TISIDB

Summary
Symbol	A2ML1
Name	alpha-2-macroglobulin-like 1
Aliases	FLJ25179; CPAMD9; C3 and PZP-like, alpha-2-macroglobulin domain containing 9; C3 and PZP-like alpha-2-macrog ......
Chromosomal Location	12p13
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
Domain	PF00207 Alpha-2-macroglobulin family PF07678 A-macroglobulin complement component PF01835 MG2 domain PF07703 Alpha-2-macroglobulin family N-terminal region PF07677 A-macroglobulin receptor PF10569 Alpha-macro-globulin thiol-ester bond-forming region
Function	Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has a peptide stretch, called the 'bait region' which contains specific cleavage sites for different proteinases. When a proteinase cleaves the bait region, a conformational change is induced in the protein which traps the proteinase. The entrapped enzyme remains active against low molecular weight substrates (activity against high molecular weight substrates is greatly reduced). Following cleavage in the bait region a thioester bond is hydrolyzed and mediates the covalent binding of the protein to the proteinase (By similarity). Displays inhibitory activity against chymotrypsin, papain, thermolysin, subtilisin A and, to a lesser extent, elastase but not trypsin. May play an important role during desquamation by inhibiting extracellular proteases.

> Gene Ontology [ TOP ]
Biological Process	GO:0010466 negative regulation of peptidase activity GO:0010951 negative regulation of endopeptidase activity GO:0045861 negative regulation of proteolysis GO:0051346 negative regulation of hydrolase activity GO:0052547 regulation of peptidase activity GO:0052548 regulation of endopeptidase activity
Molecular Function	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	-

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

Summary
Symbol	A2ML1
Name	alpha-2-macroglobulin-like 1
Aliases	FLJ25179; CPAMD9; C3 and PZP-like, alpha-2-macroglobulin domain containing 9; C3 and PZP-like alpha-2-macrog ......
Chromosomal Location	12p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between A2ML1 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	A2ML1
Name	alpha-2-macroglobulin-like 1
Aliases	FLJ25179; CPAMD9; C3 and PZP-like, alpha-2-macroglobulin domain containing 9; C3 and PZP-like alpha-2-macrog ......
Chromosomal Location	12p13
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 A2ML1 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	A2ML1
Name	alpha-2-macroglobulin-like 1
Aliases	FLJ25179; CPAMD9; C3 and PZP-like, alpha-2-macroglobulin domain containing 9; C3 and PZP-like alpha-2-macrog ......
Chromosomal Location	12p13
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 A2ML1 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	0.652	0.302
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.022	0.983
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	1.159	0.201
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.398	0.424
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.212	0.914
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.643	0.769
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.131	0.885
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.61	0.674
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.363	0.812
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.039	0.925
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	-0.039	0.951
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.952	0.0288

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of A2ML1 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	11.1	4.1	7	0.339
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	11.1	5.1	6	0.373
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	19	0	19	0.113
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	23.1	0	23.1	0.223
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	12.5	-12.5	0.52
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	22.2	-22.2	0.505
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	10.5	3.7	6.8	0.393
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	13.6	0	13.6	0.279
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	7.1	-0.9	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	A2ML1
Name	alpha-2-macroglobulin-like 1
Aliases	FLJ25179; CPAMD9; C3 and PZP-like, alpha-2-macroglobulin domain containing 9; C3 and PZP-like alpha-2-macrog ......
Chromosomal Location	12p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of A2ML1. 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	A2ML1
Name	alpha-2-macroglobulin-like 1
Aliases	FLJ25179; CPAMD9; C3 and PZP-like, alpha-2-macroglobulin domain containing 9; C3 and PZP-like alpha-2-macrog ......
Chromosomal Location	12p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of A2ML1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by A2ML1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	A2ML1
Name	alpha-2-macroglobulin-like 1
Aliases	FLJ25179; CPAMD9; C3 and PZP-like, alpha-2-macroglobulin domain containing 9; C3 and PZP-like alpha-2-macrog ......
Chromosomal Location	12p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of A2ML1. 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	A2ML1
Name	alpha-2-macroglobulin-like 1
Aliases	FLJ25179; CPAMD9; C3 and PZP-like, alpha-2-macroglobulin domain containing 9; C3 and PZP-like alpha-2-macrog ......
Chromosomal Location	12p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of A2ML1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	A2ML1
Name	alpha-2-macroglobulin-like 1
Aliases	FLJ25179; CPAMD9; C3 and PZP-like, alpha-2-macroglobulin domain containing 9; C3 and PZP-like alpha-2-macrog ......
Chromosomal Location	12p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between A2ML1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	A2ML1
Name	alpha-2-macroglobulin-like 1
Aliases	FLJ25179; CPAMD9; C3 and PZP-like, alpha-2-macroglobulin domain containing 9; C3 and PZP-like alpha-2-macrog ......
Chromosomal Location	12p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting A2ML1 collected from DrugBank database.

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

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