TISIDB

Summary
Symbol	YWHAZ
Name	tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta
Aliases	14-3-3-zeta; 14-3-3 zeta; 14-3-3 delta; YWHAD; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activatio ......
Chromosomal Location	8q22.3
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 Melanosome Note=Located to stage I to stage IV melanosomes.
Domain	PF00244 14-3-3 protein
Function	Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner.

> Gene Ontology [ TOP ]
Biological Process	GO:0001844 protein insertion into mitochondrial membrane involved in apoptotic signaling pathway GO:0006839 mitochondrial transport GO:0007006 mitochondrial membrane organization GO:0007030 Golgi organization GO:0007596 blood coagulation GO:0007599 hemostasis GO:0008637 apoptotic mitochondrial changes GO:0010608 posttranscriptional regulation of gene expression GO:0010821 regulation of mitochondrion organization GO:0010822 positive regulation of mitochondrion organization GO:0030168 platelet activation GO:0035794 positive regulation of mitochondrial membrane permeability GO:0043487 regulation of RNA stability GO:0043488 regulation of mRNA stability GO:0046902 regulation of mitochondrial membrane permeability GO:0048308 organelle inheritance GO:0048313 Golgi inheritance GO:0050817 coagulation GO:0050878 regulation of body fluid levels GO:0051204 protein insertion into mitochondrial membrane GO:0051205 protein insertion into membrane GO:0051640 organelle localization GO:0051645 Golgi localization GO:0051656 establishment of organelle localization GO:0051683 establishment of Golgi localization GO:0070585 protein localization to mitochondrion GO:0072655 establishment of protein localization to mitochondrion GO:0072657 protein localization to membrane GO:0090150 establishment of protein localization to membrane GO:0090168 Golgi reassembly GO:0090559 regulation of membrane permeability GO:0097345 mitochondrial outer membrane permeabilization GO:1900739 regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway GO:1900740 positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway GO:1901028 regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway GO:1901030 positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway GO:1902108 regulation of mitochondrial membrane permeability involved in apoptotic process GO:1902110 positive regulation of mitochondrial membrane permeability involved in apoptotic process GO:1902686 mitochondrial outer membrane permeabilization involved in programmed cell death GO:1903747 regulation of establishment of protein localization to mitochondrion GO:1903749 positive regulation of establishment of protein localization to mitochondrion GO:1903829 positive regulation of cellular protein localization GO:1904951 positive regulation of establishment of protein localization GO:2001233 regulation of apoptotic signaling pathway GO:2001235 positive regulation of apoptotic signaling pathway
Molecular Function	GO:0008134 transcription factor binding GO:0031625 ubiquitin protein ligase binding GO:0044389 ubiquitin-like protein ligase binding GO:0045296 cadherin binding GO:0050839 cell adhesion molecule binding GO:0098631 protein binding involved in cell adhesion GO:0098632 protein binding involved in cell-cell adhesion GO:0098641 cadherin binding involved in cell-cell adhesion
Cellular Component	GO:0005913 cell-cell adherens junction GO:0005924 cell-substrate adherens junction GO:0005925 focal adhesion GO:0030055 cell-substrate junction GO:0030659 cytoplasmic vesicle membrane GO:0042470 melanosome GO:0048770 pigment granule GO:0072562 blood microparticle

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04110 Cell cycle hsa04114 Oocyte meiosis hsa04151 PI3K-Akt signaling pathway hsa04390 Hippo signaling pathway
Reactome	R-HSA-111447: Activation of BAD and translocation to mitochondria R-HSA-114452: Activation of BH3-only proteins R-HSA-1280218: Adaptive Immune System R-HSA-109581: Apoptosis R-HSA-1640170: Cell Cycle R-HSA-69620: Cell Cycle Checkpoints R-HSA-75035: Chk1/Chk2(Cds1) mediated inactivation of Cyclin B R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-3769402: Deactivation of the beta-catenin transactivating complex R-HSA-69481: G2/M Checkpoints R-HSA-69473: G2/M DNA damage checkpoint R-HSA-430116: GP1b-IX-V activation signalling R-HSA-74160: Gene Expression R-HSA-212436: Generic Transcription Pathway R-HSA-109582: Hemostasis R-HSA-168256: Immune System R-HSA-512988: Interleukin-3, 5 and GM-CSF signaling R-HSA-109606: Intrinsic Pathway for Apoptosis R-HSA-450604: KSRP (KHSRP) binds and destabilizes mRNA R-HSA-199991: Membrane Trafficking R-HSA-76002: Platelet activation, signaling and aggregation R-HSA-5357801: Programmed Cell Death R-HSA-195258: RHO GTPase Effectors R-HSA-5625740: RHO GTPases activate PKNs R-HSA-392517: Rap1 signalling R-HSA-450531: Regulation of mRNA stability by proteins that bind AU-rich elements R-HSA-162582: Signal Transduction R-HSA-449147: Signaling by Interleukins R-HSA-194315: Signaling by Rho GTPases R-HSA-195721: Signaling by Wnt R-HSA-201681: TCF dependent signaling in response to WNT R-HSA-5628897: TP53 Regulates Metabolic Genes R-HSA-3700989: Transcriptional Regulation by TP53 R-HSA-1445148: Translocation of GLUT4 to the plasma membrane R-HSA-5653656: Vesicle-mediated transport

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04110 Cell cycle
hsa04114 Oocyte meiosis
hsa04151 PI3K-Akt signaling pathway
hsa04390 Hippo signaling pathway

Reactome

R-HSA-111447: Activation of BAD and translocation to mitochondria
R-HSA-114452: Activation of BH3-only proteins
R-HSA-1280218: Adaptive Immune System
R-HSA-109581: Apoptosis
R-HSA-1640170: Cell Cycle
R-HSA-69620: Cell Cycle Checkpoints
R-HSA-75035: Chk1/Chk2(Cds1) mediated inactivation of Cyclin B
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-3769402: Deactivation of the beta-catenin transactivating complex
R-HSA-69481: G2/M Checkpoints
R-HSA-69473: G2/M DNA damage checkpoint
R-HSA-430116: GP1b-IX-V activation signalling
R-HSA-74160: Gene Expression
R-HSA-212436: Generic Transcription Pathway
R-HSA-109582: Hemostasis
R-HSA-168256: Immune System
R-HSA-512988: Interleukin-3, 5 and GM-CSF signaling
R-HSA-109606: Intrinsic Pathway for Apoptosis
R-HSA-450604: KSRP (KHSRP) binds and destabilizes mRNA
R-HSA-199991: Membrane Trafficking
R-HSA-76002: Platelet activation, signaling and aggregation
R-HSA-5357801: Programmed Cell Death
R-HSA-195258: RHO GTPase Effectors
R-HSA-5625740: RHO GTPases activate PKNs
R-HSA-392517: Rap1 signalling
R-HSA-450531: Regulation of mRNA stability by proteins that bind AU-rich elements
R-HSA-162582: Signal Transduction
R-HSA-449147: Signaling by Interleukins
R-HSA-194315: Signaling by Rho GTPases
R-HSA-195721: Signaling by Wnt
R-HSA-201681: TCF dependent signaling in response to WNT
R-HSA-5628897: TP53 Regulates Metabolic Genes
R-HSA-3700989: Transcriptional Regulation by TP53
R-HSA-1445148: Translocation of GLUT4 to the plasma membrane
R-HSA-5653656: Vesicle-mediated transport

Summary
Symbol	YWHAZ
Name	tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta
Aliases	14-3-3-zeta; 14-3-3 zeta; 14-3-3 delta; YWHAD; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activatio ......
Chromosomal Location	8q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between YWHAZ 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	YWHAZ
Name	tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta
Aliases	14-3-3-zeta; 14-3-3 zeta; 14-3-3 delta; YWHAD; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activatio ......
Chromosomal Location	8q22.3
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 YWHAZ 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	logFC: -2.60; FDR: 0.02000	Resistant to T cell-mediated killing
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	STARS Score: 4.17; FDR: 0.014	Resistant to T cell-mediated killing
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	YWHAZ
Name	tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta
Aliases	14-3-3-zeta; 14-3-3 zeta; 14-3-3 delta; YWHAD; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activatio ......
Chromosomal Location	8q22.3
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 YWHAZ 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	-0.117	0.63
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.151	0.969
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.089	0.974
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.138	0.677
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.147	0.956
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.132	0.971
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.009	0.988
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.215	0.938
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.209	0.946
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.404	0.868
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	0.822	0.827
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.151	0.133

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of YWHAZ 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	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	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	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	0	0	0	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	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	6.2	4.9	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	25	0	25	0.364
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	YWHAZ
Name	tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta
Aliases	14-3-3-zeta; 14-3-3 zeta; 14-3-3 delta; YWHAD; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activatio ......
Chromosomal Location	8q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of YWHAZ. 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	YWHAZ
Name	tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta
Aliases	14-3-3-zeta; 14-3-3 zeta; 14-3-3 delta; YWHAD; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activatio ......
Chromosomal Location	8q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of YWHAZ. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by YWHAZ. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	YWHAZ
Name	tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta
Aliases	14-3-3-zeta; 14-3-3 zeta; 14-3-3 delta; YWHAD; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activatio ......
Chromosomal Location	8q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of YWHAZ. 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	YWHAZ
Name	tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta
Aliases	14-3-3-zeta; 14-3-3 zeta; 14-3-3 delta; YWHAD; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activatio ......
Chromosomal Location	8q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of YWHAZ expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	YWHAZ
Name	tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta
Aliases	14-3-3-zeta; 14-3-3 zeta; 14-3-3 delta; YWHAD; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activatio ......
Chromosomal Location	8q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between YWHAZ and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	YWHAZ
Name	tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta
Aliases	14-3-3-zeta; 14-3-3 zeta; 14-3-3 delta; YWHAD; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activatio ......
Chromosomal Location	8q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting YWHAZ collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting YWHAZ.

ID	Name	Drug Type	Targets	#Targets
DB12695	Phenethyl Isothiocyanate	Small Molecule	ACTA2, ACTB, ATP5B, ATP5I, ATP5L, CYB5B, DIABLO, FBXO41, HNRNPF, H ......	45

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