TISIDB

Summary
Symbol	PDLIM4
Name	PDZ and LIM domain 4
Aliases	RIL; LIM protein RIL; reversion-induced LIM protein; PDZ and LIM domain protein 4
Chromosomal Location	5q31.1
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	Isoform 1: Cytoplasm, cytoskeleton Nucleus Cytoplasm Cytoplasm, perinuclear region Cell projection, lamellipodium Cell projection, dendritic spine Early endosome membrane Peripheral membrane protein Cytoplasmic side Recycling endosome membrane Peripheral membrane protein Cytoplasmic side Cell junction, synapse, synaptosome Note=Localizes to actin stress fibers in nonmuscle cells. Colocalizes with GRIA1 in early endosomes. Enriched in numerous but not all spine-like structures along dendritic branches. Colocalizes with actin and enriched at sites containing larger amounts of actin and alpha-actinin. Targeted efficiently to spines via its PDZ domain-mediated interaction with the alpha-actinin/actin cytoskeletal complex. Localizes to synaptosomes in brain (By similarity). Colocalizes with F-actin (PubMed:10826496). Colocalizes with TRIP6 at cell-cell contacts and lamellipodia (PubMed:10826496). In the cytoplasm, displays a fibrillar pattern with characteristic thick fibers and occasional clusters. Colocalizes with the actin stress fibers. Oxidative stress induces redistribution from cytoskeleton to cytosol (PubMed:21636573). Colocalizes with SRC at the perinuclear region, but not at focal adhesions (PubMed:19307596). ; SUBCELLULAR LOCATION: Isoform 2: Cytoplasm Note=Stains more diffusely in the cytoplasm with thin fibers forming a dense mesh-like pattern.
Domain	PF15936 Domain of unknown function (DUF4749) PF00412 LIM domain PF00595 PDZ domain (Also known as DHR or GLGF)
Function	Isoform 1: Suppresses SRC activation by recognizing and binding to active SRC and facilitating PTPN13-mediated dephosphorylation of SRC 'Tyr-419' leading to its inactivation. Inactivated SRC dissociates from this protein allowing the initiation of a new SRC inactivation cycle (PubMed:19307596). Involved in reorganization of the actin cytoskeleton (PubMed:21636573). In nonmuscle cells, binds to ACTN1 (alpha-actinin-1), increases the affinity of ACTN1 to F-actin (filamentous actin), and promotes formation of actin stress fibers. Involved in regulation of the synaptic AMPA receptor transport in dendritic spines of hippocampal pyramidal neurons directing the receptors toward an insertion at the postsynaptic membrane. Links endosomal surface-internalized GRIA1-containing AMPA receptors to the alpha-actinin/actin cytoskeleton. Increases AMPA receptor-mediated excitatory postsynaptic currents in neurons (By similarity). ; FUNCTION: Isoform 2: Involved in reorganization of the actin cytoskeleton and in regulation of cell migration. In response to oxidative stress, binds to NQO1, which stabilizes it and protects it from ubiquitin-independent degradation by the core 20S proteasome. Stabilized protein is able to heterodimerize with isoform 1 changing the subcellular location of it from cytoskeleton and nuclei to cytosol, leading to loss of isoforms 1 ability to induce formation of actin stress fibers. Counteracts the effects produced by isoform 1 on organization of actin cytoskeleton and cell motility to fine-tune actin cytoskeleton rearrangement and to attenuate cell migration.

> Gene Ontology [ TOP ]
Biological Process	-
Molecular Function	-
Cellular Component	-

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

Summary
Symbol	PDLIM4
Name	PDZ and LIM domain 4
Aliases	RIL; LIM protein RIL; reversion-induced LIM protein; PDZ and LIM domain protein 4
Chromosomal Location	5q31.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between PDLIM4 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	PDLIM4
Name	PDZ and LIM domain 4
Aliases	RIL; LIM protein RIL; reversion-induced LIM protein; PDZ and LIM domain protein 4
Chromosomal Location	5q31.1
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 PDLIM4 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	PDLIM4
Name	PDZ and LIM domain 4
Aliases	RIL; LIM protein RIL; reversion-induced LIM protein; PDZ and LIM domain protein 4
Chromosomal Location	5q31.1
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 PDLIM4 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	-0.052	0.943
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.724	0.67
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.438	0.746
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.697	0.198
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.154	0.496
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.122	0.954
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.623	0.399
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.033	0.978
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	1.306	0.303
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.084	0.947
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	-0.108	0.948
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.671	0.000436

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of PDLIM4 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	0	0	0	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	0	0	0	1
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	0	0	0	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	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	PDLIM4
Name	PDZ and LIM domain 4
Aliases	RIL; LIM protein RIL; reversion-induced LIM protein; PDZ and LIM domain protein 4
Chromosomal Location	5q31.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PDLIM4. 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	PDLIM4
Name	PDZ and LIM domain 4
Aliases	RIL; LIM protein RIL; reversion-induced LIM protein; PDZ and LIM domain protein 4
Chromosomal Location	5q31.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PDLIM4. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PDLIM4. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	PDLIM4
Name	PDZ and LIM domain 4
Aliases	RIL; LIM protein RIL; reversion-induced LIM protein; PDZ and LIM domain protein 4
Chromosomal Location	5q31.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PDLIM4. 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	PDLIM4
Name	PDZ and LIM domain 4
Aliases	RIL; LIM protein RIL; reversion-induced LIM protein; PDZ and LIM domain protein 4
Chromosomal Location	5q31.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of PDLIM4 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	PDLIM4
Name	PDZ and LIM domain 4
Aliases	RIL; LIM protein RIL; reversion-induced LIM protein; PDZ and LIM domain protein 4
Chromosomal Location	5q31.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between PDLIM4 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	PDLIM4
Name	PDZ and LIM domain 4
Aliases	RIL; LIM protein RIL; reversion-induced LIM protein; PDZ and LIM domain protein 4
Chromosomal Location	5q31.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting PDLIM4 collected from DrugBank database.

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

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