Description: Homo sapiens hypermethylated in cancer 1 (HIC1), transcript variant 2, mRNA. RefSeq Summary (NM_001098202): This gene functions as a growth regulatory and tumor repressor gene. Hypermethylation or deletion of the region of this gene have been associated with tumors and the contiguous-gene syndrome, Miller-Dieker syndrome. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2010]. Transcript (Including UTRs) Position: hg19 chr17:1,959,604-1,962,981 Size: 3,378 Total Exon Count: 2 Strand: + Coding Region Position: hg19 chr17:1,959,604-1,962,129 Size: 2,526 Coding Exon Count: 2
ID:HIC1_HUMAN DESCRIPTION: RecName: Full=Hypermethylated in cancer 1 protein; Short=Hic-1; AltName: Full=Zinc finger and BTB domain-containing protein 29; FUNCTION: Transcriptional repressor. Recognizes and binds to the consensus sequence '5-[CG]NG[CG]GGGCA[CA]CC-3'. May act as a tumor suppressor. May be involved in development of head, face, limbs and ventral body wall. Involved in down-regulation of SIRT1 and thereby is involved in regulation of p53/TP53-dependent apoptotic DNA-damage responses. The specific target gene promoter association seems to be depend on corepressors, such as CTBP1 or CTBP2 and MTA1. The regulation of SIRT1 transcription in response to nutrient deprivation seems to involve CTBP1. In cooperation with MTA1 (indicative for an association with the NuRD complex) represses transcription from CCND1/cyclin-D1 and CDKN1C/p57Kip2 specifically in quiescent cells. Involved in regulation of the Wnt signaling pathway probably by association with TCF7L2 and preventing TCF7L2 and CTNNB1 association with promoters of TCF- responsive genes. Seems to repress transcription from E2F1 and ATOH1 which involves ARID1A, indicative for the participation of a distinct SWI/SNF-type chromatin-remodeling complex. Probably represses transcription from CXCR7, FGFBP1 and EFNA1. SUBUNIT: Self-associates. Interacts with HIC2. Interacts with CTBP1 and CTBP2. Interacts with TCF7L2 and ARID1A. Interacts with MTA1 and MBD3; indicative for an association with the NuRD complex. INTERACTION: O14497:ARID1A; NbExp=2; IntAct=EBI-2507362, EBI-637887; Q13363:CTBP1; NbExp=4; IntAct=EBI-2507362, EBI-908846; O88712:Ctbp1 (xeno); NbExp=8; IntAct=EBI-2507362, EBI-604547; P56545:CTBP2; NbExp=2; IntAct=EBI-2507362, EBI-741533; P56546:Ctbp2 (xeno); NbExp=2; IntAct=EBI-2507362, EBI-1384883; SUBCELLULAR LOCATION: Nucleus. TISSUE SPECIFICITY: Ubiquitously expressed with highest levels found in lung, colon, prostate, thymus, testis and ovary. Expression is absent or decreased in many tumor cells. DOMAIN: The BTB domain inhibits the binding to a single consensus binding site, but mediates cooperative binding to multiple binding sites. PTM: Acetylated on several residues, including Lys-333. Lys-333 is deacetylated by SIRT1. PTM: Sumoylated on Lys-333 by a PIAS family member, which enhances interaction with MTA1, positively regulates transcriptional repression activity and is enhanced by HDAC4. MISCELLANEOUS: The HIC1 gene is frequently found epigenetically silenced or deleted in different types of solid tumors. SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein family. Hic subfamily. SIMILARITY: Contains 1 BTB (POZ) domain. SIMILARITY: Contains 5 C2H2-type zinc fingers. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/HIC1ID40819ch17p13.html";
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Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): HIC1 CDC HuGE Published Literature: HIC1 Positive Disease Associations: Cleft Lip|Cleft Palate Related Studies:
Cleft Lip|Cleft Palate Jugessur A et al. 2010, Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia., PloS one 5(7) : e11493 2010.
[PubMed 20634891]
Except for FLNB, HIC1 and ZNF189, maternal genes did not appear to influence the risk of clefting in our data. This is consistent with recent epidemiological findings showing no apparent difference between mother-to-offspring and father-to-offspring recurrence of clefts in these two populations. It is likely that fetal genes make the major genetic contribution to clefting risk in these populations, but we cannot rule out the possibility that maternal genes can affect risk through interactions with specific teratogens or fetal genes.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q14526
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0001227 transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific binding GO:0003676 nucleic acid binding GO:0003677 DNA binding GO:0003700 transcription factor activity, sequence-specific DNA binding GO:0005515 protein binding GO:0042826 histone deacetylase binding GO:0043565 sequence-specific DNA binding GO:0046872 metal ion binding
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0007275 multicellular organism development GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage GO:0016055 Wnt signaling pathway GO:0030178 negative regulation of Wnt signaling pathway GO:0043517 positive regulation of DNA damage response, signal transduction by p53 class mediator
US Server
