylase
RT primary structure consistent with the electrophoretic mobility of the
RT common isozyme, Amy2 A.";
RL Mol. Biol. Med. 2:307-322(1984).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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 [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-56.
RX PubMed=3260028; DOI=10.1093/nar/16.10.4724;
RA Groot P.C., Bleeker M.J., Pronk J.C., Arwert F., Mager W.H., Planta R.J.,
RA Eriksson A.W., Frants R.R.;
RT "Human pancreatic amylase is encoded by two different genes.";
RL Nucleic Acids Res. 16:4724-4724(1988).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-56.
RX PubMed=2452973; DOI=10.1128/mcb.8.3.1197-1205.1988;
RA Gumucio D.L., Wiebauer K., Caldwell R.M., Samuelson L.C., Meisler M.H.;
RT "Concerted evolution of human amylase genes.";
RL Mol. Cell. Biol. 8:1197-1205(1988).
RN [8]
RP SUBUNIT, AND INTERACTION WITH THE SEA ANEMONE INHIBITOR HELIANTHAMIDE.
RX PubMed=27066537; DOI=10.1021/acscentsci.5b00399;
RA Tysoe C., Williams L.K., Keyzers R., Nguyen N.T., Tarling C., Wicki J.,
RA Goddard-Borger E.D., Aguda A.H., Perry S., Foster L.J., Andersen R.J.,
RA Brayer G.D., Withers S.G.;
RT "Potent human alpha-amylase inhibition by the beta-defensin-like protein
RT helianthamide.";
RL ACS Cent. Sci. 2:154-161(2016).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
RX PubMed=8193143; DOI=10.1021/bi00186a031;
RA Qian M., Haser R., Buisson G., Duee E., Payan F.;
RT "The active center of a mammalian alpha-amylase. Structure of the complex
RT of a pancreatic alpha-amylase with a carbohydrate inhibitor refined to 2.2-
RT A resolution.";
RL Biochemistry 33:6284-6294(1994).
RN [10] {ECO:0000312|PDB:1HNY}
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 17-511 IN COMPLEX WITH CALCIUM AND
RP CHLORIDE, COFACTOR, DISULFIDE BONDS, PYROGLUTAMATE FORMATION AT GLN-16, AND
RP TISSUE SPECIFICITY.
RX PubMed=8528071; DOI=10.1002/pro.5560040908;
RA Brayer G.D., Luo Y., Withers S.G.;
RT "The structure of human pancreatic alpha-amylase at 1.8-A resolution and
RT comparisons with related enzymes.";
RL Protein Sci. 4:1730-1742(1995).
RN [11] {ECO:0000312|PDB:1BSI}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 17-511 IN COMPLEX WITH CALCIUM
RP AND CHLORIDE, CATALYTIC ACTIVITY, COFACTOR, DISULFIDE BONDS, GLYCOSYLATION
RP AT ASN-476, MUTAGENESIS OF ASP-212, AND ACTIVE SITE.
RX PubMed=10091666; DOI=10.1110/ps.8.3.635;
RA Rydberg E.H., Sidhu G., Vo H.C., Hewitt J., Cote H.C.F., Wang Y., Numao S.,
RA MacGillivray R.T.A., Overall C.M., Brayer G.D., Withers S.G.;
RT "Cloning, mutagenesis, and structural analysis of human pancreatic alpha-
RT amylase expressed in Pichia pastoris.";
RL Protein Sci. 8:635-643(1999).
RN [12] {ECO:0000312|PDB:1CPU, ECO:0000312|PDB:2CPU, ECO:0000312|PDB:3CPU}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 17-511 IN COMPLEX WITH SUBSTRATE
RP ANALOGS; CALCIUM AND CHLORIDE, CATALYTIC ACTIVITY, MUTAGENESIS OF ASP-212;
RP GLU-248 AND ASP-315, ACTIVE SITE, DISULFIDE BONDS, GLYCOSYLATION AT
RP ASN-476, AND COFACTOR.
RX PubMed=10769135; DOI=10.1021/bi9921182;
RA Brayer G.D., Sidhu G., Maurus R., Rydberg E.H., Braun C., Wang Y.,
RA Nguyen N.T., Overall C.M., Withers S.G.;
RT "Subsite mapping of the human pancreatic alpha-amylase active site through
RT structural, kinetic, and mutagenesis techniques.";
RL Biochemistry 39:4778-4791(2000).
RN [13] {ECO:0000312|PDB:1KB3, ECO:0000312|PDB:1KGU, ECO:0000312|PDB:1KGW, ECO:0000312|PDB:1KGX}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 16-511 IN COMPLEX WITH CALCIUM,
RP MUTAGENESIS OF ARG-210; ASN-313 AND ARG-352, DISULFIDE BONDS, PYROGLUTAMATE
RP FORMATION AT GLN-16, GLYCOSYLATION AT ASN-476, COFACTOR, CATALYTIC
RP ACTIVITY, AND ACTIVE SITE.
RX PubMed=11772019; DOI=10.1021/bi0115636;
RA Numao S., Maurus R., Sidhu G., Wang Y., Overall C.M., Brayer G.D.,
RA Withers S.G.;
RT "Probing the role of the chloride ion in the mechanism of human pancreatic
RT alpha-amylase.";
RL Biochemistry 41:215-225(2002).
RN [14] {ECO:0000312|PDB:1KBB, ECO:0000312|PDB:1KBK}
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 16-511 IN COMPLEX WITH CALCIUM AND
RP CHLORIDE, MUTAGENESIS OF ASP-212; GLU-248 AND ASP-315, DISULFIDE BONDS,
RP PYROGLUTAMATE FORMATION AT GLN-16, COFACTOR, AND ACTIVE SITE.
RX PubMed=11914097; DOI=10.1021/bi011821z;
RA Rydberg E.H., Li C., Maurus R., Overall C.M., Brayer G.D., Withers S.G.;
RT "Mechanistic analyses of catalysis in human pancreatic alpha-amylase:
RT detailed kinetic and structural studies of mutants of three conserved
RT carboxylic acids.";
RL Biochemistry 41:4492-4502(2002).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Endohydrolysis of (1->4)-alpha-D-glucosidic linkages in
CC polysaccharides containing three or more (1->4)-alpha-linked D-
CC glucose units.; EC=3.2.1.1; Evidence={ECO:0000269|PubMed:10091666,
CC ECO:0000269|PubMed:10769135, ECO:0000269|PubMed:11772019,
CC ECO:0000269|PubMed:11914097};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:10091666, ECO:0000269|PubMed:10769135,
CC ECO:0000269|PubMed:11772019, ECO:0000269|PubMed:11914097,
CC ECO:0000269|PubMed:8528071};
CC Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000269|PubMed:10091666,
CC ECO:0000269|PubMed:10769135, ECO:0000269|PubMed:11772019,
CC ECO:0000269|PubMed:11914097, ECO:0000269|PubMed:8528071};
CC -!- COFACTOR:
CC Name=chloride; Xref=ChEBI:CHEBI:17996;
CC Evidence={ECO:0000269|PubMed:10091666, ECO:0000269|PubMed:10769135,
CC ECO:0000269|PubMed:11772019, ECO:0000269|PubMed:11914097,
CC ECO:0000269|PubMed:8528071};
CC Note=Binds 1 Cl(-) ion per subunit. {ECO:0000269|PubMed:10091666,
CC ECO:0000269|PubMed:10769135, ECO:0000269|PubMed:11772019,
CC ECO:0000269|PubMed:11914097, ECO:0000269|PubMed:8528071};
CC -!- SUBUNIT: Monomer. Binds to the sea anemone inhibitor helianthamide
CC (PubMed:27066537). {ECO:0000269|PubMed:27066537}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P04746-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P04746-2; Sequence=VSP_055822, VSP_055823;
CC -!- TISSUE SPECIFICITY: Detected in pancreas (at protein level).
CC {ECO:0000269|PubMed:8528071}.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 13 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Amylase entry;
CC URL="https://en.wikipedia.org/wiki/Amylase";
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DR EMBL; M18785; AAA52280.1; -; Genomic_DNA.
DR EMBL; M18714; AAA52280.1; JOINED; Genomic_DNA.
DR EMBL; M18716; AAA52280.1; JOINED; Genomic_DNA.
DR EMBL; M18718; AAA52280.1; JOINED; Genomic_DNA.
DR EMBL; M18720; AAA52280.1; JOINED; Genomic_DNA.
DR EMBL; M18722; AAA52280.1; JOINED; Genomic_DNA.
DR EMBL; M18724; AAA52280.1; JOINED; Genomic_DNA.
DR EMBL; M18726; AAA52280.1; JOINED; Genomic_DNA.
DR EMBL; M18783; AAA52280.1; JOINED; Genomic_DNA.
DR EMBL; M28443; AAA51724.1; -; mRNA.
DR EMBL; BC007060; AAH07060.1; -; mRNA.
DR EMBL; BC146997; AAI46998.1; -; mRNA.
DR EMBL; M18669; AAA51723.1; -; Genomic_DNA.
DR EMBL; X07056; CAA30099.1; -; Genomic_DNA.
DR CCDS; CCDS783.1; -. [P04746-1]
DR PIR; A29614; ALHUP.
DR RefSeq; NP_000690.1; NM_000699.3. [P04746-1]
DR PDB; 1B2Y; X-ray; 3.20 A; A=16-511.
DR PDB; 1BSI; X-ray; 2.00 A; A=17-511.
DR PDB; 1CPU; X-ray; 2.00 A; A=16-511.
DR PDB; 1HNY; X-ray; 1.80 A; A=17-511.
DR PDB; 1KB3; X-ray; 2.10 A; A=16-511.
DR PDB; 1KBB; X-ray; 1.90 A; A=16-511.
DR PDB; 1KBK; X-ray; 1.90 A; A=16-511.
DR PDB; 1KGU; X-ray; 2.00 A; A=16-511.
DR PDB; 1KGW; X-ray; 2.10 A; A=16-511.
DR PDB; 1KGX; X-ray; 2.00 A; A=16-511.
DR PDB; 1U2Y; X-ray; 1.95 A; A=16-511.
DR PDB; 1U30; X-ray; 1.90 A; A=16-511.
DR PDB; 1U33; X-ray; 1.95 A; A=16-511.
DR PDB; 1XCW; X-ray; 2.00 A; A=16-511.
DR PDB; 1XCX; X-ray; 1.90 A; A=16-511.
DR PDB; 1XD0; X-ray; 2.00 A; A=16-511.
DR PDB; 1XD1; X-ray; 2.20 A; A=16-511.
DR PDB; 1XGZ; X-ray; 2.00 A; A=16-511.
DR PDB; 1XH0; X-ray; 2.00 A; A=16-511.
DR PDB; 1XH1; X-ray; 2.03 A; A=16-511.
DR PDB; 1XH2; X-ray; 2.20 A; A=16-511.
DR PDB; 2CPU; X-ray; 2.00 A; A=17-511.
DR PDB; 2QMK; X-ray; 2.30 A; A=16-511.
DR PDB; 2QV4; X-ray; 1.97 A; A=16-511.
DR PDB; 3BAI; X-ray; 1.90 A; A=16-511.
DR PDB; 3BAJ; X-ray; 2.10 A; A=16-511.
DR PDB; 3BAK; X-ray; 1.90 A; A=16-511.
DR PDB; 3BAW; X-ray; 2.00 A; A=16-511.
DR PDB; 3BAX; X-ray; 1.90 A; A=16-511.
DR PDB; 3BAY; X-ray; 1.99 A; A=16-511.
DR PDB; 3CPU; X-ray; 2.00 A; A=17-511.
DR PDB; 3IJ7; X-ray; 2.00 A; A=17-511.
DR PDB; 3IJ8; X-ray; 1.43 A; A=17-511.
DR PDB; 3IJ9; X-ray; 1.85 A; A=17-511.
DR PDB; 3OLD; X-ray; 2.00 A; A=16-511.
DR PDB; 3OLE; X-ray; 1.55 A; A=16-511.
DR PDB; 3OLG; X-ray; 2.30 A; A=16-511.
DR PDB; 3OLI; X-ray; 1.50 A; A=16-511.
DR PDB; 4GQQ; X-ray; 1.35 A; A=17-511.
DR PDB; 4GQR; X-ray; 1.20 A; A=17-511.
DR PDB; 4W93; X-ray; 1.35 A; A=17-511.
DR PDB; 4X9Y; X-ray; 1.07 A; A=17-511.
DR PDB; 5E0F; X-ray; 1.40 A; A=17-511.
DR PDB; 5EMY; X-ray; 1.23 A; A=17-511.
DR PDB; 5KEZ; X-ray; 1.83 A; A=17-511.
DR PDB; 5TD4; X-ray; 2.30 A; A=17-511.
DR PDB; 5U3A; X-ray; 0.95 A; A=16-511.
DR PDB; 5VA9; X-ray; 2.55 A; A/B=16-511.
DR PDB; 6OBX; X-ray; 1.30 A; A=17-511.
DR PDB; 6OCN; X-ray; 1.15 A; A=16-511.
DR PDB; 6Z8L; X-ray; 1.40 A; A=16-511.
DR PDBsum; 1B2Y; -.
DR PDBsum; 1BSI; -.
DR PDBsum; 1CPU; -.
DR PDBsum; 1HNY; -.
DR PDBsum; 1KB3; -.
DR PDBsum; 1KBB; -.
DR PDBsum; 1KBK; -.
DR PDBsum; 1KGU; -.
DR PDBsum; 1KGW; -.
DR PDBsum; 1KGX; -.
DR PDBsum; 1U2Y; -.
DR PDBsum; 1U30; -.
DR PDBsum; 1U33; -.
DR PDBsum; 1XCW; -.
DR PDBsum; 1XCX; -.
DR PDBsum; 1XD0; -.
DR PDBsum; 1XD1; -.
DR PDBsum; 1XGZ; -.
DR PDBsum; 1XH0; -.
DR PDBsum; 1XH1; -.
DR PDBsum; 1XH2; -.
DR PDBsum; 2CPU; -.
DR PDBsum; 2QMK; -.
DR PDBsum; 2QV4; -.
DR PDBsum; 3BAI; -.
DR PDBsum; 3BAJ; -.
DR PDBsum; 3BAK; -.
DR PDBsum; 3BAW; -.
DR PDBsum; 3BAX; -.
DR PDBsum; 3BAY; -.
DR PDBsum; 3CPU; -.
DR PDBsum; 3IJ7; -.
DR PDBsum; 3IJ8; -.
DR PDBsum; 3IJ9; -.
DR PDBsum; 3OLD; -.
DR PDBsum; 3OLE; -.
DR PDBsum; 3OLG; -.
DR PDBsum; 3OLI; -.
DR PDBsum; 4GQQ; -.
DR PDBsum; 4GQR; -.
DR PDBsum; 4W93; -.
DR PDBsum; 4X9Y; -.
DR PDBsum; 5E0F; -.
DR PDBsum; 5EMY; -.
DR PDBsum; 5KEZ; -.
DR PDBsum; 5TD4; -.
DR PDBsum; 5U3A; -.
DR PDBsum; 5VA9; -.
DR PDBsum; 6OBX; -.
DR PDBsum; 6OCN; -.
DR PDBsum; 6Z8L; -.
DR AlphaFoldDB; P04746; -.
DR SMR; P04746; -.
DR BioGRID; 106776; 19.
DR IntAct; P04746; 6.
DR STRING; 9606.ENSP00000481450; -.
DR BindingDB; P04746; -.
DR ChEMBL; CHEMBL2045; -.
DR DrugBank; DB03439; 4,6-dideoxy-4-amino-alpha-D-glucose.
DR DrugBank; DB03495; 4,6-Dideoxy-4-{[4,5,6-Trihydroxy-3-(Hydroxymethyl)Cyclohex-2-En-1-Yl]Amino}-Alpha-D-Lyxo-Hexopyranosyl-(1->4)-Alpha-D-Threo-Hexopyranosyl-(1->6)-Alpha-L-Threo-Hexopyranose.
DR DrugBank; DB04618; 4,6-DIDEOXY-4-{[4-[(4-O-HEXOPYRANOSYLHEXOPYRANOSYL)OXY]-5,6-DIHYDROXY-3-(HYDROXYMETHYL)CYCLOHEX-2-EN-1-YL]AMINO}HEXOPYRANOSYL-(1->4)HEXOPYRANOSYL-(1->4)HEXOPYRANOSE.
DR DrugBank; DB02889; 4-O-(4,6-Dideoxy-4-{[4,5,6-Trihydroxy-3-(Hydroxymethyl)Cyclohex-2-En-1-Yl]Amino}-Beta-D-Lyxo-Hexopyranosyl)-Alpha-D-Erythro-Hexopyranose.
DR DrugBank; DB04453; 4-O-(4,6-Dideoxy-4-{[4-[(4-O-Hexopyranosylhexopyranosyl)Oxy]-5,6-Dihydroxy-3-(Hydroxymethyl)Cyclohex-2-En-1-Yl]Amino}Hexopyranosyl)Hexopyranose.
DR DrugBank; DB03092; 5-Hydroxymethyl-Chonduritol.
DR DrugBank; DB00284; Acarbose.
DR DrugBank; DB03971; Acarbose Derived Hexasaccharide.
DR DrugBank; DB03773; alpha-D-quinovopyranose.
DR DrugBank; DB02379; Beta-D-Glucose.
DR DrugBank; DB00702; Icodextrin.
DR DrugBank; DB01922; Maltosyl-Alpha (1,4)-D-Gluconhydroximo-1,5-Lactam.
DR DrugBank; DB00491; Miglitol.
DR DrugBank; DB02218; N-[4-hydroxymethyl-cyclohexan-6-yl-1,2,3-triol]-4,6-dideoxy-4-aminoglucopyranoside.
DR DrugBank; DB03088; Pidolic acid.
DR DrugCentral; P04746; -.
DR CAZy; GH13; Glycoside Hydrolase Family 13.
DR GlyGen; P04746; 2 sites.
DR iPTMnet; P04746; -.
DR PhosphoSitePlus; P04746; -.
DR BioMuta; AMY2A; -.
DR DMDM; 113803; -.
DR jPOST; P04746; -.
DR MassIVE; P04746; -.
DR MaxQB; P04746; -.
DR PaxDb; P04746; -.
DR PeptideAtlas; P04746; -.
DR PRIDE; P04746; -.
DR ProteomicsDB; 51742; -. [P04746-1]
DR Antibodypedia; 34943; 435 antibodies from 31 providers.
DR DNASU; 279; -.
DR Ensembl; ENST00000414303.7; ENSP00000397582.2; ENSG00000243480.8. [P04746-1]
DR GeneID; 279; -.
DR KEGG; hsa:279; -.
DR MANE-Select; ENST00000414303.7; ENSP00000397582.2; NM_000699.4; NP_000690.1.
DR UCSC; uc001dut.4; human. [P04746-1]
DR CTD; 279; -.
DR DisGeNET; 279; -.
DR GeneCards; AMY2A; -.
DR HGNC; HGNC:477; AMY2A.
DR HPA; ENSG00000243480; Tissue enriched (pancreas).
DR MIM; 104650; gene.
DR neXtProt; NX_P04746; -.
DR OpenTargets; ENSG00000243480; -.
DR PharmGKB; PA24784; -.
DR VEuPathDB; HostDB:ENSG00000243480; -.
DR eggNOG; KOG2212; Eukaryota.
DR GeneTree; ENSGT00940000154802; -.
DR HOGENOM; CLU_013336_2_1_1; -.
DR InParanoid; P04746; -.
DR OMA; HPWWEVY; -.
DR PhylomeDB; P04746; -.
DR TreeFam; TF312850; -.
DR BRENDA; 3.2.1.1; 2681.
DR PathwayCommons; P04746; -.
DR Reactome; R-HSA-189085; Digestion of dietary carbohydrate.
DR SABIO-RK; P04746; -.
DR SignaLink; P04746; -.
DR BioGRID-ORCS; 279; 24 hits in 985 CRISPR screens.
DR ChiTaRS; AMY2A; human.
DR EvolutionaryTrace; P04746; -.
DR GeneWiki; AMY2A; -.
DR GenomeRNAi; 279; -.
DR Pharos; P04746; Tclin.
DR PRO; PR:P04746; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P04746; protein.
DR Bgee; ENSG00000243480; Expressed in body of pancreas and 88 other tissues.
DR ExpressionAtlas; P04746; baseline and differential.
DR Genevisible; P04746; HS.
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; IDA:UniProtKB.
DR GO; GO:0004556; F:alpha-amylase activity; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0031404; F:chloride ion binding; IDA:UniProtKB.
DR GO; GO:0016052; P:carbohydrate catabolic process; IDA:UniProtKB.
DR GO; GO:0005975; P:carbohydrate metabolic process; NAS:ProtInc.
DR GO; GO:0044245; P:polysaccharide digestion; TAS:Reactome.
DR Gene3D; 2.60.40.1180; -; 1.
DR InterPro; IPR006048; A-amylase/branching_C.
DR InterPro; IPR031319; A-amylase_C.
DR InterPro; IPR006046; Alpha_amylase.
DR InterPro; IPR006047; Glyco_hydro_13_cat_dom.
DR InterPro; IPR013780; Glyco_hydro_b.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR Pfam; PF00128; Alpha-amylase; 1.
DR Pfam; PF02806; Alpha-amylase_C; 1.
DR PRINTS; PR00110; ALPHAAMYLASE.
DR SMART; SM00642; Aamy; 1.
DR SMART; SM00632; Aamy_C; 1.
DR SUPFAM; SSF51445; SSF51445; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Carbohydrate metabolism;
KW Chloride; Disulfide bond; Glycoprotein; Glycosidase; Hydrolase;
KW Metal-binding; Pyrrolidone carboxylic acid; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..15
FT CHAIN 16..511
FT /note="Pancreatic alpha-amylase"
FT /id="PRO_0000001397"
FT ACT_SITE 212
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:10091666,
FT ECO:0000305|PubMed:10769135, ECO:0000305|PubMed:11914097"
FT ACT_SITE 248
FT /note="Proton donor"
FT /evidence="ECO:0000305|PubMed:10091666,
FT ECO:0000305|PubMed:10769135, ECO:0000305|PubMed:11772019,
FT ECO:0000305|PubMed:11914097"
FT BINDING 115
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:10091666,
FT ECO:0000269|PubMed:10769135, ECO:0000269|PubMed:11772019,
FT ECO:0000269|PubMed:8528071, ECO:0007744|PDB:1HNY"
FT BINDING 173
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:10091666,
FT ECO:0000269|PubMed:10769135, ECO:0000269|PubMed:11772019,
FT ECO:0000269|PubMed:8528071, ECO:0007744|PDB:1HNY"
FT BINDING 182
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:10091666,
FT ECO:0000269|PubMed:10769135, ECO:0000269|PubMed:11772019,
FT ECO:0000269|PubMed:8528071, ECO:0007744|PDB:1HNY"
FT BINDING 210
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000269|PubMed:10091666,
FT ECO:0000269|PubMed:10769135, ECO:0000269|PubMed:11772019,
FT ECO:0000269|PubMed:8528071, ECO:0007744|PDB:1HNY"
FT BINDING 216
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:10091666,
FT ECO:0000269|PubMed:10769135, ECO:0000269|PubMed:11772019,
FT ECO:0000269|PubMed:8528071, ECO:0007744|PDB:1HNY"
FT BINDING 313
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000269|PubMed:10091666,
FT ECO:0000269|PubMed:10769135, ECO:0000269|PubMed:11772019,
FT ECO:0000269|PubMed:8528071, ECO:0007744|PDB:1HNY"
FT BINDING 352
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000269|PubMed:10091666,
FT ECO:0000269|PubMed:10769135, ECO:0000269|PubMed:11772019,
FT ECO:0000269|PubMed:8528071, ECO:0007744|PDB:1HNY"
FT SITE 315
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000305|PubMed:10091666,
FT ECO:0000305|PubMed:10769135, ECO:0000305|PubMed:11914097"
FT MOD_RES 16
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:11772019,
FT ECO:0000269|PubMed:8528071"
FT CARBOHYD 476
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:10091666,
FT ECO:0000269|PubMed:10769135, ECO:0000269|PubMed:11772019"
FT DISULFID 43..101
FT /evidence="ECO:0000269|PubMed:10091666,
FT ECO:0000269|PubMed:10769135, ECO:0000269|PubMed:11772019,
FT ECO:0000269|PubMed:8528071, ECO:0007744|PDB:1HNY"
FT DISULFID 85..130
FT /evidence="ECO:0000269|PubMed:10091666,
FT ECO:0000269|PubMed:10769135, ECO:0000269|PubMed:11772019,
FT ECO:0000269|PubMed:8528071, ECO:0007744|PDB:1HNY"
FT DISULFID 156..175
FT /evidence="ECO:0000269|PubMed:10091666,
FT ECO:0000269|PubMed:10769135, ECO:0000269|PubMed:11772019,
FT ECO:0000269|PubMed:8528071, ECO:0007744|PDB:1HNY"
FT DISULFID 393..399
FT /evidence="ECO:0000269|PubMed:10091666,
FT ECO:0000269|PubMed:10769135, ECO:0000269|PubMed:11772019,
FT ECO:0000269|PubMed:8528071, ECO:0007744|PDB:1HNY"
FT DISULFID 465..477
FT /evidence="ECO:0000269|PubMed:10091666,
FT ECO:0000269|PubMed:10769135, ECO:0000269|PubMed:11772019,
FT ECO:0000269|PubMed:8528071, ECO:0007744|PDB:1HNY"
FT VAR_SEQ 250..265
FT /note="IDLGGEPIKSSDYFGN -> HQYLYAYKISSYSLEN (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_055822"
FT VAR_SEQ 266..511
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_055823"
FT MUTAGEN 210
FT /note="R->A,Q: Abolishes chloride binding; strongly reduces
FT activity."
FT /evidence="ECO:0000269|PubMed:11772019"
FT MUTAGEN 212
FT /note="D->A,N: Abolishes activity."
FT /evidence="ECO:0000269|PubMed:10091666,
FT ECO:0000269|PubMed:11772019, ECO:0000269|PubMed:11914097"
FT MUTAGEN 248
FT /note="E->A,Q: Reduces activity."
FT /evidence="ECO:0000269|PubMed:11772019,
FT ECO:0000269|PubMed:11914097"
FT MUTAGEN 313
FT /note="N->S: Reduces affinity for chloride; reduces
FT activity."
FT /evidence="ECO:0000269|PubMed:11772019"
FT MUTAGEN 315
FT /note="D->A,N: Strongly reduces activity."
FT /evidence="ECO:0000269|PubMed:11772019,
FT ECO:0000269|PubMed:11914097"
FT MUTAGEN 352
FT /note="R->A: Abolishes chloride binding; has only slight
FT effect on activity."
FT /evidence="ECO:0000269|PubMed:11772019"
FT STRAND 27..31
FT /evidence="ECO:0007829|PDB:5U3A"
FT HELIX 36..45
FT /evidence="ECO:0007829|PDB:5U3A"
FT TURN 46..51
FT /evidence="ECO:0007829|PDB:5U3A"
FT STRAND 54..57
FT /evidence="ECO:0007829|PDB:5U3A"
FT TURN 67..70
FT /evidence="ECO:0007829|PDB:5U3A"
FT HELIX 73..77
FT /evidence="ECO:0007829|PDB:5U3A"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:5U3A"
FT HELIX 91..103
FT /evidence="ECO:0007829|PDB:5U3A"
FT STRAND 107..112
FT /evidence="ECO:0007829|PDB:5U3A"
FT STRAND 115..119
FT /evidence="ECO:0007829|PDB:5U3A"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:5U3A"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:1KGW"
FT TURN 136..139
FT /evidence="ECO:0007829|PDB:5U3A"
FT TURN 142..145
FT /evidence="ECO:0007829|PDB:5U3A"
FT HELIX 148..150
FT /evidence="ECO:0007829|PDB:5U3A"
FT TURN 153..155
FT /evidence="ECO:0007829|PDB:5U3A"
FT STRAND 158..162
FT /evidence="ECO:0007829|PDB:5U3A"
FT HELIX 169..174
FT /evidence="ECO:0007829|PDB:5U3A"
FT HELIX 177..179
FT /evidence="ECO:0007829|PDB:5U3A"
FT STRAND 180..183
FT /evidence="ECO:0007829|PDB:5U3A"
FT HELIX 188..204
FT /evidence="ECO:0007829|PDB:5U3A"
FT STRAND 208..211
FT /evidence="ECO:0007829|PDB:5U3A"
FT HELIX 214..216
FT /evidence="ECO:0007829|PDB:5U3A"
FT HELIX 219..226
FT /evidence="ECO:0007829|PDB:5U3A"
FT TURN 234..236
FT /evidence="ECO:0007829|PDB:5U3A"
FT STRAND 244..247
FT /evidence="ECO:0007829|PDB:5U3A"
FT STRAND 253..256
FT /evidence="ECO:0007829|PDB:5U3A"
FT HELIX 259..262
FT /evidence="ECO:0007829|PDB:5U3A"
FT TURN 263..265
FT /evidence="ECO:0007829|PDB:5U3A"
FT STRAND 266..269
FT /evidence="ECO:0007829|PDB:5U3A"
FT HELIX 271..282
FT /evidence="ECO:0007829|PDB:5U3A"
FT HELIX 284..286
FT /evidence="ECO:0007829|PDB:5U3A"
FT HELIX 289..294
FT /evidence="ECO:0007829|PDB:5U3A"
FT HELIX 297..299
FT /evidence="ECO:0007829|PDB:5U3A"
FT HELIX 304..306
FT /evidence="ECO:0007829|PDB:5U3A"
FT STRAND 307..309
FT /evidence="ECO:0007829|PDB:5U3A"
FT HELIX 316..318
FT /evidence="ECO:0007829|PDB:5U3A"
FT STRAND 319..321
FT /evidence="ECO:0007829|PDB:4X9Y"
FT HELIX 324..326
FT /evidence="ECO:0007829|PDB:5U3A"
FT HELIX 330..332
FT /evidence="ECO:0007829|PDB:5U3A"
FT HELIX 333..345
FT /evidence="ECO:0007829|PDB:5U3A"
FT STRAND 348..355
FT /evidence="ECO:0007829|PDB:5U3A"
FT STRAND 363..366
FT /evidence="ECO:0007829|PDB:1KBK"
FT TURN 369..372
FT /evidence="ECO:0007829|PDB:5U3A"
FT STRAND 375..378
FT /evidence="ECO:0007829|PDB:5U3A"
FT HELIX 400..402
FT /evidence="ECO:0007829|PDB:5U3A"
FT HELIX 404..415
FT /evidence="ECO:0007829|PDB:5U3A"
FT TURN 416..418
FT /evidence="ECO:0007829|PDB:5U3A"
FT STRAND 421..426
FT /evidence="ECO:0007829|PDB:5U3A"
FT STRAND 428..436
FT /evidence="ECO:0007829|PDB:5U3A"
FT TURN 437..439
FT /evidence="ECO:0007829|PDB:5U3A"
FT STRAND 440..445
FT /evidence="ECO:0007829|PDB:5U3A"
FT STRAND 447..449
FT /evidence="ECO:0007829|PDB:5U3A"
FT STRAND 451..456
FT /evidence="ECO:0007829|PDB:5U3A"
FT STRAND 461..465
FT /evidence="ECO:0007829|PDB:5U3A"
FT TURN 467..469
FT /evidence="ECO:0007829|PDB:5U3A"
FT STRAND 476..479
FT /evidence="ECO:0007829|PDB:5U3A"
FT STRAND 481..484
FT /evidence="ECO:0007829|PDB:5U3A"
FT STRAND 488..494
FT /evidence="ECO:0007829|PDB:5U3A"
FT STRAND 498..500
FT /evidence="ECO:0007829|PDB:5U3A"
FT STRAND 502..506
FT /evidence="ECO:0007829|PDB:5U3A"
FT HELIX 507..509
FT /evidence="ECO:0007829|PDB:5U3A"
SQ SEQUENCE 511 AA; 57707 MW; A77B1A34EACB3C2A CRC64;
MKFFLLLFTI GFCWAQYSPN TQQGRTSIVH LFEWRWVDIA LECERYLAPK GFGGVQVSPP
NENVAIYNPF RPWWERYQPV SYKLCTRSGN EDEFRNMVTR CNNVGVRIYV DAVINHMCGN
AVSAGTSSTC GSYFNPGSRD FPAVPYSGWD FNDGKCKTGS GDIENYNDAT QVRDCRLTGL
LDLALEKDYV RSKIAEYMNH LIDIGVAGFR LDASKHMWPG DIKAILDKLH NLNSNWFPAG
SKPFIYQEVI DLGGEPIKSS DYFGNGRVTE FKYGAKLGTV IRKWNGEKMS YLKNWGEGWG
FVPSDRALVF VDNHDNQRGH GAGGASILTF WDARLYKMAV GFMLAHPYGF TRVMSSYRWP
RQFQNGNDVN DWVGPPNNNG VIKEVTINPD TTCGNDWVCE HRWRQIRNMV IFRNVVDGQP
FTNWYDNGSN QVAFGRGNRG FIVFNNDDWS FSLTLQTGLP AGTYCDVISG DKINGNCTGI
KIYVSDDGKA HFSISNSAED PFIAIHAESK L
