HNF1A_MOUSE
ID HNF1A_MOUSE Reviewed; 628 AA.
AC P22361; E9QP86;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=Hepatocyte nuclear factor 1-alpha;
DE Short=HNF-1-alpha;
DE Short=HNF-1A;
DE AltName: Full=Liver-specific transcription factor LF-B1;
DE Short=LFB1;
DE AltName: Full=Transcription factor 1;
DE Short=TCF-1;
GN Name=Hnf1a; Synonyms=Hnf-1, Hnf-1a, Tcf1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2263635; DOI=10.1073/pnas.87.24.9838;
RA Kuo C.J., Conley P.B., Hsieh C.L., Francke U., Crabtree G.R.;
RT "Molecular cloning, functional expression, and chromosomal localization of
RT mouse hepatocyte nuclear factor 1.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:9838-9842(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP GENE STRUCTURE.
RX PubMed=1354855; DOI=10.1093/nar/20.16.4199;
RA Bach I., Pontoglio M., Yaniv M.;
RT "Structure of the gene encoding hepatocyte nuclear factor 1 (HNF1).";
RL Nucleic Acids Res. 20:4199-4204(1992).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=9566924; DOI=10.1128/mcb.18.5.3059;
RA Lee Y.H., Sauer B., Gonzalez F.J.;
RT "Laron dwarfism and non-insulin-dependent diabetes mellitus in the Hnf-
RT 1alpha knockout mouse.";
RL Mol. Cell. Biol. 18:3059-3068(1998).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18630941; DOI=10.1021/pr800223m;
RA Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H.;
RT "Specific phosphopeptide enrichment with immobilized titanium ion affinity
RT chromatography adsorbent for phosphoproteome analysis.";
RL J. Proteome Res. 7:3957-3967(2008).
RN [6]
RP FUNCTION.
RX PubMed=19289501; DOI=10.1128/mcb.01389-08;
RA Servitja J.M., Pignatelli M., Maestro M.A., Cardalda C., Boj S.F.,
RA Lozano J., Blanco E., Lafuente A., McCarthy M.I., Sumoy L., Guigo R.,
RA Ferrer J.;
RT "Hnf1alpha (MODY3) controls tissue-specific transcriptional programs and
RT exerts opposed effects on cell growth in pancreatic islets and liver.";
RL Mol. Cell. Biol. 29:2945-2959(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70; THR-74; SER-247 AND
RP SER-313, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Liver, and Pancreas;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP FUNCTION, AND INTERACTION WITH BHLHE41.
RX PubMed=30555544; DOI=10.7150/thno.28676;
RA Zhang T., Yu F., Guo L., Chen M., Yuan X., Wu B.;
RT "Small heterodimer partner regulates circadian cytochromes p450 and drug-
RT induced hepatotoxicity.";
RL Theranostics 8:5246-5258(2018).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.0 ANGSTROMS) OF 1-32, AND SUBUNIT.
RX PubMed=11106484; DOI=10.1021/bi001996t;
RA Rose R.B., Endrizzi J.A., Cronk J.D., Holton J., Alber T.;
RT "High-resolution structure of the HNF-1alpha dimerization domain.";
RL Biochemistry 39:15062-15070(2000).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 1-32 IN COMPLEX WITH PCBD1,
RP SUBUNIT, AND FUNCTION.
RX PubMed=10966642; DOI=10.1038/78966;
RA Rose R.B., Bayle J.H., Endrizzi J.A., Cronk J.D., Crabtree G.R., Alber T.;
RT "Structural basis of dimerization, coactivator recognition and MODY3
RT mutations in HNF-1alpha.";
RL Nat. Struct. Biol. 7:744-748(2000).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 2-32, AND SUBUNIT.
RX PubMed=11439029; DOI=10.1006/jmbi.2001.4780;
RA Narayana N., Hua Q., Weiss M.A.;
RT "The dimerization domain of HNF-1alpha: structure and plasticity of an
RT intertwined four-helix bundle with application to diabetes mellitus.";
RL J. Mol. Biol. 310:635-658(2001).
CC -!- FUNCTION: Transcriptional activator that regulates the tissue specific
CC expression of multiple genes, especially in pancreatic islet cells and
CC in liver (PubMed:19289501). Binds to the inverted palindrome 5'-
CC GTTAATNATTAAC-3' (PubMed:10966642). Activates the transcription of
CC CYP1A2, CYP2E1 and CYP3A11 (PubMed:30555544).
CC {ECO:0000269|PubMed:10966642, ECO:0000269|PubMed:19289501,
CC ECO:0000269|PubMed:30555544}.
CC -!- SUBUNIT: Binds DNA as a dimer (PubMed:11106484, PubMed:11439029).
CC Heterotetramer with PCBD1; formed by a dimer of dimers
CC (PubMed:10966642). Interacts with PCBD1 (By similarity). Interacts with
CC BHLHE41 (PubMed:30555544). {ECO:0000250|UniProtKB:P20823,
CC ECO:0000269|PubMed:10966642, ECO:0000269|PubMed:11106484,
CC ECO:0000269|PubMed:11439029, ECO:0000269|PubMed:30555544}.
CC -!- INTERACTION:
CC P22361; Q923E4: Sirt1; NbExp=5; IntAct=EBI-5272860, EBI-1802585;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- TISSUE SPECIFICITY: Liver.
CC -!- DISRUPTION PHENOTYPE: Mice are born at less than half of the expected
CC frequency. Neonates are slightly smaller than normal and do not grow
CC normally. After 5 weeks mice weigh only 50 to 60% as much as their
CC littermates. Mice develop non-insulin-dependent diabetes mellitus
CC (NIDDM) 2 weeks after birth. Mice exhibit elevated levels of blood
CC glucose, combined with reduced blood levels of insulin and insulin-like
CC growth factor I (IGFI). Males and females are sterile.
CC {ECO:0000269|PubMed:9566924}.
CC -!- SIMILARITY: Belongs to the HNF1 homeobox family. {ECO:0000305}.
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DR EMBL; M57966; AAA37821.1; -; mRNA.
DR EMBL; AC116500; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS19577.1; -.
DR PIR; A39262; A39262.
DR RefSeq; NP_033353.2; NM_009327.3.
DR PDB; 1F93; X-ray; 2.60 A; E/F/G/H=1-32.
DR PDB; 1G2Y; X-ray; 1.00 A; A/B/C/D=1-32.
DR PDB; 1G2Z; X-ray; 1.15 A; A/B=1-32.
DR PDB; 1G39; X-ray; 1.22 A; A/B/C/D=1-32.
DR PDB; 1JB6; X-ray; 1.70 A; A/B=1-33.
DR PDBsum; 1F93; -.
DR PDBsum; 1G2Y; -.
DR PDBsum; 1G2Z; -.
DR PDBsum; 1G39; -.
DR PDBsum; 1JB6; -.
DR AlphaFoldDB; P22361; -.
DR BMRB; P22361; -.
DR SMR; P22361; -.
DR BioGRID; 203999; 8.
DR CORUM; P22361; -.
DR IntAct; P22361; 5.
DR STRING; 10090.ENSMUSP00000031535; -.
DR iPTMnet; P22361; -.
DR PhosphoSitePlus; P22361; -.
DR MaxQB; P22361; -.
DR PaxDb; P22361; -.
DR PeptideAtlas; P22361; -.
DR PRIDE; P22361; -.
DR ProteomicsDB; 273153; -.
DR Antibodypedia; 4176; 361 antibodies from 31 providers.
DR DNASU; 21405; -.
DR Ensembl; ENSMUST00000031535; ENSMUSP00000031535; ENSMUSG00000029556.
DR GeneID; 21405; -.
DR KEGG; mmu:21405; -.
DR UCSC; uc008zcz.2; mouse.
DR CTD; 6927; -.
DR MGI; MGI:98504; Hnf1a.
DR VEuPathDB; HostDB:ENSMUSG00000029556; -.
DR eggNOG; ENOG502QRPW; Eukaryota.
DR GeneTree; ENSGT00940000153818; -.
DR HOGENOM; CLU_035503_0_0_1; -.
DR InParanoid; P22361; -.
DR OMA; LPCHMYN; -.
DR OrthoDB; 409935at2759; -.
DR PhylomeDB; P22361; -.
DR TreeFam; TF320327; -.
DR BioGRID-ORCS; 21405; 4 hits in 75 CRISPR screens.
DR ChiTaRS; Hnf1a; mouse.
DR EvolutionaryTrace; P22361; -.
DR PRO; PR:P22361; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; P22361; protein.
DR Bgee; ENSMUSG00000029556; Expressed in right kidney and 41 other tissues.
DR ExpressionAtlas; P22361; baseline and differential.
DR Genevisible; P22361; MM.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0001750; C:photoreceptor outer segment; IGI:MGI.
DR GO; GO:0045120; C:pronucleus; IDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0005667; C:transcription regulator complex; IPI:MGI.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0003690; F:double-stranded DNA binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0046983; F:protein dimerization activity; IPI:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB.
DR GO; GO:0001223; F:transcription coactivator binding; ISO:MGI.
DR GO; GO:0001221; F:transcription coregulator binding; ISO:MGI.
DR GO; GO:0032147; P:activation of protein kinase activity; ISO:MGI.
DR GO; GO:0030262; P:apoptotic nuclear changes; ISO:MGI.
DR GO; GO:0015721; P:bile acid and bile salt transport; IMP:MGI.
DR GO; GO:0006699; P:bile acid biosynthetic process; IMP:MGI.
DR GO; GO:0001824; P:blastocyst development; IMP:MGI.
DR GO; GO:0045453; P:bone resorption; IGI:MGI.
DR GO; GO:0071333; P:cellular response to glucose stimulus; ISO:MGI.
DR GO; GO:0071233; P:cellular response to leucine; ISO:MGI.
DR GO; GO:0072752; P:cellular response to rapamycin; ISO:MGI.
DR GO; GO:0008203; P:cholesterol metabolic process; IMP:MGI.
DR GO; GO:0006338; P:chromatin remodeling; IMP:UniProtKB.
DR GO; GO:0030326; P:embryonic limb morphogenesis; IGI:MGI.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IMP:MGI.
DR GO; GO:0015908; P:fatty acid transport; IMP:MGI.
DR GO; GO:0042593; P:glucose homeostasis; IDA:UniProtKB.
DR GO; GO:0046323; P:glucose import; IDA:UniProtKB.
DR GO; GO:0006783; P:heme biosynthetic process; IMP:MGI.
DR GO; GO:0016573; P:histone acetylation; IMP:MGI.
DR GO; GO:0030073; P:insulin secretion; IMP:MGI.
DR GO; GO:0001889; P:liver development; IMP:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
DR GO; GO:1903799; P:negative regulation of miRNA maturation; ISO:MGI.
DR GO; GO:0010801; P:negative regulation of peptidyl-threonine phosphorylation; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0031016; P:pancreas development; IEA:InterPro.
DR GO; GO:0048341; P:paraxial mesoderm formation; IGI:MGI.
DR GO; GO:0001890; P:placenta development; IGI:MGI.
DR GO; GO:2001171; P:positive regulation of ATP biosynthetic process; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0032024; P:positive regulation of insulin secretion; IEA:Ensembl.
DR GO; GO:0010918; P:positive regulation of mitochondrial membrane potential; ISO:MGI.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0060261; P:positive regulation of transcription initiation from RNA polymerase II promoter; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0008104; P:protein localization; IMP:MGI.
DR GO; GO:0046883; P:regulation of hormone secretion; IMP:MGI.
DR GO; GO:1902031; P:regulation of NADP metabolic process; ISO:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:MGI.
DR GO; GO:0030111; P:regulation of Wnt signaling pathway; IGI:MGI.
DR GO; GO:0035623; P:renal glucose absorption; IDA:UniProtKB.
DR GO; GO:0048608; P:reproductive structure development; IMP:MGI.
DR GO; GO:0009749; P:response to glucose; IMP:MGI.
DR GO; GO:0006979; P:response to oxidative stress; IMP:MGI.
DR GO; GO:0043691; P:reverse cholesterol transport; IMP:MGI.
DR GO; GO:0060395; P:SMAD protein signal transduction; IDA:MGI.
DR GO; GO:0006366; P:transcription by RNA polymerase II; ISO:MGI.
DR CDD; cd00086; homeodomain; 1.
DR Gene3D; 1.10.260.40; -; 1.
DR InterPro; IPR039066; HNF-1.
DR InterPro; IPR006899; HNF-1_N.
DR InterPro; IPR044869; HNF-1_POU.
DR InterPro; IPR023219; HNF1_dimer_N_dom_sf.
DR InterPro; IPR006898; HNF1a_C.
DR InterPro; IPR006897; HNF1b_C.
DR InterPro; IPR044866; HNF_P1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR010982; Lambda_DNA-bd_dom_sf.
DR PANTHER; PTHR11568; PTHR11568; 1.
DR Pfam; PF04814; HNF-1_N; 1.
DR Pfam; PF04813; HNF-1A_C; 1.
DR Pfam; PF04812; HNF-1B_C; 1.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF100957; SSF100957; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR SUPFAM; SSF47413; SSF47413; 1.
DR PROSITE; PS51937; HNF_P1; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
DR PROSITE; PS51936; POU_4; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; DNA-binding; Homeobox; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..628
FT /note="Hepatocyte nuclear factor 1-alpha"
FT /id="PRO_0000049116"
FT DOMAIN 1..32
FT /note="HNF-p1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01286"
FT DOMAIN 87..182
FT /note="POU-specific atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01285"
FT DNA_BIND 199..279
FT /note="Homeobox; HNF1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 1..31
FT /note="Dimerization"
FT REGION 47..78
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 130..132
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT REGION 143..149
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT REGION 155..158
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT REGION 183..205
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 203..206
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT REGION 263..265
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT REGION 270..273
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT REGION 284..338
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 540..585
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 197..205
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 288..302
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 304..338
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 561..585
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 70
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 74
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 93
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P20823"
FT MOD_RES 247
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 313
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CONFLICT 89
FT /note="L -> P (in Ref. 1; AAA37821)"
FT /evidence="ECO:0000305"
FT HELIX 4..18
FT /evidence="ECO:0007829|PDB:1G2Y"
FT HELIX 23..30
FT /evidence="ECO:0007829|PDB:1G2Y"
SQ SEQUENCE 628 AA; 67253 MW; 737920D47BA1F081 CRC64;
MVSKLSQLQT ELLAALLESG LSKEALIQAL GEPGPYLMVG EGPLDKGESC GGSRGDLTEL
PNGLGETRGS EDDTDDDGED FAPPILKELE NLSPEEAAHQ KAVVESLLQE DPWRVAKMVK
SYLQQHNIPQ REVVDTTGLN QSHLSQHLNK GTPMKTQKRA ALYTWYVRKQ REVAQQFTHA
GQGGLIEEPT GDELPTKKGR RNRFKWGPAS QQILFQAYER QKNPSKEERE TLVEECNRAE
CIQRGVSPSQ AQGLGSNLVT EVRVYNWFAN RRKEEAFRHK LAMDTYNGPP PGPGPGPALP
AHSSPGLPTT TLSPSKVHGV RYGQSATSEA AEVPSSSGGP LVTVSAALHQ VSPTGLEPSS
LLSTEAKLVS ATGGPLPPVS TLTALHSLEQ TSPGLNQQPQ NLIMASLPGV MTIGPGEPAS
LGPTFTNTGA STLVIGLAST QAQSVPVINS MGSSLTTLQP VQFSQPLHPS YQQPLMPPVQ
SHVAQSPFMA TMAQLQSPHA LYSHKPEVAQ YTHTSLLPQT MLITDTNLST LASLTPTKQV
FTSDTEASSE PGLHEPPSPA TTIHIPSQDP SNIQHLQPAH RLSTSPTVSS SSLVLYQSSD
SNGHSHLLPS NHSVIETFIS TQMASSSQ
