TISIDB

Summary
Symbol	SERPINA1
Name	serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1
Aliases	AAT; A1A; PI1; alpha-1-antitrypsin; A1AT; alpha1AT; protease inhibitor 1 (anti-elastase), alpha-1-antitrypsi ......
Chromosomal Location	14q32.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Secreted. Endoplasmic reticulum. Note=The S and Z allele are not secreted effectively and accumulate intracellularly in the endoplasmic reticulum.; SUBCELLULAR LOCATION: Short peptide from AAT: Secreted, extracellular space, extracellular matrix.
Domain	PF00079 Serpin (serine protease inhibitor)
Function	Inhibitor 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.; FUNCTION: Short 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).

> Gene Ontology [ TOP ]
Biological Process	GO:0002526 acute inflammatory response GO:0002576 platelet degranulation GO:0006887 exocytosis GO:0006888 ER to Golgi vesicle-mediated transport GO:0006900 membrane budding GO:0006901 vesicle coating GO:0006903 vesicle targeting GO:0006953 acute-phase response GO:0007596 blood coagulation GO:0007599 hemostasis GO:0010466 negative regulation of peptidase activity GO:0010951 negative regulation of endopeptidase activity GO:0016050 vesicle organization GO:0045055 regulated exocytosis GO:0045861 negative regulation of proteolysis GO:0048193 Golgi vesicle transport GO:0048199 vesicle targeting, to, from or within Golgi GO:0048207 vesicle targeting, rough ER to cis-Golgi GO:0048208 COPII vesicle coating GO:0050817 coagulation GO:0050878 regulation of body fluid levels GO:0051346 negative regulation of hydrolase activity GO:0051640 organelle localization GO:0051648 vesicle localization GO:0051650 establishment of vesicle localization GO:0051656 establishment of organelle localization GO:0052547 regulation of peptidase activity GO:0052548 regulation of endopeptidase activity GO:0090114 COPII-coated vesicle budding
Molecular Function	GO:0001948 glycoprotein binding GO:0002020 protease binding GO:0004857 enzyme inhibitor activity GO:0004866 endopeptidase inhibitor activity GO:0004867 serine-type endopeptidase inhibitor activity GO:0030414 peptidase inhibitor activity GO:0061134 peptidase regulator activity GO:0061135 endopeptidase regulator activity
Cellular Component	GO:0005578 proteinaceous extracellular matrix GO:0005788 endoplasmic reticulum lumen GO:0005793 endoplasmic reticulum-Golgi intermediate compartment GO:0030133 transport vesicle GO:0030134 ER to Golgi transport vesicle GO:0030135 coated vesicle GO:0030141 secretory granule GO:0031091 platelet alpha granule GO:0031093 platelet alpha granule lumen GO:0031983 vesicle lumen GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane GO:0034774 secretory granule lumen GO:0060205 cytoplasmic membrane-bounded vesicle lumen GO:0099503 secretory vesicle

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04610 Complement and coagulation cascades
Reactome	R-HSA-446203: Asparagine N-linked glycosylation R-HSA-204005: COPII (Coat Protein 2) Mediated Vesicle Transport R-HSA-5694530: Cargo concentration in the ER R-HSA-199977: ER to Golgi Anterograde Transport R-HSA-109582: Hemostasis R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-199991: Membrane Trafficking R-HSA-392499: Metabolism of proteins R-HSA-6798695: Neutrophil degranulation R-HSA-76002: Platelet activation, signaling and aggregation R-HSA-114608: Platelet degranulation R-HSA-597592: Post-translational protein modification R-HSA-76005: Response to elevated platelet cytosolic Ca2+ R-HSA-948021: Transport to the Golgi and subsequent modification R-HSA-5653656: Vesicle-mediated transport

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04610 Complement and coagulation cascades

Reactome

R-HSA-446203: Asparagine N-linked glycosylation
R-HSA-204005: COPII (Coat Protein 2) Mediated Vesicle Transport
R-HSA-5694530: Cargo concentration in the ER
R-HSA-199977: ER to Golgi Anterograde Transport
R-HSA-109582: Hemostasis
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-199991: Membrane Trafficking
R-HSA-392499: Metabolism of proteins
R-HSA-6798695: Neutrophil degranulation
R-HSA-76002: Platelet activation, signaling and aggregation
R-HSA-114608: Platelet degranulation
R-HSA-597592: Post-translational protein modification
R-HSA-76005: Response to elevated platelet cytosolic Ca2+
R-HSA-948021: Transport to the Golgi and subsequent modification
R-HSA-5653656: Vesicle-mediated transport

Summary
Symbol	SERPINA1
Name	serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1
Aliases	AAT; A1A; PI1; alpha-1-antitrypsin; A1AT; alpha1AT; protease inhibitor 1 (anti-elastase), alpha-1-antitrypsi ......
Chromosomal Location	14q32.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between SERPINA1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

[ TOP ]

Literatures describing the relation between SERPINA1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
18438953	Cervical carcinoma	Inhibit immunity	Elevated expression of SerpinA1 and SerpinA3 in HLA-positive cervical carcinoma. Especially SerpinA1 and SerpinA3 were found to be up-regulated in HLA-positive tumours (3.6- and 8.2-fold, respectively), and this was confirmed by real-time PCR and immunohistochemistry. In a group of 117 tumours, high SerpinA1 and SerpinA3 expression in association with normal/partial HLA expression correlated significantly with poor overall survival (p = 0.035 and p = 0.05, respectively). Thus, HLA-positive tumours are characterized by higher expression of genes associated with an inflammatory profile. In addition, expression of the acute phase proteins SerpinA1 and SerpinA3 in HLA-positive tumours is associated with worse prognosis.

Summary
Symbol	SERPINA1
Name	serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1
Aliases	AAT; A1A; PI1; alpha-1-antitrypsin; A1AT; alpha1AT; protease inhibitor 1 (anti-elastase), alpha-1-antitrypsi ......
Chromosomal Location	14q32.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

[ TOP ]

Statistical results of SERPINA1 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	SERPINA1
Name	serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1
Aliases	AAT; A1A; PI1; alpha-1-antitrypsin; A1AT; alpha1AT; protease inhibitor 1 (anti-elastase), alpha-1-antitrypsi ......
Chromosomal Location	14q32.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the expression difference of SERPINA1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.046	0.956
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-1.43	0.54
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	1.13	0.514
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.377	0.598
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.377	0.84
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	1.335	0.582
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.396	0.641
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.807	0.655
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.228	0.916
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.069	0.983
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.467	0.923
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.594	0.0584

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of SERPINA1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	7.1	5.9	1.2	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	33.3	-23.3	0.423
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	6.8	-6.8	0.32
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	8.5	-8.5	0.32
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	5.9	-1.1	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	9.1	-1.4	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	0	11.1	0.36
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	0	20	0.357
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	SERPINA1
Name	serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1
Aliases	AAT; A1A; PI1; alpha-1-antitrypsin; A1AT; alpha1AT; protease inhibitor 1 (anti-elastase), alpha-1-antitrypsi ......
Chromosomal Location	14q32.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of SERPINA1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	SERPINA1
Name	serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1
Aliases	AAT; A1A; PI1; alpha-1-antitrypsin; A1AT; alpha1AT; protease inhibitor 1 (anti-elastase), alpha-1-antitrypsi ......
Chromosomal Location	14q32.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of SERPINA1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by SERPINA1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	SERPINA1
Name	serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1
Aliases	AAT; A1A; PI1; alpha-1-antitrypsin; A1AT; alpha1AT; protease inhibitor 1 (anti-elastase), alpha-1-antitrypsi ......
Chromosomal Location	14q32.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of SERPINA1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	SERPINA1
Name	serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1
Aliases	AAT; A1A; PI1; alpha-1-antitrypsin; A1AT; alpha1AT; protease inhibitor 1 (anti-elastase), alpha-1-antitrypsi ......
Chromosomal Location	14q32.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of SERPINA1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	SERPINA1
Name	serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1
Aliases	AAT; A1A; PI1; alpha-1-antitrypsin; A1AT; alpha1AT; protease inhibitor 1 (anti-elastase), alpha-1-antitrypsi ......
Chromosomal Location	14q32.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between SERPINA1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	SERPINA1
Name	serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1
Aliases	AAT; A1A; PI1; alpha-1-antitrypsin; A1AT; alpha1AT; protease inhibitor 1 (anti-elastase), alpha-1-antitrypsi ......
Chromosomal Location	14q32.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting SERPINA1 collected from DrugBank database.

> Drugs from DrugBank database

[ TOP ]

Details on drugs targeting SERPINA1.

ID	Name	Drug Type	Targets	#Targets
DB01593	Zinc	Small Molecule	A1BG, A2M, AGT, AHSG, ALDOA, APCS, APLP1, APLP2, APOA1, APOA2, APO ......	119
DB01998	2-[3,4-Dihydroxy-2-Hydroxymethyl-5-(2-Hydroxy-Nonyl)-Tetrahydro-Furan-2-Yloxy]-6-Hydroxymethyl-Tetra Hydro-Pyran-3,4,5-Triol	Small Molecule	SERPINA1	1
DB03345	Beta-Mercaptoethanol	Small Molecule	GLO1, LGALS1, PNPO, SCMH1, SERPINA1	5
DB05481	Recombinant alpha 1-antitrypsin	Small Molecule	SERPINA1	1
DB05961	PPL-100	Small Molecule	SERPINA1, SERPINA5, SERPING1	3
DB09130	Copper	Small Molecule	A1BG, ACTG1, ACTN1, ACY1, AFM, AGT, AHCY, AHSG, AKR1A1, ANXA4, ANX ......	141

Browse SERPINA1