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 27-MAR-2024, entry version 229. 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 GlyCosmos; P04746; 1 site, No reported glycans. 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; 9606-ENSP00000481450; -. DR PeptideAtlas; P04746; -. DR PRIDE; P04746; -. DR ProteomicsDB; 51742; -. [P04746-1] DR Pumba; P04746; -. DR Antibodypedia; 34943; 453 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 AGR; HGNC:477; -. 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; EHREVWS; -. DR OrthoDB; 3249969at2759; -. 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; 26 hits in 1045 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 89 other cell types or tissues. DR ExpressionAtlas; P04746; baseline and differential. 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; IBA:GO_Central. DR GO; GO:0044245; P:polysaccharide digestion; TAS:Reactome. DR CDD; cd11317; AmyAc_bac_euk_AmyA; 1. DR Gene3D; 3.20.20.80; Glycosidases; 1. DR Gene3D; 2.60.40.1180; Golgi alpha-mannosidase II; 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 PANTHER; PTHR43447; ALPHA-AMYLASE; 1. DR PANTHER; PTHR43447:SF56; PANCREATIC ALPHA-AMYLASE; 1. 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; (Trans)glycosidases; 1. DR SUPFAM; SSF51011; Glycosyl hydrolase domain; 1. DR Genevisible; P04746; HS. 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 //