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Showing AMY1A — AMY1 is a alias.

AMY1A

Alpha-amylase 1A · UniProt P0DUB6

Length
511 aa
Mass
57.8 kDa
Annotated
2026-06-09
53 papers in source corpus 11 papers cited in narrative 11 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 3/4 claims corpus-supported (75%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AMY1A encodes a secreted alpha-amylase that hydrolyzes starch and oligosaccharides, and its defining biological feature in this corpus is dual-promoter, tissue-specific transcriptional control of a single gene locus (PMID:6190572, PMID:6162570). In the mouse ortholog Amy-1a, a strong promoter active exclusively in the parotid gland and a ~30-fold weaker promoter active across all alpha-amylase-producing tissues generate transcripts that differ only in their 5' leader sequences via alternative initiation and tissue-specific splicing, while alternative polyadenylation further diversifies the 3' ends (PMID:6190572, PMID:6162570, PMID:6166922, PMID:6186131). During postnatal parotid differentiation these promoters activate in sequence—the weak downstream promoter first, then the strong parotid-specific promoter—and commitment to strong-promoter transcription is heritably propagated to daughter cells, with the weak promoter also driving expression in liver, pancreas, and adipose tissue (PMID:3872721, PMID:3877171, PMID:2785714). At the protein level, an N-linked carbohydrate chain is required for thermostability and normal starch-hydrolysis kinetics (PMID:7957256), and domain-swap analysis assigns soluble-starch hydrolysis and protein stability to the N-terminal domain while the catalytic barrel domain governs oligosaccharide hydrolysis (PMID:9163949).

Mechanistic history

Synthesis pass · year-by-year structured walk · 7 steps
  1. 1981 High

    Established that a single alpha-amylase gene, not separate genes, produces the distinct salivary and liver mRNAs, resolving how one locus yields tissue-specific transcripts.

    Evidence Genomic cloning, DNA sequencing, and S1 nuclease mapping of mouse Amy-1a across tissues

    PMID:6162570 PMID:6166922

    Open questions at the time
    • Did not resolve whether the 5' leader difference arises from alternative initiation versus differential processing
    • No characterization of the encoded protein's enzymatic properties
  2. 1982 Medium

    Defined the gene architecture (10 introns) and located regulation primarily at the transcriptional level via tissue-specific splicing.

    Evidence S1 nuclease mapping of nuclear transcripts and cDNA/genomic sequence comparison

    PMID:6186131

    Open questions at the time
    • Review-format presentation from a single lab
    • Splice-site usage not mapped at nucleotide resolution across all introns
  3. 1983 High

    Showed that two promoters of different strengths, not post-transcriptional events, drive the tissue-specific leader mRNAs, defining the core regulatory mechanism.

    Evidence Nuclear run-on transcription and S1 mapping across parotid, liver, and non-expressing tissues

    PMID:6190572

    Open questions at the time
    • cis-elements and trans-acting factors conferring promoter strength not identified
    • Mechanism restricting the strong promoter to parotid unknown
  4. 1985 High

    Demonstrated developmental sequencing and heritable commitment of promoter usage during parotid differentiation, and mapped the locus physically relative to Amy-2a.

    Evidence Run-on transcription, in situ hybridization across developmental time points, and genomic cloning/restriction mapping of a 106-kb segment

    PMID:2989529 PMID:3872721 PMID:3877171

    Open questions at the time
    • Molecular basis of heritable commitment (epigenetic marks) not determined
    • Transcription factors driving sequential promoter activation unidentified
  5. 1989 Medium

    Revealed adipose tissue as an unrecognized endogenous expression site through the activity of the weak liver promoter, broadening the tissue scope of the gene.

    Evidence Transgenic mice expressing the Amy-1a liver promoter fused to SV40 T antigen plus expression analysis of non-transgenic adipose tissue

    PMID:2785714

    Open questions at the time
    • Functional role of amylase in adipose tissue not addressed
    • Single-lab transgenic readout
  6. 1994 High

    Established that N-linked glycosylation is functionally required, not merely decorative, for enzyme thermostability and kinetics.

    Evidence Site-directed mutagenesis of the N-glycosylation site with in vitro kinetic and thermostability assays (rice ortholog)

    PMID:7957256

    Open questions at the time
    • Conducted on a plant ortholog; conservation of the requirement in mammalian AMY1A not tested in this corpus
    • Structural basis of glycan-dependent stabilization not resolved
  7. 1997 High

    Mapped distinct enzymatic functions to specific protein domains, separating soluble-starch from oligosaccharide hydrolysis.

    Evidence Construction of Amy1A/Amy3D chimeric enzymes and in vitro activity assays on soluble starch and oligosaccharide substrates (rice ortholog)

    PMID:9163949

    Open questions at the time
    • Performed on plant orthologs
    • Atomic-level structural rationale for domain contributions not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • The transcription factors and cis-regulatory elements that confer parotid-exclusive strong-promoter activity and enforce heritable lineage commitment remain unidentified.
  • No trans-acting factor isolated for either promoter
  • Epigenetic basis of heritable commitment uncharacterized
  • Physiological function of amylase expression in liver and adipose tissue undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 2 GO:0140098 catalytic activity, acting on RNA 2
Pathway
R-HSA-1430728 Metabolism 2 R-HSA-74160 Gene expression (Transcription) 2

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1981 A single mouse alpha-amylase gene Amy-1a (AMY1A ortholog) generates two tissue-specific mRNAs (salivary gland and liver) that are identical except for their 5' non-translated sequences; the liver mRNA has a unique 161-nt leader specified by DNA 4.5 kb upstream of the common body, while the salivary gland mRNA has a 50-nt leader from sequences 7.5 kb upstream, demonstrating differential transcription and/or processing from the same gene locus. Genomic cloning, DNA sequencing, S1 nuclease mapping, Northern blot hybridization Cell High 6162570
1981 The Amy-1a gene uses alternative polyadenylation sites to produce two mRNA species differing in 3' non-translated region length in both liver and salivary gland; sequence analysis shows transcription can read through the major polyadenylation site, and flanking sequences downstream of each site share extensive homology implicated in polyadenylation or transcription termination. Genomic DNA sequencing, S1 nuclease mapping, Northern blot Nucleic acids research High 6166922
1983 Two promoters of different strengths control Amy-1a transcription: a strong promoter active exclusively in the parotid gland (~30-fold stronger, drives parotid-specific leader mRNA) and a weaker promoter active in both parotid and liver (drives liver-type leader mRNA); neither promoter is used in tissues lacking cytoplasmic alpha-amylase mRNA (brain, kidney, spleen). Run-on transcription, S1 nuclease mapping, Northern blot, tissue fractionation Cell High 6190572
1982 Amy-1a is interrupted by 10 introns and the two tissue-specific mRNAs are generated by tissue-specific splicing events; regulation of Amy-1a expression occurs primarily at the transcriptional level, with a strong promoter exclusive to salivary gland and a weak promoter active in both salivary gland and liver. S1 nuclease mapping of nuclear transcripts, cDNA/genomic sequence comparison Advances in experimental medicine and biology Medium 6186131
1985 During postnatal mouse parotid gland differentiation, the two Amy-1a promoters are differentially activated in sequence: the weaker downstream promoter is first activated (active in virtually all acinar cells by 2 weeks), followed progressively by the strong parotid-specific promoter; once an acinar cell commits to expressing the strong-promoter transcript, this commitment is heritably passed to daughter cells. Run-on transcription, Northern blot, in situ hybridization Cell High 3872721
1985 Amy-1a and Amy-2a are closely linked on the same chromosome, with Amy-2a located ~23 kb downstream of Amy-1a within a contiguous 106-kb cloned segment; transcription termination of Amy-1a occurs within 3 kb downstream of the polyadenylation site in both parotid and liver. Genomic cloning, restriction mapping, Northern blot, run-on transcription Journal of molecular biology High 2989529
1985 The weak Amy-1a promoter that directs liver-type leader mRNA synthesis is also active in the pancreas, making it active in all alpha-amylase-producing tissues (salivary gland, liver, and pancreas), while the strong parotid-specific promoter is exclusive to the parotid. In vitro elongation of nascent transcripts mapped to restriction fragments, Northern blot Journal of molecular biology Medium 3877171
1989 The Amy-1a liver promoter, when fused to SV40 T antigen in transgenic mice, drives expression in adipose tissue (brown and white), revealing that the endogenous Amy-1a gene is expressed in adipose tissue—a previously unrecognized site of expression. Transgenic mouse generation, Southern blot, gene expression analysis of adipose tissue from non-transgenic mice Science Medium 2785714
1994 The N-linked carbohydrate chain on rice alpha-amylase Amy1A (AMY1A ortholog) is required for thermostability; its removal reduces thermostability and alters kinetic parameters (Vm and Km) for starch hydrolysis as well as substrate recognition. Site-directed mutagenesis to eliminate N-glycosylation site, in vitro enzyme kinetics assay, thermal stability assay European journal of biochemistry High 7957256
1997 Domain-swap experiments between rice Amy1A and Amy3D established that the Amy1A-type N-terminal domain confers high activity against soluble starch and contributes to protein stability, while the barrel structure (active site domain) predominantly determines oligosaccharide hydrolysis activity. Chimeric enzyme construction (Amy1A/3D and Amy3D/1A), in vitro enzyme activity assays with soluble starch and oligosaccharide substrates Applied microbiology and biotechnology High 9163949
1979 Variant Amy1A proteins (Amy1R1 and Amy1R2 alleles) differ from the normal Amy1A protein by enhanced deamidation of asparagine and/or glutamine residues, as determined by isoelectric focusing and electrophoretic analysis of purified protein products. Isoelectric focusing, electrophoresis of purified proteins, family segregation analysis Human heredity Medium 468278

Source papers

Stage 0 corpus · 53 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1983 Two promoters of different strengths control the transcription of the mouse alpha-amylase gene Amy-1a in the parotid gland and the liver. Cell 466 6190572
1981 A single mouse alpha-amylase gene specifies two different tissue-specific mRNAs. Cell 371 6162570
2017 Update on the pharmacology of calcitonin/CGRP family of peptides: IUPHAR Review 25. British journal of pharmacology 296 29059473
2005 Pharmacological discrimination of calcitonin receptor: receptor activity-modifying protein complexes. Molecular pharmacology 173 15692146
1981 Multiple polyadenylation sites in a mouse alpha-amylase gene. Nucleic acids research 160 6166922
2013 Identification of proteomic signatures associated with lung cancer and COPD. Journal of proteomics 124 23665002
2012 Suppression of α-amylase genes improves quality of rice grain ripened under high temperature. Plant biotechnology journal 116 22967050
2014 Beneficial effect of a high number of copies of salivary amylase AMY1 gene on obesity risk in Mexican children. Diabetologia 84 25394825
1989 The human alpha-amylase multigene family consists of haplotypes with variable numbers of genes. Genomics 78 2788608
2006 Determinants of 1-piperidinecarboxamide, N-[2-[[5-amino-l-[[4-(4-pyridinyl)-l-piperazinyl]carbonyl]pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl) (BIBN4096BS) affinity for calcitonin gene-related peptide and amylin receptors--the role of receptor activity modifying protein 1. Molecular pharmacology 76 16959943
2004 Amylin receptors: molecular composition and pharmacology. Biochemical Society transactions 66 15494035
1999 Differential expression of rice alpha-amylase genes during seedling development under anoxia. Plant molecular biology 64 10527416
2016 Primary Salivary Human Stem/Progenitor Cells Undergo Microenvironment-Driven Acinar-Like Differentiation in Hyaluronate Hydrogel Culture. Stem cells translational medicine 60 28170182
1985 The two promoters of the mouse alpha-amylase gene Amy-1a are differentially activated during parotid gland differentiation. Cell 47 3872721
2017 Comparative Proteomics Analysis of Urine Reveals Down-Regulation of Acute Phase Response Signaling and LXR/RXR Activation Pathways in Prostate Cancer. Proteomes 44 29286311
1991 Interpretation of polymorphic DNA patterns in the human alpha-amylase multigene family. Genomics 35 1679752
1994 The roles of the N-linked carbohydrate chain of rice alpha-amylase in thermostability and enzyme kinetics. European journal of biochemistry 34 7957256
2010 A key role for tryptophan 84 in receptor activity-modifying protein 1 in the amylin 1 receptor. Peptides 30 20347903
1989 Metastatic hibernomas in transgenic mice expressing an alpha-amylase-SV40 T antigen hybrid gene. Science (New York, N.Y.) 29 2785714
2018 Brain alpha-amylase: a novel energy regulator important in Alzheimer disease? Brain pathology (Zurich, Switzerland) 28 29485701
2014 Structure-activity relationships of the N-terminus of calcitonin gene-related peptide: key roles of alanine-5 and threonine-6 in receptor activation. British journal of pharmacology 28 24125506
1979 New genetic variants of parotid salivary amylase. Human heredity 21 468278
1985 Expression of mouse Amy-2a alpha-amylase genes is regulated by strong pancreas-specific promoters. Journal of molecular biology 20 3877171
2024 Progression from healthy periodontium to gingivitis and periodontitis: Insights from bioinformatics-driven proteomics - A systematic review with meta-analysis. Journal of periodontal research 19 38873831
2007 What makes a CGRP2 receptor? Clinical and experimental pharmacology & physiology 19 17714080
2021 Polymorphisms of AMY1A gene and their association with growth, carcass traits and feed intake efficiency in chickens. Genomics 18 33485951
1994 Syntenic assignment of human chromosome 1 homologous loci in the bovine. Genomics 18 8001974
2017 Taxotere-induced elevated expression of IL8 in carcinoma-associated fibroblasts of breast invasive ductal cancer. Oncology letters 17 28454334
2020 Cordycepin attenuates Salivary Hypofunction through the Prevention of Oxidative Stress in Human Submandibular Gland Cells. International journal of medical sciences 16 32714076
2018 AMYCNE: Confident copy number assessment using whole genome sequencing data. PloS one 16 29579039
2013 Amylase α-1A (AMY1A): a novel immunohistochemical marker to differentiate chromophobe renal cell carcinoma from benign oncocytoma. The American journal of surgical pathology 14 24225843
2020 Association of AMY1A/AMY2A copy numbers and AMY1/AMY2 serum enzymatic activity with obesity in Mexican children. Pediatric obesity 12 32314532
2020 Alpha-amylase 1A copy number variants and the association with memory performance and Alzheimer's dementia. Alzheimer's research & therapy 12 33220711
1985 Mouse alpha-amylase loci, Amy-1a and Amy-2a, are closely linked. Journal of molecular biology 12 2989529
2024 Exploring the Antidiabetic Potential of Salvia officinalis Using Network Pharmacology, Molecular Docking and ADME/Drug-Likeness Predictions. Plants (Basel, Switzerland) 11 39458839
2018 Untargeted analysis of the airway proteomes of children with respiratory infections using mass spectrometry based proteomics. Scientific reports 9 30217988
1997 Functional roles of protein domains on rice alpha-amylase activity. Applied microbiology and biotechnology 9 9163949
2016 Synthesis and amylin receptor activity of glycomimetics of pramlintide using click chemistry. Organic & biomolecular chemistry 8 27139251
2010 An expectation-maximization program for determining allelic spectrum from CNV data (CoNVEM): insights into population allelic architecture and its mutational history. Human mutation 8 20077501
2021 Influence of AMY1A copy number variations on obesity and other cardiometabolic risk factors: A review of the evidence. Obesity reviews : an official journal of the International Association for the Study of Obesity 6 33432778
1980 Protein polymorphism in a randombred chicken population. Animal blood groups and biochemical genetics 6 6166222
2019 Analysis of five deep-sequenced trio-genomes of the Peninsular Malaysia Orang Asli and North Borneo populations. BMC genomics 5 31718558
1982 Tissue specific expression of mouse alpha-amylase genes. Advances in experimental medicine and biology 5 6186131
2024 Detecting adaptive changes in gene copy number distribution accompanying the human out-of-Africa expansion. Human genome variation 3 39313504
2023 Plasma proteins as potential biomarkers of aging of single tissue and cell type. Biogerontology 2 37707684
2023 Draft genome sequencing of halotolerant bacterium Salinicola sp. DM10 unravels plant growth-promoting potentials. 3 Biotech 2 38009164
2020 Diagnostic utility of amylase α-1A, MOC 31, and CD 82 in renal oncocytoma versus chromophobe renal cell carcinoma. Indian journal of pathology & microbiology 2 32769329
1992 [Genetic profile of LIBP/1 inbred strain derived from the Kunming outbred stock of the mouse]. Jikken dobutsu. Experimental animals 2 1451766
2024 Large-scale transcriptomic and genomic analyses reveal a novel functional gene SERPINB6 for chicken carcass traits. Journal of animal science and biotechnology 1 38730308
2026 ​The inverse relationship between copy number variation burden and age of onset of metabolic syndrome in Korean middle-aged adults. BMC medical genomics 0 41928242
2026 Carbohydrate-dependent interaction between AMY1A/AMY2B copy number variation and APOA5 rs651821 associated with hypertriglyceridemia in Korean middle-aged adults. BMC nutrition 0 42152161
2023 [From genotype to phenotype: amylase gene in childhood obesity]. Revista medica del Instituto Mexicano del Seguro Social 0 37216679
2005 On the genetic polymorphism of the serum alpha-amylase in the population of the south western Bulgaria (second communication). Folia medica 0 16152770

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