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MGP002278

UniProt Annotations

Entry Information
Gene Nameserpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1
Protein EntryA1AT_HUMAN
UniProt IDP01009
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=1; IsoId=P01009-1; Sequence=Displayed; Name=2; IsoId=P01009-2; Sequence=VSP_028889; Note=No experimental confirmation available.; Name=3; IsoId=P01009-3; Sequence=VSP_028890; Note=No experimental confirmation available. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.;
DiseaseAlpha-1-antitrypsin deficiency (A1ATD) [MIM:613490]: A disorder whose most common manifestation is emphysema, which becomes evident by the third to fourth decade. A less common manifestation of the deficiency is liver disease, which occurs in children and adults, and may result in cirrhosis and liver failure. Environmental factors, particularly cigarette smoking, greatly increase the risk of emphysema at an earlier age. {ECO:0000269|PubMed:1905728, ECO:0000269|PubMed:2227940, ECO:0000269|PubMed:2390072}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DomainThe reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the carboxyl group of the serpin reactive site and the serine hydroxyl of the protease. The resulting inactive serpin-protease complex is highly stable.
FunctionInhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Irreversibly inhibits trypsin, chymotrypsin and plasminogen activator. The aberrant form inhibits insulin-induced NO synthesis in platelets, decreases coagulation time and has proteolytic activity against insulin and plasmin.
FunctionShort peptide from AAT: reversible chymotrypsin inhibitor. It also inhibits elastase, but not trypsin. Its major physiological function is the protection of the lower respiratory tract against proteolytic destruction by human leukocyte elastase (HLE).
InteractionSelf; NbExp=5; IntAct=EBI-986224, EBI-986224; P00760:- (xeno); NbExp=5; IntAct=EBI-986224, EBI-986385; P00772:CELA1 (xeno); NbExp=2; IntAct=EBI-986224, EBI-986248; P71213:espB (xeno); NbExp=3; IntAct=EBI-986224, EBI-2615322; P43307:SSR1; NbExp=4; IntAct=EBI-986224, EBI-714168;
MiscellaneousThe aberrant form is found in the plasma of chronic smokers, and persists after smoking is ceased. It can still be found ten years after smoking has ceased.
PolymorphismThe sequence shown is that of the M1V allele which is the most common form of PI (44 to 49%). Other frequent alleles are: M1A 20 to 23%; M2 10 to 11%; M3 14 to 19%.
PtmN-glycosylated. Differential glycosylation produces a number of isoforms. N-linked glycan at Asn-107 is alternatively di- antennary, tri-antennary or tetra-antennary. The glycan at Asn-70 is di-antennary with trace amounts of tri-antennary. Glycan at Asn-271 is exclusively di-antennary. Structure of glycans at Asn- 70 and Asn-271 is Hex5HexNAc4. The structure of the antennae is Neu5Ac(alpha1-6)Gal(beta1-4)GlcNAc attached to the core structure Man(alpha1-6)[Man(alpha1-3)]Man(beta1-4)GlcNAc(beta1-4)GlcNAc. Some antennae are fucosylated, which forms a Lewis-X determinant. {ECO:0000269|PubMed:12754519, ECO:0000269|PubMed:14760718, ECO:0000269|PubMed:15084671, ECO:0000269|PubMed:16263699, ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:16622833, ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19838169, ECO:0000269|PubMed:22171320, ECO:0000269|PubMed:23826168}.
PtmProteolytic processing may yield the truncated form that ranges from Asp-30 to Lys-418.
Sequence CautionSequence=CAD62334.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; Sequence=CAD62585.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
SimilarityBelongs to the serpin family. {ECO:0000305}.
Subcellular LocationSecreted. Endoplasmic reticulum. Note=The S and Z allele are not secreted effectively and accumulate intracellularly in the endoplasmic reticulum.
Subcellular LocationShort peptide from AAT: Secreted, extracellular space, extracellular matrix.
SubunitThe variants S and Z interact with CANX AND PDIA3. {ECO:0000269|PubMed:11057674}.
Tissue SpecificityUbiquitous. Expressed in leukocytes and plasma. {ECO:0000269|PubMed:23826168}.
Web ResourceName=Wikipedia; Note=Alpha-1 antitrypsin entry; URL="http://en.wikipedia.org/wiki/Alpha_1-antitrypsin";
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