HNF1A_HUMAN
ID HNF1A_HUMAN Reviewed; 631 AA.
AC P20823; A5Z2R8; E0YMJ5; E0YMK0; E0YMK1; E2I9R4; E2I9R5; F5H5U3; Q2M3H2;
AC Q99861;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 2.
DT 03-AUG-2022, entry version 244.
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=TCF1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
RC TISSUE=Liver;
RX PubMed=1707031; DOI=10.1016/0888-7543(90)90238-p;
RA Bach I., Galcheva-Gargova Z., Mattei M.-G., Simon-Chazottes D.,
RA Guenet J.-L., Cereghini S., Yaniv M.;
RT "Cloning of human hepatic nuclear factor 1 (HNF1) and chromosomal
RT localization of its gene in man and mouse.";
RL Genomics 8:155-164(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), AND ALTERNATIVE SPLICING.
RC TISSUE=Liver;
RX PubMed=7900999; DOI=10.1002/j.1460-2075.1993.tb06107.x;
RA Bach I., Yaniv M.;
RT "More potent transcriptional activators or a transdominant inhibitor of the
RT HNF1 homeoprotein family are generated by alternative RNA processing.";
RL EMBO J. 12:4229-4242(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT MODY3 LEU-447.
RX PubMed=8945470; DOI=10.1038/384455a0;
RA Yamagata K., Oda N., Kaisaki P.J., Menzel S., Furuta H., Vaxillaire M.,
RA Southam L., Cox R.D., Lathrop G.M., Boriraj V.V., Chen X., Cox N.J.,
RA Oda Y., Yano H., le Beau M.M., Yamada S., Nishigori H., Takeda J.,
RA Fajans S.S., Hattersley A.T., Iwasaki N., Hansen T., Pedersen O.,
RA Polonsky K.S., Turner R.C., Velho G., Chevre J.-C., Froguel P., Bell G.I.;
RT "Mutations in the hepatocyte nuclear factor-1alpha gene in maturity-onset
RT diabetes of the young (MODY3).";
RL Nature 384:455-458(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4; 5 AND 6).
RA Yang C.-W., Tsai D.-Y.;
RT "Homo sapiens HNF1 alpha B mRNA splicing variants.";
RL Submitted (APR-2010) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 7), AND VARIANT SER-574.
RA Gonzalez Ruano E., Gonzalez Sarmiento R.;
RT "New isoforms in HNF1A.";
RL Submitted (JUN-2010) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-27; VAL-98; ASN-487 AND
RP SER-574.
RG SeattleSNPs variation discovery resource;
RL Submitted (MAY-2007) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-27.
RC TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-93 AND SER-247, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 85-278 IN COMPLEX WITH DNA,
RP FUNCTION, DNA-BINDING, MUTAGENESIS OF ASN-127; GLU-132; PHE-177; ILE-186;
RP THR-190; ASN-202; VAL-246 AND ASN-257, AND CHARACTERIZATION OF VARIANTS
RP MODY3 PHE-142 AND GLN-205.
RX PubMed=12453420; DOI=10.1016/s1097-2765(02)00704-9;
RA Chi Y.I., Frantz J.D., Oh B.C., Hansen L., Dhe-Paganon S., Shoelson S.E.;
RT "Diabetes mutations delineate an atypical POU domain in HNF-1alpha.";
RL Mol. Cell 10:1129-1137(2002).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 2-32, AND CIRCULAR DICHROISM.
RX PubMed=16930618; DOI=10.1016/j.jmb.2006.06.086;
RA Narayana N., Phillips N.B., Hua Q.X., Jia W., Weiss M.A.;
RT "Diabetes mellitus due to misfolding of a beta-cell transcription factor:
RT stereospecific frustration of a Schellman motif in HNF-1alpha.";
RL J. Mol. Biol. 362:414-429(2006).
RN [13]
RP VARIANTS MODY3 ARG-107; TRP-131; MET-260 AND HIS-272.
RX PubMed=9166684; DOI=10.2337/diab.46.6.1081;
RA Glucksmann M.A., Lehto M., Tayber O., Scotti S., Berkemeier L.,
RA Pulido J.C., Wu Y., Nir W.-J., Fang L., Markel P., Munnelly K.D.,
RA Goranson J., Orho M., Young B.M., Whitacre J.L., McMenimen C., Wantman M.,
RA Tuomi T., Warram J., Forsblom C.M., Carlsson M., Rosenzweig J., Kennedy G.,
RA Duyk G.M., Krolewski A.S., Groop L.C., Thomas J.D.;
RT "Novel mutations and a mutational hotspot in the MODY3 gene.";
RL Diabetes 46:1081-1086(1997).
RN [14]
RP VARIANTS MODY3 HIS-12; GLN-131; GLN-205 AND CYS-263, AND VARIANT NIDDM
RP ASP-191.
RX PubMed=9287053; DOI=10.2337/diab.46.9.1504;
RA Iwasaki N., Oda N., Ogata M., Hara M., Hinokio Y., Oda Y., Yamagata K.,
RA Kanematsu S., Ohgawara H., Omori Y., Bell G.I.;
RT "Mutations in the hepatocyte nuclear factor-1alpha/MODY3 gene in Japanese
RT subjects with early- and late-onset NIDDM.";
RL Diabetes 46:1504-1508(1997).
RN [15]
RP VARIANT NIDDM MET-254, AND VARIANTS LEU-27 AND ASN-487.
RX PubMed=9287055; DOI=10.2337/diab.46.9.1512;
RA Yamada S., Nishigori H., Onda H., Takahashi K., Kitano N., Morikawa A.,
RA Takeuchi T., Takeda J.;
RT "Mutations in the hepatocyte nuclear factor-1alpha gene (MODY3) are not a
RT major cause of late-onset NIDDM in Japanese subjects.";
RL Diabetes 46:1512-1513(1997).
RN [16]
RP VARIANTS IDDM20 HIS-272 AND GLY-583.
RX PubMed=9313763; DOI=10.2337/diacare.46.10.1643;
RA Yamada S., Nishigori H., Onda H., Utsugi T., Yanagawa T., Maruyama T.,
RA Onigata K., Nagashima K., Nagai R., Morikawa A., Takeuchi T., Takeda J.;
RT "Identification of mutations in the hepatocyte nuclear factor (HNF)-1-alpha
RT gene in Japanese subjects with IDDM.";
RL Diabetes 46:1643-1647(1997).
RN [17]
RP VARIANTS MODY3, AND VARIANT ATYPICAL DIABETES SER-574.
RX PubMed=9392505; DOI=10.2337/diab.46.12.2108;
RA Boutin P., Chevre J.-C., Hani E.H., Gomis R., Pardini V.C.,
RA Guillausseau P.-J., Vaxillaire M., Velho G., Froguel P.;
RT "An automated fluorescent single-strand conformation polymorphism technique
RT for screening mutations in the hepatocyte nuclear factor-1alpha gene
RT (maturity-onset diabetes of the young).";
RL Diabetes 46:2108-2109(1997).
RN [18]
RP VARIANTS MODY3 GLN-131; GLN-229; GLY-241 AND HIS-272.
RX PubMed=9032114; DOI=10.2337/diab.46.3.528;
RA Kaisaki P.J., Menzel S., Lindner T., Oda N., Rjasanowski I., Sahm J.,
RA Meincke G., Schulze J., Schmechel H., Petzold C., Ledermann H.M.,
RA Sachse G., Boriraj V.V., Menzel R., Kerner W., Turner R.C., Yamagata K.,
RA Bell G.I.;
RT "Mutations in the hepatocyte nuclear factor-1alpha gene in MODY and early-
RT onset NIDDM: evidence for a mutational hotspot in exon 4.";
RL Diabetes 46:528-535(1997).
RN [19]
RP VARIANTS MODY3 THR-129; TRP-131; TRP-159; LEU-519 AND ILE-620.
RX PubMed=9075818; DOI=10.2337/diab.46.4.720;
RA Frayling T.M., Bulman M.P., Ellard S., Appleton M., Dronsfield M.J.,
RA Mackie A.D., Baird J.D., Kaisaki P.J., Yamagata K., Bell G.I., Bain S.C.,
RA Hattersley A.T.;
RT "Mutations in the hepatocyte nuclear factor-1alpha gene are a common cause
RT of maturity-onset diabetes of the young in the U.K.";
RL Diabetes 46:720-725(1997).
RN [20]
RP VARIANTS MODY3 ASN-128; TYR-143 AND LEU-447.
RX PubMed=9075819; DOI=10.2337/diab.46.4.726;
RA Hansen T., Eiberg H., Rouard M., Vaxillaire M., Moeller A.M.,
RA Rasmussen S.K., Fridberg M., Urhammer S.A., Holst J.J., Almind K.,
RA Echwald S.M., Hansen L., Bell G.I., Pedersen O.;
RT "Novel MODY3 mutations in the hepatocyte nuclear factor-1alpha gene:
RT evidence for a hyperexcitability of pancreatic beta-cells to intravenous
RT secretagogues in a glucose-tolerant carrier of a P447L mutation.";
RL Diabetes 46:726-730(1997).
RN [21]
RP VARIANTS LEU-27; VAL-98 AND ASN-487.
RX PubMed=9133564; DOI=10.2337/diab.46.5.912;
RA Urhammer S.A., Fridberg M., Hansen T., Rasmussen S.K., Moeller A.M.,
RA Clausen J.O., Pedersen O.;
RT "A prevalent amino acid polymorphism at codon 98 in the hepatocyte nuclear
RT factor-1alpha gene is associated with reduced serum C-peptide and insulin
RT responses to an oral glucose challenge.";
RL Diabetes 46:912-916(1997).
RN [22]
RP VARIANT NIDDM GLN-583, AND VARIANTS LEU-27; VAL-98 AND ASN-487.
RX PubMed=9112026; DOI=10.1007/s001250050703;
RA Urhammer S.A., Rasmussen S.K., Kaisaki P.J., Oda N., Yamagata K.,
RA Moeller A.M., Fridberg M., Hansen L., Hansen T., Bell G.I., Pedersen O.;
RT "Genetic variation in the hepatocyte nuclear factor-1 alpha gene in Danish
RT Caucasians with late-onset NIDDM.";
RL Diabetologia 40:473-475(1997).
RN [23]
RP VARIANTS MODY3 CYS-122; PHE-142 AND GLN-159.
RX PubMed=9097962; DOI=10.1093/hmg/6.4.583;
RA Vaxillaire M., Rouard M., Yamagata K., Oda N., Kaisaki P.J., Boriraj V.V.,
RA Chevre J.-C., Boccio V., Cox R.D., Lathrop G.M., Dussoix P., Philippe J.,
RA Timsit J., Charpentier G., Velho G., Bell G.I., Froguel P.;
RT "Identification of nine novel mutations in the hepatocyte nuclear factor 1
RT alpha gene associated with maturity-onset diabetes of the young (MODY3).";
RL Hum. Mol. Genet. 6:583-586(1997).
RN [24]
RP VARIANTS LEU-27; ASN-487 AND ARG-514.
RX PubMed=9604876; DOI=10.2337/diabetes.47.6.967;
RA Behn P.S., Wasson J., Chayen S., Smolovitch I., Thomas J.D., Glaser B.,
RA Permutt M.A.;
RT "Hepatocyte nuclear factor 1alpha coding mutations are an uncommon
RT contributor to early-onset type 2 diabetes in Ashkenazi Jews.";
RL Diabetes 47:967-969(1998).
RN [25]
RP VARIANTS MODY3 ASP-31; TRP-159; THR-161; TRP-200 AND TRP-271.
RX PubMed=9754819; DOI=10.1007/s001250051025;
RA Chevre J.-C., Hani E.H., Boutin P., Vaxillaire M., Blanche H., Vionnet N.,
RA Pardini V.C., Timsit J., Larger E., Charpentier G., Beckers D., Maes M.,
RA Bellanne-Chantelot C., Velho G., Froguel P.;
RT "Mutation screening in 18 Caucasian families suggest the existence of other
RT MODY genes.";
RL Diabetologia 41:1017-1023(1998).
RN [26]
RP VARIANTS IDDM20 LYS-48 AND GLY-241.
RX PubMed=9867222; DOI=10.1007/s001250051101;
RA Moeller A.M., Dalgaard L.T., Pociot F., Nerup J., Hansen T., Pedersen O.;
RT "Mutations in the hepatocyte nuclear factor-1alpha gene in Caucasian
RT families originally classified as having type I diabetes.";
RL Diabetologia 41:1528-1531(1998).
RN [27]
RP VARIANTS MODY3 ARG-537 AND LYS-619.
RX PubMed=9626139; DOI=10.1210/jcem.83.6.4874;
RA Elbein S.C., Teng K., Yount P., Scroggin E.;
RT "Linkage and molecular scanning analyses of MODY3/hepatocyte nuclear
RT factor-1 alpha gene in typical familial type 2 diabetes: evidence for novel
RT mutations in exons 8 and 10.";
RL J. Clin. Endocrinol. Metab. 83:2059-2065(1998).
RN [28]
RP VARIANTS LEU-27 AND ASN-487.
RX PubMed=9621514; DOI=10.1007/s100380050049;
RA Nishigori H., Yamada S., Kohama T., Utsugi T., Shimizu H., Takeuchi T.,
RA Takeda J.;
RT "Mutations in the hepatocyte nuclear factor-1 alpha gene 'MODY3' are not a
RT major cause of early-onset non-insulin-dependent 'type 2' diabetes mellitus
RT in Japanese.";
RL J. Hum. Genet. 43:107-110(1998).
RN [29]
RP VARIANTS MODY3 HIS-12; ASN-158; GLN-159 AND CYS-203.
RX PubMed=10078571; DOI=10.2337/diabetes.48.3.645;
RA Yamada S., Tomura H., Nishigori H., Sho K., Mabe H., Iwatani N., Takumi T.,
RA Kito Y., Moriya N., Muroya K., Ogata T., Onigata K., Morikawa A., Inoue I.,
RA Takeda J.;
RT "Identification of mutations in the hepatocyte nuclear factor-1alpha gene
RT in Japanese subjects with early-onset NIDDM and functional analysis of the
RT mutant proteins.";
RL Diabetes 48:645-648(1999).
RN [30]
RP VARIANTS MODY3 GLU-117 AND TYR-143.
RX PubMed=10102714; DOI=10.2337/diabetes.48.4.921;
RA Ellard S., Bulman M.P., Frayling T.M., Allen L.I.S., Dronsfield M.J.,
RA Tack C.J., Hattersley A.T.;
RT "Allelic drop-out in exon 2 of the hepatocyte nuclear factor-1alpha gene
RT hinders the identification of mutations in three families with maturity-
RT onset diabetes of the young.";
RL Diabetes 48:921-923(1999).
RN [31]
RP VARIANT NIDDM CYS-272, VARIANT IDDM20 ARG-415, CHARACTERIZATION OF VARIANT
RP NIDDM CYS-272, AND CHARACTERIZATION OF VARIANT IDDM20 ARG-415.
RX PubMed=10333057; DOI=10.1007/s001250051204;
RA Yoshiuchi I., Yamagata K., Yang Q., Iwahashi H., Okita K., Yamamoto K.,
RA Oue T., Imagawa A., Hamaguchi T., Yamasaki T., Horikawa Y., Satoh T.,
RA Nakajima H., Miyazaki J., Higashiyama S., Miyagawa J., Namba M.,
RA Hanafusa T., Matsuzawa Y.;
RT "Three new mutations in the hepatocyte nuclear factor-1alpha gene in
RT Japanese subjects with diabetes mellitus: clinical features and functional
RT characterization.";
RL Diabetologia 42:621-626(1999).
RN [32]
RP VARIANTS MODY3 ARG-20; HIS-203; CYS-432 AND MET-618.
RX PubMed=10588527; DOI=10.1046/j.1464-5491.1999.00188.x;
RA Ng M.C.Y., Cockburn B.N., Lindner T.H., Yeung V.T.F., Chow C.-C., So W.-Y.,
RA Li J.K.Y., Lo Y.M.D., Lee Z.S.K., Cockram C.S., Critchley J.A.J.H.,
RA Bell G.I., Chan J.C.N.;
RT "Molecular genetics of diabetes mellitus in Chinese subjects:
RT identification of mutations in glucokinase and hepatocyte nuclear factor-
RT 1alpha genes in patients with early-onset type 2 diabetes mellitus/MODY.";
RL Diabet. Med. 16:956-963(1999).
RN [33]
RP VARIANT MODY3 ILE-620.
RX PubMed=10482964; DOI=10.1038/sj.ejhg.5200358;
RA Miedzybrodzka Z., Hattersley A.T., Ellard S., Pearson D., de Silva D.,
RA Harvey R., Haites N.;
RT "Non-penetrance in a MODY 3 family with a mutation in the hepatic nuclear
RT factor 1alpha gene: implications for predictive testing.";
RL Eur. J. Hum. Genet. 7:729-732(1999).
RN [34]
RP VARIANT SER-319.
RX PubMed=10084598; DOI=10.1210/jcem.84.3.5528;
RA Hegele R.A., Cao H., Harris S.B., Hanley A.J.G., Zinman B.;
RT "The hepatic nuclear factor-1alpha G319S variant is associated with early-
RT onset type 2 diabetes in Canadian Oji-Cree.";
RL J. Clin. Endocrinol. Metab. 84:1077-1082(1999).
RN [35]
RP CHARACTERIZATION OF VARIANTS MODY3 HIS-12; ARG-20 AND ASP-31, FUNCTION,
RP SUBCELLULAR LOCATION, AND INTERACTION WITH PCBD1.
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 [36]
RP INVOLVEMENT IN HEPATIC ADENOMAS, AND VARIANTS TYR-127; CYS-165; CYS-206;
RP LEU-206; SER-237; GLY-244; PRO-250; CYS-268; GLU-273; SER-574 AND GLN-583.
RX PubMed=12355088; DOI=10.1038/ng1001;
RA Bluteau O., Jeannot E., Bioulac-Sage P., Marques J.M., Blanc J.-F., Bui H.,
RA Beaudoin J.-C., Franco D., Balabaud C., Laurent-Puig P., Zucman-Rossi J.;
RT "Bi-allelic inactivation of TCF1 in hepatic adenomas.";
RL Nat. Genet. 32:312-315(2002).
RN [37]
RP VARIANT [LARGE SCALE ANALYSIS] GLU-273.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [38]
RP VARIANTS MODY3 ASP-31; MET-133; 171-ARG--GLN-631 DEL; GLY-271 AND LEU-447.
RX PubMed=17573900; DOI=10.1111/j.1365-2265.2007.02921.x;
RG Spanish MODY Group;
RA Estalella I., Rica I., Perez de Nanclares G., Bilbao J.R., Vazquez J.A.,
RA San Pedro J.I., Busturia M.A., Castano L.;
RT "Mutations in GCK and HNF-1alpha explain the majority of cases with
RT clinical diagnosis of MODY in Spain.";
RL Clin. Endocrinol. (Oxf.) 67:538-546(2007).
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' (PubMed:12453420, PubMed:10966642). Activates the
CC transcription of CYP1A2, CYP2E1 and CYP3A11 (By similarity).
CC {ECO:0000250|UniProtKB:P22361, ECO:0000269|PubMed:10966642,
CC ECO:0000269|PubMed:12453420}.
CC -!- SUBUNIT: Binds DNA as a dimer (PubMed:12453420). Heterotetramer with
CC PCBD1; formed by a dimer of dimers (By similarity). Interacts with
CC PCBD1 (PubMed:10966642). Interacts with BHLHE41 (By similarity).
CC {ECO:0000250|UniProtKB:P22361, ECO:0000269|PubMed:10966642,
CC ECO:0000269|PubMed:12453420}.
CC -!- INTERACTION:
CC P20823; Q9Y463: DYRK1B; NbExp=4; IntAct=EBI-636034, EBI-634187;
CC P20823; P61457: PCBD1; NbExp=3; IntAct=EBI-636034, EBI-740475;
CC P20823; Q92786: PROX1; NbExp=3; IntAct=EBI-636034, EBI-3912635;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108,
CC ECO:0000269|PubMed:10966642}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Name=A;
CC IsoId=P20823-1; Sequence=Displayed;
CC Name=B;
CC IsoId=P20823-2; Sequence=VSP_002250, VSP_002251;
CC Name=C;
CC IsoId=P20823-3; Sequence=VSP_002252, VSP_002253;
CC Name=4;
CC IsoId=P20823-4; Sequence=VSP_047736, VSP_047739;
CC Name=5;
CC IsoId=P20823-5; Sequence=VSP_047737, VSP_047738;
CC Name=6;
CC IsoId=P20823-6; Sequence=VSP_053324, VSP_053325, VSP_053326;
CC Name=7; Synonyms=insIVS8;
CC IsoId=P20823-7; Sequence=VSP_054302;
CC Name=8; Synonyms=delta 2;
CC IsoId=P20823-8; Sequence=VSP_054300, VSP_054301;
CC -!- TISSUE SPECIFICITY: Liver.
CC -!- POLYMORPHISM: The Ala-98/Val-98 polymorphism is associated with a
CC reduction in glucose-induced serum C-peptide and insulin responses.
CC {ECO:0000269|PubMed:9133564}.
CC -!- DISEASE: Hepatic adenomas familial (HEPAF) [MIM:142330]: Rare benign
CC liver tumors of presumable epithelial origin that develop in an
CC otherwise normal liver. Hepatic adenomas may be single or multiple.
CC They consist of sheets of well-differentiated hepatocytes that contain
CC fat and glycogen and can produce bile. Bile ducts or portal areas are
CC absent. Kupffer cells, if present, are reduced in number and are non-
CC functional. Conditions associated with adenomas are insulin-dependent
CC diabetes mellitus and glycogen storage diseases (types 1 and 3).
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry. Bi-allelic inactivation of HNF1A, whether sporadic or
CC associated with MODY3, may be an early step in the development of some
CC hepatocellular carcinomas.
CC -!- DISEASE: Maturity-onset diabetes of the young 3 (MODY3) [MIM:600496]: A
CC form of diabetes that is characterized by an autosomal dominant mode of
CC inheritance, onset in childhood or early adulthood (usually before 25
CC years of age), a primary defect in insulin secretion and frequent
CC insulin-independence at the beginning of the disease.
CC {ECO:0000269|PubMed:10078571, ECO:0000269|PubMed:10102714,
CC ECO:0000269|PubMed:10482964, ECO:0000269|PubMed:10588527,
CC ECO:0000269|PubMed:10966642, ECO:0000269|PubMed:12453420,
CC ECO:0000269|PubMed:17573900, ECO:0000269|PubMed:8945470,
CC ECO:0000269|PubMed:9032114, ECO:0000269|PubMed:9075818,
CC ECO:0000269|PubMed:9075819, ECO:0000269|PubMed:9097962,
CC ECO:0000269|PubMed:9166684, ECO:0000269|PubMed:9287053,
CC ECO:0000269|PubMed:9392505, ECO:0000269|PubMed:9626139,
CC ECO:0000269|PubMed:9754819}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Diabetes mellitus, insulin-dependent, 20 (IDDM20)
CC [MIM:612520]: A multifactorial disorder of glucose homeostasis that is
CC characterized by susceptibility to ketoacidosis in the absence of
CC insulin therapy. Clinical features are polydipsia, polyphagia and
CC polyuria which result from hyperglycemia-induced osmotic diuresis and
CC secondary thirst. These derangements result in long-term complications
CC that affect the eyes, kidneys, nerves, and blood vessels.
CC {ECO:0000269|PubMed:10333057, ECO:0000269|PubMed:9313763,
CC ECO:0000269|PubMed:9867222}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 7]: Due to intron retention. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the HNF1 homeobox family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Hepatocyte nuclear factors entry;
CC URL="https://en.wikipedia.org/wiki/Hepatocyte_nuclear_factors";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/tcf1/";
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DR EMBL; M57732; AAA88077.1; -; mRNA.
DR EMBL; X71346; CAB59201.1; -; mRNA.
DR EMBL; U72618; AAC51137.1; -; Genomic_DNA.
DR EMBL; U72612; AAC51137.1; JOINED; Genomic_DNA.
DR EMBL; U72613; AAC51137.1; JOINED; Genomic_DNA.
DR EMBL; U72614; AAC51137.1; JOINED; Genomic_DNA.
DR EMBL; U72615; AAC51137.1; JOINED; Genomic_DNA.
DR EMBL; U72616; AAC51137.1; JOINED; Genomic_DNA.
DR EMBL; U72617; AAC51137.1; JOINED; Genomic_DNA.
DR EMBL; HM116552; ADM43489.1; -; mRNA.
DR EMBL; HM116557; ADM43494.1; -; mRNA.
DR EMBL; HM116558; ADM43495.1; -; mRNA.
DR EMBL; HM449088; ADK56177.1; -; mRNA.
DR EMBL; HM449089; ADK56178.1; -; mRNA.
DR EMBL; EF641294; ABR09270.1; -; Genomic_DNA.
DR EMBL; AC079602; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471054; EAW98226.1; -; Genomic_DNA.
DR EMBL; BC104908; AAI04909.1; -; mRNA.
DR EMBL; BC104910; AAI04911.1; -; mRNA.
DR CCDS; CCDS9209.1; -. [P20823-1]
DR PIR; A36749; A36749.
DR RefSeq; NP_000536.5; NM_000545.6.
DR RefSeq; NP_001293108.1; NM_001306179.1.
DR PDB; 1IC8; X-ray; 2.60 A; A/B=85-278.
DR PDB; 2GYP; X-ray; 1.40 A; A/B=2-32.
DR PDBsum; 1IC8; -.
DR PDBsum; 2GYP; -.
DR AlphaFoldDB; P20823; -.
DR BMRB; P20823; -.
DR SMR; P20823; -.
DR BioGRID; 112789; 62.
DR DIP; DIP-33544N; -.
DR IntAct; P20823; 32.
DR MINT; P20823; -.
DR STRING; 9606.ENSP00000257555; -.
DR DrugBank; DB04419; D-norleucine.
DR GlyGen; P20823; 15 sites, 1 O-linked glycan (15 sites).
DR iPTMnet; P20823; -.
DR PhosphoSitePlus; P20823; -.
DR BioMuta; HNF1A; -.
DR DMDM; 51338763; -.
DR jPOST; P20823; -.
DR MassIVE; P20823; -.
DR MaxQB; P20823; -.
DR PaxDb; P20823; -.
DR PeptideAtlas; P20823; -.
DR PRIDE; P20823; -.
DR ProteomicsDB; 15197; -.
DR ProteomicsDB; 15200; -.
DR ProteomicsDB; 15201; -.
DR ProteomicsDB; 15217; -.
DR ProteomicsDB; 26985; -.
DR ProteomicsDB; 53806; -. [P20823-1]
DR ProteomicsDB; 53807; -. [P20823-2]
DR ProteomicsDB; 53808; -. [P20823-3]
DR DNASU; 6927; -.
DR Ensembl; ENST00000538646.5; ENSP00000443964.1; ENSG00000135100.19. [P20823-4]
DR Ensembl; ENST00000540108.1; ENSP00000445445.1; ENSG00000135100.19. [P20823-8]
DR Ensembl; ENST00000541924.5; ENSP00000440361.1; ENSG00000135100.19. [P20823-5]
DR GeneID; 6927; -.
DR KEGG; hsa:6927; -.
DR UCSC; uc021rfb.2; human. [P20823-1]
DR CTD; 6927; -.
DR DisGeNET; 6927; -.
DR GeneCards; HNF1A; -.
DR GeneReviews; HNF1A; -.
DR HGNC; HGNC:11621; HNF1A.
DR MalaCards; HNF1A; -.
DR MIM; 142330; phenotype.
DR MIM; 142410; gene.
DR MIM; 600496; phenotype.
DR MIM; 606391; phenotype.
DR MIM; 612520; phenotype.
DR neXtProt; NX_P20823; -.
DR OpenTargets; ENSG00000135100; -.
DR Orphanet; 319303; Chromophobe renal cell carcinoma.
DR Orphanet; 404511; Clear cell papillary renal cell carcinoma.
DR Orphanet; 324575; Hyperinsulinism due to HNF1A deficiency.
DR Orphanet; 552; MODY.
DR PharmGKB; PA36380; -.
DR VEuPathDB; HostDB:ENSG00000135100; -.
DR eggNOG; ENOG502QRPW; Eukaryota.
DR GeneTree; ENSGT00940000153818; -.
DR HOGENOM; CLU_068818_0_0_1; -.
DR InParanoid; P20823; -.
DR PhylomeDB; P20823; -.
DR TreeFam; TF320327; -.
DR PathwayCommons; P20823; -.
DR Reactome; R-HSA-210745; Regulation of gene expression in beta cells.
DR SignaLink; P20823; -.
DR SIGNOR; P20823; -.
DR BioGRID-ORCS; 6927; 50 hits in 1101 CRISPR screens.
DR ChiTaRS; HNF1A; human.
DR EvolutionaryTrace; P20823; -.
DR GeneWiki; HNF1A; -.
DR GenomeRNAi; 6927; -.
DR Pharos; P20823; Tbio.
DR PRO; PR:P20823; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P20823; protein.
DR Bgee; ENSG00000135100; Expressed in right lobe of liver and 57 other tissues.
DR ExpressionAtlas; P20823; baseline and differential.
DR Genevisible; P20823; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISS:BHF-UCL.
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; ISA:NTNU_SB.
DR GO; GO:0046983; F:protein dimerization activity; IPI:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB.
DR GO; GO:0046323; P:glucose import; IMP:UniProtKB.
DR GO; GO:0030073; P:insulin secretion; IMP:UniProtKB.
DR GO; GO:0001889; P:liver development; IEA:InterPro.
DR GO; GO:0031016; P:pancreas development; IEA:InterPro.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:BHF-UCL.
DR GO; GO:0060261; P:positive regulation of transcription initiation from RNA polymerase II promoter; IGI:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0035623; P:renal glucose absorption; IMP:UniProtKB.
DR CDD; cd00086; homeodomain; 1.
DR DisProt; DP01620; -.
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; Alternative splicing; Diabetes mellitus;
KW Disease variant; DNA-binding; Homeobox; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..631
FT /note="Hepatocyte nuclear factor 1-alpha"
FT /id="PRO_0000049115"
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 40..81
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 130..132
FT /note="Interaction with DNA"
FT REGION 143..149
FT /note="Interaction with DNA"
FT REGION 155..158
FT /note="Interaction with DNA"
FT REGION 183..205
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 203..206
FT /note="Interaction with DNA"
FT REGION 263..265
FT /note="Interaction with DNA"
FT REGION 270..273
FT /note="Interaction with DNA"
FT REGION 283..358
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 545..573
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 197..205
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000305"
FT COMPBIAS 288..312
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 328..358
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 545..570
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:0000250|UniProtKB:P22361"
FT MOD_RES 93
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 247
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 313
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P22361"
FT VAR_SEQ 1..117
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_053324"
FT VAR_SEQ 110..119
FT /note="EDPWRVAKMV -> VHPCRAGRAD (in isoform 8)"
FT /evidence="ECO:0000305"
FT /id="VSP_054300"
FT VAR_SEQ 120..631
FT /note="Missing (in isoform 8)"
FT /evidence="ECO:0000305"
FT /id="VSP_054301"
FT VAR_SEQ 176..278
FT /note="QFTHAGQGGLIEEPTGDELPTKKGRRNRFKWGPASQQILFQAYERQKNPSKE
FT ERETLVEECNRAECIQRGVSPSQAQGLGSNLVTEVRVYNWFANRRKEEAFR -> RRNA
FT SREGCPHHRHRGWAPTSSRRCVSTTGLPTGAKKKPSGTSWPWTRTAGPPQGQARDLRCP
FT LTAPLACLHLPSPPVRSTVCAMDSLRPVRLQKYPQAAAVP (in isoform 4)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_047736"
FT VAR_SEQ 239..247
FT /note="AECIQRGVS -> CALWTACDQ (in isoform 5)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_047737"
FT VAR_SEQ 248..631
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_047738"
FT VAR_SEQ 279..631
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_047739"
FT VAR_SEQ 438..520
FT /note="LASTQAQSVPVINSMGSSLTTLQPVQFSQPLHPSYQQPLMPPVQSHVTQSPF
FT MATMAQLQSPHALYSHKPEVAQYTHTGLLPQ -> KLVGMGGHLGGRLMGQPQNPGAGR
FT ATGTHSFIHTTCIYPVPTLDQSLCYISDTWVNQTDQNLSNSSREAGTKHNTSILWYLRR
FT (in isoform 6)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_053325"
FT VAR_SEQ 438..494
FT /note="LASTQAQSVPVINSMGSSLTTLQPVQFSQPLHPSYQQPLMPPVQSHVTQSPF
FT MATMA -> KLVGMGGHLGGRLMGQPQNPGAGRATGTHSFIHSFIQHVFIQCLLWTSHC
FT ATSVIPG (in isoform C)"
FT /evidence="ECO:0000305"
FT /id="VSP_002252"
FT VAR_SEQ 495..601
FT /note="Missing (in isoform C)"
FT /evidence="ECO:0000305"
FT /id="VSP_002253"
FT VAR_SEQ 501..542
FT /note="ALYSHKPEVAQYTHTGLLPQTMLITDTTNLSALASLTPTKQV -> GEHPVP
FT HTAGDDDRGWLSMDAGERGAWQALQSACVSGTSVFP (in isoform B)"
FT /evidence="ECO:0000305"
FT /id="VSP_002250"
FT VAR_SEQ 521..631
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_053326"
FT VAR_SEQ 540
FT /note="K -> KQVRSRPAGPPLACDRAPHPHIPRAQEAALLP (in isoform
FT 7)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_054302"
FT VAR_SEQ 543..601
FT /note="Missing (in isoform B)"
FT /evidence="ECO:0000305"
FT /id="VSP_002251"
FT VARIANT 12
FT /note="L -> H (in MODY3; abolishes interaction with PCBD1
FT and DNA)"
FT /evidence="ECO:0000269|PubMed:10078571,
FT ECO:0000269|PubMed:10966642, ECO:0000269|PubMed:9287053"
FT /id="VAR_010537"
FT VARIANT 20
FT /note="G -> R (in MODY3; abolishes interaction with PCBD1
FT and DNA)"
FT /evidence="ECO:0000269|PubMed:10588527,
FT ECO:0000269|PubMed:10966642"
FT /id="VAR_012483"
FT VARIANT 27
FT /note="I -> L (in dbSNP:rs1169288)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:9112026, ECO:0000269|PubMed:9133564,
FT ECO:0000269|PubMed:9287055, ECO:0000269|PubMed:9604876,
FT ECO:0000269|PubMed:9621514, ECO:0000269|Ref.6"
FT /id="VAR_007905"
FT VARIANT 31
FT /note="G -> D (in MODY3; no effect on interaction with
FT PCBD1 and DNA)"
FT /evidence="ECO:0000269|PubMed:10966642,
FT ECO:0000269|PubMed:17573900, ECO:0000269|PubMed:9754819"
FT /id="VAR_010538"
FT VARIANT 48
FT /note="E -> K (in IDDM20)"
FT /evidence="ECO:0000269|PubMed:9867222"
FT /id="VAR_010539"
FT VARIANT 98
FT /note="A -> V (in dbSNP:rs1800574)"
FT /evidence="ECO:0000269|PubMed:9112026,
FT ECO:0000269|PubMed:9133564, ECO:0000269|Ref.6"
FT /id="VAR_010540"
FT VARIANT 107
FT /note="L -> R (in MODY3)"
FT /evidence="ECO:0000269|PubMed:9166684"
FT /id="VAR_010541"
FT VARIANT 117
FT /note="K -> E (in MODY3)"
FT /evidence="ECO:0000269|PubMed:10102714"
FT /id="VAR_010542"
FT VARIANT 122
FT /note="Y -> C (in MODY3)"
FT /evidence="ECO:0000269|PubMed:9097962"
FT /id="VAR_003756"
FT VARIANT 127
FT /note="N -> Y (in a hepatocellular carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:12355088"
FT /id="VAR_033088"
FT VARIANT 128
FT /note="I -> N (in MODY3)"
FT /evidence="ECO:0000269|PubMed:9075819"
FT /id="VAR_010543"
FT VARIANT 129
FT /note="P -> T (in MODY3)"
FT /evidence="ECO:0000269|PubMed:9075818"
FT /id="VAR_010544"
FT VARIANT 131
FT /note="R -> Q (in MODY3)"
FT /evidence="ECO:0000269|PubMed:9032114,
FT ECO:0000269|PubMed:9287053"
FT /id="VAR_010545"
FT VARIANT 131
FT /note="R -> W (in MODY3)"
FT /evidence="ECO:0000269|PubMed:9075818,
FT ECO:0000269|PubMed:9166684"
FT /id="VAR_010546"
FT VARIANT 133
FT /note="V -> M (in MODY3)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_010547"
FT VARIANT 142
FT /note="S -> F (in MODY3; reduces transcription activation
FT by about 80%)"
FT /evidence="ECO:0000269|PubMed:12453420,
FT ECO:0000269|PubMed:9097962"
FT /id="VAR_003757"
FT VARIANT 143
FT /note="H -> Y (in MODY3)"
FT /evidence="ECO:0000269|PubMed:10102714,
FT ECO:0000269|PubMed:9075819"
FT /id="VAR_010548"
FT VARIANT 158
FT /note="K -> N (in MODY3)"
FT /evidence="ECO:0000269|PubMed:10078571"
FT /id="VAR_010549"
FT VARIANT 159
FT /note="R -> Q (in MODY3)"
FT /evidence="ECO:0000269|PubMed:10078571,
FT ECO:0000269|PubMed:9097962"
FT /id="VAR_003758"
FT VARIANT 159
FT /note="R -> W (in MODY3)"
FT /evidence="ECO:0000269|PubMed:9075818,
FT ECO:0000269|PubMed:9754819"
FT /id="VAR_010550"
FT VARIANT 161
FT /note="A -> T (in MODY3)"
FT /evidence="ECO:0000269|PubMed:9754819"
FT /id="VAR_010551"
FT VARIANT 165
FT /note="W -> C (in a hepatocellular carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:12355088"
FT /id="VAR_033089"
FT VARIANT 171..631
FT /note="Missing (in MODY3)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079478"
FT VARIANT 191
FT /note="G -> D (in late-onset NIDDM)"
FT /evidence="ECO:0000269|PubMed:9287053"
FT /id="VAR_010552"
FT VARIANT 200
FT /note="R -> W (in MODY3)"
FT /evidence="ECO:0000269|PubMed:9754819"
FT /id="VAR_063069"
FT VARIANT 203
FT /note="R -> C (in MODY3)"
FT /evidence="ECO:0000269|PubMed:10078571"
FT /id="VAR_010554"
FT VARIANT 203
FT /note="R -> H (in MODY3)"
FT /evidence="ECO:0000269|PubMed:10588527"
FT /id="VAR_012484"
FT VARIANT 205
FT /note="K -> Q (in MODY3; reduces transcription activation
FT by about 50%)"
FT /evidence="ECO:0000269|PubMed:12453420,
FT ECO:0000269|PubMed:9287053"
FT /id="VAR_010555"
FT VARIANT 206
FT /note="W -> C (in a hepatic adenoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:12355088"
FT /id="VAR_033090"
FT VARIANT 206
FT /note="W -> L (in a hepatic adenoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:12355088"
FT /id="VAR_033091"
FT VARIANT 229
FT /note="R -> Q (in MODY3)"
FT /evidence="ECO:0000269|PubMed:9032114"
FT /id="VAR_010556"
FT VARIANT 237
FT /note="N -> S (in a hepatic multiple adenoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:12355088"
FT /id="VAR_033092"
FT VARIANT 241
FT /note="C -> G (in IDDM20 and MODY3)"
FT /evidence="ECO:0000269|PubMed:9032114,
FT ECO:0000269|PubMed:9867222"
FT /id="VAR_010557"
FT VARIANT 244
FT /note="R -> G (in a hepatic adenoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:12355088"
FT /id="VAR_033093"
FT VARIANT 250
FT /note="Q -> P (in a hepatocellular carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:12355088"
FT /id="VAR_033094"
FT VARIANT 254
FT /note="L -> M (in late-onset NIDDM; low penetrance; unknown
FT pathological significance)"
FT /evidence="ECO:0000269|PubMed:9287055"
FT /id="VAR_010558"
FT VARIANT 259
FT /note="V -> D (in MODY3)"
FT /id="VAR_010559"
FT VARIANT 260
FT /note="T -> M (in MODY3)"
FT /evidence="ECO:0000269|PubMed:9166684"
FT /id="VAR_010560"
FT VARIANT 263
FT /note="R -> C (in MODY3)"
FT /evidence="ECO:0000269|PubMed:9287053"
FT /id="VAR_010561"
FT VARIANT 268
FT /note="F -> C (in a hepatic adenoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:12355088"
FT /id="VAR_033095"
FT VARIANT 271
FT /note="R -> G (in MODY3)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079479"
FT VARIANT 271
FT /note="R -> W (in MODY3)"
FT /evidence="ECO:0000269|PubMed:9754819"
FT /id="VAR_010562"
FT VARIANT 272
FT /note="R -> C (in NIDDM; loss of function in positive
FT regulation of DNA-templated transcription)"
FT /evidence="ECO:0000269|PubMed:10333057"
FT /id="VAR_010563"
FT VARIANT 272
FT /note="R -> H (in IDDM20 and MODY3)"
FT /evidence="ECO:0000269|PubMed:9032114,
FT ECO:0000269|PubMed:9166684, ECO:0000269|PubMed:9313763"
FT /id="VAR_003759"
FT VARIANT 273
FT /note="K -> E (in a hepatic adenoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:12355088,
FT ECO:0000269|PubMed:16959974"
FT /id="VAR_033096"
FT VARIANT 319
FT /note="G -> S (strong association with NIDDM
FT susceptibility; unique to the Canadian Oji-Cree
FT population)"
FT /evidence="ECO:0000269|PubMed:10084598"
FT /id="VAR_010564"
FT VARIANT 415
FT /note="G -> R (in IDDM20; decreased function in positive
FT regulation of DNA-templated transcription)"
FT /evidence="ECO:0000269|PubMed:10333057"
FT /id="VAR_010565"
FT VARIANT 432
FT /note="S -> C (in MODY3)"
FT /evidence="ECO:0000269|PubMed:10588527"
FT /id="VAR_012485"
FT VARIANT 447
FT /note="P -> L (in MODY3)"
FT /evidence="ECO:0000269|PubMed:17573900,
FT ECO:0000269|PubMed:8945470, ECO:0000269|PubMed:9075819"
FT /id="VAR_003760"
FT VARIANT 487
FT /note="S -> N (in dbSNP:rs2464196)"
FT /evidence="ECO:0000269|PubMed:9112026,
FT ECO:0000269|PubMed:9133564, ECO:0000269|PubMed:9287055,
FT ECO:0000269|PubMed:9604876, ECO:0000269|PubMed:9621514,
FT ECO:0000269|Ref.6"
FT /id="VAR_007906"
FT VARIANT 514
FT /note="H -> R"
FT /evidence="ECO:0000269|PubMed:9604876"
FT /id="VAR_010566"
FT VARIANT 519
FT /note="P -> L (in MODY3)"
FT /evidence="ECO:0000269|PubMed:9075818"
FT /id="VAR_010567"
FT VARIANT 537
FT /note="T -> R (in MODY3; incomplete penetrance)"
FT /evidence="ECO:0000269|PubMed:9626139"
FT /id="VAR_010568"
FT VARIANT 574
FT /note="G -> S (in a black African with an atypical form of
FT diabetes; also in an individual with hepatic adenoma and
FT familial early-onset diabetes; dbSNP:rs1169305)"
FT /evidence="ECO:0000269|PubMed:12355088,
FT ECO:0000269|PubMed:9392505, ECO:0000269|Ref.5,
FT ECO:0000269|Ref.6"
FT /id="VAR_010569"
FT VARIANT 583
FT /note="R -> G (in IDDM20)"
FT /evidence="ECO:0000269|PubMed:9313763"
FT /id="VAR_003761"
FT VARIANT 583
FT /note="R -> Q (in late-onset NIDDM; also in an individual
FT with hepatic hyperplasia and familial early-onset
FT diabetes)"
FT /evidence="ECO:0000269|PubMed:12355088,
FT ECO:0000269|PubMed:9112026"
FT /id="VAR_010570"
FT VARIANT 594
FT /note="S -> I (in MODY3)"
FT /id="VAR_010571"
FT VARIANT 618
FT /note="I -> M (in MODY3)"
FT /evidence="ECO:0000269|PubMed:10588527"
FT /id="VAR_012486"
FT VARIANT 619
FT /note="E -> K (in MODY3)"
FT /evidence="ECO:0000269|PubMed:9626139"
FT /id="VAR_010572"
FT VARIANT 620
FT /note="T -> I (in MODY3; incomplete penetrance)"
FT /evidence="ECO:0000269|PubMed:10482964,
FT ECO:0000269|PubMed:9075818"
FT /id="VAR_010573"
FT MUTAGEN 127
FT /note="N->W: Abolishes transcription activation."
FT /evidence="ECO:0000269|PubMed:12453420"
FT MUTAGEN 132
FT /note="E->K: Abolishes transcription activation."
FT /evidence="ECO:0000269|PubMed:12453420"
FT MUTAGEN 177
FT /note="F->S: No significant effect on transcription
FT activation."
FT /evidence="ECO:0000269|PubMed:12453420"
FT MUTAGEN 186
FT /note="I->Q: No effect on transcription activation."
FT /evidence="ECO:0000269|PubMed:12453420"
FT MUTAGEN 190
FT /note="T->Q: No effect on transcription activation."
FT /evidence="ECO:0000269|PubMed:12453420"
FT MUTAGEN 202
FT /note="N->D: Reduces transcription activation by 70%."
FT /evidence="ECO:0000269|PubMed:12453420"
FT MUTAGEN 246
FT /note="V->D: Reduces transcription activation by 75%."
FT /evidence="ECO:0000269|PubMed:12453420"
FT MUTAGEN 257
FT /note="N->W: Reduces transcription activation by 70%."
FT /evidence="ECO:0000269|PubMed:12453420"
FT HELIX 4..19
FT /evidence="ECO:0007829|PDB:2GYP"
FT HELIX 23..30
FT /evidence="ECO:0007829|PDB:2GYP"
FT HELIX 94..107
FT /evidence="ECO:0007829|PDB:1IC8"
FT HELIX 112..125
FT /evidence="ECO:0007829|PDB:1IC8"
FT HELIX 130..137
FT /evidence="ECO:0007829|PDB:1IC8"
FT HELIX 141..149
FT /evidence="ECO:0007829|PDB:1IC8"
FT HELIX 156..169
FT /evidence="ECO:0007829|PDB:1IC8"
FT TURN 170..173
FT /evidence="ECO:0007829|PDB:1IC8"
FT HELIX 174..177
FT /evidence="ECO:0007829|PDB:1IC8"
FT HELIX 208..221
FT /evidence="ECO:0007829|PDB:1IC8"
FT TURN 226..229
FT /evidence="ECO:0007829|PDB:1IC8"
FT HELIX 230..243
FT /evidence="ECO:0007829|PDB:1IC8"
FT HELIX 255..257
FT /evidence="ECO:0007829|PDB:1IC8"
FT HELIX 261..274
FT /evidence="ECO:0007829|PDB:1IC8"
FT CONFLICT P20823-7:551
FT /note="L -> S (in Ref. 5; ADK56177)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 631 AA; 67356 MW; 8327CD4FDC39254A CRC64;
MVSKLSQLQT ELLAALLESG LSKEALIQAL GEPGPYLLAG EGPLDKGESC GGGRGELAEL
PNGLGETRGS EDETDDDGED FTPPILKELE NLSPEEAAHQ KAVVETLLQE DPWRVAKMVK
SYLQQHNIPQ REVVDTTGLN QSHLSQHLNK GTPMKTQKRA ALYTWYVRKQ REVAQQFTHA
GQGGLIEEPT GDELPTKKGR RNRFKWGPAS QQILFQAYER QKNPSKEERE TLVEECNRAE
CIQRGVSPSQ AQGLGSNLVT EVRVYNWFAN RRKEEAFRHK LAMDTYSGPP PGPGPGPALP
AHSSPGLPPP ALSPSKVHGV RYGQPATSET AEVPSSSGGP LVTVSTPLHQ VSPTGLEPSH
SLLSTEAKLV SAAGGPLPPV STLTALHSLE QTSPGLNQQP QNLIMASLPG VMTIGPGEPA
SLGPTFTNTG ASTLVIGLAS TQAQSVPVIN SMGSSLTTLQ PVQFSQPLHP SYQQPLMPPV
QSHVTQSPFM ATMAQLQSPH ALYSHKPEVA QYTHTGLLPQ TMLITDTTNL SALASLTPTK
QVFTSDTEAS SESGLHTPAS QATTLHVPSQ DPAGIQHLQP AHRLSASPTV SSSSLVLYQS
SDSSNGQSHL LPSNHSVIET FISTQMASSS Q
