Q86YP4 (P66A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transcriptional repressor p66-alpha
Short name=Hp66alpha

Alternative name(s):
GATA zinc finger domain-containing protein 2A

Gene names

Name:

GATAD2A

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	633 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcriptional repressor. Enhances MBD2-mediated repression. Efficient repression requires the presence of GATAD2B. Ref.1 Ref.7
Subunit structure	Binds MBD2 and MBD3. Interaction with MBD2 is required for the enhancement of MBD2-mediated repression and for targeting to the chromatin. Component of the MeCP1 histone deacetylase complex. Interacts with histone tails, including that of histones H2A, H2B, H3 and H4. This interaction is reduced by histone acetylation. Ref.1 Ref.7 Ref.15
Subcellular location	Nucleus speckle. Note: Speckled nuclear localization requires both CR1 and CR2 regions. Ref.1 Ref.7
Tissue specificity	Ubiquitous, both in fetal and adult tissues. Ref.1
Domain	Both CR1 and CR2 regions are required for speckled nuclear localization.
Sequence similarities	Contains 1 GATA-type zinc finger.
Sequence caution	The sequence AAH11684.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAA90939.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Repressor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA methylation Traceable author statement Ref.1. Source: UniProtKB anterior neuropore closure Inferred from electronic annotation. Source: Compara blood vessel development Inferred from electronic annotation. Source: Compara embryonic body morphogenesis Inferred from electronic annotation. Source: Compara in utero embryonic development Inferred from electronic annotation. Source: Compara negative regulation of transcription, DNA-dependent Inferred from direct assay Ref.1. Source: UniProtKB neural fold formation Inferred from electronic annotation. Source: Compara programmed cell death Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	NuRD complex Inferred from direct assay Ref.1. Source: UniProtKB nuclear speck Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	protein binding, bridging Inferred from direct assay Ref.1. Source: UniProtKB sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q86YP4-1)

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: Q86YP4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     500-524: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 633

633

Transcriptional repressor p66-alpha

PRO_0000083500

Regions

Zinc finger

411 – 464

54

GATA-type

Region

144 – 178

35

CR1; MBD2-binding

Region

340 – 480

141

CR2; histone tail-binding

Coiled coil

139 – 174

36

Potential

Amino acid modifications

Modified residue

49

1

Phosphothreonine Ref.8 Ref.10 Ref.11 Ref.12 Ref.14

Modified residue

100

1

Phosphoserine Ref.6 Ref.8 Ref.10 Ref.11 Ref.12 Ref.14

Modified residue

107

1

Phosphoserine Ref.6 Ref.8 Ref.10 Ref.11 Ref.12 Ref.14

Modified residue

114

1

Phosphoserine Ref.6 Ref.10 Ref.11

Modified residue

189

1

Phosphothreonine Ref.11

Modified residue

340

1

Phosphoserine Ref.11

Modified residue

343

1

Phosphoserine Ref.14

Modified residue

546

1

Phosphoserine Ref.10 Ref.12

Modified residue

548

1

Phosphoserine Ref.10 Ref.12

Modified residue

598

1

Phosphoserine Ref.10

Natural variations

Alternative sequence

500 – 524

25

Missing in isoform 2.

VSP_010929

Natural variant

17

1

R → Q.
Corresponds to variant rs10426883 [ dbSNP | Ensembl ].

VAR_059308

Natural variant

296

1

N → S.
Corresponds to variant rs2288851 [ dbSNP | Ensembl ].

VAR_059309

Experimental info

Mutagenesis

149

1

K → R: Disruption of MBD2-binding, loss of enhancement of MBD2-mediated repression and loss of speckled nuclear localization. Ref.7

Sequence conflict

401

1

Q → QA in AAH12902. Ref.2

Sequence conflict

432

1

K → E in BAA90939. Ref.3

Secondary structure

1

.

.

.

633

Helix Strand Turn

Details...

Helix

138 – 168

31

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2003. Version 1. Checksum: 64F0066B4BEFCB39	FASTA	633	68,063
	10 20 30 40 50 60 MTEEACRTRS QKRALERDPT EDDVESKKIK MERGLLASDL NTDGDMRVTP EPGAGPTQGL 70 80 90 100 110 120 LRATEATAMA MGRGEGLVGD GPVDMRTSHS DMKSERRPPS PDVIVLSDNE QPSSPRVNGL 130 140 150 160 170 180 TTVALKETST EALMKSSPEE RERMIKQLKE ELRLEEAKLV LLKKLRQSQI QKEATAQKPT 190 200 210 220 230 240 GSVGSTVTTP PPLVRGTQNI PAGKPSLQTS SARMPGSVIP PPLVRGGQQA SSKLGPQASS 250 260 270 280 290 300 QVVMPPLVRG AQQIHSIRQH SSTGPPPLLL APRASVPSVQ IQGQRIIQQG LIRVANVPNT 310 320 330 340 350 360 SLLVNIPQPT PASLKGTTAT SAQANSTPTS VASVVTSAES PASRQAAAKL ALRKQLEKTL 370 380 390 400 410 420 LEIPPPKPPA PEMNFLPSAA NNEFIYLVGL EEVVQNLLET QGRMSAATVL SREPYMCAQC 430 440 450 460 470 480 KTDFTCRWRE EKSGAIMCEN CMTTNQKKAL KVEHTSRLKA AFVKALQQEQ EIEQRLLQQG 490 500 510 520 530 540 TAPAQAKAEP TAAPHPVLKQ VIKPRRKLAF RSGEARDWSN GAVLQASSQL SRGSATTPRG 550 560 570 580 590 600 VLHTFSPSPK LQNSASATAL VSRTGRHSER TVSAGKGSAT SNWKKTPLST GGTLAFVSPS 610 620 630 LAVHKSSSAV DRQREYLLDM IPPRSIPQSA TWK
	Isoform 2 [UniParc]. Checksum: 751DB0FC42DA3BC8	FASTA	608	65,225
	10 20 30 40 50 60 MTEEACRTRS QKRALERDPT EDDVESKKIK MERGLLASDL NTDGDMRVTP EPGAGPTQGL 70 80 90 100 110 120 LRATEATAMA MGRGEGLVGD GPVDMRTSHS DMKSERRPPS PDVIVLSDNE QPSSPRVNGL 130 140 150 160 170 180 TTVALKETST EALMKSSPEE RERMIKQLKE ELRLEEAKLV LLKKLRQSQI QKEATAQKPT 190 200 210 220 230 240 GSVGSTVTTP PPLVRGTQNI PAGKPSLQTS SARMPGSVIP PPLVRGGQQA SSKLGPQASS 250 260 270 280 290 300 QVVMPPLVRG AQQIHSIRQH SSTGPPPLLL APRASVPSVQ IQGQRIIQQG LIRVANVPNT 310 320 330 340 350 360 SLLVNIPQPT PASLKGTTAT SAQANSTPTS VASVVTSAES PASRQAAAKL ALRKQLEKTL 370 380 390 400 410 420 LEIPPPKPPA PEMNFLPSAA NNEFIYLVGL EEVVQNLLET QGRMSAATVL SREPYMCAQC 430 440 450 460 470 480 KTDFTCRWRE EKSGAIMCEN CMTTNQKKAL KVEHTSRLKA AFVKALQQEQ EIEQRLLQQG 490 500 510 520 530 540 TAPAQAKAEP TAAPHPVLKQ ASSQLSRGSA TTPRGVLHTF SPSPKLQNSA SATALVSRTG 550 560 570 580 590 600 RHSERTVSAG KGSATSNWKK TPLSTGGTLA FVSPSLAVHK SSSAVDRQRE YLLDMIPPRS IPQSATWK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Two highly related p66 proteins comprise a new family of potent transcriptional repressors interacting with MBD2 and MBD3." Brackertz M., Boeke J., Zhang R., Renkawitz R. J. Biol. Chem. 277:40958-40966(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH MBD2 AND MBD3, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Ovary and Skin.
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 417-633 (ISOFORM 1). Tissue: Colon.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 465-633 (ISOFORM 2). Tissue: Brain.
[5]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[6]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-100; SER-107 AND SER-114, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[7]	"p66alpha and p66beta of the Mi-2/NuRD complex mediate MBD2 and histone interaction." Brackertz M., Gong Z., Leers J., Renkawitz R. Nucleic Acids Res. 34:397-406(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MBD2 AND HISTONE TAILS, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-149.
[8]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-49; SER-100 AND SER-107, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[10]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-49; SER-100; SER-107; SER-114; SER-546; SER-548 AND SER-598, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-49; SER-100; SER-107; SER-114; THR-189 AND SER-340, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[12]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-49; SER-100; SER-107; SER-546 AND SER-548, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-49; SER-100; SER-107 AND SER-343, MASS SPECTROMETRY.
[15]	"p66Alpha-MBD2 coiled-coil interaction and recruitment of Mi-2 are critical for globin gene silencing by the MBD2-NuRD complex." Gnanapragasam M.N., Scarsdale J.N., Amaya M.L., Webb H.D., Desai M.A., Walavalkar N.M., Wang S.Z., Zu Zhu S., Ginder G.D., Williams D.C. Jr. Proc. Natl. Acad. Sci. U.S.A. 108:7487-7492(2011) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 137-178 IN COMPLEX WITH MBD2, SUBUNIT, INTERACTION WITH MBD2.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY186731 mRNA. Translation: AAO31797.1.
BC011684 mRNA. Translation: AAH11684.1. Different initiation.
BC012902 mRNA. Translation: AAH12902.2.
AK000092 mRNA. Translation: BAA90939.1. Different initiation.
AL390164 mRNA. Translation: CAB99095.1.

IPI

IPI00410330.
IPI00444526.

PIR

T51878.

RefSeq

NP_060130.3. NM_017660.3.

UniGene

Hs.118964.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2L2L	NMR	-	A	137-178	[»]

ProteinModelPortal

Q86YP4.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q86YP4. 11 interactions.

MINT

MINT-1387810.

STRING

9606.ENSP00000351552.

PTM databases

PhosphoSite

Q86YP4.

Polymorphism databases

DMDM

50401012.

Proteomic databases

PaxDb

Q86YP4.

PRIDE

Q86YP4.

Protocols and materials databases

DNASU

54815.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000252577; ENSP00000252577; ENSG00000167491.
ENST00000358713; ENSP00000351552; ENSG00000167491.
ENST00000360315; ENSP00000353463; ENSG00000167491.

GeneID

54815.

KEGG

hsa:54815.

UCSC

uc010xqt.2. human.

Organism-specific databases

CTD

54815.

GeneCards

GC19P019496.

H-InvDB

HIX0014940.

HGNC

HGNC:29989. GATAD2A.

HPA

HPA006759.
HPA024373.

MIM

614997. gene.

neXtProt

NX_Q86YP4.

PharmGKB

PA142671746.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG252421.

HOGENOM

HOG000074070.

HOVERGEN

HBG053401.

PhylomeDB

Q86YP4.

Enzyme and pathway databases

Pathway_Interaction_DB

hdac_classi_pathway. Signaling events mediated by HDAC Class I.

Gene expression databases

ArrayExpress

Q86YP4.

Bgee

Q86YP4.

CleanEx

HS_GATAD2A.

Genevestigator

Q86YP4.

Family and domain databases

Gene3D

3.30.50.10. 1 hit.

InterPro

IPR000679. Znf_GATA.
IPR013088. Znf_NHR/GATA.
[Graphical view]

Pfam

PF00320. GATA. 1 hit.
[Graphical view]

PROSITE

PS00344. GATA_ZN_FINGER_1. 1 hit.
PS50114. GATA_ZN_FINGER_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

54815.

NextBio

57553.

PMAP-CutDB

Q86YP4.

SOURCE

Search...

Entry information

Entry name

P66A_HUMAN

Accession

Primary (citable) accession number: Q86YP4
Secondary accession number(s): Q7L3J2 , Q96F28, Q9NPU2, Q9NXS1

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	June 1, 2003
Last modified:	May 1, 2013
This is version 101 of the entry and version 1 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.