HNF1A_RAT
ID HNF1A_RAT Reviewed; 628 AA.
AC P15257;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 200.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=2571419; DOI=10.1016/0092-8674(89)90877-5;
RA Frain M., Swart G., Monaci P., Nicosia A., Staempfli S., Frank R.,
RA Cortese R.;
RT "The liver-specific transcription factor LF-B1 contains a highly diverged
RT homeobox DNA binding domain.";
RL Cell 59:145-157(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2216777; DOI=10.1093/nar/18.19.5853;
RA Chouard T., Blumenfeld M., Bach I., Vandekerckhove J., Cereghini S.,
RA Yaniv M.;
RT "A distal dimerization domain is essential for DNA-binding by the atypical
RT HNF1 homeodomain.";
RL Nucleic Acids Res. 18:5853-5863(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-12.
RC STRAIN=Sprague-Dawley;
RX PubMed=7937157; DOI=10.1093/nar/22.20.4284;
RA Piaggio G., Tomei L., Toniatti C., De Francesco R., Gerstner J.,
RA Cortese R.;
RT "LFB1/HNF1 acts as a repressor of its own transcription.";
RL Nucleic Acids Res. 22:4284-4290(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 166-628.
RX PubMed=1970973; DOI=10.1101/gad.4.3.372;
RA Baumhueter S., Mendel D.B., Conley P.B., Kuo C.J., Turk C., Graves M.K.,
RA Edwards C.A., Courtois G., Crabtree G.R.;
RT "HNF-1 shares three sequence motifs with the POU domain proteins and is
RT identical to LF-B1 and APF.";
RL Genes Dev. 4:372-379(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE OF 199-279.
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 [6]
RP POSITION OF HOMEOBOX.
RX PubMed=1967225; DOI=10.1016/0092-8674(90)90708-m;
RA Finney M.;
RT "The homeodomain of the transcription factor LF-B1 has a 21 amino acid loop
RT between helix 2 and helix 3.";
RL Cell 60:5-6(1990).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-74 AND SER-247, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [8]
RP STRUCTURE BY NMR OF 1-32.
RX PubMed=1988016; DOI=10.1021/bi00215a022;
RA Pastore A., de Francesco R., Barbato G., Castiglione Morelli M.A.,
RA Motta A., Cortese R.;
RT "1H resonance assignment and secondary structure determination of the
RT dimerization domain of transcription factor LFB1.";
RL Biochemistry 30:148-153(1991).
RN [9]
RP STRUCTURE BY NMR OF 195-286.
RX PubMed=8491172; DOI=10.1002/j.1460-2075.1993.tb05827.x;
RA Leiting B., de Francesco R., Tomei L., Cortese R., Otting G., Wuethrich K.;
RT "The three-dimensional NMR-solution structure of the polypeptide fragment
RT 195-286 of the LFB1/HNF1 transcription factor from rat liver comprises a
RT nonclassical homeodomain.";
RL EMBO J. 12:1797-1803(1993).
RN [10]
RP STRUCTURE BY NMR OF 195-286.
RX PubMed=9126845; DOI=10.1006/jmbi.1997.0905;
RA Schott O., Billeter M., Leiting B., Wider G., Wuethrich K.;
RT "The NMR solution structure of the non-classical homeodomain from the rat
RT liver LFB1/HNF1 transcription factor.";
RL J. Mol. Biol. 267:673-683(1997).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 195-286, AND SUBUNIT.
RX PubMed=8491173; DOI=10.2210/pdb1lfb/pdb;
RA Ceska T.A., Lamers M., Monaci P., Nicosia A., Cortese R., Suck D.;
RT "The X-ray structure of an atypical homeodomain present in the rat liver
RT transcription factor LFB1/HNF1 and implications for DNA binding.";
RL EMBO J. 12:1805-1810(1993).
CC -!- FUNCTION: Transcriptional activator that regulates the tissue specific
CC expression of multiple genes, especially in pancreatic islet cells and
CC in liver (By similarity). Binds to the inverted palindrome 5'-
CC GTTAATNATTAAC-3' (By similarity). Activates the transcription of
CC CYP1A2, CYP2E1 and CYP3A11 (By similarity).
CC {ECO:0000250|UniProtKB:P22361}.
CC -!- SUBUNIT: Binds DNA as a dimer (PubMed:8491173). Heterotetramer with
CC PCBD1; formed by a dimer of dimers (By similarity). Interacts with
CC PCBD1 (By similarity). Interacts with BHLHE41 (By similarity).
CC {ECO:0000250|UniProtKB:P20823, ECO:0000250|UniProtKB:P22361,
CC ECO:0000269|PubMed:8491173}.
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- TISSUE SPECIFICITY: Liver.
CC -!- SIMILARITY: Belongs to the HNF1 homeobox family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA37387.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; J03170; AAA41524.1; -; mRNA.
DR EMBL; X54423; CAA38295.1; -; mRNA.
DR EMBL; X67649; CAA47891.1; -; Genomic_DNA.
DR EMBL; X53297; CAA37387.1; ALT_INIT; mRNA.
DR PIR; A33333; A33333.
DR PIR; S25485; S25485.
DR RefSeq; NP_036801.1; NM_012669.1.
DR PDB; 1LFB; X-ray; 2.80 A; A=195-286.
DR PDB; 2LFB; NMR; -; A=195-286.
DR PDBsum; 1LFB; -.
DR PDBsum; 2LFB; -.
DR AlphaFoldDB; P15257; -.
DR BMRB; P15257; -.
DR SMR; P15257; -.
DR BioGRID; 246939; 1.
DR STRING; 10116.ENSRNOP00000001565; -.
DR iPTMnet; P15257; -.
DR PhosphoSitePlus; P15257; -.
DR PaxDb; P15257; -.
DR PRIDE; P15257; -.
DR Ensembl; ENSRNOT00000001565; ENSRNOP00000001565; ENSRNOG00000001183.
DR GeneID; 24817; -.
DR KEGG; rno:24817; -.
DR CTD; 6927; -.
DR RGD; 3828; Hnf1a.
DR eggNOG; ENOG502QRPW; Eukaryota.
DR GeneTree; ENSGT00940000153818; -.
DR HOGENOM; CLU_035503_0_0_1; -.
DR InParanoid; P15257; -.
DR OMA; LPCHMYN; -.
DR OrthoDB; 409935at2759; -.
DR PhylomeDB; P15257; -.
DR TreeFam; TF320327; -.
DR EvolutionaryTrace; P15257; -.
DR PRO; PR:P15257; -.
DR Proteomes; UP000002494; Chromosome 12.
DR Bgee; ENSRNOG00000001183; Expressed in adult mammalian kidney and 10 other tissues.
DR Genevisible; P15257; RN.
DR GO; GO:0000785; C:chromatin; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0001750; C:photoreceptor outer segment; ISO:RGD.
DR GO; GO:0045120; C:pronucleus; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0005667; C:transcription regulator complex; ISO:RGD.
DR GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:BHF-UCL.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
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; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0046983; F:protein dimerization activity; ISO:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:RGD.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB.
DR GO; GO:0001223; F:transcription coactivator binding; IPI:RGD.
DR GO; GO:0001221; F:transcription coregulator binding; IPI:RGD.
DR GO; GO:0032147; P:activation of protein kinase activity; IMP:RGD.
DR GO; GO:0030262; P:apoptotic nuclear changes; IMP:RGD.
DR GO; GO:0015721; P:bile acid and bile salt transport; ISO:RGD.
DR GO; GO:0006699; P:bile acid biosynthetic process; ISO:RGD.
DR GO; GO:0001824; P:blastocyst development; ISO:RGD.
DR GO; GO:0045453; P:bone resorption; ISO:RGD.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IMP:RGD.
DR GO; GO:0071233; P:cellular response to leucine; IMP:RGD.
DR GO; GO:0072752; P:cellular response to rapamycin; IMP:RGD.
DR GO; GO:0008203; P:cholesterol metabolic process; ISO:RGD.
DR GO; GO:0006338; P:chromatin remodeling; ISO:RGD.
DR GO; GO:0030326; P:embryonic limb morphogenesis; ISO:RGD.
DR GO; GO:0031018; P:endocrine pancreas development; ISO:RGD.
DR GO; GO:0006633; P:fatty acid biosynthetic process; ISO:RGD.
DR GO; GO:0015908; P:fatty acid transport; ISO:RGD.
DR GO; GO:0042593; P:glucose homeostasis; ISO:RGD.
DR GO; GO:0046323; P:glucose import; ISO:RGD.
DR GO; GO:0006783; P:heme biosynthetic process; ISO:RGD.
DR GO; GO:0016573; P:histone acetylation; ISO:RGD.
DR GO; GO:0030073; P:insulin secretion; ISO:RGD.
DR GO; GO:0001889; P:liver development; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:RGD.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:RGD.
DR GO; GO:1903799; P:negative regulation of miRNA maturation; IMP:RGD.
DR GO; GO:0010801; P:negative regulation of peptidyl-threonine phosphorylation; IMP:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:RGD.
DR GO; GO:0048341; P:paraxial mesoderm formation; ISO:RGD.
DR GO; GO:0001890; P:placenta development; ISO:RGD.
DR GO; GO:2001171; P:positive regulation of ATP biosynthetic process; IMP:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:RGD.
DR GO; GO:0032024; P:positive regulation of insulin secretion; IEP:RGD.
DR GO; GO:0010918; P:positive regulation of mitochondrial membrane potential; IMP:RGD.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IMP:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0060261; P:positive regulation of transcription initiation from RNA polymerase II promoter; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IPI:MGI.
DR GO; GO:0008104; P:protein localization; ISO:RGD.
DR GO; GO:0046883; P:regulation of hormone secretion; ISO:RGD.
DR GO; GO:1902031; P:regulation of NADP metabolic process; IMP:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0030111; P:regulation of Wnt signaling pathway; ISO:RGD.
DR GO; GO:0035623; P:renal glucose absorption; ISO:RGD.
DR GO; GO:0048608; P:reproductive structure development; ISO:RGD.
DR GO; GO:0009749; P:response to glucose; ISO:RGD.
DR GO; GO:0006979; P:response to oxidative stress; ISO:RGD.
DR GO; GO:0043691; P:reverse cholesterol transport; ISO:RGD.
DR GO; GO:0060395; P:SMAD protein signal transduction; ISO:RGD.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IDA:RGD.
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_0000049117"
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..79
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 541..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 MOD_RES 70
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P22361"
FT MOD_RES 74
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
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:22673903"
FT MOD_RES 313
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P22361"
FT HELIX 208..218
FT /evidence="ECO:0007829|PDB:1LFB"
FT HELIX 226..241
FT /evidence="ECO:0007829|PDB:1LFB"
FT TURN 242..245
FT /evidence="ECO:0007829|PDB:1LFB"
FT TURN 251..254
FT /evidence="ECO:0007829|PDB:1LFB"
FT HELIX 255..257
FT /evidence="ECO:0007829|PDB:1LFB"
FT HELIX 261..273
FT /evidence="ECO:0007829|PDB:1LFB"
SQ SEQUENCE 628 AA; 67213 MW; 8D28099308C86A52 CRC64;
MVSKLSQLQT ELLAALLESG LSKEALIQAL GEPGPYLMVG DGPLDKGESC GGTRGDLTEL
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 PGLHEPSSPA TTIHIPSQDP SNIQHLQPAH RLSTSPTVSS SSLVLYQSSD
SNGHSHLLPS NHGVIETFIS TQMASSSQ
