TISIDB

Summary
Symbol	HTRA3
Name	HtrA serine peptidase 3
Aliases	Prsp; pregnancy-related serine protease; high-temperature requirement factor A3; probable serine protease HT ......
Chromosomal Location	4p16.1
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 Note=Secretion increased during decidualization of endometrial stromal cells.
Domain	PF00219 Insulin-like growth factor binding protein PF07648 Kazal-type serine protease inhibitor domain PF13180 PDZ domain
Function	Serine protease that cleaves beta-casein/CSN2 as well as several extracellular matrix (ECM) proteoglycans such as decorin/DCN, biglycan/BGN and fibronectin/FN1. Inhibits signaling mediated by TGF-beta family proteins possibly indirectly by degradation of these ECM proteoglycans (By similarity). May act as a tumor suppressor. Negatively regulates, in vitro, trophoblast invasion during placental development and may be involved in the development of the placenta in vivo. May also have a role in ovarian development, granulosa cell differentiation and luteinization (PubMed:21321049, PubMed:22229724).

> Gene Ontology [ TOP ]
Biological Process	GO:0001558 regulation of cell growth GO:0007178 transmembrane receptor protein serine/threonine kinase signaling pathway GO:0007179 transforming growth factor beta receptor signaling pathway GO:0016049 cell growth GO:0017015 regulation of transforming growth factor beta receptor signaling pathway GO:0030509 BMP signaling pathway GO:0030510 regulation of BMP signaling pathway GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway GO:0030514 negative regulation of BMP signaling pathway GO:0071559 response to transforming growth factor beta GO:0071560 cellular response to transforming growth factor beta stimulus GO:0071772 response to BMP GO:0071773 cellular response to BMP stimulus GO:0090092 regulation of transmembrane receptor protein serine/threonine kinase signaling pathway GO:0090101 negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway GO:0090287 regulation of cellular response to growth factor stimulus GO:0090288 negative regulation of cellular response to growth factor stimulus GO:1903844 regulation of cellular response to transforming growth factor beta stimulus GO:1903845 negative regulation of cellular response to transforming growth factor beta stimulus
Molecular Function	GO:0004175 endopeptidase activity GO:0004252 serine-type endopeptidase activity GO:0005520 insulin-like growth factor binding GO:0008236 serine-type peptidase activity GO:0017171 serine hydrolase activity GO:0019838 growth factor binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	-

Summary
Symbol	HTRA3
Name	HtrA serine peptidase 3
Aliases	Prsp; pregnancy-related serine protease; high-temperature requirement factor A3; probable serine protease HT ......
Chromosomal Location	4p16.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between HTRA3 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	HTRA3
Name	HtrA serine peptidase 3
Aliases	Prsp; pregnancy-related serine protease; high-temperature requirement factor A3; probable serine protease HT ......
Chromosomal Location	4p16.1
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

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Statistical results of HTRA3 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	HTRA3
Name	HtrA serine peptidase 3
Aliases	Prsp; pregnancy-related serine protease; high-temperature requirement factor A3; probable serine protease HT ......
Chromosomal Location	4p16.1
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

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Points in the above scatter plot represent the expression difference of HTRA3 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	-1.772	0.00304
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-2.725	0.13
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-1.051	0.337
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-1.141	0.0531
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.231	0.459
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-1.023	0.642
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.01	0.988
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.668	0.607
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.885	0.559
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.388	0.413
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	3.339	0.119
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.611	0.00891

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of HTRA3 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	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	7.1	-7.1	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	0	3.7	0.27
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	0	3.7	0.314
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	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	0	7.7	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	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	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	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	HTRA3
Name	HtrA serine peptidase 3
Aliases	Prsp; pregnancy-related serine protease; high-temperature requirement factor A3; probable serine protease HT ......
Chromosomal Location	4p16.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of HTRA3. 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	HTRA3
Name	HtrA serine peptidase 3
Aliases	Prsp; pregnancy-related serine protease; high-temperature requirement factor A3; probable serine protease HT ......
Chromosomal Location	4p16.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of HTRA3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by HTRA3. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	HTRA3
Name	HtrA serine peptidase 3
Aliases	Prsp; pregnancy-related serine protease; high-temperature requirement factor A3; probable serine protease HT ......
Chromosomal Location	4p16.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of HTRA3. 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	HTRA3
Name	HtrA serine peptidase 3
Aliases	Prsp; pregnancy-related serine protease; high-temperature requirement factor A3; probable serine protease HT ......
Chromosomal Location	4p16.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of HTRA3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	HTRA3
Name	HtrA serine peptidase 3
Aliases	Prsp; pregnancy-related serine protease; high-temperature requirement factor A3; probable serine protease HT ......
Chromosomal Location	4p16.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between HTRA3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	HTRA3
Name	HtrA serine peptidase 3
Aliases	Prsp; pregnancy-related serine protease; high-temperature requirement factor A3; probable serine protease HT ......
Chromosomal Location	4p16.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting HTRA3 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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