SERPINA1

Protein identityUniProt · HPA

UniProt accession

P01009

Gene

SERPINA1

Ensembl

ENSG00000197249

Chromosome

14

Canonical length

418 aa

Protein class

Cancer-related genes, Candidate cardiovascular disease genes, Disease related genes, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins

Subcellular location

Vesicles

Secretome location

Secreted to blood

OverviewNCBI Gene

The protein encoded by this gene is a serine protease inhibitor belonging to the serpin superfamily whose targets include elastase, plasmin, thrombin, trypsin, chymotrypsin, and plasminogen activator. This protein is produced in the liver, the bone marrow, by lymphocytic and monocytic cells in lymphoid tissue, and by the Paneth cells of the gut. Defects in this gene are associated with chronic obstructive pulmonary disease, emphysema, and chronic liver disease. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Aug 2020]

Canonical amino-acid sequenceUniProt

418 residues, UniProt reviewed canonical sequence.

>P01009|SERPINA1
     1  MPSSVSWGIL LLAGLCCLVP VSLAEDPQGD AAQKTDTSHH DQDHPTFNKI TPNLAEFAFS
    61  LYRQLAHQSN STNIFFSPVS IATAFAMLSL GTKADTHDEI LEGLNFNLTE IPEAQIHEGF
   121  QELLRTLNQP DSQLQLTTGN GLFLSEGLKL VDKFLEDVKK LYHSEAFTVN FGDTEEAKKQ
   181  INDYVEKGTQ GKIVDLVKEL DRDTVFALVN YIFFKGKWER PFEVKDTEEE DFHVDQVTTV
   241  KVPMMKRLGM FNIQHCKKLS SWVLLMKYLG NATAIFFLPD EGKLQHLENE LTHDIITKFL
   301  ENEDRRSASL HLPKLSITGT YDLKSVLGQL GITKVFSNGA DLSGVTEEAP LKLSKAVHKA
   361  VLTIDEKGTE AAGAMFLEAI PMSIPPEVKF NKPFVFLMIE QNTKSPLFMG KVVNPTQK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SERPINA1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.28

Highest tissue expression

31,417 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SERPINA1.

Disease | AllUniProt

Conditions SERPINA1 is implicated in, by any mechanism.

• Alpha-1-antitrypsin deficiency (A1ATD) MIM:613490

Disease | GeneticClinVar

83 pathogenic / likely-pathogenic of 525 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Alpha-1-antitrypsin deficiency
• SERPINA1-related disorder
• Inborn genetic diseases
• Chronic obstructive pulmonary disease
• See cases

Disease | ImmuneIEDB

Conditions an epitope on SERPINA1 was assayed in.

• rheumatoid arthritis B cell
• osteoarthritis B cell

ReferencesPubMed · IEDB

Publications for SERPINA1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.63

gnomAD pLI

0

gnomAD missense Z

-0.37

DepMap mean gene effect

-0.01

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• acute-phase response
• blood coagulation

Molecular functions

• identical protein binding
• protease binding
• serine-type endopeptidase inhibitor activity

Cellular components

• COPII-coated ER to Golgi transport vesicle
• endoplasmic reticulum
• endoplasmic reticulum lumen
• endoplasmic reticulum-Golgi intermediate compartment membrane
• extracellular exosome
• extracellular matrix
• extracellular region
• extracellular space
• ficolin-1-rich granule lumen
• Golgi apparatus
• platelet alpha granule lumen

Protein domainsUniProt · Pfam · InterPro

• Serpin family
• Serpin, conserved site
• Serpin domain
• Serpin superfamily
• Serpin superfamily, domain 1
• Serpin superfamily, domain 2
• Serpin (serine protease inhibitor)

KeywordsUniProt

• Acute phase
• Blood coagulation
• Endoplasmic reticulum
• Extracellular matrix
• Glycoprotein
• Hemostasis
• Phosphoprotein
• Protease inhibitor
• Secreted
• Serine protease inhibitor
• Signal

InteractionsUniProt · HPA

Protein binding partners of SERPINA1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CELA2A
• ERGIC3
• PRSS1