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Q9R1Y5

- HIC1_MOUSE

UniProt

Q9R1Y5 - HIC1_MOUSE

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Protein
Hypermethylated in cancer 1 protein
Gene
Hic1
Organism
Mus musculus (Mouse)
Status
Reviewed - 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 EFNA1.2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri437 – 46428C2H2-type 1
Add
BLAST
Zinc fingeri507 – 53428C2H2-type 2
Add
BLAST
Zinc fingeri535 – 56228C2H2-type 3
Add
BLAST
Zinc fingeri563 – 59028C2H2-type 4
Add
BLAST
Zinc fingeri591 – 61828C2H2-type 5
Add
BLAST

GO - Molecular functioni

  1. histone deacetylase binding Source: UniProtKB
  2. metal ion binding Source: UniProtKB-KW
  3. protein binding Source: IntAct
  4. sequence-specific DNA binding Source: UniProtKB
  5. sequence-specific DNA binding transcription factor activity Source: UniProtKB

GO - Biological processi

  1. Wnt signaling pathway Source: UniProtKB-KW
  2. intrinsic apoptotic signaling pathway in response to DNA damage Source: UniProtKB
  3. multicellular organismal development Source: UniProtKB-KW
  4. negative regulation of Wnt signaling pathway Source: UniProtKB
  5. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  6. positive regulation of DNA damage response, signal transduction by p53 class mediator Source: UniProtKB
  7. transcription, DNA-templated Source: UniProtKB-KW
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

Names & Taxonomyi

Protein namesi
Recommended name:
Hypermethylated in cancer 1 protein
Short name:
Hic-1
Gene namesi
Name:Hic1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Unplaced

Organism-specific databases

MGIiMGI:1338010. Hic1.

Subcellular locationi

Nucleus Inferred

GO - Cellular componenti

  1. chromatin Source: UniProtKB
  2. nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Defects in Hic1 are the cause of perinatal death with serious developmental anomalies, including acrania, exencephaly, cleft palate, omphalocele, craniofacial and limb anomalies.1 Publication

Disruption phenotypei

Impaired development resulting in embryonic and perinatal lethality. Mice disrupted in the germ line for only one allele of Hic1 develop many different spontaneous malignant tumors, including a predominance of epithelial cancers in males and lymphomas and sarcomas in females. The complete loss of Hic1 function in the heterozygous mice seems to involve dense methylation of the promoter of the remaining wild-type allele.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 733733Hypermethylated in cancer 1 protein
PRO_0000046943Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei333 – 3331N6-acetyllysine; alternate By similarity
Cross-linki333 – 333Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate By similarity

Post-translational modificationi

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

Keywords - PTMi

Acetylation, Isopeptide bond, Ubl conjugation

Proteomic databases

PaxDbiQ9R1Y5.
PRIDEiQ9R1Y5.

PTM databases

PhosphoSiteiQ9R1Y5.

Expressioni

Tissue specificityi

Ubiquitously expressed with highest levels in heart and lung.1 Publication

Developmental stagei

Expression is first detected in the embryo after 9 dpc. In the embryo, expression is found in restricted regions of somite derivatives, limb anlagen and cranio-facial mesenchyme. In the fetus, it is additionally expressed in mesenchymes apposed to precartilaginous condensations, at many interfaces to budding epithelia of inner organs, and weakly in muscles.1 Publication

Gene expression databases

ArrayExpressiQ9R1Y5.
BgeeiQ9R1Y5.
CleanExiMM_HIC1.
GenevestigatoriQ9R1Y5.

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 By similarity.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Sirt1Q923E42EBI-5236187,EBI-1802585
Tcf7l2Q924A04EBI-5236187,EBI-646713

Protein-protein interaction databases

BioGridi200302. 1 interaction.
IntActiQ9R1Y5. 4 interactions.
MINTiMINT-2731109.

Structurei

3D structure databases

ProteinModelPortaliQ9R1Y5.
SMRiQ9R1Y5. Positions 25-145, 429-613.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini47 – 11064BTB
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni154 – 315162Mediates HDAC-dependent transcriptional repression By similarity
Add
BLAST
Regioni241 – 2477Interaction with CTBP1 By similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi1 – 1313Arg/Gly/Pro-rich
Add
BLAST
Compositional biasi112 – 1198Poly-Ala
Compositional biasi160 – 1678Poly-Gly
Compositional biasi195 – 1995Poly-Pro

Domaini

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

Sequence similaritiesi

Contains 1 BTB (POZ) domain.

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiCOG5048.
HOGENOMiHOG000026793.
HOVERGENiHBG031606.
InParanoidiB1ARH0.
TreeFamiTF333488.

Family and domain databases

Gene3Di3.30.160.60. 4 hits.
3.30.710.10. 1 hit.
InterProiIPR000210. BTB/POZ-like.
IPR011333. BTB/POZ_fold.
IPR013069. BTB_POZ.
IPR028424. HIC1.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PANTHERiPTHR11389:SF322. PTHR11389:SF322. 1 hit.
PfamiPF00651. BTB. 1 hit.
PF00096. zf-C2H2. 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]

Sequencei

Sequence statusi: Complete.

This entry describes 1 isoform i produced by alternative splicing. Align

Note: A number of isoforms may be produced.

Isoform 1 (identifier: Q9R1Y5-1) [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

MTFPEADILL KSGECAGQTM LDTMEAPGHS RQLLLQLNNQ RTKGFLCDVI    50
IVVQNALFRA HKNVLAASSA YLKSLVVHDN LLNLDHDMVS PAVFRLVLDF 100
IYTGRLTDSV EAAAAAAVAP GAEPSLGAVL AAASYLQIPD LVALCKKRLK 150
RHGKYCHLRG GGSGGGGYAP YGRPGRGLRA ATPVIQACYS SPAGPPPPPA 200
AEPPSGPDAA VNTHCAELYA SGPGPAASLC APERRCSPLC GLDLSKKSPP 250
GSSVPERPLS ERELPPRPDS PPGAGPAVYK EPSLALPPLP PLPFQKLEEA 300
VPTPDPFRGS GGSPGPEPPG RPDGSSLLYR WMKHEPGLGS YGDELVRDRG 350
SPGERLEERG GDPAASPGGP PLGLVPPPRY PGSLDGPGTG ADGDDYKSSS 400
EETGSSEDPS PPGGHLEGYP CPHLAYGEPE SFGDNLYVCI PCGKGFPSSE 450
QLNAHVEAHV EEEEALYGRA EAAEVAAGAA GLGPPFGGGG DKVTGAPGGL 500
GELLRPYRCA SCDKSYKDPA TLRQHEKTHW LTRPYPCTIC GKKFTQRGTM 550
TRHMRSHLGL KPFACDACGM RFTRQYRLTE HMRIHSGEKP YECQVCGGKF 600
AQQRNLISHM KMHAVGGAAG AAGALAGLGG LPGVPGPDGK GKLDFPEGVF 650
AVARLTAEQL SLKQQDKAAA AELLAQTTHF LHDPKVALES LYPLAKFTAE 700
LGLSPDKAAE VLSQGAHLAA GPDSRTIDRF SPT 733
Length:733
Mass (Da):76,828
Last modified:December 14, 2011 - v4
Checksum:i912C253ED2C25E61
GO

Sequence cautioni

The sequence AAD30654.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.
The sequence AAD30655.1 differs from that shown. Reason: Erroneous gene model prediction.

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti19 – 191T → M in AAD30654. 1 Publication
Sequence conflicti19 – 191T → M in AAD30655. 1 Publication
Sequence conflicti19 – 191T → M no nucleotide entry 1 Publication
Sequence conflicti83 – 831N → S in AAD30654. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF036334 mRNA. Translation: AAD30654.1. Different initiation.
AF036582 Genomic DNA. Translation: AAD30655.1. Sequence problems.
AL603905 Genomic DNA. Translation: CAI35087.1.
AJ132691 Genomic DNA. Translation: CAB44493.1.
RefSeqiNP_001091673.1. NM_001098203.1. [Q9R1Y5-1]
UniGeneiMm.57250.

Genome annotation databases

GeneIDi15248.
KEGGimmu:15248.
UCSCiuc007kdc.1. mouse. [Q9R1Y5-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF036334 mRNA. Translation: AAD30654.1 . Different initiation.
AF036582 Genomic DNA. Translation: AAD30655.1 . Sequence problems.
AL603905 Genomic DNA. Translation: CAI35087.1 .
AJ132691 Genomic DNA. Translation: CAB44493.1 .
RefSeqi NP_001091673.1. NM_001098203.1. [Q9R1Y5-1 ]
UniGenei Mm.57250.

3D structure databases

ProteinModelPortali Q9R1Y5.
SMRi Q9R1Y5. Positions 25-145, 429-613.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 200302. 1 interaction.
IntActi Q9R1Y5. 4 interactions.
MINTi MINT-2731109.

PTM databases

PhosphoSitei Q9R1Y5.

Proteomic databases

PaxDbi Q9R1Y5.
PRIDEi Q9R1Y5.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 15248.
KEGGi mmu:15248.
UCSCi uc007kdc.1. mouse. [Q9R1Y5-1 ]

Organism-specific databases

CTDi 3090.
MGIi MGI:1338010. Hic1.

Phylogenomic databases

eggNOGi COG5048.
HOGENOMi HOG000026793.
HOVERGENi HBG031606.
InParanoidi B1ARH0.
TreeFami TF333488.

Miscellaneous databases

ChiTaRSi HIC1. mouse.
NextBioi 287857.
PROi Q9R1Y5.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q9R1Y5.
Bgeei Q9R1Y5.
CleanExi MM_HIC1.
Genevestigatori Q9R1Y5.

Family and domain databases

Gene3Di 3.30.160.60. 4 hits.
3.30.710.10. 1 hit.
InterProi IPR000210. BTB/POZ-like.
IPR011333. BTB/POZ_fold.
IPR013069. BTB_POZ.
IPR028424. HIC1.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view ]
PANTHERi PTHR11389:SF322. PTHR11389:SF322. 1 hit.
Pfami PF00651. BTB. 1 hit.
PF00096. zf-C2H2. 2 hits.
[Graphical view ]
SMARTi SM00225. BTB. 1 hit.
SM00355. ZnF_C2H2. 5 hits.
[Graphical view ]
SUPFAMi SSF54695. SSF54695. 1 hit.
PROSITEi PS50097. BTB. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 5 hits.
PS50157. ZINC_FINGER_C2H2_2. 5 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Isolation and embryonic expression of the novel mouse gene Hic1, the homologue of HIC1, a candidate gene for the Miller-Dieker syndrome."
    Grimm C., Spoerle R., Schmid T.E., Adler I.-D., Adamski J., Schughart K., Graw J.
    Hum. Mol. Genet. 8:697-710(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], NUCLEOTIDE SEQUENCE [MRNA] OF 13-733, DEVELOPMENTAL STAGE.
    Strain: 129/Sv and Swiss Webster.
    Tissue: Embryo.
  2. "Mice deficient in the candidate tumor suppressor gene Hic1 exhibit developmental defects of structures affected in the Miller-Dieker syndrome."
    Carter M.G., Johns M.A., Zeng X., Zhou L., Zink M.C., Mankowski J.L., Donovan D.M., Baylin S.B.
    Hum. Mol. Genet. 9:413-419(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE, DISEASE, TISSUE SPECIFICITY.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  4. "Identification in the human candidate tumor suppressor gene HIC-1 of a new major alternative TATA-less promoter positively regulated by p53."
    Guerardel C., Deltour S., Pinte S., Monte D., Begue A., Godwin A.K., Leprince D.
    J. Biol. Chem. 276:3078-3089(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-20, PROMOTER USAGE.
  5. "Evolutionary divergence in the broad complex, tramtrack and bric a brac/poxviruses and zinc finger domain from the candidate tumor suppressor gene hypermethylated in cancer."
    Guerardel C., Deltour S., Leprince D.
    FEBS Lett. 451:253-256(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 20-179.
    Strain: 129/Sv.
    Tissue: Liver.
  6. "Heterozygous disruption of Hic1 predisposes mice to a gender-dependent spectrum of malignant tumors."
    Chen W.Y., Zeng X., Carter M.G., Morrell C.N., Chiu Yen R.W., Esteller M., Watkins D.N., Herman J.G., Mankowski J.L., Baylin S.B.
    Nat. Genet. 33:197-202(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  7. "Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNA-damage responses."
    Chen W.Y., Wang D.H., Yen R.C., Luo J., Gu W., Baylin S.B.
    Cell 123:437-448(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH SIRT1.
  8. "Cooperation between the Hic1 and Ptch1 tumor suppressors in medulloblastoma."
    Briggs K.J., Corcoran-Schwartz I.M., Zhang W., Harcke T., Devereux W.L., Baylin S.B., Eberhart C.G., Watkins D.N.
    Genes Dev. 22:770-785(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiHIC1_MOUSE
AccessioniPrimary (citable) accession number: Q9R1Y5
Secondary accession number(s): B1ARH0, Q9R1Y6, Q9R2B0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 2, 2002
Last sequence update: December 14, 2011
Last modified: June 11, 2014
This is version 117 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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