TISIDB

Summary
Symbol	SERPINA5
Name	serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 5
Aliases	PAI3; PROCI; PLANH3; PCI; serine (or cysteine) proteinase inhibitor, clade A (alpha-1 antiproteinase, antitr ......
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, extracellular space Note=Localized on the plasma membrane overlying the acrosomal head of spermatozoa of ependymal spermatozoa and ejaculated sperm. Localized at the equatorial segment of acrosome-reacted spematozoa. Localized in alpha granules in resting platelets and on the external plasma membrane and within the surface-connected cannalicular system in activated platelets.
Domain	PF00079 Serpin (serine protease inhibitor)
Function	Heparin-dependent serine protease inhibitor acting in body fluids and secretions. Inactivates serine proteases by binding irreversibly to their serine activation site. Involved in the regulation of intravascular and extravascular proteolytic activities. Plays hemostatic roles in the blood plasma. Acts as a procoagulant and proinflammatory factor by inhibiting the anticoagulant activated protein C factor as well as the generation of activated protein C factor by the thrombin/thrombomodulin complex. Acts as an anticoagulant factor by inhibiting blood coagulation factors like prothrombin, factor XI, factor Xa, plasma kallikrein and fibrinolytic enzymes such as tissue- and urinary-type plasminogen activators. In seminal plasma, inactivates several serine proteases implicated in the reproductive system. Inhibits the serpin acrosin; indirectly protects component of the male genital tract from being degraded by excessive released acrosin. Inhibits tissue-and urinary-type plasminogen activator, prostate-specific antigen and kallikrein activities; has a control on the sperm motility and fertilization. Inhibits the activated protein C-catalyzed degradation of SEMG1 and SEMG2; regulates the degradation of semenogelin during the process of transfer of spermatozoa from the male reproductive tract into the female tract. In urine, inhibits urinary-type plasminogen activator and kallikrein activities. Inactivates membrane-anchored serine proteases activities such as MPRSS7 and TMPRSS11E. Inhibits urinary-type plasminogen activator-dependent tumor cell invasion and metastasis. May also play a non-inhibitory role in seminal plasma and urine as a hydrophobic hormone carrier by its binding to retinoic acid.

> Gene Ontology [ TOP ]
Biological Process	GO:0006869 lipid transport GO:0007283 spermatogenesis GO:0007338 single fertilization GO:0007342 fusion of sperm to egg plasma membrane GO:0007596 blood coagulation GO:0007599 hemostasis GO:0009566 fertilization GO:0010466 negative regulation of peptidase activity GO:0010876 lipid localization GO:0010951 negative regulation of endopeptidase activity GO:0022412 cellular process involved in reproduction in multicellular organism GO:0044801 single-organism membrane fusion GO:0045026 plasma membrane fusion GO:0045861 negative regulation of proteolysis GO:0048232 male gamete generation GO:0050817 coagulation GO:0050878 regulation of body fluid levels GO:0051346 negative regulation of hydrolase activity GO:0052547 regulation of peptidase activity GO:0052548 regulation of endopeptidase activity GO:0061025 membrane fusion
Molecular Function	GO:0001972 retinoic acid binding GO:0002020 protease binding GO:0004857 enzyme inhibitor activity GO:0004866 endopeptidase inhibitor activity GO:0004867 serine-type endopeptidase inhibitor activity GO:0005501 retinoid binding GO:0005539 glycosaminoglycan binding GO:0008201 heparin binding GO:0019840 isoprenoid binding GO:0030414 peptidase inhibitor activity GO:0031210 phosphatidylcholine binding GO:0031406 carboxylic acid binding GO:0032190 acrosin binding GO:0033293 monocarboxylic acid binding GO:0043168 anion binding GO:0061134 peptidase regulator activity GO:0061135 endopeptidase regulator activity GO:0070405 ammonium ion binding GO:1901681 sulfur compound binding
Cellular Component	GO:0001669 acrosomal vesicle GO:0002080 acrosomal membrane GO:0009897 external side of plasma membrane GO:0030141 secretory granule GO:0030659 cytoplasmic vesicle membrane GO:0030667 secretory granule membrane GO:0031091 platelet alpha granule GO:0031094 platelet dense tubular network GO:0036024 protein C inhibitor-TMPRSS7 complex GO:0036025 protein C inhibitor-TMPRSS11E complex GO:0036026 protein C inhibitor-PLAT complex GO:0036027 protein C inhibitor-PLAU complex GO:0036028 protein C inhibitor-thrombin complex GO:0036029 protein C inhibitor-KLK3 complex GO:0036030 protein C inhibitor-plasma kallikrein complex GO:0097179 protease inhibitor complex GO:0097180 serine protease inhibitor complex GO:0097181 protein C inhibitor-coagulation factor V complex GO:0097182 protein C inhibitor-coagulation factor Xa complex GO:0097183 protein C inhibitor-coagulation factor XI complex GO:0097223 sperm part GO:0098552 side of membrane GO:0099503 secretory vesicle

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04610 Complement and coagulation cascades
Reactome	R-HSA-140875: Common Pathway of Fibrin Clot Formation R-HSA-140877: Formation of Fibrin Clot (Clotting Cascade) R-HSA-109582: Hemostasis R-HSA-140837: Intrinsic Pathway of Fibrin Clot Formation

Summary
Symbol	SERPINA5
Name	serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 5
Aliases	PAI3; PROCI; PLANH3; PCI; serine (or cysteine) proteinase inhibitor, clade A (alpha-1 antiproteinase, antitr ......
Chromosomal Location	14q32.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between SERPINA5 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 ]
There is no record.

Summary
Symbol	SERPINA5
Name	serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 5
Aliases	PAI3; PROCI; PLANH3; PCI; serine (or cysteine) proteinase inhibitor, clade A (alpha-1 antiproteinase, antitr ......
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 SERPINA5 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	SERPINA5
Name	serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 5
Aliases	PAI3; PROCI; PLANH3; PCI; serine (or cysteine) proteinase inhibitor, clade A (alpha-1 antiproteinase, antitr ......
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 SERPINA5 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	1.248	0.0789
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	1.865	0.173
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.799	0.474
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.219	0.81
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.613	0.676
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.271	0.867
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.118	0.895
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.195	0.89
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.114	0.938
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.121	0.945
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	1.096	0.625
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-1.033	0.00239

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of SERPINA5 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	0	5.9	-5.9	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	33.3	-33.3	0.231
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	3.7	4.1	-0.4	1
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	3.7	5.1	-1.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	11.8	-11.8	0.193
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	16.7	-16.7	0.429
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	9.1	-9.1	0.458
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	6.2	4.9	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	11.1	8.9	1
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	7.9	3.7	4.2	0.636
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	7.7	1.4	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	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	SERPINA5
Name	serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 5
Aliases	PAI3; PROCI; PLANH3; PCI; serine (or cysteine) proteinase inhibitor, clade A (alpha-1 antiproteinase, antitr ......
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 SERPINA5. 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	SERPINA5
Name	serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 5
Aliases	PAI3; PROCI; PLANH3; PCI; serine (or cysteine) proteinase inhibitor, clade A (alpha-1 antiproteinase, antitr ......
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 SERPINA5. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by SERPINA5. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	SERPINA5
Name	serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 5
Aliases	PAI3; PROCI; PLANH3; PCI; serine (or cysteine) proteinase inhibitor, clade A (alpha-1 antiproteinase, antitr ......
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 SERPINA5. 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	SERPINA5
Name	serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 5
Aliases	PAI3; PROCI; PLANH3; PCI; serine (or cysteine) proteinase inhibitor, clade A (alpha-1 antiproteinase, antitr ......
Chromosomal Location	14q32.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of SERPINA5 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	SERPINA5
Name	serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 5
Aliases	PAI3; PROCI; PLANH3; PCI; serine (or cysteine) proteinase inhibitor, clade A (alpha-1 antiproteinase, antitr ......
Chromosomal Location	14q32.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between SERPINA5 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	SERPINA5
Name	serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 5
Aliases	PAI3; PROCI; PLANH3; PCI; serine (or cysteine) proteinase inhibitor, clade A (alpha-1 antiproteinase, antitr ......
Chromosomal Location	14q32.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting SERPINA5 collected from DrugBank database.

> Drugs from DrugBank database

[ TOP ]

Details on drugs targeting SERPINA5.

ID	Name	Drug Type	Targets	#Targets
DB00013	Urokinase	Biotech	LRP2, NID1, PLAT, PLAU, PLAUR, PLG, SERPINA5, SERPINB2, SERPINE1, ......	10
DB00055	Drotrecogin alfa	Biotech	CP, F2, F5, F8, GGCX, PF4, PROCR, PROS1, SERPINA5, SERPINB6, SERPI ......	12
DB05413	Tifuvirtide	Small Molecule	SERPINA5	1
DB05961	PPL-100	Small Molecule	SERPINA1, SERPINA5, SERPING1	3

Browse SERPINA5