P04746 (AMYP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Pancreatic alpha-amylase
Short name=PA
EC=3.2.1.1

Alternative name(s):
1,4-alpha-D-glucan glucanohydrolase

Gene names

Name:

AMY2A

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	511 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	Endohydrolysis of (1->4)-alpha-D-glucosidic linkages in polysaccharides containing three or more (1->4)-alpha-linked D-glucose units.
Cofactor	Binds 1 calcium ion per subunit. Binds 1 chloride ion per subunit.
Subunit structure	Monomer.
Subcellular location	Secreted › extracellular space.
Sequence similarities	Belongs to the glycosyl hydrolase 13 family.

Ontologies

Keywords
Biological process	Carbohydrate metabolism
Cellular component	Secreted
Domain	Signal
Ligand	Calcium Chloride Metal-binding
Molecular function	Glycosidase Hydrolase
PTM	Disulfide bond Glycoprotein Pyrrolidone carboxylic acid
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	carbohydrate catabolic process Inferred from direct assay Ref.11. Source: UniProtKB polysaccharide digestion Traceable author statement. Source: Reactome
Cellular component	extracellular space Inferred from direct assay Ref.11. Source: UniProtKB
Molecular function	alpha-amylase activity Inferred from direct assay Ref.11. Source: UniProtKB calcium ion binding Inferred from direct assay Ref.11. Source: UniProtKB chloride ion binding Inferred from direct assay Ref.11. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 15

15

Chain

16 – 511

496

Pancreatic alpha-amylase

PRO_0000001397

Sites

Active site

212

1

Nucleophile

Active site

248

1

Proton donor

Metal binding

115

1

Calcium

Metal binding

173

1

Calcium; via carbonyl oxygen

Metal binding

182

1

Calcium

Metal binding

216

1

Calcium; via carbonyl oxygen

Binding site

210

1

Chloride

Binding site

313

1

Chloride

Binding site

352

1

Chloride

Site

315

1

Transition state stabilizer By similarity

Amino acid modifications

Modified residue

16

1

Pyrrolidone carboxylic acid

Glycosylation

476

1

N-linked (GlcNAc...)

Disulfide bond

43 ↔ 101

Disulfide bond

85 ↔ 130

Disulfide bond

156 ↔ 175

Disulfide bond

393 ↔ 399

Disulfide bond

465 ↔ 477

Experimental info

Mutagenesis

210

1

R → A or Q: Abolishes chloride binding; strongly reduces activity. Ref.12

Mutagenesis

212

1

D → A or N: Abolishes activity. Ref.10 Ref.13

Mutagenesis

248

1

E → A or Q: Reduces activity. Ref.13

Mutagenesis

313

1

N → S: Reduces affinity for chloride; reduces activity. Ref.12

Mutagenesis

315

1

D → A or N: Strongly reduces activity. Ref.13

Mutagenesis

352

1

R → A: Abolishes chloride binding; has only slight effect on activity. Ref.12

Secondary structure

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511

Helix Strand Turn

Details...

Beta strand

27 – 31

5

Helix

36 – 45

10

Turn

46 – 51

6

Beta strand

54 – 57

4

Turn

67 – 70

4

Helix

73 – 77

5

Beta strand

78 – 80

3

Helix

91 – 102

12

Turn

103 – 105

3

Beta strand

107 – 112

6

Beta strand

115 – 119

5

Beta strand

124 – 126

3

Turn

136 – 139

4

Turn

142 – 145

4

Helix

148 – 150

3

Turn

153 – 155

3

Beta strand

158 – 162

5

Helix

169 – 174

6

Beta strand

175 – 177

3

Beta strand

180 – 183

4

Helix

188 – 204

17

Beta strand

208 – 211

4

Helix

214 – 216

3

Helix

219 – 226

8

Turn

234 – 236

3

Beta strand

244 – 247

4

Helix

259 – 262

4

Turn

263 – 265

3

Beta strand

266 – 269

4

Helix

272 – 281

10

Helix

284 – 286

3

Helix

289 – 294

6

Helix

297 – 299

3

Helix

304 – 306

3

Beta strand

307 – 309

3

Helix

316 – 318

3

Helix

324 – 326

3

Helix

330 – 332

3

Helix

333 – 345

13

Beta strand

348 – 355

8

Turn

369 – 372

4

Beta strand

375 – 378

4

Helix

400 – 402

3

Helix

404 – 415

12

Turn

416 – 418

3

Beta strand

421 – 426

6

Beta strand

428 – 436

9

Turn

437 – 439

3

Beta strand

440 – 445

6

Beta strand

447 – 449

3

Beta strand

451 – 456

6

Beta strand

461 – 465

5

Turn

467 – 469

3

Beta strand

476 – 479

4

Beta strand

481 – 484

4

Beta strand

488 – 494

7

Beta strand

498 – 500

3

Beta strand

502 – 506

5

Helix

507 – 509

3

Sequences

	Sequence		Length	Mass (Da)
	P04746 [UniParc]. Last modified July 1, 1989. Version 2. Checksum: A77B1A34EACB3C2A	FASTA	511	57,707
	10 20 30 40 50 60 MKFFLLLFTI GFCWAQYSPN TQQGRTSIVH LFEWRWVDIA LECERYLAPK GFGGVQVSPP 70 80 90 100 110 120 NENVAIYNPF RPWWERYQPV SYKLCTRSGN EDEFRNMVTR CNNVGVRIYV DAVINHMCGN 130 140 150 160 170 180 AVSAGTSSTC GSYFNPGSRD FPAVPYSGWD FNDGKCKTGS GDIENYNDAT QVRDCRLTGL 190 200 210 220 230 240 LDLALEKDYV RSKIAEYMNH LIDIGVAGFR LDASKHMWPG DIKAILDKLH NLNSNWFPAG 250 260 270 280 290 300 SKPFIYQEVI DLGGEPIKSS DYFGNGRVTE FKYGAKLGTV IRKWNGEKMS YLKNWGEGWG 310 320 330 340 350 360 FVPSDRALVF VDNHDNQRGH GAGGASILTF WDARLYKMAV GFMLAHPYGF TRVMSSYRWP 370 380 390 400 410 420 RQFQNGNDVN DWVGPPNNNG VIKEVTINPD TTCGNDWVCE HRWRQIRNMV IFRNVVDGQP 430 440 450 460 470 480 FTNWYDNGSN QVAFGRGNRG FIVFNNDDWS FSLTLQTGLP AGTYCDVISG DKINGNCTGI 490 500 510 KIYVSDDGKA HFSISNSAED PFIAIHAESK L

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Corrected sequences of cDNAs for human salivary and pancreatic alpha-amylases." Nakamura Y., Ogawa M., Nishide T., Emi M., Kosaki G., Himeno S., Matsubara K. Gene 28:263-270(1984) [PubMed: 6610603] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	Erratum Nakamura Y., Ogawa M., Nishide T., Emi M., Kosaki G., Himeno S., Matsubara K. Gene 50:371-372(1986) Cited for: SEQUENCE REVISION.
[3]	"Primary structure of human pancreatic alpha-amylase gene: its comparison with human salivary alpha-amylase gene." Horii A., Emi M., Tomita N., Nishide T., Ogawa M., Mori T., Matsubara K. Gene 60:57-64(1987) [PubMed: 2450054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Pancreas.
[4]	"A complementary DNA sequence that predicts a human pancreatic amylase primary structure consistent with the electrophoretic mobility of the common isozyme, Amy2 A." Wise R.J., Karn R.C., Larsen S.H., Hodes M.E., Gardell S.J., Rutter W.J. Mol. Biol. Med. 2:307-322(1984) [PubMed: 6336237] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Pancreas.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pancreas.
[6]	"Human pancreatic amylase is encoded by two different genes." Groot P.C., Bleeker M.J., Pronk J.C., Arwert F., Mager W.H., Planta R.J., Eriksson A.W., Frants R.R. Nucleic Acids Res. 16:4724-4724(1988) [PubMed: 3260028] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-56.
[7]	"Concerted evolution of human amylase genes." Gumucio D.L., Wiebauer K., Caldwell R.M., Samuelson L.C., Meisler M.H. Mol. Cell. Biol. 8:1197-1205(1988) [PubMed: 2452973] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-56.
[8]	"The active center of a mammalian alpha-amylase. Structure of the complex of a pancreatic alpha-amylase with a carbohydrate inhibitor refined to 2.2-A resolution." Qian M., Haser R., Buisson G., Duee E., Payan F. Biochemistry 33:6284-6294(1994) [PubMed: 8193143] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[9]	"The structure of human pancreatic alpha-amylase at 1.8-A resolution and comparisons with related enzymes." Brayer G.D., Luo Y., Withers S.G. Protein Sci. 4:1730-1742(1995) [PubMed: 8528071] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS), PYROGLUTAMATE FORMATION AT GLU-16.
[10]	"Cloning, mutagenesis, and structural analysis of human pancreatic alpha-amylase expressed in Pichia pastoris." Rydberg E.H., Sidhu G., Vo H.C., Hewitt J., Cote H.C.F., Wang Y., Numao S., MacGillivray R.T.A., Overall C.M., Brayer G.D., Withers S.G. Protein Sci. 8:635-643(1999) [PubMed: 10091666] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), MUTAGENESIS OF ASP-212.
[11]	"Subsite mapping of the human pancreatic alpha-amylase active site through structural, kinetic, and mutagenesis techniques." Brayer G.D., Sidhu G., Maurus R., Rydberg E.H., Braun C., Wang Y., Nguyen N.T., Overall C.M., Withers S.G. Biochemistry 39:4778-4791(2000) [PubMed: 10769135] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
[12]	"Probing the role of the chloride ion in the mechanism of human pancreatic alpha-amylase." Numao S., Maurus R., Sidhu G., Wang Y., Overall C.M., Brayer G.D., Withers S.G. Biochemistry 41:215-225(2002) [PubMed: 11772019] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS), MUTAGENESIS OF ARG-210; ASN-313 AND ARG-352.
[13]	"Mechanistic analyses of catalysis in human pancreatic alpha-amylase: detailed kinetic and structural studies of mutants of three conserved carboxylic acids." Rydberg E.H., Li C., Maurus R., Overall C.M., Brayer G.D., Withers S.G. Biochemistry 41:4492-4502(2002) [PubMed: 11914097] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS), MUTAGENESIS OF ASP-212; GLU-248 AND ASP-315.
+	Additional computationally mapped references.

Web resources

Wikipedia

Amylase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M18785 , M18714, M18716, M18718, M18720, M18722, M18724, M18726, M18783 Genomic DNA. Translation: AAA52280.1.
M28443 mRNA. Translation: AAA51724.1.
BC007060 mRNA. Translation: AAH07060.1.
M18669 Genomic DNA. Translation: AAA51723.1.
X07056 Genomic DNA. Translation: CAA30099.1.

IPI

IPI00025476.

PIR

ALHUP. A29614.

RefSeq

NP_000690.1. NM_000699.2.

UniGene

Hs.654437.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1B2Y	X-ray	3.20	A	16-511	[»]
1BSI	X-ray	2.00	A	17-511	[»]
1CPU	X-ray	2.00	A	17-511	[»]
1HNY	X-ray	1.80	A	17-511	[»]
1KB3	X-ray	2.10	A	17-511	[»]
1KBB	X-ray	1.90	A	17-511	[»]
1KBK	X-ray	1.90	A	17-511	[»]
1KGU	X-ray	2.00	A	17-511	[»]
1KGW	X-ray	2.10	A	17-511	[»]
1KGX	X-ray	2.00	A	17-511	[»]
1U2Y	X-ray	1.95	A	17-511	[»]
1U30	X-ray	1.90	A	17-511	[»]
1U33	X-ray	1.95	A	17-511	[»]
1XCW	X-ray	2.00	A	17-511	[»]
1XCX	X-ray	1.90	A	17-511	[»]
1XD0	X-ray	2.00	A	17-511	[»]
1XD1	X-ray	2.20	A	17-511	[»]
1XGZ	X-ray	2.00	A	17-511	[»]
1XH0	X-ray	2.00	A	17-511	[»]
1XH1	X-ray	2.03	A	17-511	[»]
1XH2	X-ray	2.20	A	17-511	[»]
2CPU	X-ray	2.00	A	17-511	[»]
2QMK	X-ray	2.30	A	17-511	[»]
2QV4	X-ray	1.97	A	17-511	[»]
3BAI	X-ray	1.90	A	17-511	[»]
3BAJ	X-ray	2.10	A	17-511	[»]
3BAK	X-ray	1.90	A	17-511	[»]
3BAW	X-ray	2.00	A	17-511	[»]
3BAX	X-ray	1.90	A	17-511	[»]
3BAY	X-ray	1.99	A	17-511	[»]
3CPU	X-ray	2.00	A	17-511	[»]
3IJ7	X-ray	2.00	A	17-511	[»]
3IJ8	X-ray	1.43	A	17-511	[»]
3IJ9	X-ray	1.85	A	17-511	[»]
3OLD	X-ray	2.00	A	16-511	[»]
3OLE	X-ray	1.55	A	16-511	[»]
3OLG	X-ray	2.30	A	16-511	[»]
3OLI	X-ray	1.50	A	16-511	[»]

ProteinModelPortal

P04746.

SMR

P04746. Positions 16-511.

ModBase

Search...

Protein-protein interaction databases

IntAct

P04746. 2 interactions.

STRING

P04746.

Protein family/group databases

CAZy

GH13. Glycoside Hydrolase Family 13.

PTM databases

PhosphoSite

P04746.

Polymorphism databases

DMDM

113803.

Proteomic databases

PRIDE

P04746.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000393932; ENSP00000377509; ENSG00000243480.
ENST00000414303; ENSP00000397582; ENSG00000243480.

GeneID

279.

KEGG

hsa:279.

UCSC

uc001dut.1. human.

Organism-specific databases

CTD

279.

GeneCards

GC01P104115.

HGNC

HGNC:477. AMY2A.

MIM

104650. gene.

neXtProt

NX_P04746.

PharmGKB

PA24784.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG12837.

HOVERGEN

HBG000061.

InParanoid

P04746.

OrthoDB

EOG4RV2R1.

PhylomeDB

P04746.

Enzyme and pathway databases

BRENDA

3.2.1.1. 5538.

Reactome

REACT_474. Metabolism of carbohydrates.

Gene expression databases

ArrayExpress

P04746.

Bgee

P04746.

CleanEx

HS_AMY2A.

Genevestigator

P04746.

GermOnline

ENSG00000196318. Homo sapiens.

Family and domain databases

InterPro

IPR006048. A-amylase_b_C.
IPR015902. Alpha_amylase.
IPR006046. Glyco_hydro_13.
IPR013780. Glyco_hydro_13_b.
IPR006047. Glyco_hydro_13_cat_dom.
IPR006589. Glyco_hydro_13_sub_cat_dom.
IPR013781. Glyco_hydro_subgr_catalytic.
IPR017853. Glycoside_hydrolase_SF.
[Graphical view]

Gene3D

G3DSA:2.60.40.1180. Glyco_hydro_13_b. 1 hit.
G3DSA:3.20.20.80. Glyco_hydro_cat. 1 hit.

KO

K01176.

PANTHER

PTHR10357. Alpha_amylase. 1 hit.

Pfam

PF00128. Alpha-amylase. 1 hit.
PF02806. Alpha-amylase_C. 1 hit.
[Graphical view]

PRINTS

PR00110. ALPHAAMYLASE.

SMART

SM00642. Aamy. 1 hit.
SM00632. Aamy_C. 1 hit.
[Graphical view]

SUPFAM

SSF51445. Glyco_hydro_cat. 1 hit.

ProtoNet

Search...

Other

DrugBank

DB00284. Acarbose.
DB00522. Bentiromide.
DB00702. Icodextrin.
DB00491. Miglitol.
DB00085. Pancrelipase.

NextBio

1129.

SOURCE

Search...

Entry information

Entry name

AMYP_HUMAN

Accession

Primary (citable) accession number: P04746
Secondary accession number(s): Q9UBH3

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	July 1, 1989
Last modified:	January 25, 2012
This is version 137 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.