HNF1B_HUMAN
ID HNF1B_HUMAN Reviewed; 557 AA.
AC P35680; B4DKM3; E0YMJ9;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 230.
DE RecName: Full=Hepatocyte nuclear factor 1-beta;
DE Short=HNF-1-beta;
DE Short=HNF-1B;
DE AltName: Full=Homeoprotein LFB3;
DE AltName: Full=Transcription factor 2;
DE Short=TCF-2;
DE AltName: Full=Variant hepatic nuclear factor 1;
DE Short=vHNF1;
GN Name=HNF1B; Synonyms=TCF2;
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=1677179; DOI=10.1093/nar/19.13.3553;
RA Bach I., Mattei M.-G., Cereghini S., Yaniv M.;
RT "Two members of an HNF1 homeoprotein family are expressed in human liver.";
RL Nucleic Acids Res. 19:3553-3559(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B AND C), AND FUNCTION.
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].
RX PubMed=9398836; DOI=10.1038/ng1297-384;
RA Horikawa Y., Iwasaki N., Hara M., Furuta H., Hinokio Y., Cockburn B.N.,
RA Lindner T., Yamagata K., Ogata M., Tomonaga O., Kuroki H., Kasahara T.,
RA Iwamoto Y., Bell G.I.;
RT "Mutation in hepatocyte nuclear factor-1 beta gene (TCF2) associated with
RT MODY.";
RL Nat. Genet. 17:384-385(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RA Yang C.-W., Tsai D.-Y.;
RT "Homo sapiens HNF1 beta A mRNA splicing variant 4.";
RL Submitted (APR-2010) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RC TISSUE=Colon;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [8]
RP INVOLVEMENT IN RCAD.
RX PubMed=10484768; DOI=10.1093/hmg/8.11.2001;
RA Lindner T.H., Njoelstad P.R., Horikawa Y., Bostad L., Bell G.I., Soevik O.;
RT "A novel syndrome of diabetes mellitus, renal dysfunction and genital
RT malformation associated with a partial deletion of the pseudo-POU domain of
RT hepatocyte nuclear factor-1beta.";
RL Hum. Mol. Genet. 8:2001-2008(1999).
RN [9]
RP STRUCTURE BY NMR OF 233-321.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the homeobox domain of hepatocyte nuclear factor 1-
RT beta (HNF-1beta).";
RL Submitted (DEC-2006) to the PDB data bank.
RN [10]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 91-310 IN COMPLEX WITH DNA, AND
RP FUNCTION.
RX PubMed=17924661; DOI=10.1021/bi7010527;
RA Lu P., Rha G.B., Chi Y.I.;
RT "Structural basis of disease-causing mutations in hepatocyte nuclear factor
RT 1beta.";
RL Biochemistry 46:12071-12080(2007).
RN [11]
RP VARIANT RCAD THR-241, AND VARIANT DIABETES SER-492.
RX PubMed=10672455; DOI=10.1007/s001250050018;
RA Weng J.P., Lehto M., Forsblom C., Huang X., Li H., Groop L.C.;
RT "Hepatocyte nuclear factor-1 beta (MODY5) gene mutations in Scandinavian
RT families with early-onset diabetes or kidney disease or both.";
RL Diabetologia 43:131-132(2000).
RN [12]
RP VARIANT RCAD PHE-36, AND CHARACTERIZATION OF VARIANT RCAD PHE-36.
RX PubMed=11845238; DOI=10.1007/s125-002-8259-5;
RA Yoshiuchi I., Yamagata K., Zhu Q., Tamada I., Takahashi Y., Onigata K.,
RA Takeda J., Miyagawa J., Matsuzawa Y.;
RT "Identification of a gain-of-function mutation in the HNF-1beta gene in a
RT Japanese family with MODY.";
RL Diabetologia 45:154-155(2002).
RN [13]
RP VARIANT RCAD PRO-151.
RX PubMed=11918730; DOI=10.1046/j.1523-1755.2002.00272.x;
RA Bingham C., Ellard S., Cole T.R.P., Jones K.E., Allen L.I.S.,
RA Goodship J.A., Goodship T.H.J., Bakalinova-Pugh D., Russell G.I.,
RA Woolf A.S., Nicholls A.J., Hattersley A.T.;
RT "Solitary functioning kidney and diverse genital tract malformations
RT associated with hepatocyte nuclear factor-1beta mutations.";
RL Kidney Int. 61:1243-1251(2002).
RN [14]
RP VARIANT NIDDM ARG-465.
RX PubMed=12161522; DOI=10.1210/jcem.87.8.8776;
RA Furuta H., Furuta M., Sanke T., Ekawa K., Hanabusa T., Nishi M., Sasaki H.,
RA Nanjo K.;
RT "Nonsense and missense mutations in the human hepatocyte nuclear factor-1
RT beta gene (TCF2) and their relation to type 2 diabetes in Japanese.";
RL J. Clin. Endocrinol. Metab. 87:3859-3863(2002).
RN [15]
RP VARIANT RCAD ASP-260, AND CHARACTERIZATION OF VARIANT RCAD ASP-260.
RX PubMed=14583183; DOI=10.1016/s1056-8727(02)00221-0;
RA So W.Y., Ng M.C.Y., Horikawa Y., Njoelstad P.R., Li J.K.Y., Ma R.C.W.,
RA Bell G.I., Chan J.C.N.;
RT "Genetic variants of hepatocyte nuclear factor-1beta in Chinese young-onset
RT diabetic patients with nephropathy.";
RL J. Diabetes Complications 17:369-373(2003).
RN [16]
RP VARIANTS RCAD PRO-112; GLU-136; GLN-164; HIS-165 AND HIS-295.
RX PubMed=15068978; DOI=10.7326/0003-4819-140-7-200404060-00009;
RA Bellanne-Chantelot C., Chauveau D., Gautier J.-F., Dubois-Laforgue D.,
RA Clauin S., Beaufils S., Wilhelm J.-M., Boitard C., Noeel L.-H., Velho G.,
RA Timsit J.;
RT "Clinical spectrum associated with hepatocyte nuclear factor-1beta
RT mutations.";
RL Ann. Intern. Med. 140:510-517(2004).
RN [17]
RP VARIANT RCAD ASN-153, AND CHARACTERIZATION OF VARIANT RCAD ASN-153.
RX PubMed=15001636; DOI=10.1210/jc.2003-031308;
RA Kitanaka S., Miki Y., Hayashi Y., Igarashi T.;
RT "Promoter-specific repression of hepatocyte nuclear factor (HNF)-1beta and
RT HNF-1alpha transcriptional activity by an HNF-1beta missense mutant
RT associated with type 5 maturity-onset diabetes of the young with hepatic
RT and biliary manifestations.";
RL J. Clin. Endocrinol. Metab. 89:1369-1378(2004).
RN [18]
RP VARIANT RCAD TRP-148.
RX PubMed=15181075; DOI=10.1210/jc.2003-031828;
RA Yorifuji T., Kurokawa K., Mamada M., Imai T., Kawai M., Nishi Y.,
RA Shishido S., Hasegawa Y., Nakahata T.;
RT "Neonatal diabetes mellitus and neonatal polycystic, dysplastic kidneys:
RT phenotypically discordant recurrence of a mutation in the hepatocyte
RT nuclear factor-1beta gene due to germline mosaicism.";
RL J. Clin. Endocrinol. Metab. 89:2905-2908(2004).
RN [19]
RP VARIANTS RCAD CYS-76; PRO-112; GLU-136; GLN-164; HIS-165; GLN-235; GLY-276;
RP ASP-285; CYS-295; HIS-295 AND SER-370.
RX PubMed=16249435; DOI=10.2337/diabetes.54.11.3126;
RA Bellanne-Chantelot C., Clauin S., Chauveau D., Collin P., Daumont M.,
RA Douillard C., Dubois-Laforgue D., Dusselier L., Gautier J.-F., Jadoul M.,
RA Laloi-Michelin M., Jacquesson L., Larger E., Louis J., Nicolino M.,
RA Subra J.-F., Wilhem J.-M., Young J., Velho G., Timsit J.;
RT "Large genomic rearrangements in the hepatocyte nuclear factor-1beta (TCF2)
RT gene are the most frequent cause of maturity-onset diabetes of the young
RT type 5.";
RL Diabetes 54:3126-3132(2005).
RN [20]
RP VARIANTS RCAD GLY-61; GLY-110; LEU-148; GLU-156; GLN-276 AND PRO-295.
RX PubMed=15930087; DOI=10.1136/jmg.2005.032854;
RA Edghill E.L., Bingham C., Ellard S., Hattersley A.T.;
RT "Mutations in hepatocyte nuclear factor-1beta and their related
RT phenotypes.";
RL J. Med. Genet. 43:84-90(2006).
RN [21]
RP INVOLVEMENT IN SUSCEPTIBILITY TO HEREDITARY PROSTATE CANCER.
RX PubMed=18264097; DOI=10.1038/ng.90;
RG The UK genetic prostate cancer study collaborators;
RG British association of urological surgeons section of oncology;
RG The UK protecT study collaborators;
RA Eeles R.A., Kote-Jarai Z., Giles G.G., Al Olama A.A., Guy M.,
RA Jugurnauth S.K., Mulholland S., Leongamornlert D.A., Edwards S.M.,
RA Morrison J., Field H.I., Southey M.C., Severi G., Donovan J.L., Hamdy F.C.,
RA Dearnaley D.P., Muir K.R., Smith C., Bagnato M., Ardern-Jones A.T.,
RA Hall A.L., O'Brien L.T., Gehr-Swain B.N., Wilkinson R.A., Cox A., Lewis S.,
RA Brown P.M., Jhavar S.G., Tymrakiewicz M., Lophatananon A., Bryant S.L.,
RA Horwich A., Huddart R.A., Khoo V.S., Parker C.C., Woodhouse C.J.,
RA Thompson A., Christmas T., Ogden C., Fisher C., Jamieson C., Cooper C.S.,
RA English D.R., Hopper J.L., Neal D.E., Easton D.F.;
RT "Multiple newly identified loci associated with prostate cancer
RT susceptibility.";
RL Nat. Genet. 40:316-321(2008).
RN [22]
RP CHARACTERIZATION OF VARIANTS RCAD GLU-156 AND GLY-276, FUNCTION,
RP INTERACTION WITH PCBD1, AND MUTAGENESIS OF 1-MET--LEU-30 AND GLN-253.
RX PubMed=24204001; DOI=10.1681/asn.2013040337;
RA Ferre S., de Baaij J.H., Ferreira P., Germann R., de Klerk J.B.,
RA Lavrijsen M., van Zeeland F., Venselaar H., Kluijtmans L.A.,
RA Hoenderop J.G., Bindels R.J.;
RT "Mutations in PCBD1 cause hypomagnesemia and renal magnesium wasting.";
RL J. Am. Soc. Nephrol. 25:574-586(2014).
CC -!- FUNCTION: Transcription factor that binds to the inverted palindrome
CC 5'-GTTAATNATTAAC-3' (PubMed:7900999, PubMed:17924661). Binds to the FPC
CC element in the cAMP regulatory unit of the PLAU gene (By similarity).
CC Transcriptional activity is increased by coactivator PCBD1
CC (PubMed:24204001). {ECO:0000250|UniProtKB:Q03365,
CC ECO:0000269|PubMed:17924661, ECO:0000269|PubMed:24204001,
CC ECO:0000269|PubMed:7900999}.
CC -!- SUBUNIT: Binds DNA as a dimer. Can form homodimer or heterodimer with
CC HNF1-alpha. Interacts (via HNF-p1 domain) with PCBD1; the interaction
CC increases its transactivation activity (PubMed:24204001).
CC {ECO:0000269|PubMed:17924661, ECO:0000269|PubMed:24204001}.
CC -!- INTERACTION:
CC P35680; Q9NP55: BPIFA1; NbExp=3; IntAct=EBI-2798841, EBI-953896;
CC P35680; Q5SWW7: C10orf55; NbExp=3; IntAct=EBI-2798841, EBI-12809220;
CC P35680; O43186: CRX; NbExp=3; IntAct=EBI-2798841, EBI-748171;
CC P35680; Q6PEX3: KRTAP26-1; NbExp=3; IntAct=EBI-2798841, EBI-3957672;
CC P35680; P55197-2: MLLT10; NbExp=3; IntAct=EBI-2798841, EBI-12853322;
CC P35680; P32243-2: OTX2; NbExp=3; IntAct=EBI-2798841, EBI-9087860;
CC P35680; Q8TDS5: OXER1; NbExp=3; IntAct=EBI-2798841, EBI-12813389;
CC P35680; P61457: PCBD1; NbExp=7; IntAct=EBI-2798841, EBI-740475;
CC P35680; P78424: POU6F2; NbExp=3; IntAct=EBI-2798841, EBI-12029004;
CC P35680; Q6NVU6: UFSP1; NbExp=3; IntAct=EBI-2798841, EBI-12068150;
CC P35680; Q70EL1-9: USP54; NbExp=3; IntAct=EBI-2798841, EBI-11975223;
CC P35680; Q08AM6: VAC14; NbExp=3; IntAct=EBI-2798841, EBI-2107455;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=A;
CC IsoId=P35680-1; Sequence=Displayed;
CC Name=B;
CC IsoId=P35680-2; Sequence=VSP_002254;
CC Name=C;
CC IsoId=P35680-3; Sequence=VSP_002255, VSP_002256;
CC Name=4;
CC IsoId=P35680-4; Sequence=VSP_053327, VSP_002254, VSP_053328,
CC VSP_053329;
CC -!- DISEASE: Renal cysts and diabetes syndrome (RCAD) [MIM:137920]: An
CC autosomal dominant disorder comprising non-diabetic renal disease
CC resulting from abnormal renal development, and diabetes, which in some
CC cases occurs earlier than age 25 years and is thus consistent with a
CC diagnosis of maturity-onset diabetes of the young (MODY5). The renal
CC disease is highly variable and includes renal cysts, glomerular tufts,
CC aberrant nephrogenesis, primitive tubules, irregular collecting
CC systems, oligomeganephronia, enlarged renal pelves, abnormal calyces,
CC small kidney, single kidney, horseshoe kidney, and hyperuricemic
CC nephropathy. Affected individuals may also have abnormalities of the
CC genital tract. {ECO:0000269|PubMed:10484768,
CC ECO:0000269|PubMed:10672455, ECO:0000269|PubMed:11845238,
CC ECO:0000269|PubMed:11918730, ECO:0000269|PubMed:14583183,
CC ECO:0000269|PubMed:15001636, ECO:0000269|PubMed:15068978,
CC ECO:0000269|PubMed:15181075, ECO:0000269|PubMed:15930087,
CC ECO:0000269|PubMed:16249435, ECO:0000269|PubMed:24204001}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]:
CC A multifactorial disorder of glucose homeostasis caused by a lack of
CC sensitivity to the body's own insulin. Affected individuals usually
CC have an obese body habitus and manifestations of a metabolic syndrome
CC characterized by diabetes, insulin resistance, hypertension and
CC hypertriglyceridemia. The disease results in long-term complications
CC that affect the eyes, kidneys, nerves, and blood vessels.
CC {ECO:0000269|PubMed:12161522}. Note=Disease susceptibility may be
CC associated with variants affecting the gene represented in this entry.
CC -!- DISEASE: Prostate cancer, hereditary, 11 (HPC11) [MIM:611955]: A
CC condition associated with familial predisposition to cancer of the
CC prostate. Most prostate cancers are adenocarcinomas that develop in the
CC acini of the prostatic ducts. Other rare histopathologic types of
CC prostate cancer that occur in approximately 5% of patients include
CC small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma,
CC transitional cell carcinoma, squamous cell carcinoma, basal cell
CC carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell
CC carcinoma and neuroendocrine carcinoma. {ECO:0000269|PubMed:18264097}.
CC Note=Disease susceptibility is associated with variants affecting the
CC gene represented in this entry.
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";
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DR EMBL; X58840; CAA41652.1; -; mRNA.
DR EMBL; X71348; CAB59223.1; -; mRNA.
DR EMBL; U90287; AAC63388.1; -; Genomic_DNA.
DR EMBL; U90279; AAC63388.1; JOINED; Genomic_DNA.
DR EMBL; U90280; AAC63388.1; JOINED; Genomic_DNA.
DR EMBL; U90281; AAC63388.1; JOINED; Genomic_DNA.
DR EMBL; U90282; AAC63388.1; JOINED; Genomic_DNA.
DR EMBL; U90283; AAC63388.1; JOINED; Genomic_DNA.
DR EMBL; U90284; AAC63388.1; JOINED; Genomic_DNA.
DR EMBL; U90285; AAC63388.1; JOINED; Genomic_DNA.
DR EMBL; U90286; AAC63388.1; JOINED; Genomic_DNA.
DR EMBL; HM116556; ADM43493.1; -; mRNA.
DR EMBL; AK296633; BAG59235.1; -; mRNA.
DR EMBL; AC091199; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC113211; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC017714; AAH17714.1; -; mRNA.
DR CCDS; CCDS11324.1; -. [P35680-1]
DR CCDS; CCDS58538.1; -. [P35680-2]
DR PIR; S34412; S34412.
DR RefSeq; NP_000449.1; NM_000458.3. [P35680-1]
DR RefSeq; NP_001159395.1; NM_001165923.3. [P35680-2]
DR RefSeq; NP_001291215.1; NM_001304286.1.
DR PDB; 2DA6; NMR; -; A=233-321.
DR PDB; 2H8R; X-ray; 3.20 A; A/B=91-310.
DR PDB; 5K9S; X-ray; 2.40 A; B/C=227-237.
DR PDBsum; 2DA6; -.
DR PDBsum; 2H8R; -.
DR PDBsum; 5K9S; -.
DR AlphaFoldDB; P35680; -.
DR BMRB; P35680; -.
DR SMR; P35680; -.
DR BioGRID; 112790; 193.
DR IntAct; P35680; 142.
DR STRING; 9606.ENSP00000480291; -.
DR iPTMnet; P35680; -.
DR PhosphoSitePlus; P35680; -.
DR BioMuta; HNF1B; -.
DR DMDM; 547664; -.
DR jPOST; P35680; -.
DR MassIVE; P35680; -.
DR MaxQB; P35680; -.
DR PaxDb; P35680; -.
DR PeptideAtlas; P35680; -.
DR PRIDE; P35680; -.
DR ProteomicsDB; 15199; -.
DR ProteomicsDB; 55134; -. [P35680-1]
DR ProteomicsDB; 55135; -. [P35680-2]
DR ProteomicsDB; 55136; -. [P35680-3]
DR Antibodypedia; 72795; 530 antibodies from 38 providers.
DR DNASU; 6928; -.
DR Ensembl; ENST00000610754.4; ENSP00000484591.1; ENSG00000276194.4. [P35680-1]
DR Ensembl; ENST00000617811.5; ENSP00000480291.1; ENSG00000275410.6. [P35680-1]
DR Ensembl; ENST00000621123.4; ENSP00000482711.1; ENSG00000275410.6. [P35680-2]
DR Ensembl; ENST00000633792.1; ENSP00000488080.1; ENSG00000276194.4. [P35680-2]
DR GeneID; 6928; -.
DR KEGG; hsa:6928; -.
DR MANE-Select; ENST00000617811.5; ENSP00000480291.1; NM_000458.4; NP_000449.1.
DR UCSC; uc010wdi.3; human. [P35680-1]
DR CTD; 6928; -.
DR DisGeNET; 6928; -.
DR GeneCards; HNF1B; -.
DR GeneReviews; HNF1B; -.
DR HGNC; HGNC:11630; HNF1B.
DR HPA; ENSG00000275410; Tissue enhanced (kidney, pancreas).
DR MalaCards; HNF1B; -.
DR MIM; 125853; phenotype.
DR MIM; 137920; phenotype.
DR MIM; 189907; gene.
DR MIM; 611955; phenotype.
DR neXtProt; NX_P35680; -.
DR OpenTargets; ENSG00000275410; -.
DR Orphanet; 261265; 17q12 microdeletion syndrome.
DR Orphanet; 97364; Bilateral multicystic dysplastic kidney.
DR Orphanet; 1331; Familial prostate cancer.
DR Orphanet; 93111; HNF1B-related autosomal dominant tubulointerstitial kidney disease.
DR Orphanet; 1309; Medullary sponge kidney.
DR Orphanet; 93173; Renal dysplasia, bilateral.
DR Orphanet; 93172; Renal dysplasia, unilateral.
DR Orphanet; 97363; Unilateral multicystic dysplastic kidney.
DR PharmGKB; PA162391083; -.
DR VEuPathDB; HostDB:ENSG00000275410; -.
DR eggNOG; ENOG502QRPW; Eukaryota.
DR GeneTree; ENSGT00940000153818; -.
DR HOGENOM; CLU_035503_0_0_1; -.
DR InParanoid; P35680; -.
DR OMA; DDTCSEP; -.
DR PhylomeDB; P35680; -.
DR TreeFam; TF320327; -.
DR PathwayCommons; P35680; -.
DR Reactome; R-HSA-210744; Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells.
DR Reactome; R-HSA-210747; Regulation of gene expression in early pancreatic precursor cells.
DR SignaLink; P35680; -.
DR SIGNOR; P35680; -.
DR BioGRID-ORCS; 6928; 67 hits in 1091 CRISPR screens.
DR ChiTaRS; HNF1B; human.
DR EvolutionaryTrace; P35680; -.
DR GeneWiki; HNF1B; -.
DR GenomeRNAi; 6928; -.
DR Pharos; P35680; Tbio.
DR PRO; PR:P35680; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P35680; protein.
DR Bgee; ENSG00000275410; Expressed in metanephros cortex and 53 other tissues.
DR ExpressionAtlas; P35680; baseline and differential.
DR Genevisible; P35680; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; IEA:Ensembl.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
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:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0001221; F:transcription coregulator binding; IPI:UniProtKB.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IEA:Ensembl.
DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; IEA:Ensembl.
DR GO; GO:0032922; P:circadian regulation of gene expression; IEA:Ensembl.
DR GO; GO:0048557; P:embryonic digestive tract morphogenesis; IEA:Ensembl.
DR GO; GO:0031018; P:endocrine pancreas development; IMP:UniProtKB.
DR GO; GO:0001714; P:endodermal cell fate specification; IEA:Ensembl.
DR GO; GO:0050673; P:epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0048806; P:genitalia development; IMP:UniProtKB.
DR GO; GO:0061017; P:hepatoblast differentiation; IEA:Ensembl.
DR GO; GO:0070365; P:hepatocyte differentiation; IEA:Ensembl.
DR GO; GO:0030902; P:hindbrain development; IEA:Ensembl.
DR GO; GO:0001826; P:inner cell mass cell differentiation; IEA:Ensembl.
DR GO; GO:0030073; P:insulin secretion; IEA:Ensembl.
DR GO; GO:0001822; P:kidney development; IDA:UniProtKB.
DR GO; GO:1900200; P:mesenchymal cell apoptotic process involved in metanephros development; IEA:Ensembl.
DR GO; GO:0072181; P:mesonephric duct formation; IEA:Ensembl.
DR GO; GO:0061296; P:negative regulation of mesenchymal cell apoptotic process involved in mesonephric nephron morphogenesis; IEA:Ensembl.
DR GO; GO:1900212; P:negative regulation of mesenchymal cell apoptotic process involved in metanephros development; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
DR GO; GO:0031016; P:pancreas development; IEA:InterPro.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0060261; P:positive regulation of transcription initiation from RNA polymerase II promoter; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0039020; P:pronephric nephron tubule development; IGI:UniProtKB.
DR GO; GO:0048793; P:pronephros development; IMP:UniProtKB.
DR GO; GO:0065004; P:protein-DNA complex assembly; IEA:Ensembl.
DR GO; GO:0072095; P:regulation of branch elongation involved in ureteric bud branching; IEA:Ensembl.
DR GO; GO:0035565; P:regulation of pronephros size; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0030111; P:regulation of Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0009749; P:response to glucose; IEA:Ensembl.
DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0060677; P:ureteric bud elongation; IEA:Ensembl.
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; 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; 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..557
FT /note="Hepatocyte nuclear factor 1-beta"
FT /id="PRO_0000049121"
FT DOMAIN 1..32
FT /note="HNF-p1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01286"
FT DOMAIN 93..188
FT /note="POU-specific atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01285"
FT DNA_BIND 231..311
FT /note="Homeobox; HNF1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 1..31
FT /note="Dimerization"
FT /evidence="ECO:0000250"
FT REGION 64..85
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 324..352
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 49
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P27889"
FT MOD_RES 52
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P27889"
FT MOD_RES 75
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P27889"
FT MOD_RES 80
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P27889"
FT VAR_SEQ 96..125
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_053327"
FT VAR_SEQ 183..208
FT /note="Missing (in isoform B and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:7900999, ECO:0000303|Ref.4"
FT /id="VSP_002254"
FT VAR_SEQ 350..400
FT /note="VRYSQQGNNEITSSSTISHHGNSAMVTSQSVLQQVSPASLDPGHNLLSPDG
FT -> KQRLGLTASATQPSWFLPRILSGLRVFRGANAFEMILGPLSHCQNILPWK (in
FT isoform C)"
FT /evidence="ECO:0000303|PubMed:7900999"
FT /id="VSP_002255"
FT VAR_SEQ 401..557
FT /note="Missing (in isoform C)"
FT /evidence="ECO:0000303|PubMed:7900999"
FT /id="VSP_002256"
FT VAR_SEQ 447..483
FT /note="SLNTSQAQSVPVINSVAGSLAALQPVQFSQQLHSPHQ -> MSSTSLVMPTH
FT HLLRAQQQGPCFPHHHPLGSCHGKAQ (in isoform 4)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_053328"
FT VAR_SEQ 484..557
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_053329"
FT VARIANT 36
FT /note="S -> F (in RCAD; gain-of-function mutation;
FT dbSNP:rs544890850)"
FT /evidence="ECO:0000269|PubMed:11845238"
FT /id="VAR_046012"
FT VARIANT 61
FT /note="V -> G (in RCAD; dbSNP:rs147816724)"
FT /evidence="ECO:0000269|PubMed:15930087"
FT /id="VAR_046013"
FT VARIANT 76
FT /note="G -> C (in RCAD; unknown pathological significance;
FT dbSNP:rs144425830)"
FT /evidence="ECO:0000269|PubMed:16249435"
FT /id="VAR_046014"
FT VARIANT 110
FT /note="V -> G (in RCAD; dbSNP:rs894213416)"
FT /evidence="ECO:0000269|PubMed:15930087"
FT /id="VAR_046015"
FT VARIANT 112
FT /note="R -> P (in RCAD)"
FT /evidence="ECO:0000269|PubMed:15068978,
FT ECO:0000269|PubMed:16249435"
FT /id="VAR_046016"
FT VARIANT 136
FT /note="Q -> E (in RCAD)"
FT /evidence="ECO:0000269|PubMed:15068978,
FT ECO:0000269|PubMed:16249435"
FT /id="VAR_046017"
FT VARIANT 148
FT /note="S -> L (in RCAD)"
FT /evidence="ECO:0000269|PubMed:15930087"
FT /id="VAR_046018"
FT VARIANT 148
FT /note="S -> W (in RCAD; dbSNP:rs121918674)"
FT /evidence="ECO:0000269|PubMed:15181075"
FT /id="VAR_046019"
FT VARIANT 151
FT /note="S -> P (in RCAD)"
FT /evidence="ECO:0000269|PubMed:11918730"
FT /id="VAR_046020"
FT VARIANT 153
FT /note="H -> N (in RCAD; has diminished transcriptional
FT activity by loss of DNA binding activity)"
FT /evidence="ECO:0000269|PubMed:15001636"
FT /id="VAR_046021"
FT VARIANT 156
FT /note="K -> E (in RCAD; no impact on interaction with
FT PCBD1; reduced coactivation by PCBD1)"
FT /evidence="ECO:0000269|PubMed:15930087,
FT ECO:0000269|PubMed:24204001"
FT /id="VAR_046022"
FT VARIANT 164
FT /note="K -> Q (in RCAD)"
FT /evidence="ECO:0000269|PubMed:15068978,
FT ECO:0000269|PubMed:16249435"
FT /id="VAR_046023"
FT VARIANT 165
FT /note="R -> H (in RCAD; dbSNP:rs121918675)"
FT /evidence="ECO:0000269|PubMed:15068978,
FT ECO:0000269|PubMed:16249435"
FT /id="VAR_046024"
FT VARIANT 235
FT /note="R -> Q (in RCAD)"
FT /evidence="ECO:0000269|PubMed:16249435"
FT /id="VAR_046025"
FT VARIANT 241
FT /note="A -> T (in RCAD; dbSNP:rs761415487)"
FT /evidence="ECO:0000269|PubMed:10672455"
FT /id="VAR_046026"
FT VARIANT 260
FT /note="E -> D (in RCAD; insignificant differences in
FT transactivation ability between wild-type and mutated
FT HNF1B; dbSNP:rs536638039)"
FT /evidence="ECO:0000269|PubMed:14583183"
FT /id="VAR_046027"
FT VARIANT 276
FT /note="R -> G (in RCAD; no impact on interaction with
FT PCBD1; reduced coactivation by PCBD1)"
FT /evidence="ECO:0000269|PubMed:16249435,
FT ECO:0000269|PubMed:24204001"
FT /id="VAR_046028"
FT VARIANT 276
FT /note="R -> Q (in RCAD)"
FT /evidence="ECO:0000269|PubMed:15930087"
FT /id="VAR_046029"
FT VARIANT 285
FT /note="G -> D (in RCAD)"
FT /evidence="ECO:0000269|PubMed:16249435"
FT /id="VAR_046030"
FT VARIANT 295
FT /note="R -> C (in RCAD)"
FT /evidence="ECO:0000269|PubMed:16249435"
FT /id="VAR_046031"
FT VARIANT 295
FT /note="R -> H (in RCAD; dbSNP:rs886043813)"
FT /evidence="ECO:0000269|PubMed:15068978,
FT ECO:0000269|PubMed:16249435"
FT /id="VAR_046032"
FT VARIANT 295
FT /note="R -> P (in RCAD)"
FT /evidence="ECO:0000269|PubMed:15930087"
FT /id="VAR_046033"
FT VARIANT 370
FT /note="G -> S (in RCAD; dbSNP:rs113042313)"
FT /evidence="ECO:0000269|PubMed:16249435"
FT /id="VAR_046034"
FT VARIANT 465
FT /note="S -> R (in NIDDM; 22% reduction in activity;
FT dbSNP:rs121918673)"
FT /evidence="ECO:0000269|PubMed:12161522"
FT /id="VAR_017665"
FT VARIANT 492
FT /note="G -> S (in diabetes; early onset association;
FT unknown pathological significance; dbSNP:rs187556368)"
FT /evidence="ECO:0000269|PubMed:10672455"
FT /id="VAR_012058"
FT MUTAGEN 1..32
FT /note="Missing: Loss of interaction with PCBD1. Loss of
FT PCBD1 recruitment to the nucleus."
FT /evidence="ECO:0000269|PubMed:24204001"
FT MUTAGEN 253
FT /note="Q->P: No impact on interaction with PCBD1. Reduced
FT PCBD1 recruitment to the nucleus. Reduced coactivation by
FT PCBD1."
FT /evidence="ECO:0000269|PubMed:24204001"
FT HELIX 91..98
FT /evidence="ECO:0007829|PDB:2H8R"
FT HELIX 101..113
FT /evidence="ECO:0007829|PDB:2H8R"
FT HELIX 118..132
FT /evidence="ECO:0007829|PDB:2H8R"
FT HELIX 136..143
FT /evidence="ECO:0007829|PDB:2H8R"
FT HELIX 147..154
FT /evidence="ECO:0007829|PDB:2H8R"
FT HELIX 162..181
FT /evidence="ECO:0007829|PDB:2H8R"
FT TURN 182..185
FT /evidence="ECO:0007829|PDB:2H8R"
FT HELIX 240..252
FT /evidence="ECO:0007829|PDB:2H8R"
FT HELIX 258..275
FT /evidence="ECO:0007829|PDB:2H8R"
FT HELIX 283..286
FT /evidence="ECO:0007829|PDB:2H8R"
FT HELIX 293..304
FT /evidence="ECO:0007829|PDB:2H8R"
FT STRAND 316..321
FT /evidence="ECO:0007829|PDB:2DA6"
SQ SEQUENCE 557 AA; 61324 MW; 9E1ECC7423B73980 CRC64;
MVSKLTSLQQ ELLSALLSSG VTKEVLVQAL EELLPSPNFG VKLETLPLSP GSGAEPDTKP
VFHTLTNGHA KGRLSGDEGS EDGDDYDTPP ILKELQALNT EEAAEQRAEV DRMLSEDPWR
AAKMIKGYMQ QHNIPQREVV DVTGLNQSHL SQHLNKGTPM KTQKRAALYT WYVRKQREIL
RQFNQTVQSS GNMTDKSSQD QLLFLFPEFS QQSHGPGQSD DACSEPTNKK MRRNRFKWGP
ASQQILYQAY DRQKNPSKEE REALVEECNR AECLQRGVSP SKAHGLGSNL VTEVRVYNWF
ANRRKEEAFR QKLAMDAYSS NQTHSLNPLL SHGSPHHQPS SSPPNKLSGV RYSQQGNNEI
TSSSTISHHG NSAMVTSQSV LQQVSPASLD PGHNLLSPDG KMISVSGGGL PPVSTLTNIH
SLSHHNPQQS QNLIMTPLSG VMAIAQSLNT SQAQSVPVIN SVAGSLAALQ PVQFSQQLHS
PHQQPLMQQS PGSHMAQQPF MAAVTQLQNS HMYAHKQEPP QYSHTSRFPS AMVVTDTSSI
STLTNMSSSK QCPLQAW
