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P22361 (HNF1A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Hepatocyte nuclear factor 1-alpha

Short name=HNF-1-alpha
Short name=HNF-1A
Alternative name(s):
Liver-specific transcription factor LF-B1
Short name=LFB1
Transcription factor 1
Short name=TCF-1
Gene names
Name:Hnf1a
Synonyms:Hnf-1, Hnf-1a, Tcf1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length628 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcriptional activator that regulates the tissue specific expression of multiple genes, especially in pancreatic islet cells and in liver. Required for the expression of several liver specific genes. Binds to the inverted palindrome 5'-GTTAATNATTAAC-3'. Ref.6 Ref.8

Subunit structure

Binds DNA as a dimer. Interacts with PCBD1. Heterotetramer with PCBD1; formed by a dimer of dimers. Ref.7 Ref.8 Ref.9

Subcellular location

Nucleus.

Tissue specificity

Liver.

Disruption phenotype

Mice are born at less than half of the expected frequency. Neonates are slightly smaller than normal and do not grow normally. After 5 weeks mice weigh only 50 to 60% as much as their littermates. Mice develop non-insulin-dependent diabetes mellitus (NIDDM) 2 weeks after birth. Mice exhibit elevated levels of blood glucose, combined with reduced blood levels of insulin and insulin-like growth factor I (IGFI). Males and females are sterile. Ref.4

Sequence similarities

Belongs to the HNF1 homeobox family.

Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   DomainHomeobox
   LigandDNA-binding
   Molecular functionActivator
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processSMAD protein signal transduction

Inferred from direct assay PubMed 9420335. Source: MGI

bile acid and bile salt transport

Inferred from mutant phenotype PubMed 11279518. Source: MGI

bile acid biosynthetic process

Inferred from mutant phenotype PubMed 11279518. Source: MGI

blastocyst development

Inferred from mutant phenotype PubMed 16880268. Source: MGI

bone resorption

Inferred from genetic interaction PubMed 15866165. Source: MGI

cholesterol metabolic process

Inferred from mutant phenotype PubMed 11279518. Source: MGI

chromatin remodeling

Inferred from mutant phenotype PubMed 12367519. Source: UniProtKB

embryonic limb morphogenesis

Inferred from genetic interaction PubMed 10090727. Source: MGI

endocrine pancreas development

Inferred from mutant phenotype PubMed 9609100. Source: MGI

fatty acid biosynthetic process

Inferred from mutant phenotype PubMed 10852923. Source: MGI

fatty acid transport

Inferred from mutant phenotype PubMed 10852923. Source: MGI

glucose homeostasis

Inferred from direct assay PubMed 11269503. Source: UniProtKB

glucose import

Inferred from direct assay PubMed 11269503. Source: UniProtKB

heme biosynthetic process

Inferred from mutant phenotype PubMed 10617683. Source: MGI

insulin secretion

Inferred from mutant phenotype PubMed 15142986PubMed 9593777PubMed 9733737. Source: MGI

liver development

Inferred from mutant phenotype Ref.4. Source: MGI

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

paraxial mesoderm formation

Inferred from genetic interaction PubMed 10090727. Source: MGI

placenta development

Inferred from genetic interaction PubMed 10090727. Source: MGI

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 15581617. Source: MGI

positive regulation of transcription initiation from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 11269503. Source: UniProtKB

protein localization

Inferred from mutant phenotype PubMed 16880268. Source: MGI

regulation of Wnt signaling pathway

Inferred from genetic interaction PubMed 10090727. Source: MGI

regulation of hormone secretion

Inferred from mutant phenotype Ref.4. Source: MGI

regulation of insulin secretion

Inferred from mutant phenotype Ref.4. Source: MGI

regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 9689059. Source: MGI

regulation of transcription, DNA-templated

Inferred from mutant phenotype PubMed 16880268. Source: MGI

renal glucose absorption

Inferred from direct assay PubMed 11269503. Source: UniProtKB

reproductive structure development

Inferred from mutant phenotype Ref.4. Source: MGI

response to glucose

Inferred from mutant phenotype PubMed 9733737. Source: MGI

response to oxidative stress

Inferred from mutant phenotype PubMed 10617683. Source: MGI

reverse cholesterol transport

Inferred from mutant phenotype PubMed 15793583. Source: MGI

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 16880268. Source: MGI

nucleus

Inferred from direct assay PubMed 12367519. Source: UniProtKB

photoreceptor outer segment

Inferred from genetic interaction PubMed 10090727. Source: MGI

pronucleus

Inferred from direct assay PubMed 16880268. Source: MGI

transcription factor complex

Inferred from physical interaction PubMed 14570708. Source: MGI

   Molecular_functionDNA binding

Inferred from direct assay PubMed 12367519. Source: UniProtKB

RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription

Inferred from electronic annotation. Source: Ensembl

double-stranded DNA binding

Inferred from electronic annotation. Source: Ensembl

protein dimerization activity

Inferred from physical interaction Ref.7. Source: UniProtKB

protein heterodimerization activity

Inferred from physical interaction PubMed 1673925PubMed 2044952. Source: MGI

protein homodimerization activity

Inferred from physical interaction PubMed 15182178PubMed 1685988PubMed 2044952. Source: MGI

sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 12367519. Source: UniProtKB

transcription regulatory region DNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sirt1Q923E45EBI-5272860,EBI-1802585

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 628628Hepatocyte nuclear factor 1-alpha
PRO_0000049116

Regions

DNA binding199 – 27981Homeobox; HNF1-type
Region1 – 3131Dimerization
Region130 – 1323Interaction with DNA By similarity
Region143 – 1497Interaction with DNA By similarity
Region155 – 1584Interaction with DNA By similarity
Region203 – 2064Interaction with DNA By similarity
Region263 – 2653Interaction with DNA By similarity
Region270 – 2734Interaction with DNA By similarity
Motif197 – 2059Nuclear localization signal Potential
Compositional bias71 – 8010Asp/Glu-rich (acidic; potential involvement with transcription)

Experimental info

Sequence conflict891L → P in AAA37821. Ref.1

Secondary structure

..... 628
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P22361 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 737920D47BA1F081

FASTA62867,253
        10         20         30         40         50         60 
MVSKLSQLQT ELLAALLESG LSKEALIQAL GEPGPYLMVG EGPLDKGESC GGSRGDLTEL 

        70         80         90        100        110        120 
PNGLGETRGS EDDTDDDGED FAPPILKELE NLSPEEAAHQ KAVVESLLQE DPWRVAKMVK 

       130        140        150        160        170        180 
SYLQQHNIPQ REVVDTTGLN QSHLSQHLNK GTPMKTQKRA ALYTWYVRKQ REVAQQFTHA 

       190        200        210        220        230        240 
GQGGLIEEPT GDELPTKKGR RNRFKWGPAS QQILFQAYER QKNPSKEERE TLVEECNRAE 

       250        260        270        280        290        300 
CIQRGVSPSQ AQGLGSNLVT EVRVYNWFAN RRKEEAFRHK LAMDTYNGPP PGPGPGPALP 

       310        320        330        340        350        360 
AHSSPGLPTT TLSPSKVHGV RYGQSATSEA AEVPSSSGGP LVTVSAALHQ VSPTGLEPSS 

       370        380        390        400        410        420 
LLSTEAKLVS ATGGPLPPVS TLTALHSLEQ TSPGLNQQPQ NLIMASLPGV MTIGPGEPAS 

       430        440        450        460        470        480 
LGPTFTNTGA STLVIGLAST QAQSVPVINS MGSSLTTLQP VQFSQPLHPS YQQPLMPPVQ 

       490        500        510        520        530        540 
SHVAQSPFMA TMAQLQSPHA LYSHKPEVAQ YTHTSLLPQT MLITDTNLST LASLTPTKQV 

       550        560        570        580        590        600 
FTSDTEASSE PGLHEPPSPA TTIHIPSQDP SNIQHLQPAH RLSTSPTVSS SSLVLYQSSD 

       610        620 
SNGHSHLLPS NHSVIETFIS TQMASSSQ 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning, functional expression, and chromosomal localization of mouse hepatocyte nuclear factor 1."
Kuo C.J., Conley P.B., Hsieh C.L., Francke U., Crabtree G.R.
Proc. Natl. Acad. Sci. U.S.A. 87:9838-9842(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[3]"Structure of the gene encoding hepatocyte nuclear factor 1 (HNF1)."
Bach I., Pontoglio M., Yaniv M.
Nucleic Acids Res. 20:4199-4204(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: GENE STRUCTURE.
[4]"Laron dwarfism and non-insulin-dependent diabetes mellitus in the Hnf-1alpha knockout mouse."
Lee Y.H., Sauer B., Gonzalez F.J.
Mol. Cell. Biol. 18:3059-3068(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[5]"Specific phosphopeptide enrichment with immobilized titanium ion affinity chromatography adsorbent for phosphoproteome analysis."
Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H.
J. Proteome Res. 7:3957-3967(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[6]"Hnf1alpha (MODY3) controls tissue-specific transcriptional programs and exerts opposed effects on cell growth in pancreatic islets and liver."
Servitja J.M., Pignatelli M., Maestro M.A., Cardalda C., Boj S.F., Lozano J., Blanco E., Lafuente A., McCarthy M.I., Sumoy L., Guigo R., Ferrer J.
Mol. Cell. Biol. 29:2945-2959(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"High-resolution structure of the HNF-1alpha dimerization domain."
Rose R.B., Endrizzi J.A., Cronk J.D., Holton J., Alber T.
Biochemistry 39:15062-15070(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.0 ANGSTROMS) OF 1-32, SUBUNIT.
[8]"Structural basis of dimerization, coactivator recognition and MODY3 mutations in HNF-1alpha."
Rose R.B., Bayle J.H., Endrizzi J.A., Cronk J.D., Crabtree G.R., Alber T.
Nat. Struct. Biol. 7:744-748(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 1-32 IN COMPLEX WITH PCBD1, SUBUNIT, FUNCTION.
[9]"The dimerization domain of HNF-1alpha: structure and plasticity of an intertwined four-helix bundle with application to diabetes mellitus."
Narayana N., Hua Q., Weiss M.A.
J. Mol. Biol. 310:635-658(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 2-32, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M57966 mRNA. Translation: AAA37821.1.
AC116500 Genomic DNA. No translation available.
PIRA39262.
RefSeqNP_033353.2. NM_009327.3.
UniGeneMm.332607.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1F93X-ray2.60E/F/G/H1-32[»]
1G2YX-ray1.00A/B/C/D1-32[»]
1G2ZX-ray1.15A/B1-32[»]
1G39X-ray1.22A/B/C/D1-32[»]
1JB6X-ray1.70A/B2-32[»]
ProteinModelPortalP22361.
SMRP22361. Positions 2-31, 85-286.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid203999. 8 interactions.
IntActP22361. 2 interactions.
MINTMINT-4097610.
STRING10090.ENSMUSP00000031535.

PTM databases

PhosphoSiteP22361.

Proteomic databases

PaxDbP22361.
PRIDEP22361.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000031535; ENSMUSP00000031535; ENSMUSG00000029556.
GeneID21405.
KEGGmmu:21405.
UCSCuc008zcz.2. mouse.

Organism-specific databases

CTD6927.
MGIMGI:98504. Hnf1a.

Phylogenomic databases

eggNOGNOG79356.
GeneTreeENSGT00730000110937.
HOGENOMHOG000015305.
HOVERGENHBG005980.
InParanoidP22361.
KOK08036.
OMASHVAQSP.
OrthoDBEOG769ZJ9.
TreeFamTF320327.

Gene expression databases

ArrayExpressP22361.
BgeeP22361.
CleanExMM_HNF1A.
GenevestigatorP22361.

Family and domain databases

Gene3D1.10.10.60. 1 hit.
1.10.260.40. 1 hit.
InterProIPR006899. HNF-1_N.
IPR023219. HNF1_dimer_dom.
IPR006898. HNF1a_C.
IPR006897. HNF1b_C.
IPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
IPR010982. Lambda_DNA-bd_dom.
[Graphical view]
PfamPF04814. HNF-1_N. 1 hit.
PF04813. HNF-1A_C. 1 hit.
PF04812. HNF-1B_C. 1 hit.
PF00046. Homeobox. 1 hit.
[Graphical view]
SMARTSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMSSF100957. SSF100957. 1 hit.
SSF46689. SSF46689. 1 hit.
SSF47413. SSF47413. 1 hit.
PROSITEPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP22361.
NextBio300672.
PROP22361.
SOURCESearch...

Entry information

Entry nameHNF1A_MOUSE
AccessionPrimary (citable) accession number: P22361
Secondary accession number(s): E9QP86
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: July 27, 2011
Last modified: April 16, 2014
This is version 144 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot