TISIDB

Summary
Symbol	ASTL
Name	astacin-like metallo-endopeptidase (M12 family)
Aliases	ovastacin; SAS1B; sperm acrosomal SLLP1 binding; astacin-like metalloendopeptidase (M12 family); oocyte asta ......
Chromosomal Location	2q11.1
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	Cytoplasm Cell membrane Cytoplasmic granule Cytoplasmic vesicle, secretory vesicle Note=Secretory granules. Localizes to the peripheral cortical granules of ovulated eggs. Probably exocytosed from cortical granules during post-fertilization. Detected throughout the ooplasm of germinal vesicle stage oocytes in early bilaminar secondary follicles shortly after birth. Detected in the microvillar domain of the oolemma in arrested ovulated secondary oocytes and in the first polar body prior to fertilization. Upon fertilization, detected in the perivitelline space (PVS). Colocalizes with SPACA3 at the microvillar domain of the oolemma and in the perivitelline space (PVS) (By similarity).
Domain	PF01400 Astacin (Peptidase family M12A)
Function	Oocyte-specific oolemmal receptor involved in sperm and egg adhesion and fertilization. Plays a role in the polyspermy inhibition. Probably acts as a protease for the post-fertilization cleavage of ZP2. Cleaves the sperm-binding ZP2 at the surface of the zona pellucida after fertilization and cortical granule exocytosis, rendering the zona pellucida unable to support further sperm binding (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0007338 single fertilization GO:0007339 binding of sperm to zona pellucida GO:0007343 egg activation GO:0008037 cell recognition GO:0009566 fertilization GO:0009988 cell-cell recognition GO:0010954 positive regulation of protein processing GO:0016485 protein processing GO:0035036 sperm-egg recognition GO:0043900 regulation of multi-organism process GO:0043901 negative regulation of multi-organism process GO:0045862 positive regulation of proteolysis GO:0051604 protein maturation GO:0060467 negative regulation of fertilization GO:0060468 prevention of polyspermy GO:0070613 regulation of protein processing GO:1903317 regulation of protein maturation GO:1903319 positive regulation of protein maturation GO:2000241 regulation of reproductive process GO:2000242 negative regulation of reproductive process GO:2000359 regulation of binding of sperm to zona pellucida GO:2000360 negative regulation of binding of sperm to zona pellucida
Molecular Function	GO:0004175 endopeptidase activity GO:0004222 metalloendopeptidase activity GO:0008237 metallopeptidase activity GO:0070001 aspartic-type peptidase activity GO:0070002 glutamic-type peptidase activity
Cellular Component	GO:0030133 transport vesicle GO:0030141 secretory granule GO:0060473 cortical granule GO:0099503 secretory vesicle

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

Summary
Symbol	ASTL
Name	astacin-like metallo-endopeptidase (M12 family)
Aliases	ovastacin; SAS1B; sperm acrosomal SLLP1 binding; astacin-like metalloendopeptidase (M12 family); oocyte asta ......
Chromosomal Location	2q11.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between ASTL 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

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

PMID	Cancer type	Relation to immunity	Evidence sentences
26327203	Endometrioids, malignant mixed Mullerian tumor	Inhibit immunity	SAS1B is a potential immunotherapy target for uterine tumors. Targeting of SAS1B help to arrest cell and cause cell death. Gene-specific PCR and immunohistochemical studies revealed ASTL messages and SAS1B protein in both endometrioid [74%] and malignant mixed Mullerian tumors (MMMT) [87%] of the uterus. Treatment of SNU539 cells with anti-SAS1B polyclonal antibodies caused growth arrest in the presence of active complement. A saporin-immunotoxin directed to SAS1B induced growth arrest and cell death.

Summary
Symbol	ASTL
Name	astacin-like metallo-endopeptidase (M12 family)
Aliases	ovastacin; SAS1B; sperm acrosomal SLLP1 binding; astacin-like metalloendopeptidase (M12 family); oocyte asta ......
Chromosomal Location	2q11.1
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 ASTL 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	ASTL
Name	astacin-like metallo-endopeptidase (M12 family)
Aliases	ovastacin; SAS1B; sperm acrosomal SLLP1 binding; astacin-like metalloendopeptidase (M12 family); oocyte asta ......
Chromosomal Location	2q11.1
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 ASTL 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	1
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0	1
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0	1
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-1.156	0.169
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.281	0.393
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-1.015	0.506
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0	1
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0	1
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0	1
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0	1
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	1
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.311	0.182

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of ASTL 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	0	0	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	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	2.7	1	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	3.4	0.3	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	9.5	0	9.5	0.492
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	15.4	0	15.4	0.482
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	ASTL
Name	astacin-like metallo-endopeptidase (M12 family)
Aliases	ovastacin; SAS1B; sperm acrosomal SLLP1 binding; astacin-like metalloendopeptidase (M12 family); oocyte asta ......
Chromosomal Location	2q11.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ASTL. 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	ASTL
Name	astacin-like metallo-endopeptidase (M12 family)
Aliases	ovastacin; SAS1B; sperm acrosomal SLLP1 binding; astacin-like metalloendopeptidase (M12 family); oocyte asta ......
Chromosomal Location	2q11.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ASTL. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ASTL. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	ASTL
Name	astacin-like metallo-endopeptidase (M12 family)
Aliases	ovastacin; SAS1B; sperm acrosomal SLLP1 binding; astacin-like metalloendopeptidase (M12 family); oocyte asta ......
Chromosomal Location	2q11.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ASTL. 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	ASTL
Name	astacin-like metallo-endopeptidase (M12 family)
Aliases	ovastacin; SAS1B; sperm acrosomal SLLP1 binding; astacin-like metalloendopeptidase (M12 family); oocyte asta ......
Chromosomal Location	2q11.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of ASTL expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	ASTL
Name	astacin-like metallo-endopeptidase (M12 family)
Aliases	ovastacin; SAS1B; sperm acrosomal SLLP1 binding; astacin-like metalloendopeptidase (M12 family); oocyte asta ......
Chromosomal Location	2q11.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between ASTL and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	ASTL
Name	astacin-like metallo-endopeptidase (M12 family)
Aliases	ovastacin; SAS1B; sperm acrosomal SLLP1 binding; astacin-like metalloendopeptidase (M12 family); oocyte asta ......
Chromosomal Location	2q11.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting ASTL collected from DrugBank database.

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

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