TISIDB

Summary
Symbol	STAT5A
Name	signal transducer and activator of transcription 5A
Aliases
Chromosomal Location	17q11.2
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 Nucleus Note=Translocated into the nucleus in response to phosphorylation.
Domain	PF00017 SH2 domain PF01017 STAT protein PF02864 STAT protein PF02865 STAT protein
Function	Carries out a dual function: signal transduction and activation of transcription. Mediates cellular responses to the cytokine KITLG/SCF and other growth factors. Mediates cellular responses to ERBB4. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Binds to the GAS element and activates PRL-induced transcription. Regulates the expression of milk proteins during lactation.

> Gene Ontology [ TOP ]
Biological Process	GO:0000255 allantoin metabolic process GO:0001667 ameboidal-type cell migration GO:0001935 endothelial cell proliferation GO:0001936 regulation of endothelial cell proliferation GO:0001938 positive regulation of endothelial cell proliferation GO:0006101 citrate metabolic process GO:0006103 2-oxoglutarate metabolic process GO:0006105 succinate metabolic process GO:0006107 oxaloacetate metabolic process GO:0006520 cellular amino acid metabolic process GO:0006549 isoleucine metabolic process GO:0006573 valine metabolic process GO:0006600 creatine metabolic process GO:0006631 fatty acid metabolic process GO:0006790 sulfur compound metabolic process GO:0007259 JAK-STAT cascade GO:0007589 body fluid secretion GO:0007595 lactation GO:0009081 branched-chain amino acid metabolic process GO:0009755 hormone-mediated signaling pathway GO:0010594 regulation of endothelial cell migration GO:0010595 positive regulation of endothelial cell migration GO:0010631 epithelial cell migration GO:0010632 regulation of epithelial cell migration GO:0010634 positive regulation of epithelial cell migration GO:0018108 peptidyl-tyrosine phosphorylation GO:0018212 peptidyl-tyrosine modification GO:0019530 taurine metabolic process GO:0030335 positive regulation of cell migration GO:0030879 mammary gland development GO:0032941 secretion by tissue GO:0035264 multicellular organism growth GO:0038161 prolactin signaling pathway GO:0040014 regulation of multicellular organism growth GO:0040017 positive regulation of locomotion GO:0043434 response to peptide hormone GO:0043534 blood vessel endothelial cell migration GO:0043535 regulation of blood vessel endothelial cell migration GO:0043536 positive regulation of blood vessel endothelial cell migration GO:0043542 endothelial cell migration GO:0043648 dicarboxylic acid metabolic process GO:0046449 creatinine metabolic process GO:0048638 regulation of developmental growth GO:0048732 gland development GO:0050673 epithelial cell proliferation GO:0050678 regulation of epithelial cell proliferation GO:0050679 positive regulation of epithelial cell proliferation GO:0050878 regulation of body fluid levels GO:0051272 positive regulation of cellular component movement GO:0060396 growth hormone receptor signaling pathway GO:0060397 JAK-STAT cascade involved in growth hormone signaling pathway GO:0060416 response to growth hormone GO:0071375 cellular response to peptide hormone stimulus GO:0071378 cellular response to growth hormone stimulus GO:0071417 cellular response to organonitrogen compound GO:0072338 cellular lactam metabolic process GO:0072350 tricarboxylic acid metabolic process GO:0090130 tissue migration GO:0090132 epithelium migration GO:0097696 STAT cascade GO:1901605 alpha-amino acid metabolic process GO:1901652 response to peptide GO:1901653 cellular response to peptide GO:2000147 positive regulation of cell motility
Molecular Function	GO:0004713 protein tyrosine kinase activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04012 ErbB signaling pathway hsa04630 Jak-STAT signaling pathway hsa04917 Prolactin signaling pathway
Reactome	R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-1643685: Disease R-HSA-5663202: Diseases of signal transduction R-HSA-186763: Downstream signal transduction R-HSA-1839124: FGFR1 mutant receptor activation R-HSA-982772: Growth hormone receptor signaling R-HSA-168256: Immune System R-HSA-451927: Interleukin-2 signaling R-HSA-512988: Interleukin-3, 5 and GM-CSF signaling R-HSA-1266695: Interleukin-7 signaling R-HSA-1251985: Nuclear signaling by ERBB4 R-HSA-1170546: Prolactin receptor signaling R-HSA-162582: Signal Transduction R-HSA-1236394: Signaling by ERBB4 R-HSA-1226099: Signaling by FGFR in disease R-HSA-5655302: Signaling by FGFR1 in disease R-HSA-449147: Signaling by Interleukins R-HSA-2586552: Signaling by Leptin R-HSA-186797: Signaling by PDGF R-HSA-1433557: Signaling by SCF-KIT R-HSA-1839117: Signaling by cytosolic FGFR1 fusion mutants

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04012 ErbB signaling pathway
hsa04630 Jak-STAT signaling pathway
hsa04917 Prolactin signaling pathway

Reactome

R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-1643685: Disease
R-HSA-5663202: Diseases of signal transduction
R-HSA-186763: Downstream signal transduction
R-HSA-1839124: FGFR1 mutant receptor activation
R-HSA-982772: Growth hormone receptor signaling
R-HSA-168256: Immune System
R-HSA-451927: Interleukin-2 signaling
R-HSA-512988: Interleukin-3, 5 and GM-CSF signaling
R-HSA-1266695: Interleukin-7 signaling
R-HSA-1251985: Nuclear signaling by ERBB4
R-HSA-1170546: Prolactin receptor signaling
R-HSA-162582: Signal Transduction
R-HSA-1236394: Signaling by ERBB4
R-HSA-1226099: Signaling by FGFR in disease
R-HSA-5655302: Signaling by FGFR1 in disease
R-HSA-449147: Signaling by Interleukins
R-HSA-2586552: Signaling by Leptin
R-HSA-186797: Signaling by PDGF
R-HSA-1433557: Signaling by SCF-KIT
R-HSA-1839117: Signaling by cytosolic FGFR1 fusion mutants

Summary
Symbol	STAT5A
Name	signal transducer and activator of transcription 5A
Aliases
Chromosomal Location	17q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between STAT5A 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

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Literatures describing the relation between STAT5A and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
27465917	B-cell Lymphoma	Promote immunity (NK cell function)	IL-15 augmented mammalian target of rapamycin (mTOR) signaling, which correlated with increased expression of genes related to cell metabolism and respiration. Moreover, mTOR-independent STAT-5 signaling contributed to improved NK-cell function during cytokine activation but not following cytokine withdrawal. Finally, expression of IL-15 correlated with cytolytic immune functions in patients with B-cell lymphoma and favorable clinical outcome. These findings highlight the importance of mTOR-regulated metabolic processes for immune cell functions and argue for implementation of IL-15 in adoptive NK-cell cancer therapy.
16169484	Melanoma	Resistant to immunotherapy	Significantly, the knockdown of STAT5 in interferon-resistant melanoma cells restored the growth-inhibitory response to IFNalpha. The overexpressed STAT5 diminished IFNalpha-triggered STAT1 activation, most evidently through upregulation of the inhibitor of cytokine-signaling CIS. Our data demonstrate that overexpression and activation of STAT5 enable melanoma cells to overcome cytokine-mediated antiproliferative signaling.
25125657	melanoma	Promote immunity	Mechanistically, in CD8(+) T cells, exposure to CCDC134 promoted cell proliferation through the JAK3-STAT5 pathway, a classic feature of many cytokines of the common gamma-chain (gamma(c)) cytokine receptor family.
21796616	Melanoma	Promote immunity	The production of multiple cytokines (IFNgamma, TNFalpha, IL-2) and upregulation of LAMP-1 (CD107a) by tumor (Melan-A/MART-1) specific T-cells was comparable to virus (EBV-BMLF1) specific CD8 T-cells. Furthermore, phosphorylation of STAT1, STAT5 and ERK1/2, and expression of CD3 zeta chain were similar in tumor- and virus-specific T-cells, demonstrating functional signaling pathways.

Summary
Symbol	STAT5A
Name	signal transducer and activator of transcription 5A
Aliases
Chromosomal Location	17q11.2
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 STAT5A 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	STAT5A
Name	signal transducer and activator of transcription 5A
Aliases
Chromosomal Location	17q11.2
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 STAT5A 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	0.322	0.261
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.291	0.885
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.346	0.813
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.025	0.947
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.515	0.817
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.709	0.807
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.022	0.953
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.179	0.914
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.371	0.854
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.006	0.476
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	1.125	0.591
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.036	0.699

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of STAT5A in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% 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	11.1	11.1	0.0181
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	11.1	11.1	0.0286
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
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	11.1	11.1	0.36
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	20	0.357
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	2.6	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	4.5	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	STAT5A
Name	signal transducer and activator of transcription 5A
Aliases
Chromosomal Location	17q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of STAT5A. 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	STAT5A
Name	signal transducer and activator of transcription 5A
Aliases
Chromosomal Location	17q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of STAT5A. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by STAT5A. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	STAT5A
Name	signal transducer and activator of transcription 5A
Aliases
Chromosomal Location	17q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of STAT5A. 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	STAT5A
Name	signal transducer and activator of transcription 5A
Aliases
Chromosomal Location	17q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of STAT5A expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	STAT5A
Name	signal transducer and activator of transcription 5A
Aliases
Chromosomal Location	17q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between STAT5A and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	STAT5A
Name	signal transducer and activator of transcription 5A
Aliases
Chromosomal Location	17q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting STAT5A collected from DrugBank database.

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

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