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Protein

Hypermethylated in cancer 1 protein

Gene

Hic1

Organism
Mus musculus (Mouse)
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 EFNA1.2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri437 – 464C2H2-type 1PROSITE-ProRule annotationAdd BLAST28
Zinc fingeri507 – 534C2H2-type 2PROSITE-ProRule annotationAdd BLAST28
Zinc fingeri535 – 562C2H2-type 3PROSITE-ProRule annotationAdd BLAST28
Zinc fingeri563 – 590C2H2-type 4PROSITE-ProRule annotationAdd BLAST28
Zinc fingeri591 – 618C2H2-type 5PROSITE-ProRule annotationAdd BLAST28

GO - Molecular functioni

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

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
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1338010. Hic1.

Subcellular locationi

GO - Cellular componenti

  • chromatin Source: UniProtKB
  • cytoplasm Source: MGI
  • nucleoplasm Source: MGI
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.

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)DescriptionActionsGraphical viewLength
ChainiPRO_00000469431 – 733Hypermethylated in cancer 1 proteinAdd BLAST733

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei159Omega-N-methylarginineCombined sources1
Modified residuei237PhosphoserineBy similarity1
Modified residuei248PhosphoserineBy similarity1
Modified residuei333N6-acetyllysine; alternateBy similarity1
Cross-linki333Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity
Modified residuei366PhosphoserineBy similarity1
Modified residuei704PhosphoserineCombined sources1

Post-translational modificationi

Acetylated on several residues, including Lys-333. Lys-333 is deacetylated by SIRT1 (By similarity).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, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ9R1Y5.
PaxDbiQ9R1Y5.
PeptideAtlasiQ9R1Y5.
PRIDEiQ9R1Y5.

PTM databases

iPTMnetiQ9R1Y5.
PhosphoSitePlusiQ9R1Y5.

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

CleanExiMM_HIC1.

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).By similarity

Binary interactionsi

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi200302. 1 interactor.
IntActiQ9R1Y5. 4 interactors.
MINTiMINT-2731109.
STRINGi10090.ENSMUSP00000053483.

Structurei

3D structure databases

ProteinModelPortaliQ9R1Y5.
SMRiQ9R1Y5.
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 repressionBy similarityAdd BLAST162
Regioni241 – 247Interaction with CTBP1By similarity7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1 – 13Arg/Gly/Pro-richAdd BLAST13
Compositional biasi112 – 119Poly-Ala8
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.By similarity

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 fingeri437 – 464C2H2-type 1PROSITE-ProRule annotationAdd BLAST28
Zinc fingeri507 – 534C2H2-type 2PROSITE-ProRule annotationAdd BLAST28
Zinc fingeri535 – 562C2H2-type 3PROSITE-ProRule annotationAdd BLAST28
Zinc fingeri563 – 590C2H2-type 4PROSITE-ProRule annotationAdd BLAST28
Zinc fingeri591 – 618C2H2-type 5PROSITE-ProRule annotationAdd BLAST28

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1721. Eukaryota.
COG5048. LUCA.
HOGENOMiHOG000026793.
HOVERGENiHBG031606.
InParanoidiQ9R1Y5.
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]

Sequencei

Sequence statusi: Complete.

This entry describes 1 isoform i produced by alternative splicing. AlignAdd to basket

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

        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
IYTGRLTDSV EAAAAAAVAP GAEPSLGAVL AAASYLQIPD LVALCKKRLK
160 170 180 190 200
RHGKYCHLRG GGSGGGGYAP YGRPGRGLRA ATPVIQACYS SPAGPPPPPA
210 220 230 240 250
AEPPSGPDAA VNTHCAELYA SGPGPAASLC APERRCSPLC GLDLSKKSPP
260 270 280 290 300
GSSVPERPLS ERELPPRPDS PPGAGPAVYK EPSLALPPLP PLPFQKLEEA
310 320 330 340 350
VPTPDPFRGS GGSPGPEPPG RPDGSSLLYR WMKHEPGLGS YGDELVRDRG
360 370 380 390 400
SPGERLEERG GDPAASPGGP PLGLVPPPRY PGSLDGPGTG ADGDDYKSSS
410 420 430 440 450
EETGSSEDPS PPGGHLEGYP CPHLAYGEPE SFGDNLYVCI PCGKGFPSSE
460 470 480 490 500
QLNAHVEAHV EEEEALYGRA EAAEVAAGAA GLGPPFGGGG DKVTGAPGGL
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 GPDSRTIDRF SPT
Length:733
Mass (Da):76,828
Last modified:December 14, 2011 - v4
Checksum:i912C253ED2C25E61
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti19T → M in AAD30654 (PubMed:10072440).Curated1
Sequence conflicti19T → M in AAD30655 (PubMed:10072440).Curated1
Sequence conflicti19T → M no nucleotide entry (PubMed:11073960).Curated1
Sequence conflicti83N → S in AAD30654 (PubMed:10072440).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

ProteinModelPortaliQ9R1Y5.
SMRiQ9R1Y5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200302. 1 interactor.
IntActiQ9R1Y5. 4 interactors.
MINTiMINT-2731109.
STRINGi10090.ENSMUSP00000053483.

PTM databases

iPTMnetiQ9R1Y5.
PhosphoSitePlusiQ9R1Y5.

Proteomic databases

MaxQBiQ9R1Y5.
PaxDbiQ9R1Y5.
PeptideAtlasiQ9R1Y5.
PRIDEiQ9R1Y5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi3090.
MGIiMGI:1338010. Hic1.

Phylogenomic databases

eggNOGiKOG1721. Eukaryota.
COG5048. LUCA.
HOGENOMiHOG000026793.
HOVERGENiHBG031606.
InParanoidiQ9R1Y5.
TreeFamiTF333488.

Miscellaneous databases

ChiTaRSiHic1. mouse.
PROiQ9R1Y5.
SOURCEiSearch...

Gene expression databases

CleanExiMM_HIC1.

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_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: November 2, 2016
This is version 136 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

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.