TISIDB

Summary
Symbol	SYNPO2
Name	synaptopodin 2
Aliases	MYOPODIN; genethonin-2; Synaptopodin-2
Chromosomal Location	4q26
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	Nucleus Cytoplasm Cytoplasm, cytoskeleton Cytoplasm, myofibril, sarcomere, Z line Cell junction, focal adhesion Note=Shuttles between the nucleus and the cytoplasm in a differentiation-dependent and stress-induced fashion. In undifferentiated myoblasts strongly expressed in the nucleus, after induction of myotube differentiation is located to both nucleus and cytoplasm along acting filaments, and in differentiated myotubes is located at the Z lines. Upon stress redistributes from cytoplasm of myoblasts and myotubes to the nucleus. Nuclear import is KPNA2-dependent and promoted by phosphorylation by PKA and/or CaMK2, and inhibition of calcineurin. The nuclear export is XPO1-dependent (By similarity). Localized in a fiber-like pattern, partly overlapping with filamentous actin (PubMed:18371299). ; SUBCELLULAR LOCATION: Isoform 1: Cytoplasm, cytoskeleton Note=Localizes to induced actin bundles with contiguous staining. ; SUBCELLULAR LOCATION: Isoform 2: Cytoplasm, cytoskeleton Note=Localizes to induced actin bundles with punctuate staining. ; SUBCELLULAR LOCATION: Isoform 3: Cytoplasm, cytoskeleton Note=Localizes to induced irregular actin bundles with contiguous and punctuated staining. ; SUBCELLULAR LOCATION: Isoform 4: Cytoplasm, cytoskeleton Note=Localizes to induced actin bundles with punctuate staining. ; SUBCELLULAR LOCATION: Isoform 5: Cytoplasm, cytoskeleton Note=Localizes to induced actin bundles with contiguous staining.
Domain	PF00595 PDZ domain (Also known as DHR or GLGF)
Function	Has an actin-binding and actin-bundling activity. Can induce the formation of F-actin networks in an isoform-specific manner (PubMed:24005909, PubMed:23225103). At the sarcomeric Z lines is proposed to act as adapter protein that links nascent myofibers to the sarcolemma via ZYX and may play a role in early assembly and stabilization of the Z lines. Involved in autophagosome formation. May play a role in chaperone-assisted selective autophagy (CASA) involved in Z lines maintenance in striated muscle under mechanical tension; may link the client-processing CASA chaperone machinery to a membrane-tethering and fusion complex providing autophagosome membranes (By similarity). Involved in regulation of cell migration (PubMed:22915763, PubMed:25883213). May be a tumor suppressor (PubMed:16885336). ; FUNCTION: Isoform 1: Involved in regulation of cell migration. Can induce formation of thick, irregular actin bundles in the cell body. ; FUNCTION: Isoform 2: Involved in regulation of cell migration. Can induce long, well-organized actin bundles frequently orientated in parallel along the long axis of the cell showing characteristics of contractile ventral stress fibers. ; FUNCTION: Isoform 3: Involved in regulation of cell migration. Can induce an amorphous actin meshwork throughout the cell body containing a mixture of long and short, randomly organized thick and thin actin bundles. ; FUNCTION: Isoform 4: Can induce long, well-organized actin bundles frequently orientated in parallel along the long axis of the cell showing characteristics of contractile ventral stress fibers. ; FUNCTION: Isoform 5: Involved in regulation of cell migration in part dependent on the Rho-ROCK cascade; can promote formation of nascent focal adhesions, actin bundles at the leading cell edge and lamellipodia (PubMed:22915763, PubMed:25883213). Can induce formation of thick, irregular actin bundles in the cell body; the induced actin network is associated with enhanced cell migration in vitro.

> Gene Ontology [ TOP ]
Biological Process	GO:0007015 actin filament organization GO:0032231 regulation of actin filament bundle assembly GO:0032233 positive regulation of actin filament bundle assembly GO:0032956 regulation of actin cytoskeleton organization GO:0032970 regulation of actin filament-based process GO:0044089 positive regulation of cellular component biogenesis GO:0051017 actin filament bundle assembly GO:0051493 regulation of cytoskeleton organization GO:0051495 positive regulation of cytoskeleton organization GO:0061572 actin filament bundle organization
Molecular Function	GO:0003779 actin binding GO:0042805 actinin binding GO:0051371 muscle alpha-actinin binding GO:0051393 alpha-actinin binding GO:0071889 14-3-3 protein binding
Cellular Component	GO:0005924 cell-substrate adherens junction GO:0005925 focal adhesion GO:0015629 actin cytoskeleton GO:0030016 myofibril GO:0030017 sarcomere GO:0030018 Z disc GO:0030055 cell-substrate junction GO:0031674 I band GO:0043292 contractile fiber GO:0044449 contractile fiber part

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

Summary
Symbol	SYNPO2
Name	synaptopodin 2
Aliases	MYOPODIN; genethonin-2; Synaptopodin-2
Chromosomal Location	4q26
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between SYNPO2 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	SYNPO2
Name	synaptopodin 2
Aliases	MYOPODIN; genethonin-2; Synaptopodin-2
Chromosomal Location	4q26
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 SYNPO2 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	SYNPO2
Name	synaptopodin 2
Aliases	MYOPODIN; genethonin-2; Synaptopodin-2
Chromosomal Location	4q26
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 SYNPO2 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	-0.272	0.489
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.315	0.719
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.229	0.7
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.335	0.744
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.058	0.987
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.686	0.872
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.845	0.119
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.853	0.55
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.922	0.536
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.747	0.517
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	2.179	0.128
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.502	0.0233

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of SYNPO2 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	22.2	1.4	20.8	0.00141
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	22.2	1.7	20.5	0.00342
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	9.5	11.8	-2.3	1
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	7.7	18.2	-10.5	0.576
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	5.3	0	5.3	0.507
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	0	9.1	0.519
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	SYNPO2
Name	synaptopodin 2
Aliases	MYOPODIN; genethonin-2; Synaptopodin-2
Chromosomal Location	4q26
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of SYNPO2. 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	SYNPO2
Name	synaptopodin 2
Aliases	MYOPODIN; genethonin-2; Synaptopodin-2
Chromosomal Location	4q26
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of SYNPO2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by SYNPO2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	SYNPO2
Name	synaptopodin 2
Aliases	MYOPODIN; genethonin-2; Synaptopodin-2
Chromosomal Location	4q26
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of SYNPO2. 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	SYNPO2
Name	synaptopodin 2
Aliases	MYOPODIN; genethonin-2; Synaptopodin-2
Chromosomal Location	4q26
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of SYNPO2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	SYNPO2
Name	synaptopodin 2
Aliases	MYOPODIN; genethonin-2; Synaptopodin-2
Chromosomal Location	4q26
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between SYNPO2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	SYNPO2
Name	synaptopodin 2
Aliases	MYOPODIN; genethonin-2; Synaptopodin-2
Chromosomal Location	4q26
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting SYNPO2 collected from DrugBank database.

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

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