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hypermethylated in cancer 1 protein; Hic-1; zinc finger & BTB domain-containing protein 29 (HIC1, ZBTB29)

Function: - transcriptional repressor - recognizes & binds to the consensus sequence '5-[CG]NG[CG]GGGCA[CA]CC-3' - tumor suppressor - development of head, face, limbs, ventral body wall - interacts with CtBP - role in down-regulation of SIRT1 thus role in regulation of p53/TP53-dependent apoptotic DNA-damage responses - specific target gene promoter association seems to be depend on corepressors, such as CTBP1 or CTBP2 & MTA1 - regulation of SIRT1 transcription in response to nutrient deprivation seems to involve CTBP1 - in cooperation with MTA1 represses transcription from CCND1/cyclin-D1 & CDKN1C/p57Kip2 in quiescent cells - role in regulation of the Wnt signaling pathway probably by association with TCF7L2 & preventing TCF7L2 & CTNNB1 association with promoters of TCF-responsive genes - seems to repress transcription from E2F1 & ATOH1 which involves ARID1A - probably represses transcription from ACKR3, FGFBP1 & EFNA1 - acetylated on several residues, including Lys-333 - Lys-333 is deacetylated by SIRT1 - sumoylated on Lys-333 by a PIAS family member, which enhances interaction with MTA1, positively regulates transcriptional repression activity & is enhanced by HDAC4 - interacts with HIC2 - interacts with CTBP1 & CTBP2 - interacts with TCF7L2 & ARID1A - interacts with MTA1 & MBD3; indicative for an association with the NuRD complex Structure: - self-associates - the BTB domain inhibits the binding to a single consensus binding site, but mediates cooperative binding to multiple binding sites - belongs to the krueppel C2H2-type Zn+2-finger protein family, Hic subfamily - contains 1 BTB/POZ domain - contains 5 C2H2-type Zn+2 fingers Compartment: nucleus Alternative splicing: named isoforms=2 Expression: - ubiquitously expressed, highest levels in lung, colon, prostate, thymus, testis, ovary Pathology: - expression is absent or decreased in many tumor cells - epigenetically silenced or deleted - defects in HIC1 associated with Miller-Dieker syndrome

Related

HIC1 (hypermethylated in cancer 1) gene

General

phosphoprotein zinc finger protein

Properties

SIZE: entity length = 733 aa MW = 77 kD COMPARTMENT: cell nucleus MOTIF: BTB domain {47-110} MOTIF: Zinc finger NAME: Zinc finger EFFECTOR-BOUND: Zn+2 alanine-rich region {110-119} MOTIF: alanine residue (SEVERAL) silencer element SITE: 154-315 MOTIF: glycine-rich region {160-167} proline-rich region SITE: 195-199 MOTIF: proline residue (SEVERAL) Ser phosphorylation site {S237} CTBP1 interaction {241-247} Ser phosphorylation site {S248} Ser phosphorylation site {S366} Zn finger C2H2-type SITE: 439-459 EFFECTOR-BOUND: Zn+2 Zn finger C2H2-type SITE: 509-529 EFFECTOR-BOUND: Zn+2 Zn finger C2H2-type SITE: 537-557 EFFECTOR-BOUND: Zn+2 Zn finger C2H2-type SITE: 565-585 EFFECTOR-BOUND: Zn+2 Zn finger C2H2-type SITE: 593-613 EFFECTOR-BOUND: Zn+2

Database Correlations

OMIM 603825 UniProt Q14526 PFAM correlations Entrez Gene 3090 Kegg hsa:3090

References

  1. UniProt :accession Q14526
  2. PMID: 16269335
  3. PMID: 16690027
  4. PMID: 16724116
  5. PMID: 17213307
  6. PMID: 18347096
  7. PMID: 19486893
  8. PMID: 19525223
  9. PMID: 20154726
  10. PMID: 20547755
  11. PMID: 12052894
  12. PMID: 16762039
  13. Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/HIC1ID40819ch17p13.html