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 27-MAR-2024, entry version 217. 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). Interacts with NR5A2 (By similarity). CC Interacts with SPOP; this interaction promotes ubiquitination and CC degradation of HNF1A (By similarity). {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 -!- PTM: Ubiquitinated in s SPOP-dependent manner; leading to prteasomal CC degradation. {ECO:0000250|UniProtKB:P20823}. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 10090-ENSMUSP00000031535; -. DR PeptideAtlas; P22361; -. DR ProteomicsDB; 273153; -. DR Antibodypedia; 4176; 380 antibodies from 31 providers. DR DNASU; 21405; -. DR Ensembl; ENSMUST00000031535.12; ENSMUSP00000031535.5; ENSMUSG00000029556.13. DR GeneID; 21405; -. DR KEGG; mmu:21405; -. DR UCSC; uc008zcz.2; mouse. DR AGR; MGI:98504; -. 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; EPCPDIP; -. DR OrthoDB; 5398560at2759; -. DR PhylomeDB; P22361; -. DR TreeFam; TF320327; -. DR BioGRID-ORCS; 21405; 4 hits in 80 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 43 other cell types or tissues. DR ExpressionAtlas; P22361; baseline and differential. 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: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: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:1903799; P:negative regulation of miRNA processing; 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:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. 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 phosphatidylinositol 3-kinase/protein kinase B signal transduction; 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 by RNA polymerase II; ISO:MGI. DR GO; GO:0008104; P:protein localization; IMP:MGI. DR GO; GO:0006355; P:regulation of DNA-templated transcription; 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: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:0006366; P:transcription by RNA polymerase II; ISO:MGI. DR CDD; cd00086; homeodomain; 1. DR Gene3D; 1.10.10.60; Homeodomain-like; 1. DR Gene3D; 1.10.260.40; lambda repressor-like DNA-binding domains; 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; HEPATOCYTE NUCLEAR FACTOR 1; 1. DR PANTHER; PTHR11568:SF4; HEPATOCYTE NUCLEAR FACTOR 1-ALPHA; 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; Dimerization cofactor of HNF-1 alpha; 1. DR SUPFAM; SSF46689; Homeodomain-like; 1. DR SUPFAM; SSF47413; lambda repressor-like DNA-binding domains; 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. DR Genevisible; P22361; MM. PE 1: Evidence at protein level; KW 3D-structure; Activator; DNA-binding; Homeobox; Isopeptide bond; Nucleus; KW Phosphoprotein; Reference proteome; Transcription; KW Transcription regulation; Ubl conjugation. 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 CROSSLNK 117 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P20823" 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 //