P23769 (GATA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Endothelial transcription factor GATA-2

Alternative name(s):
GATA-binding protein 2

Gene names

Name:

GATA2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	480 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcriptional activator which regulates endothelin-1 gene expression in endothelial cells. Binds to the consensus sequence 5'-AGATAG-3'.
Subcellular location	Nucleus.
Tissue specificity	Endothelial cells.
Involvement in disease	Defects in GATA2 are the cause of dendritic cell monocyte lymphocyte B and natural killer lymphocyte deficiency (DCML) [MIM:614172]. DCML is an immunodeficiency disease characterized by profoundly decreased or absent monocytes, B lymphocytes, natural killer lymphocytes, and circulating and tissue dendritic cells, with little or no effect on T cell numbers. Clinical features of DCML include susceptibility to disseminated non-tuberculous mycobacterial infections, papillomavirus infections, opportunistic fungal infections, and pulmonary alveolar proteinosis. Bone marrow hypocellularity and dysplasia of myeloid, erythroid, and megakaryocytic lineages are present in most patients, as are karyotypic abnormalities, including monosomy 7 and trisomy 8. Ref.8 Defects in GATA2 are a cause of lymphedema primary with myelodysplasia (LMPM) [MIM:614038]. A chronic disabling condition characterized by swelling of the extremities due to altered lymphatic flow, associated with myelodysplasia. Patients with lymphedema suffer from recurrent local infections, and physical impairment. Ref.9 Defects in GATA2 are a cause of myelodysplastic syndrome (MDS) [MIM:614286]. A heterogeneous group of closely related clonal hematopoietic disorders. All are characterized by a hypercellular or hypocellular bone marrow with impaired morphology and maturation, dysplasia of the myeloid, megakaryocytic and/or erythroid lineages, and peripheral blood cytopenias resulting from ineffective blood cell production. Included diseases are: refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB), refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS); chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative disease. MDS is considered a premalignant condition in a subgroup of patients that often progresses to acute myeloid leukemia (AML). Ref.10
Sequence similarities	Contains 2 GATA-type zinc fingers.
Sequence caution	The sequence AAA35869.1 differs from that shown. Reason: Several sequencing errors.

Ontologies

Keywords
Biological process	Phagocytosis Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	blood coagulation Traceable author statement. Source: Reactome eosinophil fate commitment Inferred from direct assay. Source: BHF-UCL negative regulation of Notch signaling pathway Inferred from direct assay. Source: MGI negative regulation of fat cell differentiation Inferred from mutant phenotype. Source: UniProtKB negative regulation of fat cell proliferation Inferred from mutant phenotype. Source: UniProtKB negative regulation of neural precursor cell proliferation Inferred from direct assay. Source: MGI phagocytosis Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of angiogenesis Inferred from direct assay. Source: MGI positive regulation of phagocytosis Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	nucleoplasm Traceable author statement. Source: Reactome
Molecular function	C2H2 zinc finger domain binding Inferred from physical interaction. Source: BHF-UCL chromatin binding Inferred from direct assay. Source: MGI transcription factor binding Inferred from physical interaction. Source: BHF-UCL zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Lmo2	P25801	3	EBI-2806671,EBI-3903256	From a different organism.
SMAD4	Q13485	2	EBI-2806671,EBI-347263

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P23769-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P23769-2)

The sequence of this isoform differs from the canonical sequence as follows:
     340-353: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 480	480	Endothelial transcription factor GATA-2		PRO_0000083403
Regions
	Zinc finger	295 – 319	25	GATA-type 1
	Zinc finger	349 – 373	25	GATA-type 2
Natural variations
	Alternative sequence	340 – 353	14	Missing in isoform 2.		VSP_041126
	Natural variant	164	1	A → T. Ref.3 Ref.4 Ref.7 Corresponds to variant rs2335052 [ dbSNP | Ensembl ].		VAR_055004
	Natural variant	235	1	T → N. Corresponds to variant rs35079193 [ dbSNP | Ensembl ].		VAR_055005
	Natural variant	254	1	P → L in DCML. Ref.8		VAR_066405
	Natural variant	354	1	T → M in DCML and MDS. Ref.8 Ref.10		VAR_066406
	Natural variant	355	1	Missing in MDS.		VAR_066643
	Natural variant	361	1	R → P in LMPM. Ref.9		VAR_066644
	Natural variant	373	1	C → R in LMPM. Ref.9		VAR_066645
	Natural variant	398	1	R → W in DCML. Ref.8		VAR_066407
Experimental info
	Sequence conflict	9	1	R → G in AAA35868. Ref.1
	Sequence conflict	20 – 21	2	QH → HD in AAA35868. Ref.1
	Sequence conflict	38 – 39	2	QL → HV in AAA35868. Ref.1
	Sequence conflict	69	1	R → A in AAA35868. Ref.1
	Sequence conflict	82	1	G → S in AAA35868. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 5, 2009. Version 3. Checksum: C879CC932C355E6A	FASTA	480	50,500
	10 20 30 40 50 60 MEVAPEQPRW MAHPAVLNAQ HPDSHHPGLA HNYMEPAQLL PPDEVDVFFN HLDSQGNPYY 70 80 90 100 110 120 ANPAHARARV SYSPAHARLT GGQMCRPHLL HSPGLPWLDG GKAALSAAAA HHHNPWTVSP 130 140 150 160 170 180 FSKTPLHPSA AGGPGGPLSV YPGAGGGSGG GSGSSVASLT PTAAHSGSHL FGFPPTPPKE 190 200 210 220 230 240 VSPDPSTTGA ASPASSSAGG SAARGEDKDG VKYQVSLTES MKMESGSPLR PGLATMGTQP 250 260 270 280 290 300 ATHHPIPTYP SYVPAAAHDY SSGLFHPGGF LGGPASSFTP KQRSKARSCS EGRECVNCGA 310 320 330 340 350 360 TATPLWRRDG TGHYLCNACG LYHKMNGQNR PLIKPKRRLS AARRAGTCCA NCQTTTTTLW 370 380 390 400 410 420 RRNANGDPVC NACGLYYKLH NVNRPLTMKK EGIQTRNRKM SNKSKKSKKG AECFEELSKC 430 440 450 460 470 480 MQEKSSPFSA AALAGHMAPV GHLPPFSHSG HILPTPTPIH PSSSLSFGHP HPSSMVTAMG
	Isoform 2 [UniParc]. Checksum: B074D2E927CE263B	FASTA	466	49,106
	10 20 30 40 50 60 MEVAPEQPRW MAHPAVLNAQ HPDSHHPGLA HNYMEPAQLL PPDEVDVFFN HLDSQGNPYY 70 80 90 100 110 120 ANPAHARARV SYSPAHARLT GGQMCRPHLL HSPGLPWLDG GKAALSAAAA HHHNPWTVSP 130 140 150 160 170 180 FSKTPLHPSA AGGPGGPLSV YPGAGGGSGG GSGSSVASLT PTAAHSGSHL FGFPPTPPKE 190 200 210 220 230 240 VSPDPSTTGA ASPASSSAGG SAARGEDKDG VKYQVSLTES MKMESGSPLR PGLATMGTQP 250 260 270 280 290 300 ATHHPIPTYP SYVPAAAHDY SSGLFHPGGF LGGPASSFTP KQRSKARSCS EGRECVNCGA 310 320 330 340 350 360 TATPLWRRDG TGHYLCNACG LYHKMNGQNR PLIKPKRRLT TTTTLWRRNA NGDPVCNACG 370 380 390 400 410 420 LYYKLHNVNR PLTMKKEGIQ TRNRKMSNKS KKSKKGAECF EELSKCMQEK SSPFSAAALA 430 440 450 460 GHMAPVGHLP PFSHSGHILP TPTPIHPSSS LSFGHPHPSS MVTAMG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the GATA-binding protein that regulates endothelin-1 gene expression in endothelial cells." Lee M.-E., Temizer D.T., Clifford J.A., Quertermous T. J. Biol. Chem. 266:16188-16192(1991) [PubMed: 1714909] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Human transcription factor GATA-2. Evidence for regulation of preproendothelin-1 gene expression in endothelial cells." Dorfman D.M., Wilson D.B., Bruns G.A.P., Orkin S.H. J. Biol. Chem. 267:1279-1285(1992) [PubMed: 1370462] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Endothelial cell.
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT THR-164.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT THR-164. Tissue: Placenta.
[5]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed: 16641997] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT THR-164. Tissue: Brain and Placenta.
[8]	"Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome." Hsu A.P., Sampaio E.P., Khan J., Calvo K.R., Lemieux J.E., Patel S.Y., Frucht D.M., Vinh D.C., Auth R.D., Freeman A.F., Olivier K.N., Uzel G., Zerbe C.S., Spalding C., Pittaluga S., Raffeld M., Kuhns D.B., Ding L. , Paulson M.L., Marciano B.E., Gea-Banacloche J.C., Orange J.S., Cuellar-Rodriguez J., Hickstein D.D., Holland S.M. Blood 118:2653-2655(2011) [PubMed: 21670465] [Abstract] Cited for: VARIANTS DCML LEU-254; MET-354 AND TRP-398.
[9]	"Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome)." Ostergaard P., Simpson M.A., Connell F.C., Steward C.G., Brice G., Woollard W.J., Dafou D., Kilo T., Smithson S., Lunt P., Murday V.A., Hodgson S., Keenan R., Pilz D.T., Martinez-Corral I., Makinen T., Mortimer P.S., Jeffery S., Trembath R.C., Mansour S. Nat. Genet. 43:929-931(2011) [PubMed: 21892158] [Abstract] Cited for: VARIANTS LMPM PRO-361 AND ARG-373.
[10]	"Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia." Hahn C.N., Chong C.E., Carmichael C.L., Wilkins E.J., Brautigan P.J., Li X.C., Babic M., Lin M., Carmagnac A., Lee Y.K., Kok C.H., Gagliardi L., Friend K.L., Ekert P.G., Butcher C.M., Brown A.L., Lewis I.D., To L.B. , Timms A.E., Storek J., Moore S., Altree M., Escher R., Bardy P.G., Suthers G.K., D'Andrea R.J., Horwitz M.S., Scott H.S. Nat. Genet. 43:1012-1017(2011) [PubMed: 21892162] [Abstract] Cited for: VARIANTS MDS MET-354 AND THR-355 DEL.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	M68891 mRNA. Translation: AAA35868.1. M77810 mRNA. Translation: AAA35869.1. Sequence problems. BT006671 mRNA. Translation: AAP35317.1. AK314826 mRNA. Translation: BAG37347.1. AC080005 Genomic DNA. No translation available. CH471052 Genomic DNA. Translation: EAW79313.1. CH471052 Genomic DNA. Translation: EAW79314.1. CH471052 Genomic DNA. Translation: EAW79315.1. CH471052 Genomic DNA. Translation: EAW79316.1. CH471052 Genomic DNA. Translation: EAW79317.1. BC002557 mRNA. Translation: AAH02557.1. BC015613 mRNA. Translation: AAH15613.1. BC015577 mRNA. Translation: AAH15577.1. BC018988 mRNA. Translation: AAH18988.1. BC051272 mRNA. Translation: AAH51272.1. BC051342 mRNA. Translation: AAH51342.1.
IPI	IPI00012900. IPI00794907.
PIR	A40815. A41782.
RefSeq	NP_001139133.1. NM_001145661.1. NP_001139134.1. NM_001145662.1. NP_116027.2. NM_032638.4.
UniGene	Hs.367725.
3D structure databases
ProteinModelPortal	P23769.
SMR	P23769. Positions 291-329, 343-398.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29711N.
IntAct	P23769. 5 interactions.
STRING	P23769.
PTM databases
PhosphoSite	P23769.
Polymorphism databases
DMDM	229462971.
Proteomic databases
PRIDE	P23769.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000341105; ENSP00000345681; ENSG00000179348. ENST00000487848; ENSP00000417074; ENSG00000179348.
GeneID	2624.
KEGG	hsa:2624.
Organism-specific databases
CTD	2624.
GeneCards	GC03M128198.
H-InvDB	HIX0003652.
HGNC	HGNC:4171. GATA2.
HPA	CAB024847. HPA005633.
MIM	137295. gene. 614038. phenotype. 614172. phenotype. 614286. phenotype.
neXtProt	NX_P23769.
Orphanet	228423. Monocytopenia with susceptibility to infections.
PharmGKB	PA28585.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG11724.
GeneTree	ENSGT00550000074470.
HOGENOM	HBG716943.
HOVERGEN	HBG051705.
InParanoid	P23769.
OMA	MEPMAPL.
OrthoDB	EOG4S1T85.
PhylomeDB	P23769.
Enzyme and pathway databases
Pathway_Interaction_DB	hif1_tfpathway. HIF-1-alpha transcription factor network. ar_tf_pathway. Regulation of Androgen receptor activity. hdac_classi_pathway. Signaling events mediated by HDAC Class I. hdac_classii_pathway. Signaling events mediated by HDAC Class II.
Reactome	REACT_604. Hemostasis.
Gene expression databases
ArrayExpress	P23769.
Bgee	P23769.
CleanEx	HS_GATA2.
Genevestigator	P23769.
GermOnline	ENSG00000179348. Homo sapiens.
Family and domain databases
InterPro	IPR016374. TF_GATA-1/2/3. IPR000679. Znf_GATA. IPR013088. Znf_NHR/GATA. [Graphical view]
Gene3D	G3DSA:3.30.50.10. Znf_NHR/GATA. 2 hits.
KO	K09182.
Pfam	PF00320. GATA. 2 hits. [Graphical view]
PIRSF	PIRSF003027. TF_GATA-1/2/3. 1 hit.
PRINTS	PR00619. GATAZNFINGER.
SMART	SM00401. ZnF_GATA. 2 hits. [Graphical view]
PROSITE	PS00344. GATA_ZN_FINGER_1. 2 hits. PS50114. GATA_ZN_FINGER_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

GATA2_HUMAN

Accession

Primary (citable) accession number: P23769
Secondary accession number(s): D3DNB3 , Q53YE0, Q96BH0, Q96BH8, Q9BUJ6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1991
Last sequence update:	May 5, 2009
Last modified:	January 25, 2012
This is version 110 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.