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Protein

Hypermethylated in cancer 1 protein

Gene

HIC1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 ACKR3, FGFBP1 and EFNA1.11 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri439 – 459C2H2-type 1PROSITE-ProRule annotationAdd BLAST21
Zinc fingeri509 – 529C2H2-type 2PROSITE-ProRule annotationAdd BLAST21
Zinc fingeri537 – 557C2H2-type 3PROSITE-ProRule annotationAdd BLAST21
Zinc fingeri565 – 585C2H2-type 4PROSITE-ProRule annotationAdd BLAST21
Zinc fingeri593 – 613C2H2-type 5PROSITE-ProRule annotationAdd BLAST21

GO - Molecular functioni

  • histone deacetylase binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • sequence-specific DNA binding Source: UniProtKB
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Repressor

Keywords - Biological processi

Transcription, Transcription regulation, Wnt signaling pathway

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000177374-MONOMER.
SignaLinkiQ14526.

Names & Taxonomyi

Protein namesi
Recommended name:
Hypermethylated in cancer 1 protein
Short name:
Hic-1
Alternative name(s):
Zinc finger and BTB domain-containing protein 29
Gene namesi
Name:HIC1
Synonyms:ZBTB29
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:4909. HIC1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi244L → A: Abolishes interaction with CTBP1 and CTBP2. Impairs transcriptional repression. 1 Publication1
Mutagenesisi333K → Q: Mimicks acetylation. Impairs interaction with RBBP4 and MTA1 and no effect on interaction with CTBP2. Reduces transcriptional repression. 2 Publications1
Mutagenesisi333K → R: Abolishes sumoylation; impairs transcriptional repression activity. 2 Publications1
Mutagenesisi335E → A: Impairs transcriptional repression activity. Decreases interaction with MTA1. 2 Publications1
Mutagenesisi336P → A: Impairs K-333 acetylation; no effect on sumoylation. Decreases interaction with MTA1. 2 Publications1
Mutagenesisi540C → S: Abolishes repression activity. 1 Publication1

Keywords - Diseasei

Tumor suppressor

Organism-specific databases

DisGeNETi3090.
MalaCardsiHIC1.
OpenTargetsiENSG00000177374.
Orphaneti531. Miller-Dieker syndrome.
PharmGKBiPA29282.

Polymorphism and mutation databases

BioMutaiHIC1.
DMDMi296439502.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000469421 – 733Hypermethylated in cancer 1 proteinAdd BLAST733

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei159Omega-N-methylarginineBy similarity1
Modified residuei237PhosphoserineCombined sources1
Modified residuei248PhosphoserineCombined sources1
Modified residuei333N6-acetyllysine; alternate1 Publication1
Cross-linki333Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate
Modified residuei366PhosphoserineCombined sources1
Modified residuei704PhosphoserineBy similarity1

Post-translational modificationi

Acetylated on several residues, including Lys-333. Lys-333 is deacetylated by SIRT1.1 Publication
Sumoylated on Lys-333 by a PIAS family member, which enhances interaction with MTA1, positively regulates transcriptional repression activity and is enhanced by HDAC4.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ14526.
PeptideAtlasiQ14526.
PRIDEiQ14526.
TopDownProteomicsiQ14526-1. [Q14526-1]

PTM databases

iPTMnetiQ14526.
PhosphoSitePlusiQ14526.

Expressioni

Tissue specificityi

Ubiquitously expressed with highest levels found in lung, colon, prostate, thymus, testis and ovary. Expression is absent or decreased in many tumor cells.

Gene expression databases

BgeeiENSG00000177374.
CleanExiHS_HIC1.
ExpressionAtlasiQ14526. baseline and differential.
GenevisibleiQ14526. HS.

Organism-specific databases

HPAiHPA043372.

Interactioni

Subunit structurei

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.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ARID1AO144972EBI-2507362,EBI-637887
CTBP1Q133634EBI-2507362,EBI-908846
Ctbp1O8871210EBI-2507362,EBI-604547From a different organism.
CTBP2P565452EBI-2507362,EBI-741533
Ctbp2P565462EBI-2507362,EBI-1384883From a different organism.
TCF7L2Q9NQB06EBI-2507362,EBI-924724

GO - Molecular functioni

  • histone deacetylase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi109337. 27 interactors.
IntActiQ14526. 11 interactors.
MINTiMINT-2730619.
STRINGi9606.ENSP00000314080.

Structurei

3D structure databases

ProteinModelPortaliQ14526.
SMRiQ14526.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini47 – 110BTBPROSITE-ProRule annotationAdd BLAST64

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni154 – 315Mediates HDAC-dependent transcriptional repressionAdd BLAST162
Regioni241 – 247Interaction with CTBP17

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi110 – 119Poly-Ala10
Compositional biasi160 – 167Poly-Gly8
Compositional biasi195 – 199Poly-Pro5

Domaini

The BTB domain inhibits the binding to a single consensus binding site, but mediates cooperative binding to multiple binding sites.

Sequence similaritiesi

Contains 1 BTB (POZ) domain.PROSITE-ProRule annotation
Contains 5 C2H2-type zinc fingers.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri439 – 459C2H2-type 1PROSITE-ProRule annotationAdd BLAST21
Zinc fingeri509 – 529C2H2-type 2PROSITE-ProRule annotationAdd BLAST21
Zinc fingeri537 – 557C2H2-type 3PROSITE-ProRule annotationAdd BLAST21
Zinc fingeri565 – 585C2H2-type 4PROSITE-ProRule annotationAdd BLAST21
Zinc fingeri593 – 613C2H2-type 5PROSITE-ProRule annotationAdd BLAST21

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1721. Eukaryota.
COG5048. LUCA.
GeneTreeiENSGT00850000132251.
HOGENOMiHOG000026793.
HOVERGENiHBG031606.
InParanoidiQ14526.
OMAiPPDPFRG.
OrthoDBiEOG091G051O.
PhylomeDBiQ14526.
TreeFamiTF333488.

Family and domain databases

Gene3Di3.30.160.60. 4 hits.
InterProiIPR000210. BTB/POZ_dom.
IPR028424. HIC1.
IPR011333. SKP1/BTB/POZ.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PANTHERiPTHR24409:SF69. PTHR24409:SF69. 1 hit.
PfamiPF00651. BTB. 1 hit.
PF00096. zf-C2H2. 1 hit.
PF13912. zf-C2H2_6. 2 hits.
[Graphical view]
SMARTiSM00225. BTB. 1 hit.
SM00355. ZnF_C2H2. 5 hits.
[Graphical view]
SUPFAMiSSF54695. SSF54695. 1 hit.
PROSITEiPS50097. BTB. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 5 hits.
PS50157. ZINC_FINGER_C2H2_2. 5 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: Q14526-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MTFPEADILL KSGECAGQTM LDTMEAPGHS RQLLLQLNNQ RTKGFLCDVI
60 70 80 90 100
IVVQNALFRA HKNVLAASSA YLKSLVVHDN LLNLDHDMVS PAVFRLVLDF
110 120 130 140 150
IYTGRLADGA EAAAAAAVAP GAEPSLGAVL AAASYLQIPD LVALCKKRLK
160 170 180 190 200
RHGKYCHLRG GGGGGGGYAP YGRPGRGLRA ATPVIQACYP SPVGPPPPPA
210 220 230 240 250
AEPPSGPEAA VNTHCAELYA SGPGPAAALC ASERRCSPLC GLDLSKKSPP
260 270 280 290 300
GSAAPERPLA ERELPPRPDS PPSAGPAAYK EPPLALPSLP PLPFQKLEEA
310 320 330 340 350
APPSDPFRGG SGSPGPEPPG RPDGPSLLYR WMKHEPGLGS YGDELGRERG
360 370 380 390 400
SPSERCEERG GDAAVSPGGP PLGLAPPPRY PGSLDGPGAG GDGDDYKSSS
410 420 430 440 450
EETGSSEDPS PPGGHLEGYP CPHLAYGEPE SFGDNLYVCI PCGKGFPSSE
460 470 480 490 500
QLNAHVEAHV EEEEALYGRA EAAEVAAGAA GLGPPFGGGG DKVAGAPGGL
510 520 530 540 550
GELLRPYRCA SCDKSYKDPA TLRQHEKTHW LTRPYPCTIC GKKFTQRGTM
560 570 580 590 600
TRHMRSHLGL KPFACDACGM RFTRQYRLTE HMRIHSGEKP YECQVCGGKF
610 620 630 640 650
AQQRNLISHM KMHAVGGAAG AAGALAGLGG LPGVPGPDGK GKLDFPEGVF
660 670 680 690 700
AVARLTAEQL SLKQQDKAAA AELLAQTTHF LHDPKVALES LYPLAKFTAE
710 720 730
LGLSPDKAAE VLSQGAHLAA GPDGRTIDRF SPT
Length:733
Mass (Da):76,508
Last modified:May 18, 2010 - v5
Checksum:i6DDD0F49C4E490D3
GO
Isoform 2 (identifier: Q14526-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-19: Missing.

Show »
Length:714
Mass (Da):74,514
Checksum:i3AB8B6CB2C97218D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti190P → R in AAD09201 (PubMed:7585125).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_063109725R → G.1 PublicationCorresponds to variant rs1063317dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0068261 – 19Missing in isoform 2. CuratedAdd BLAST19

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L41919 Genomic DNA. Translation: AAD09201.1.
AC090617 Genomic DNA. No translation available.
CH471108 Genomic DNA. Translation: EAW90562.1.
CH471108 Genomic DNA. Translation: EAW90563.1.
CCDSiCCDS42229.1. [Q14526-1]
CCDS42230.1. [Q14526-2]
RefSeqiNP_001091672.1. NM_001098202.1. [Q14526-1]
NP_006488.2. NM_006497.3. [Q14526-2]
UniGeneiHs.695682.
Hs.72956.

Genome annotation databases

EnsembliENST00000322941; ENSP00000314080; ENSG00000177374. [Q14526-1]
ENST00000399849; ENSP00000382742; ENSG00000177374. [Q14526-2]
ENST00000619757; ENSP00000477858; ENSG00000177374. [Q14526-2]
GeneIDi3090.
KEGGihsa:3090.
UCSCiuc002fty.5. human. [Q14526-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L41919 Genomic DNA. Translation: AAD09201.1.
AC090617 Genomic DNA. No translation available.
CH471108 Genomic DNA. Translation: EAW90562.1.
CH471108 Genomic DNA. Translation: EAW90563.1.
CCDSiCCDS42229.1. [Q14526-1]
CCDS42230.1. [Q14526-2]
RefSeqiNP_001091672.1. NM_001098202.1. [Q14526-1]
NP_006488.2. NM_006497.3. [Q14526-2]
UniGeneiHs.695682.
Hs.72956.

3D structure databases

ProteinModelPortaliQ14526.
SMRiQ14526.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109337. 27 interactors.
IntActiQ14526. 11 interactors.
MINTiMINT-2730619.
STRINGi9606.ENSP00000314080.

PTM databases

iPTMnetiQ14526.
PhosphoSitePlusiQ14526.

Polymorphism and mutation databases

BioMutaiHIC1.
DMDMi296439502.

Proteomic databases

PaxDbiQ14526.
PeptideAtlasiQ14526.
PRIDEiQ14526.
TopDownProteomicsiQ14526-1. [Q14526-1]

Protocols and materials databases

DNASUi3090.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000322941; ENSP00000314080; ENSG00000177374. [Q14526-1]
ENST00000399849; ENSP00000382742; ENSG00000177374. [Q14526-2]
ENST00000619757; ENSP00000477858; ENSG00000177374. [Q14526-2]
GeneIDi3090.
KEGGihsa:3090.
UCSCiuc002fty.5. human. [Q14526-1]

Organism-specific databases

CTDi3090.
DisGeNETi3090.
GeneCardsiHIC1.
H-InvDBHIX0039113.
HGNCiHGNC:4909. HIC1.
HPAiHPA043372.
MalaCardsiHIC1.
MIMi603825. gene.
neXtProtiNX_Q14526.
OpenTargetsiENSG00000177374.
Orphaneti531. Miller-Dieker syndrome.
PharmGKBiPA29282.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1721. Eukaryota.
COG5048. LUCA.
GeneTreeiENSGT00850000132251.
HOGENOMiHOG000026793.
HOVERGENiHBG031606.
InParanoidiQ14526.
OMAiPPDPFRG.
OrthoDBiEOG091G051O.
PhylomeDBiQ14526.
TreeFamiTF333488.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000177374-MONOMER.
SignaLinkiQ14526.

Miscellaneous databases

GeneWikiiHIC1.
GenomeRNAii3090.
PROiQ14526.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000177374.
CleanExiHS_HIC1.
ExpressionAtlasiQ14526. baseline and differential.
GenevisibleiQ14526. HS.

Family and domain databases

Gene3Di3.30.160.60. 4 hits.
InterProiIPR000210. BTB/POZ_dom.
IPR028424. HIC1.
IPR011333. SKP1/BTB/POZ.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PANTHERiPTHR24409:SF69. PTHR24409:SF69. 1 hit.
PfamiPF00651. BTB. 1 hit.
PF00096. zf-C2H2. 1 hit.
PF13912. zf-C2H2_6. 2 hits.
[Graphical view]
SMARTiSM00225. BTB. 1 hit.
SM00355. ZnF_C2H2. 5 hits.
[Graphical view]
SUPFAMiSSF54695. SSF54695. 1 hit.
PROSITEiPS50097. BTB. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 5 hits.
PS50157. ZINC_FINGER_C2H2_2. 5 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHIC1_HUMAN
AccessioniPrimary (citable) accession number: Q14526
Secondary accession number(s): D3DTI4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 2, 2002
Last sequence update: May 18, 2010
Last modified: November 2, 2016
This is version 156 of the entry and version 5 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Miscellaneous

The HIC1 gene is frequently found epigenetically silenced or deleted in different types of solid tumors.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.