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P22361

- HNF1A_MOUSE

UniProt

P22361 - HNF1A_MOUSE

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Protein

Hepatocyte nuclear factor 1-alpha

Gene

Hnf1a

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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'.2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi199 – 27981Homeobox; HNF1-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. DNA binding Source: UniProtKB
  2. double-stranded DNA binding Source: Ensembl
  3. protein dimerization activity Source: UniProtKB
  4. protein heterodimerization activity Source: MGI
  5. protein homodimerization activity Source: MGI
  6. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: Ensembl
  7. RNA polymerase II core promoter sequence-specific DNA binding Source: MGI
  8. sequence-specific DNA binding transcription factor activity Source: UniProtKB
  9. transcription regulatory region DNA binding Source: UniProtKB

GO - Biological processi

  1. bile acid and bile salt transport Source: MGI
  2. bile acid biosynthetic process Source: MGI
  3. blastocyst development Source: MGI
  4. bone resorption Source: MGI
  5. cholesterol metabolic process Source: MGI
  6. chromatin remodeling Source: UniProtKB
  7. embryonic limb morphogenesis Source: MGI
  8. endocrine pancreas development Source: MGI
  9. fatty acid biosynthetic process Source: MGI
  10. fatty acid transport Source: MGI
  11. glucose homeostasis Source: UniProtKB
  12. glucose import Source: UniProtKB
  13. heme biosynthetic process Source: MGI
  14. insulin secretion Source: MGI
  15. liver development Source: MGI
  16. negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
  17. paraxial mesoderm formation Source: MGI
  18. placenta development Source: MGI
  19. positive regulation of transcription, DNA-templated Source: UniProtKB
  20. positive regulation of transcription from RNA polymerase II promoter Source: MGI
  21. protein localization Source: MGI
  22. regulation of hormone secretion Source: MGI
  23. regulation of insulin secretion Source: MGI
  24. regulation of transcription, DNA-templated Source: MGI
  25. regulation of transcription from RNA polymerase II promoter Source: MGI
  26. regulation of Wnt signaling pathway Source: MGI
  27. renal glucose absorption Source: UniProtKB
  28. reproductive structure development Source: MGI
  29. response to glucose Source: MGI
  30. response to oxidative stress Source: MGI
  31. reverse cholesterol transport Source: MGI
  32. SMAD protein signal transduction Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_214529. Regulation of gene expression in beta cells.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Hnf1a
Synonyms:Hnf-1, Hnf-1a, Tcf1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 5

Organism-specific databases

MGIiMGI:98504. Hnf1a.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: MGI
  2. nucleus Source: UniProtKB
  3. photoreceptor outer segment Source: MGI
  4. pronucleus Source: MGI
  5. transcription factor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

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.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 628628Hepatocyte nuclear factor 1-alphaPRO_0000049116Add
BLAST

Proteomic databases

MaxQBiP22361.
PaxDbiP22361.
PRIDEiP22361.

PTM databases

PhosphoSiteiP22361.

Expressioni

Tissue specificityi

Liver.

Gene expression databases

BgeeiP22361.
CleanExiMM_HNF1A.
ExpressionAtlasiP22361. baseline and differential.
GenevestigatoriP22361.

Interactioni

Subunit structurei

Binds DNA as a dimer. Interacts with PCBD1. Heterotetramer with PCBD1; formed by a dimer of dimers.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Sirt1Q923E45EBI-5272860,EBI-1802585

Protein-protein interaction databases

BioGridi203999. 8 interactions.
IntActiP22361. 2 interactions.
MINTiMINT-4097610.
STRINGi10090.ENSMUSP00000031535.

Structurei

Secondary structure

1
628
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi4 – 1815
Helixi23 – 308

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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/B1-33[»]
ProteinModelPortaliP22361.
SMRiP22361. Positions 2-31, 85-286.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP22361.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 3131DimerizationAdd
BLAST
Regioni130 – 1323Interaction with DNABy similarity
Regioni143 – 1497Interaction with DNABy similarity
Regioni155 – 1584Interaction with DNABy similarity
Regioni203 – 2064Interaction with DNABy similarity
Regioni263 – 2653Interaction with DNABy similarity
Regioni270 – 2734Interaction with DNABy similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi197 – 2059Nuclear localization signalSequence Analysis

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi71 – 8010Asp/Glu-rich (acidic; potential involvement with transcription)

Sequence similaritiesi

Belongs to the HNF1 homeobox family.Curated
Contains 1 homeobox DNA-binding domain.PROSITE-ProRule annotation

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiNOG79356.
GeneTreeiENSGT00730000110937.
HOGENOMiHOG000015305.
HOVERGENiHBG005980.
InParanoidiP22361.
KOiK08036.
OMAiSHVAQSP.
OrthoDBiEOG769ZJ9.
TreeFamiTF320327.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
1.10.260.40. 1 hit.
InterProiIPR006899. 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]
PfamiPF04814. HNF-1_N. 1 hit.
PF04813. HNF-1A_C. 1 hit.
PF04812. HNF-1B_C. 1 hit.
PF00046. Homeobox. 1 hit.
[Graphical view]
SMARTiSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMiSSF100957. SSF100957. 1 hit.
SSF46689. SSF46689. 1 hit.
SSF47413. SSF47413. 1 hit.
PROSITEiPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P22361 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MVSKLSQLQT ELLAALLESG LSKEALIQAL GEPGPYLMVG EGPLDKGESC
60 70 80 90 100
GGSRGDLTEL PNGLGETRGS EDDTDDDGED FAPPILKELE NLSPEEAAHQ
110 120 130 140 150
KAVVESLLQE DPWRVAKMVK SYLQQHNIPQ REVVDTTGLN QSHLSQHLNK
160 170 180 190 200
GTPMKTQKRA ALYTWYVRKQ REVAQQFTHA GQGGLIEEPT GDELPTKKGR
210 220 230 240 250
RNRFKWGPAS QQILFQAYER QKNPSKEERE TLVEECNRAE CIQRGVSPSQ
260 270 280 290 300
AQGLGSNLVT EVRVYNWFAN RRKEEAFRHK LAMDTYNGPP PGPGPGPALP
310 320 330 340 350
AHSSPGLPTT TLSPSKVHGV RYGQSATSEA AEVPSSSGGP LVTVSAALHQ
360 370 380 390 400
VSPTGLEPSS LLSTEAKLVS ATGGPLPPVS TLTALHSLEQ TSPGLNQQPQ
410 420 430 440 450
NLIMASLPGV MTIGPGEPAS LGPTFTNTGA STLVIGLAST QAQSVPVINS
460 470 480 490 500
MGSSLTTLQP VQFSQPLHPS YQQPLMPPVQ SHVAQSPFMA TMAQLQSPHA
510 520 530 540 550
LYSHKPEVAQ YTHTSLLPQT MLITDTNLST LASLTPTKQV FTSDTEASSE
560 570 580 590 600
PGLHEPPSPA TTIHIPSQDP SNIQHLQPAH RLSTSPTVSS SSLVLYQSSD
610 620
SNGHSHLLPS NHSVIETFIS TQMASSSQ
Length:628
Mass (Da):67,253
Last modified:July 27, 2011 - v2
Checksum:i737920D47BA1F081
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti89 – 891L → P in AAA37821. (PubMed:2263635)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M57966 mRNA. Translation: AAA37821.1.
AC116500 Genomic DNA. No translation available.
CCDSiCCDS19577.1.
PIRiA39262.
RefSeqiNP_033353.2. NM_009327.3.
UniGeneiMm.332607.

Genome annotation databases

EnsembliENSMUST00000031535; ENSMUSP00000031535; ENSMUSG00000029556.
GeneIDi21405.
KEGGimmu:21405.
UCSCiuc008zcz.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M57966 mRNA. Translation: AAA37821.1 .
AC116500 Genomic DNA. No translation available.
CCDSi CCDS19577.1.
PIRi A39262.
RefSeqi NP_033353.2. NM_009327.3.
UniGenei Mm.332607.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1F93 X-ray 2.60 E/F/G/H 1-32 [» ]
1G2Y X-ray 1.00 A/B/C/D 1-32 [» ]
1G2Z X-ray 1.15 A/B 1-32 [» ]
1G39 X-ray 1.22 A/B/C/D 1-32 [» ]
1JB6 X-ray 1.70 A/B 1-33 [» ]
ProteinModelPortali P22361.
SMRi P22361. Positions 2-31, 85-286.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 203999. 8 interactions.
IntActi P22361. 2 interactions.
MINTi MINT-4097610.
STRINGi 10090.ENSMUSP00000031535.

PTM databases

PhosphoSitei P22361.

Proteomic databases

MaxQBi P22361.
PaxDbi P22361.
PRIDEi P22361.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000031535 ; ENSMUSP00000031535 ; ENSMUSG00000029556 .
GeneIDi 21405.
KEGGi mmu:21405.
UCSCi uc008zcz.2. mouse.

Organism-specific databases

CTDi 6927.
MGIi MGI:98504. Hnf1a.

Phylogenomic databases

eggNOGi NOG79356.
GeneTreei ENSGT00730000110937.
HOGENOMi HOG000015305.
HOVERGENi HBG005980.
InParanoidi P22361.
KOi K08036.
OMAi SHVAQSP.
OrthoDBi EOG769ZJ9.
TreeFami TF320327.

Enzyme and pathway databases

Reactomei REACT_214529. Regulation of gene expression in beta cells.

Miscellaneous databases

EvolutionaryTracei P22361.
NextBioi 300672.
PROi P22361.
SOURCEi Search...

Gene expression databases

Bgeei P22361.
CleanExi MM_HNF1A.
ExpressionAtlasi P22361. baseline and differential.
Genevestigatori P22361.

Family and domain databases

Gene3Di 1.10.10.60. 1 hit.
1.10.260.40. 1 hit.
InterProi IPR006899. 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 ]
Pfami PF04814. HNF-1_N. 1 hit.
PF04813. HNF-1A_C. 1 hit.
PF04812. HNF-1B_C. 1 hit.
PF00046. Homeobox. 1 hit.
[Graphical view ]
SMARTi SM00389. HOX. 1 hit.
[Graphical view ]
SUPFAMi SSF100957. SSF100957. 1 hit.
SSF46689. SSF46689. 1 hit.
SSF47413. SSF47413. 1 hit.
PROSITEi PS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.

Entry informationi

Entry nameiHNF1A_MOUSE
AccessioniPrimary (citable) accession number: P22361
Secondary accession number(s): E9QP86
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: July 27, 2011
Last modified: October 29, 2014
This is version 150 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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

External Data

Dasty 3