TISIDB

Summary
Symbol	FKBP4
Name	FK506 binding protein 4, 59kDa
Aliases	FKBP59; FKBP52; FK506-binding protein 4 (59kD); HBI; HSP binding immunophilin; T-cell FK506-binding protein, ......
Chromosomal Location	12p13.33
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, cytosol Mitochondrion Nucleus Cytoplasm, cytoskeleton Cell projection, axon Note=Shuttles from mitochondria to nucleus; co-localizes in mitochondria with the glucocorticoid receptor (PubMed:21730050). Colocalized with MAPT/TAU in the distal part of the primary cortical neurons (By similarity).
Domain	PF00254 FKBP-type peptidyl-prolyl cis-trans isomerase PF00515 Tetratricopeptide repeat PF07719 Tetratricopeptide repeat
Function	Immunophilin protein with PPIase and co-chaperone activities. Component of steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). May play a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors between cytoplasm and nuclear compartments. The isomerase activity controls neuronal growth cones via regulation of TRPC1 channel opening. Acts also as a regulator of microtubule dynamics by inhibiting MAPT/TAU ability to promote microtubule assembly. May have a protective role against oxidative stress in mitochondria.

> Gene Ontology [ TOP ]
Biological Process	GO:0000041 transition metal ion transport GO:0000226 microtubule cytoskeleton organization GO:0000413 protein peptidyl-prolyl isomerization GO:0001655 urogenital system development GO:0006457 protein folding GO:0006463 steroid hormone receptor complex assembly GO:0006825 copper ion transport GO:0007548 sex differentiation GO:0007565 female pregnancy GO:0007566 embryo implantation GO:0009266 response to temperature stimulus GO:0009408 response to heat GO:0009755 hormone-mediated signaling pathway GO:0010639 negative regulation of organelle organization GO:0010721 negative regulation of cell development GO:0010975 regulation of neuron projection development GO:0010977 negative regulation of neuron projection development GO:0018208 peptidyl-proline modification GO:0030518 intracellular steroid hormone receptor signaling pathway GO:0030521 androgen receptor signaling pathway GO:0030522 intracellular receptor signaling pathway GO:0030850 prostate gland development GO:0031109 microtubule polymerization or depolymerization GO:0031110 regulation of microtubule polymerization or depolymerization GO:0031111 negative regulation of microtubule polymerization or depolymerization GO:0031113 regulation of microtubule polymerization GO:0031115 negative regulation of microtubule polymerization GO:0031333 negative regulation of protein complex assembly GO:0031345 negative regulation of cell projection organization GO:0031503 protein complex localization GO:0032271 regulation of protein polymerization GO:0032272 negative regulation of protein polymerization GO:0032886 regulation of microtubule-based process GO:0034605 cellular response to heat GO:0043254 regulation of protein complex assembly GO:0043401 steroid hormone mediated signaling pathway GO:0044706 multi-multicellular organism process GO:0045665 negative regulation of neuron differentiation GO:0046661 male sex differentiation GO:0046785 microtubule polymerization GO:0048545 response to steroid hormone GO:0048608 reproductive structure development GO:0048732 gland development GO:0050768 negative regulation of neurogenesis GO:0051258 protein polymerization GO:0051493 regulation of cytoskeleton organization GO:0051494 negative regulation of cytoskeleton organization GO:0051961 negative regulation of nervous system development GO:0061077 chaperone-mediated protein folding GO:0061458 reproductive system development GO:0070507 regulation of microtubule cytoskeleton organization GO:0071383 cellular response to steroid hormone stimulus GO:0071396 cellular response to lipid GO:0071407 cellular response to organic cyclic compound GO:1900034 regulation of cellular response to heat
Molecular Function	GO:0003755 peptidyl-prolyl cis-trans isomerase activity GO:0005525 GTP binding GO:0005527 macrolide binding GO:0005528 FK506 binding GO:0008144 drug binding GO:0016853 isomerase activity GO:0016859 cis-trans isomerase activity GO:0019001 guanyl nucleotide binding GO:0030674 protein binding, bridging GO:0031072 heat shock protein binding GO:0032561 guanyl ribonucleotide binding GO:0032767 copper-dependent protein binding GO:0035257 nuclear hormone receptor binding GO:0035258 steroid hormone receptor binding GO:0035259 glucocorticoid receptor binding GO:0048156 tau protein binding GO:0051219 phosphoprotein binding GO:0051427 hormone receptor binding GO:0060090 binding, bridging
Cellular Component	GO:0005874 microtubule GO:0030424 axon GO:0030426 growth cone GO:0030427 site of polarized growth GO:0033267 axon part GO:0043025 neuronal cell body GO:0044295 axonal growth cone GO:0044297 cell body

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04915 Estrogen signaling pathway
Reactome	R-HSA-3371568: Attenuation phase R-HSA-3371556: Cellular response to heat stress R-HSA-2262752: Cellular responses to stress R-HSA-3371511: HSF1 activation R-HSA-3371571: HSF1-dependent transactivation R-HSA-3371453: Regulation of HSF1-mediated heat shock response

Summary
Symbol	FKBP4
Name	FK506 binding protein 4, 59kDa
Aliases	FKBP59; FKBP52; FK506-binding protein 4 (59kD); HBI; HSP binding immunophilin; T-cell FK506-binding protein, ......
Chromosomal Location	12p13.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between FKBP4 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 ]

Literatures describing the relation between FKBP4 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
25132599	glioblastoma	Promote immunity	Knockdown of FKBP52 and treatment with the FK-binding immunosuppressant FK506 enhanced TDO expression and activity in glioblastoma cells.

Summary
Symbol	FKBP4
Name	FK506 binding protein 4, 59kDa
Aliases	FKBP59; FKBP52; FK506-binding protein 4 (59kD); HBI; HSP binding immunophilin; T-cell FK506-binding protein, ......
Chromosomal Location	12p13.33
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 FKBP4 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	FKBP4
Name	FK506 binding protein 4, 59kDa
Aliases	FKBP59; FKBP52; FK506-binding protein 4 (59kD); HBI; HSP binding immunophilin; T-cell FK506-binding protein, ......
Chromosomal Location	12p13.33
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 FKBP4 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	-0.266	0.369
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.233	0.925
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.292	0.873
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.422	0.232
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.497	0.825
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.33	0.91
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.318	0.519
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.07	0.971
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.628	0.77
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.244	0.895
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	0.531	0.849
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.288	0.00517

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of FKBP4 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	0	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	5.9	-5.9	0.447
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	16.7	-16.7	0.429
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	FKBP4
Name	FK506 binding protein 4, 59kDa
Aliases	FKBP59; FKBP52; FK506-binding protein 4 (59kD); HBI; HSP binding immunophilin; T-cell FK506-binding protein, ......
Chromosomal Location	12p13.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of FKBP4. 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	FKBP4
Name	FK506 binding protein 4, 59kDa
Aliases	FKBP59; FKBP52; FK506-binding protein 4 (59kD); HBI; HSP binding immunophilin; T-cell FK506-binding protein, ......
Chromosomal Location	12p13.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of FKBP4. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by FKBP4. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	FKBP4
Name	FK506 binding protein 4, 59kDa
Aliases	FKBP59; FKBP52; FK506-binding protein 4 (59kD); HBI; HSP binding immunophilin; T-cell FK506-binding protein, ......
Chromosomal Location	12p13.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of FKBP4. 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	FKBP4
Name	FK506 binding protein 4, 59kDa
Aliases	FKBP59; FKBP52; FK506-binding protein 4 (59kD); HBI; HSP binding immunophilin; T-cell FK506-binding protein, ......
Chromosomal Location	12p13.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of FKBP4 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	FKBP4
Name	FK506 binding protein 4, 59kDa
Aliases	FKBP59; FKBP52; FK506-binding protein 4 (59kD); HBI; HSP binding immunophilin; T-cell FK506-binding protein, ......
Chromosomal Location	12p13.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between FKBP4 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	FKBP4
Name	FK506 binding protein 4, 59kDa
Aliases	FKBP59; FKBP52; FK506-binding protein 4 (59kD); HBI; HSP binding immunophilin; T-cell FK506-binding protein, ......
Chromosomal Location	12p13.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting FKBP4 collected from DrugBank database.

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

Browse FKBP4