GATA3

GATA binding protein 3

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
4HC7, 4HC9, 4HCA

Identifiers

Symbols

GATA3 ; HDR; HDRS

External IDs

OMIM: 131320 MGI: 95663 HomoloGene: 1550 GeneCards: GATA3 Gene

Gene ontology
Molecular function	• transcription regulatory region sequence-specific DNA binding • RNA polymerase II core promoter sequence-specific DNA binding • core promoter proximal region sequence-specific DNA binding • core promoter sequence-specific DNA binding • nucleic acid binding transcription factor activity • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding • transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding • enhancer sequence-specific DNA binding • DNA binding • transcription factor activity, sequence-specific DNA binding • transcription coactivator activity • interleukin-2 receptor binding • protein binding • transcription factor binding • zinc ion binding • transcription regulatory region DNA binding • protein dimerization activity • E-box binding • HMG box domain binding
Cellular component	• nuclear chromatin • nucleus • nucleoplasm • nucleolus
Biological process	• negative regulation of transcription from RNA polymerase II promoter • in utero embryonic development • cell fate determination • neuron migration • type IV hypersensitivity • kidney development • mesonephros development • lens development in camera-type eye • pro-T cell differentiation • aortic valve morphogenesis • cardiac right ventricle morphogenesis • ventricular septum development • transcription from RNA polymerase II promoter • defense response • humoral immune response • signal transduction • axon guidance • blood coagulation • negative regulation of cell proliferation • male gonad development • response to virus • anatomical structure morphogenesis • post-embryonic development • positive regulation of signal transduction • response to gamma radiation • positive regulation of endothelial cell migration • regulation of neuron projection development • phosphatidylinositol 3-kinase signaling • erythrocyte differentiation • TOR signaling • negative regulation of interferon-gamma production • negative regulation of interleukin-2 production • positive regulation of interleukin-4 production • negative regulation of mammary gland epithelial cell proliferation • embryonic hemopoiesis • cellular response to interferon-alpha • ureter maturation • parathyroid hormone secretion • regulation of cytokine biosynthetic process • norepinephrine biosynthetic process • inner ear morphogenesis • response to drug • regulation of CD4-positive, alpha-beta T cell differentiation • regulation of neuron apoptotic process • ear development • response to estrogen • thymic T cell selection • T-helper 2 cell differentiation • innate immune response • response to ethanol • positive regulation of T cell differentiation • negative regulation of fat cell differentiation • negative regulation of cell cycle • negative regulation of transcription, DNA-templated • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • cell maturation • sympathetic nervous system development • thymus development • developmental growth • anatomical structure formation involved in morphogenesis • negative regulation of inflammatory response • T cell receptor signaling pathway • regulation of histone H3-K4 methylation • positive regulation of protein kinase B signaling • parathyroid gland development • pharyngeal system development • uterus development • mesenchymal to epithelial transition • mast cell differentiation • ureteric bud formation • regulation of histone H3-K27 methylation • canonical Wnt signaling pathway involved in metanephric kidney development • cellular response to interleukin-4 • cellular response to tumor necrosis factor • otic vesicle development • cellular response to BMP stimulus • positive regulation of ureteric bud formation • nephric duct morphogenesis • nephric duct formation • regulation of nephron tubule epithelial cell differentiation • interleukin-4 secretion • interferon-gamma secretion • lymphocyte migration • regulation of establishment of cell polarity • negative regulation of cell motility • negative regulation of endothelial cell apoptotic process • negative regulation of cell proliferation involved in mesonephros development • positive regulation of thyroid hormone generation • positive regulation of interleukin-5 secretion • positive regulation of interleukin-13 secretion • positive regulation of transcription regulatory region DNA binding • regulation of cellular response to X-ray • negative regulation of fibroblast growth factor receptor signaling pathway involved in ureteric bud formation • negative regulation of glial cell-derived neurotrophic factor receptor signaling pathway involved in ureteric bud formation
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 10:
8.05 – 8.08 Mb

Chr 2:
9.86 – 9.89 Mb

PubMed search

Trans-acting T-cell-specific transcription factor GATA-3 is a protein that in humans is encoded by the GATA3 gene.^[1]^[2]^[3]

Function

GATA-3 belongs to the GATA family of transcription factors. It regulates luminal epithelial cell differentiation in the mammary gland.^[4] The protein contains two GATA-type zinc fingers and is an important regulator of T cell development and plays an important role in endothelial cell biology. GATA-3 has been shown to promote the secretion of IL-4, IL-5, and IL-13 from Th2 cells, and induces the differentiation of Th0 cells towards this T cell subtype while suppressing their differentiation towards Th1 cells.^[5] It is hypothesised that GATA-3 may play tissue-specific roles.^[6] It has been suggested that GATA-3 is regulated in CD4+ T cells at a transcriptional level through the IL-4 receptor, as well as translationally through T cell receptor signaling. ^[7]

Clinical significance

Defects in this gene are the cause of hypoparathyroidism with sensorineural deafness and renal dysplasia.

Breast cancer

GATA-3 is one of the three genes mutated in >10% of breast cancers (Cancer Genome Atlas).^[8]

GATA-3 was shown to be required for the luminal A type of breast cancer, intertwined in pathways with ERα^[9]^[10] but also androgen receptor signaling in ER-/AR+ tumors.^[11]

Nuclear expression of GATA-3 in breast cancer is considered a marker of luminal cancer in ER+ cancer and luminal androgen responsive cancer in ER-/AR+ tumors.^[12] It is highly coexpressed with FOXA1 and serves as negative predictor of basal subtype and ERBB2 subtype.^[11]^[13]^[14] GATA-3 was shown to directly regulate luminal cell differentiation in mouse models of breast cancer.^[15] It is also considered a strong predictor of taxane and platin salts insensitivity.

Insulin has been shown in experimental models to downregulate expression of GATA3 by causing overexpression of T-bet, resulting in resistance to endocrine therapy.^[16]

Interactions

GATA3 has been shown to interact with LMO1,^[17]^[18] ER and FOXA1.^[14]

References

↑ Joulin V, Bories D, Eléouet JF, Labastie MC, Chrétien S, Mattéi MG, Roméo PH (Jul 1991). "A T-cell specific TCR delta DNA binding protein is a member of the human GATA family". The EMBO Journal 10 (7): 1809–16. PMC 452855. PMID 2050118.
↑ Yamashita M, Ukai-Tadenuma M, Miyamoto T, Sugaya K, Hosokawa H, Hasegawa A, Kimura M, Taniguchi M, DeGregori J, Nakayama T (Jun 2004). "Essential role of GATA3 for the maintenance of type 2 helper T (Th2) cytokine production and chromatin remodeling at the Th2 cytokine gene loci". The Journal of Biological Chemistry 279 (26): 26983–90. doi:10.1074/jbc.M403688200. PMID 15087456.
↑ "Entrez Gene: GATA3 GATA binding protein 3".
↑ Kouros-Mehr H, Slorach EM, Sternlicht MD, Werb Z (Dec 2006). "GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland". Cell 127 (5): 1041–55. doi:10.1016/j.cell.2006.09.048. PMC 2646406. PMID 17129787.
↑ Yagi R, Zhu J, Paul WE (Jul 2011). "An updated view on transcription factor GATA3-mediated regulation of Th1 and Th2 cell differentiation". International Immunology 23 (7): 415–20. doi:10.1093/intimm/dxr029. PMID 21632975.
↑ Wilson BJ (2008). "Does GATA3 act in tissue-specific pathways? A meta-analysis-based approach". Journal of Carcinogenesis 7: 6. doi:10.4103/1477-3163.43426. PMC 2669725. PMID 19008565.
↑ Cook KD, Miller J (September 15, 2010). "TCR-dependent translational control of GATA-3 enhances Th2 differentiation". Journal of Immunology 185 (6): 3209–3216. doi:10.4049/jimmunol.0902544. PMC 3993005. PMID 20696860.
↑ Koboldt DC, Fulton RS, McLellan MD (Oct 2012). "Comprehensive molecular portraits of human breast tumours". Nature 490 (7418): 61–70. doi:10.1038/nature11412. PMC 3465532. PMID 23000897.
↑ Wilson BJ, Giguère V (2008). "Meta-analysis of human cancer microarrays reveals GATA3 is integral to the estrogen receptor alpha pathway". Molecular Cancer 7: 49. doi:10.1186/1476-4598-7-49. PMC 2430971. PMID 18533032.
↑ Dydensborg AB, Rose AA, Wilson BJ, Grote D, Paquet M, Giguère V, Siegel PM, Bouchard M (Jul 2009). "GATA3 inhibits breast cancer growth and pulmonary breast cancer metastasis". Oncogene 28 (29): 2634–42. doi:10.1038/onc.2009. PMID 19483726.
1 2 Sanga S, Broom BM, Cristini V, Edgerton ME (2009). "Gene expression meta-analysis supports existence of molecular apocrine breast cancer with a role for androgen receptor and implies interactions with ErbB family". BMC Medical Genomics 2: 59. doi:10.1186/1755-8794-2-59. PMC 2753593. PMID 19747394.
↑ Kouros-Mehr H, Kim JW, Bechis SK, Werb Z (Apr 2008). "GATA-3 and the regulation of the mammary luminal cell fate". Current Opinion in Cell Biology 20 (2): 164–70. doi:10.1016/j.ceb.2008.02.003. PMC 2397451. PMID 18358709.
↑ Jacquemier J, Charafe-Jauffret E, Monville F, Esterni B, Extra JM, Houvenaeghel G, Xerri L, Bertucci F, Birnbaum D (2009). "Association of GATA3, P53, Ki67 status and vascular peritumoral invasion are strongly prognostic in luminal breast cancer". Breast Cancer Research 11 (2): R23. doi:10.1186/bcr2249. PMC 2688952. PMID 19405945.
1 2 Albergaria A, Paredes J, Sousa B, Milanezi F, Carneiro V, Bastos J, Costa S, Vieira D, Lopes N, Lam EW, Lunet N, Schmitt F (2009). "Expression of FOXA1 and GATA-3 in breast cancer: the prognostic significance in hormone receptor-negative tumours". Breast Cancer Research 11 (3): R40. doi:10.1186/bcr2327. PMC 2716509. PMID 19549328.
↑ Kouros-Mehr H, Bechis SK, Slorach EM, Littlepage LE, Egeblad M, Ewald AJ, Pai SY, Ho IC, Werb Z (Feb 2008). "GATA-3 links tumor differentiation and dissemination in a luminal breast cancer model". Cancer Cell 13 (2): 141–52. doi:10.1016/j.ccr.2008.01.011. PMC 2262951. PMID 18242514.
↑ McCune K, Bhat-Nakshatri P, Thorat MA, Nephew KP, Badve S, Nakshatri H (Jan 2010). "Prognosis of hormone-dependent breast cancers: implications of the presence of dysfunctional transcriptional networks activated by insulin via the immune transcription factor T-bet". Cancer Research 70 (2): 685–96. doi:10.1158/0008-5472.CAN-09-1530. PMC 2807987. PMID 20068169.
↑ Ono Y, Fukuhara N, Yoshie O (Dec 1998). "TAL1 and LIM-only proteins synergistically induce retinaldehyde dehydrogenase 2 expression in T-cell acute lymphoblastic leukemia by acting as cofactors for GATA3". Molecular and Cellular Biology 18 (12): 6939–50. PMC 109277. PMID 9819382.
↑ Ono Y, Fukuhara N, Yoshie O (Feb 1997). "Transcriptional activity of TAL1 in T cell acute lymphoblastic leukemia (T-ALL) requires RBTN1 or -2 and induces TALLA1, a highly specific tumor marker of T-ALL". The Journal of Biological Chemistry 272 (7): 4576–81. doi:10.1074/jbc.272.7.4576. PMID 9020185.

External links

GATA3 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
FactorBook GATA3

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Transcription factors and intracellular receptors

(1) Basic domains

(1.1) Basic leucine zipper (bZIP)	Activating transcription factor AATF 1 2 3 4 5 6 7 AP-1 c-Fos FOSB FOSL1 FOSL2 JDP2 c-Jun JUNB JunD BACH 1 2 BATF BLZF1 C/EBP α β γ δ ε ζ CREB 1 3 L1 CREM DBP DDIT3 GABPA HLF MAF B F G K NFE 2 L1 L2 L3 NFIL3 NRL NRF 1 2 3 XBP1

(1.2) Basic helix-loop-helix (bHLH)	ATOH1 AhR AHRR ARNT ASCL1 BHLH 2 3 9 ARNTL ARNTL ARNTL2 CLOCK EPAS1 FIGLA HAND 1 2 HES 5 6 HEY 1 2 L HES1 HIF 1A 3A ID 1 2 3 4 LYL1 MESP2 MXD4 MYCL1 MYCN Myogenic regulatory factors MyoD Myogenin MYF5 MYF6 Neurogenins 1 2 3 NeuroD 1 2 NPAS 1 2 3 OLIG 1 2 Pho4 Scleraxis SIM 1 2 TAL 1 2 Twist USF1

(1.3) bHLH-ZIP	AP-4 MAX MXD3 MITF MNT MLX MXI1 Myc SREBP 1 2

(1.4) NF-1	NFI A B C X SMAD R-SMAD 1 2 3 5 9 I-SMAD 6 7 4)

(1.5) RF-X	RFX 1 2 3 4 5 6 ANK

(1.6) Basic helix-span-helix (bHSH)	AP-2 α β γ δ ε

(2) Zinc finger DNA-binding domains

(2.1) Nuclear receptor (Cys₄)

subfamily 1	Thyroid hormone α β CAR FXR LXR α β PPAR α β/δ γ PXR RAR α β γ ROR α β γ Rev-ErbA α β VDR

subfamily 2	COUP-TF (I II Ear-2 HNF4 α γ PNR RXR α β γ Testicular receptor 2 4 TLX

subfamily 3	Steroid hormone Androgen Estrogen α β Glucocorticoid Mineralocorticoid Progesterone Estrogen related α β γ

subfamily 4	NUR NGFIB NOR1 NURR1

subfamily 5	LRH-1 SF1

subfamily 6	GCNF

subfamily 0	DAX1 SHP

(2.2) Other Cys₄

GATA
- 1
- 2
- 3
- 4
- 5
- 6
MTA
- 1
- 2
- 3
TRPS1

(2.3) Cys₂His₂

General transcription factors
- TFIIA
- TFIIB
- TFIID
- TFIIE
  - 1
  - 2
- TFIIF
- 1
- 2
  - TFIIH
  - 1
  - 2
  - 4
  - 2I
  - 3A
  - 3C1
  - 3C2

ATBF1
BCL
- 6
- 11A
- 11B
CTCF
E4F1
EGR
- 1
- 2
- 3
- 4
ERV3
GFI1
GLI-Krüppel family
- 1
- 2
- 3
- REST
- S1
- S2
- YY1
HIC
- 1
- 2
HIVEP
- 1
- 2
- 3
IKZF
- 1
- 2
- 3
ILF
- 2
- 3
KLF
- 1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 9
- 10
- 11
- 12
- 13
- 14
- 15
- 17
MTF1
MYT1
OSR1
PRDM9
SALL
- 1
- 2
- 3
- 4
SP
- 1
- 2
- 4
- 7
- 8
TSHZ3
WT1
Zbtb7
- 7A
- 7B
ZBTB
- 11
- 16
- 17
- 20
- 32
- 33
- 40
zinc finger
- 3
- 7
- 9
- 10
- 19
- 22
- 24
- 33B
- 34
- 35
- 41
- 43
- 44
- 51
- 74
- 143
- 146
- 148
- 165
- 202
- 217
- 219
- 238
- 239
- 259
- 267
- 268
- 281
- 295
- 300
- 318
- 330
- 346
- 350
- 365
- 366
- 384
- 423
- 451
- 452
- 471
- 593
- 638
- 644
- 649
- 655

(2.4) Cys₆

HIVEP1

(2.5) Alternating composition

AIRE
DIDO1
GRLF1
ING
- 1
- 2
- 4
JARID
- 1A
- 1B
- 1C
- 1D
- 2
JMJD1B

(2.6) WRKY

WRKY

(3) Helix-turn-helix domains

(3.1) Homeodomain	ARX CDX 1 2 CRX CUTL1 DBX 1 2 DLX 3 4 5 EMX 1 2 EN 1 2 FHL 1 2 3 HESX1 HHEX HLX Homeobox A1 A2 A3 A4 A5 A7 A9 A10 A11 A13 B1 B2 B3 B4 B5 B6 B7 B8 B9 B13 C4 C5 C6 C8 C9 C10 C11 C12 C13 D1 D3 D4 D8 D9 D10 D11 D12 D13 HOPX IRX 1 2 3 4 5 6 MKX LMX 1A 1B MEIS 1 2 MEOX2 MNX1 MSX 1 2 NANOG NKX 2-1 2-2 2-3 2-5 3-1 3-2 6-1 6-2 NOBOX PBX 1 2 3 PHF 1 3 6 8 10 16 17 20 21A PHOX 2A 2B PITX 1 2 3 POU domain PIT-1 BRN-3: A B C Octamer transcription factor: 1 2 3/4 6 7 11 OTX 1 2 PDX1 SATB2 SHOX2 SIX 1 2 3 4 5 VAX1 ZEB 1 2

(3.2) Paired box	PAX 1 2 3 4 5 6 7 8 9 PRRX 1 2 RAX

(3.3) Fork head / winged helix	E2F 1 2 3 4 5 FOX proteins A1 A2 A3 C1 C2 D3 D4 E1 E3 F1 G1 H1 I1 J1 J2 K1 K2 L2 M1 N1 N3 O1 O3 O4 P1 P2 P3 P4

(3.4) Heat shock factors	HSF 1 2 4

(3.5) Tryptophan clusters	ELF 2 4 5 EGF ELK 1 3 4 ERF ETS 1 2 ERG SPIB ETV 1 4 5 6 FLI1 Interferon regulatory factors 1 2 3 4 5 6 7 8 MYB MYBL2

(3.6) TEA domain	transcriptional enhancer factor 1 2 3 4

(4) β-Scaffold factors with minor groove contacts

(4.1) Rel homology region	NF-κB NFKB1 NFKB2 REL RELA RELB NFAT C1 C2 C3 C4 5

(4.2) STAT	STAT 1 2 3 4 5 6

(4.3) p53	p53 TBX 1 2 3 5 19 21 22 TBR1 TBR2 TFT MYRF TP63

(4.4) MADS box	Mef2 A B C D SRF

(4.6) TATA-binding proteins	TBP TBPL1

(4.7) High-mobility group	BBX HMGB 1 2 3 4 HMGN 1 2 3 4 HNF 1A 1B LEF1 SOX 1 2 3 4 5 6 8 9 10 11 12 13 14 15 18 21 SRY SSRP1 TCF 3 4 TOX 1 2 3 4

(4.9) Grainyhead	TFCP2

(4.10) Cold-shock domain	CSDA YBX1

(4.11) Runt	CBF CBFA2T2 CBFA2T3 RUNX1 RUNX2 RUNX3 RUNX1T1

(0) Other transcription factors

(0.2) HMGI(Y)	HMGA 1 2 HBP1

(0.3) Pocket domain	Rb RBL1 RBL2

(0.5) AP-2/EREBP-related factors	Apetala 2 EREBP B3

(0.6) Miscellaneous	ARID 1A 1B 2 3A 3B 4A CAP IFI 16 35 MLL 2 3 T1 MNDA NFY A B C Rho/Sigma

see also transcription factor/coregulator deficiencies

This article is issued from Wikipedia - version of the Tuesday, January 26, 2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.