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FLASH GENE

Symbol

STAT5B

contributors: mct/npt - updated : 24-02-2018

HGNC name	signal transducer and activator of transcription 5B
HGNC id	11367

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	GHIS3 growth hormone insensitivity 3
Location	17q21.2      Physical location : 40.351.195 - 40.428.424
Synonym name	transcription factor STAT5B
Synonym symbol(s)	STAT5

DNA

TYPE	functioning gene
STRUCTURE	77.23 kb     19 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	alternative promoter
	cytosine-phosphate-guanine/HTF
text structure	an alternative tissue specific promoter

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_012448 19 - 5171 NP_036580 - 787 - Lin (1996)

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine neuroendocrine pituitary     highly Lymphoid/Immune lymph node       highly   thymus       highly Reproductive male system testis

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol   fibroblast Lymphoid/Immune lymphocyte

cell lineage
cell lines
fluid/secretion	lymph

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a N terminus conserved domain,the coiled coil domain,
	the DNA binding domain,a linker region,
	a SRC homology domain 2 (SH2), a critical site of tyrosine phosphorylation
	the carboxy-terminal transactivation domain

mono polymer

homomer , heteromer , dimer

HOMOLOGY

Homologene

FAMILY

STAT family of transcription factors

CATEGORY

immunity/defense , transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus
text	translocated into the nucleus in response to phosphorylation

basic FUNCTION	regulator of transcription having a dual function: signal transduction and activation of transcription
	functioning to transduce signals from cytokines to the nucleus where it regulates gene expression
	playing a crucial role in mammary epithelium displaying reciprocal activation kinetics during pregnancy, lactation and involution
	signal transducer and activator of transcription 5A and 5B (STAT5A/B) is critical for the viability of prostate cancer cells (Tan 2008)
	potential role of the STAT5B-RUNX interaction in lymphocyte development
	STAT5A/B directs GM-CSF signaling through the regulation of proliferation and survival genes (Kimura 2009)
	critical role of STAT5A, STAT5B transcription factor tetramerization for cytokine responses and normal immune function
	STAT5B and STAT5A act partly as non-redundant transcription factors and that STAT5B is more critical for Treg maintenance and function in humans

CELLULAR PROCESS

nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

text	immune response

PATHWAY

metabolism

signaling

signal transduction

a component	homodimerizing or heterodimerizing with STAT5A
	PLCB3 form the multimolecular SPS complex together with PTPN6 and STAT5

INTERACTION

DNA

RNA

small molecule

protein	binds to the NCAM2 intron in the NKL natural killer cell line (this binding is induced by cytokines that activate STAT5B)
	physically interacts with RUNX1, RUNX2 and RUNX3
	BCL10 is an IL2-independent STAT5B target gene
	SLC30A2 participates in zinc transport into pancreatic zymogen granules through a glucocorticoid pathway requiring glucocorticoid receptor and STAT5, and zinc-regulated signaling pathways requiring MTF1
	functions for GAB2 in hematopoiesis in a manner that is non-redundant with STAT5B
	LYN/PLCB3-mediated regulatory mechanism of PTPN6 and STAT5B activities
	DUSP4 suppresses CD4(+) T-cell proliferation through novel regulations in STAT5B phosphorylation and IL2 signaling
	key regulator of lymphoid development, that is modified by SUMO-2 and is specifically regulated by SENP1
	crucial role of SENP1 in the regulation of STAT5B activation during early lymphoid development
	elevated SKIL promotes STAT5B signaling by enhancing its stability, thereby sharply increasing the activity of prolactin signaling at the onset of lactation
	STAT5B, but not STAT5A, was upregulated in PDZRN3-depleted cells at both mRNA and protein levels
	STAT3 increases expression of BCL6 and enhances recruitment of RNA polymerase II phosphorylated at a site associated with transcriptional initiation, but STAT5B represses BCL6 expression below basal levels and decreases the association of RNA polymerase II at the gene
	SIRT1 negatively regulates GH-induced STAT5A, STAT5B phosphorylation and IGF1 production via deacetylation of STAT5A, STAT5B in the liver
	SIRT1 deacetylates STAT5B by direct interaction
	NFIB-STAT5 modules, possibly in conjunction with other transcription factors, control cell-specific genetic programs
	STAT5B transcription factor directly bound to the promoter and an intronic region of the GATA2 gene, and the STAT5B-GATA2 pathway is critical for basophil and mast cell differentiation and maintenance
	control of CD8 T cell proliferation and terminal differentiation by active STAT5B and CDKN2A/CDKN2B
	DUSP4 regulates STAT5B protein stability and helper T cell polarization
	STAT5B was the target of GRAMD1A, GRAMD1A regulated the target genes of STAT5B and the transcriptional activity of STAT5B
	RGS4 is implicated in opioid dependent neuronal differentiation and neurite outgrowth via a "non-canonical" signaling pathway regulating STAT5B-directed responses
	BRD9-STAT5 axis as critical for leukemia maintenance

cell & other

T cell receptor and stimulating T cell proliferation

REGULATION

activated by	interleukin 2 and other cytokines
	GH, strongly activated by prolactin (PRL) towards the end of pregnancy, persists in an activated state during lactation, and is rapidly inactivated after cessation of suckling

repressed by

NCOR2

Other	its signaling can be modulated by its coupling with a specific subset of G protein subunits, revealing a novel signaling mechanism for the transcriptional regulation of STAT5B-dependent genes (Georganta 2010)
	regulated by SRC (SRC may regulate STAT5B in the intracellular signalling pathway important for the proliferation of normal human B lymphocytes)(Cayer 2009)

ASSOCIATED DISORDERS

corresponding disease(s)

GHIS3

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral fusion       with RARA, 5' - STAT5B - RARA - 3', in a small subset of acute promyelocytic leukemias

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer hemopathy   inhibitors that disrupt STAT5B function independent of tyrosine phosphorylation may be therapeutically effective in treating certain leukemias/lymphomas

ANIMAL & CELL MODELS