ZEB2

Zinc finger E-box binding homeobox 2

PDB rendering based on 2da7.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
2DA7

Identifiers

Symbols

ZEB2 ; HSPC082; SIP-1; SIP1; SMADIP1; ZFHX1B

External IDs

OMIM: 605802 MGI: 1344407 HomoloGene: 8868 GeneCards: ZEB2 Gene

Gene ontology
Molecular function	• sequence-specific DNA binding transcription factor activity • phosphatase regulator activity • sequence-specific DNA binding • metal ion binding • R-SMAD binding
Cellular component	• nucleus
Biological process	• negative regulation of transcription from RNA polymerase II promoter • neural crest cell migration • somitogenesis • neural tube closure • transcription, DNA-templated • nervous system development • hippocampus development • cell proliferation in forebrain • positive regulation of Wnt signaling pathway • positive regulation of JUN kinase activity • positive regulation of melanocyte differentiation • positive regulation of transcription from RNA polymerase II promoter • positive regulation of melanin biosynthetic process • developmental pigmentation • melanocyte migration • regulation of melanosome organization
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 2:
145.14 – 145.28 Mb

Chr 2:
44.98 – 45.12 Mb

PubMed search

Zinc finger E-box-binding homeobox 2 is a protein that in humans is encoded by the ZEB2 gene.^[1]

Function

The SMADIP1 gene (also known as SIP1) is a member of the delta-EF1 (TCF8)/Zfh1 family of 2-handed zinc finger/homeodomain proteins. SMADIP1 interacts with receptor-mediated, activated full-length SMADs.^[1]

Clinical significance

Mutations in the ZEB2 gene are associated with the Mowat-Wilson syndrome.

References

↑ 1.0 1.1 "Entrez Gene: ZEB2 zinc finger E-box binding homeobox 2".

External links

GeneReviews/NIH/NCBI/UW entry on Mowat-Wilson syndrome

Mowat DR, Wilson MJ, Goossens M (2003). "Mowat-Wilson syndrome". J. Med. Genet. 40 (5): 305–10. doi:10.1136/jmg.40.5.305. PMC 1735450. PMID 12746390.
Nagase T; Ishikawa K; Miyajima N et al. (1998). "Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro". DNA Res. 5 (1): 31–9. doi:10.1093/dnares/5.1.31. PMID 9628581.
Ueki N; Oda T; Kondo M et al. (1999). "Selection system for genes encoding nuclear-targeted proteins". Nat. Biotechnol. 16 (13): 1338–42. doi:10.1038/4315. PMID 9853615.
Verschueren K; Remacle JE; Collart C et al. (1999). "SIP1, a novel zinc finger/homeodomain repressor, interacts with Smad proteins and binds to 5'-CACCT sequences in candidate target genes". J. Biol. Chem. 274 (29): 20489–98. doi:10.1074/jbc.274.29.20489. PMID 10400677.
Wakamatsu N; Yamada Y; Yamada K et al. (2001). "Mutations in SIP1, encoding Smad interacting protein-1, cause a form of Hirschsprung disease". Nat. Genet. 27 (4): 369–70. doi:10.1038/86860. PMID 11279515.
Comijn J; Berx G; Vermassen P et al. (2001). "The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion". Mol. Cell 7 (6): 1267–78. doi:10.1016/S1097-2765(01)00260-X. PMID 11430829.
Cacheux V; Dastot-Le Moal F; Kääriäinen H et al. (2001). "Loss-of-function mutations in SIP1 Smad interacting protein 1 result in a syndromic Hirschsprung disease". Hum. Mol. Genet. 10 (14): 1503–10. doi:10.1093/hmg/10.14.1503. PMID 11448942.
Tylzanowski P, Verschueren K, Huylebroeck D, Luyten FP (2001). "Smad-interacting protein 1 is a repressor of liver/bone/kidney alkaline phosphatase transcription in bone morphogenetic protein-induced osteogenic differentiation of C2C12 cells". J. Biol. Chem. 276 (43): 40001–7. doi:10.1074/jbc.M104112200. PMID 11477103.
Yamada K; Yamada Y; Nomura N et al. (2002). "Nonsense and Frameshift Mutations in ZFHX1B, Encoding Smad-Interacting Protein 1, Cause a Complex Developmental Disorder with a Great Variety of Clinical Features". Am. J. Hum. Genet. 69 (6): 1178–85. doi:10.1086/324343. PMC 1235530. PMID 11592033.
Amiel J; Espinosa-Parrilla Y; Steffann J et al. (2002). "Large-Scale Deletions and SMADIP1 Truncating Mutations in Syndromic Hirschsprung Disease with Involvement of Midline Structures". Am. J. Hum. Genet. 69 (6): 1370–7. doi:10.1086/324342. PMC 1235547. PMID 11595972.
Zweier C; Albrecht B; Mitulla B et al. (2002). ""Mowat-Wilson" syndrome with and without Hirschsprung disease is a distinct, recognizable multiple congenital anomalies-mental retardation syndrome caused by mutations in the zinc finger homeo box 1B gene". Am. J. Med. Genet. 108 (3): 177–81. doi:10.1002/ajmg.10226. PMID 11891681.
Nagaya M; Kato J; Niimi N et al. (2002). "Clinical features of a form of Hirschsprung's disease caused by a novel genetic abnormality". J. Pediatr. Surg. 37 (8): 1117–22. doi:10.1053/jpsu.2002.34455. PMID 12149685.
Guaita S; Puig I; Franci C et al. (2002). "Snail induction of epithelial to mesenchymal transition in tumor cells is accompanied by MUC1 repression and ZEB1 expression". J. Biol. Chem. 277 (42): 39209–16. doi:10.1074/jbc.M206400200. PMID 12161443.
Espinosa-Parrilla Y; Amiel J; Augé J et al. (2003). "Expression of the SMADIP1 gene during early human development". Mech. Dev. 114 (1–2): 187–91. doi:10.1016/S0925-4773(02)00062-X. PMID 12175509.
Yoneda M; Fujita T; Yamada Y et al. (2002). "Late infantile Hirschsprung disease-mental retardation syndrome with a 3-bp deletion in ZFHX1B". Neurology 59 (10): 1637–40. doi:10.1212/01.wnl.0000034842.78350.4e. PMID 12451214.
Strausberg RL; Feingold EA; Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Postigo AA (2003). "Opposing functions of ZEB proteins in the regulation of the TGFβ/BMP signaling pathway". EMBO J. 22 (10): 2443–52. doi:10.1093/emboj/cdg225. PMC 155983. PMID 12743038.
Postigo AA, Depp JL, Taylor JJ, Kroll KL (2003). "Regulation of Smad signaling through a differential recruitment of coactivators and corepressors by ZEB proteins". EMBO J. 22 (10): 2453–62. doi:10.1093/emboj/cdg226. PMC 155984. PMID 12743039.
Zweier C; Temple IK; Beemer F et al. (2003). "Characterisation of deletions of the ZFHX1B region and genotype-phenotype analysis in Mowat-Wilson syndrome". J. Med. Genet. 40 (8): 601–5. doi:10.1136/jmg.40.8.601. PMC 1735564. PMID 12920073.

PDB gallery

2da7: Solution structure of the homeobox domain of Zinc finger homeobox protein 1b (Smad interacting protein 1)

External links

ZEB2 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

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

Index of genetics

Description	Gene expression DNA replication cycle recombination repair binding proteins Transcription factors regulators nucleic acids RNA RNA binding proteins ribonucleoproteins repeated sequence modification Translation ribosome modification nexins Proteins domains Structure primary secondary tertiary quaternary

Disease	Replication and repair Transcription factor Transcription Translation

ZEB2

Function

Clinical significance

References

External links

Further reading

External links