Reviewed, UniProtKB/Swiss-Prot P37275 (ZEB1_HUMAN)

Names and origin

Protein names

Recommended name:
    Zinc finger E-box-binding homeobox 1
Alternative name(s):
    Transcription factor 8
    NIL-2-A zinc finger protein
    Negative regulator of IL2

Gene names

Name:	ZEB1
Synonyms:	AREB6, TCF8

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	1124 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Inhibits interleukin-2 (IL-2) gene expression. May be responsible for transcriptional repression of the IL-2 gene. Enhances or represses the promoter activity of the ATP1A1 gene depending on the quantity of cDNA and on the cell type.
Subcellular location	Nucleus.
Tissue specificity	Expressed in heart and skeletal muscle, but not in liver, spleen, or pancreas.
Involvement in disease	Defects in ZEB1 are the cause of posterior polymorphous corneal dystrophy type 3 (PPCD3) [MIM:609141]. Posterior polymorphous corneal dystrophy (PPCD) is a rare disease involving metaplasia and overgrowth of corneal endothelial cells. In patients with PPCD, these cells manifest in an epithelial morphology and gene expression pattern, produce an aberrant basement membrane, and, sometimes, spread over the iris and nearby structures in a way that increases the risk for glaucoma. Ref.7
Sequence similarities	Belongs to the delta-EF1/ZFH-1 C2H2-type zinc-finger family. Contains 7 C2H2-type zinc fingers. Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Domain	Homeobox Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator Repressor
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cell proliferation Ref.5 Traceable author statement. Source: ProtInc immune response Ref.5 Traceable author statement. Source: ProtInc negative regulation of transcription from RNA polymerase II promoter Ref.5 Traceable author statement. Source: ProtInc transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro transcription coactivator activity Ref.1 Traceable author statement. Source: ProtInc transcription corepressor activity Ref.1 Traceable author statement. Source: ProtInc transcription factor activity Ref.1 Traceable author statement. Source: ProtInc zinc ion binding Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1124	1124	Zinc finger E-box-binding homeobox 1		PRO_0000047231
Regions
	Zinc finger	170 – 193	24	C2H2-type 1
	Zinc finger	200 – 222	23	C2H2-type 2
	Zinc finger	240 – 262	23	C2H2-type 3
	Zinc finger	268 – 292	25	C2H2-type 4; atypical
	DNA binding	581 – 640	60	Homeobox; atypical
	Zinc finger	904 – 926	23	C2H2-type 5
	Zinc finger	932 – 954	23	C2H2-type 6
	Zinc finger	960 – 981	22	C2H2-type 7; atypical
	Compositional bias	989 – 1124	136	Glu-rich (acidic)
Amino acid modifications
	Modified residue	31	1	Phosphoserine Ref.9
	Modified residue	33	1	Phosphoserine Ref.9
	Modified residue	322	1	Phosphoserine Ref.10
	Modified residue	646	1	Phosphoserine Ref.10
	Modified residue	679	1	Phosphoserine Ref.6
	Cross-link	347		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.8
	Cross-link	774		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.8
Natural variations
	Natural variant	90	1	G → R: dbSNP rs12217419.		VAR_052731
	Natural variant	553	1	K → R: dbSNP rs35753967.		VAR_031824
Experimental info
	Sequence conflict	420	1	V → I in AAA20602. Ref.2
	Sequence conflict	609	1	E → Q in M81699. Ref.5
	Sequence conflict	654	1	I → T in AAA20602. Ref.2
	Sequence conflict	672	1	D → H in M81699. Ref.5
	Sequence conflict	681	1	L → S in M81699. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	P37275-1 [UniParc]. Last modified July 15, 1999. Version 2. Checksum: 0A2714CC37C848D1	FASTA	1,124	124,074
	10 20 30 40 50 60 MADGPRCKRR KQANPRRNNV TNYNTVVETN SDSDDEDKLH IVEEESVTDA ADCEGVPEDD 70 80 90 100 110 120 LPTDQTVLPG RSSEREGNAK NCWEDDRKEG QEILGPEAQA DEAGCTVKDD ECESDAENEQ 130 140 150 160 170 180 NHDPNVEEFL QQQDTAVIFP EAPEEDQRQG TPEASGHDEN GTPDAFSQLL TCPYCDRGYK 190 200 210 220 230 240 RFTSLKEHIK YRHEKNEDNF SCSLCSYTFA YRTQLERHMT SHKSGRDQRH VTQSGCNRKF 250 260 270 280 290 300 KCTECGKAFK YKHHLKEHLR IHSGEKPYEC PNCKKRFSHS GSYSSHISSK KCISLIPVNG 310 320 330 340 350 360 RPRTGLKTSQ CSSPSLSASP GSPTRPQIRQ KIENKPLQEQ LSVNQIKTEP VDYEFKPIVV 370 380 390 400 410 420 ASGINCSTPL QNGVFTGGGP LQATSSPQGM VQAVVLPTVG LVSPISINLS DIQNVLKVAV 430 440 450 460 470 480 DGNVIRQVLE NNQANLASKE QETINASPIQ QGGHSVISAI SLPLVDQDGT TKIIINYSLE 490 500 510 520 530 540 QPSQLQVVPQ NLKKENPVAT NSCKSEKLPE DLTVKSEKDK SFEGGVNDST CLLCDDCPGD 550 560 570 580 590 600 INALPELKHY DLKQPTQPPP LPAAEAEKPE SSVSSATGDG NLSPSQPPLK NLLSLLKAYY 610 620 630 640 650 660 ALNAQPSAEE LSKIADSVNL PLDVVKKWFE KMQAGQISVQ SSEPSSPEPG KVNIPAKNND 670 680 690 700 710 720 QPQSANANEP QDSTVNLQSP LKMTNSPVLP VGSTTNGSRS STPSPSPLNL SSSRNTQGYL 730 740 750 760 770 780 YTAEGAQEEP QVEPLDLSLP KQQGELLERS TITSVYQNSV YSVQEEPLNL SCAKKEPQKD 790 800 810 820 830 840 SCVTDSEPVV NVIPPSANPI NIAIPTVTAQ LPTIVAIADQ NSVPCLRALA ANKQTILIPQ 850 860 870 880 890 900 VAYTYSTTVS PAVQEPPLKV IQPNGNQDER QDTSSEGVSN VEDQNDSDST PPKKKMRKTE 910 920 930 940 950 960 NGMYACDLCD KIFQKSSSLL RHKYEHTGKR PHECGICKKA FKHKHHLIEH MRLHSGEKPY 970 980 990 1000 1010 1020 QCDKCGKRFS HSGSYSQHMN HRYSYCKREA EERDSTEQEE AGPEILSNEH VGARASPSQG 1030 1040 1050 1060 1070 1080 DSDERESLTR EEDEDSEKEE EEEDKEMEEL QEEKECEKPQ GDEEEEEEEE EVEEEEVEEA 1090 1100 1110 1120 ENEGEEAKTE GLMKDDRAES QASSLGQKVG ESSEQVSEEK TNEA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Transcription factors positively and negatively regulating the Na,K-ATPase alpha 1 subunit gene." Watanabe Y., Kawakami K., Hirayama Y., Nagano K. J. Biochem. 114:849-855(1993) [PubMed: 8138542] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"A human zinc finger homeodomain protein homologous to the chicken delta-crystallin enhancer binding protein, delta EF1." Bachman N.J., Scarpulla R.C. Submitted (JUL-1994) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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].
[5]	"Identification of a zinc finger protein that inhibits IL-2 gene expression." Williams T.M., Moolten D., Burlein J., Romano J., Bhaerman R., Godillot A., Mellon M., Rauscher F.J. III, Kant J.A. Science 254:1791-1794(1991) [PubMed: 1840704] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 390-1124.
[6]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-679, MASS SPECTROMETRY. Tissue: Epithelium.
[7]	"Mutations in TCF8 cause posterior polymorphous corneal dystrophy and ectopic expression of COL4A3 by corneal endothelial cells." Krafchak C.M., Pawar H., Moroi S.E., Sugar A., Lichter P.R., Mackey D.A., Mian S., Nairus T., Elner V., Schteingart M.T., Downs C.A., Kijek T.G., Johnson J.M., Trager E.H., Rozsa F.W., Mandal M.N.A., Epstein M.P., Vollrath D. , Ayyagari R., Boehnke M., Richards J.E. Am. J. Hum. Genet. 77:694-708(2005) [PubMed: 16252232] [Abstract] Cited for: INVOLVEMENT IN PPCD3.
[8]	"Pc2-mediated sumoylation of Smad-interacting protein 1 attenuates transcriptional repression of E-cadherin." Long J., Zuo D., Park M. J. Biol. Chem. 280:35477-35489(2005) [PubMed: 16061479] [Abstract] Cited for: SUMOYLATION AT LYS-347 AND LYS-774.
[9]	"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: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-31 AND SER-33, MASS SPECTROMETRY. Tissue: Epithelium.
[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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-322 AND SER-646, MASS SPECTROMETRY.
[11]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[12]	"Solution structure of the homeobox domain from human NIL-2-A zinc finger protein, transcription factor 8." RIKEN structural genomics initiative (RSGI) Submitted (APR-2007) to the PDB data bank Cited for: STRUCTURE BY NMR OF 583-642.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

D15050 mRNA. Translation: BAA03646.1.
U12170 mRNA. Translation: AAA20602.1.
AL158080 , AL117340, AL161935, AL355148 Genomic DNA. Translation: CAI17320.1.
AL161935 , AL117340, AL158080, AL355148 Genomic DNA. Translation: CAH74132.1.
AL117340 , AL158080, AL161935, AL355148 Genomic DNA. Translation: CAI12550.1.
AL355148 , AL117340, AL158080, AL161935 Genomic DNA. Translation: CAI15108.1.
CH471072 Genomic DNA. Translation: EAW85989.1.
M81699 mRNA. No translation available.

IPI

IPI00375505.

PIR

JX0293.

RefSeq

NP_110378.3.

UniGene

Hs.124503

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2E19	NMR	-	A	586-642	[»]

ModBase

Search...

PTM databases

PhosphoSite

P37275.

Proteomic databases

PRIDE

P37275.

Genome annotation databases

Ensembl

ENSG00000148516. Homo sapiens. [Contig view]

GeneID

6935.

Organism-specific databases

GeneCards

GC10P031648.

HGNC

HGNC:11642. ZEB1.

MIM

189909. gene.
609141. phenotype.

Orphanet

34533. Corneal dystrophy.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P37275.

Gene expression databases

ArrayExpress

P37275.

Bgee

P37275.

CleanEx

HS_ZEB1.

GermOnline

ENSG00000148516. Homo sapiens.

Family and domain databases

InterPro

IPR001356. Homeobox.
IPR017970. Homeobox_CS.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]

Gene3D

G3DSA:3.30.160.60. Znf_C2H2/integrase_DNA-bd. 2 hits.

Pfam

PF00096. zf-C2H2. 7 hits.
[Graphical view]

ProDom

PD000010. Homeobox. 1 hit.
PD000003. Znf_C2H2. 2 hits.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00389. HOX. 1 hit.
SM00355. ZnF_C2H2. 7 hits.
[Graphical view]

PROSITE

PS00027. HOMEOBOX_1. False negative.
PS50071. HOMEOBOX_2. False negative.
PS00028. ZINC_FINGER_C2H2_1. 5 hits.
PS50157. ZINC_FINGER_C2H2_2. 6 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

27137.

SOURCE

Search...

Entry information

Entry name

ZEB1_HUMAN

Accession

Primary (citable) accession number: P37275
Secondary accession number(s): Q12924, Q13800, Q5T968

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	July 15, 1999
Last modified:	June 16, 2009
This is version 93 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)