AC T03828
XX
ID T03828
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DT 15.09.2000 (created); bme.
DT 10.02.2015 (updated); hna.
CO Copyright (C), QIAGEN.
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FA HNF-4alpha
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SY hepatocyte nuclear factor 4; HNF-4; HNF-4A; HNF4; NR2A1.
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OS human, Homo sapiens
OC eukaryota; animalia; metazoa; chordata; vertebrata; tetrapoda; mammalia; eutheria; primates
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GE G001926 HNF4A; HGNC: HNF4A.
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CL C0002; CC (rec); 2.1.3.2.1.
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SF forms homodimers;
SF alternative splice variants of HNF-4alpha: HNF-4alpha1 T02421, HNF-4alpha2 T00373, HNF-4alpha3 T02428 and HNF-4alpha4 T02425;
SF an additional exon 1C has been described [3];
SF interacts with co-activator PGC-1 through AF-2 domain [11];
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CP pancreas, kidney, liver, small intestine, colon, testis (barely detectable) [2]; Hep G2 [14]; Hep3B [13].
CN skeletal muscle, lung, placenta, brain, heart, peripheral blood leukocytes, ovary, prostate, thymus, spleen [2]; HeLa [13].
XX
FF HNF-4alpha directly interact with SREBP-2, both together synergistically activated the SI gene [24];
FF activator of genes involved in glucose transport and metabolism: glucose transporter 2, aldolase B, glyceraldehyde-3-phosphate dehydrogenase and liver pyruvate kinase [4];
FF controls the expression of the liver specific transcription factor HNF-1A T00368 [1];
FF activates the expression of a number of apolipoproteins (AI, AIV, B and CIII), albumin, fibrinogen and the coagulation factors VII, VIII, IX and X [6] [7];
FF activates the expression of the alpha1-antitrypsin, alpha1-antichymotrypsin, alpha-fetal protein, ceruloplasmin, IGF binding protein 1 and transferrin [7];
FF ligands: fatty acyl-CoA thioesters binds to the ligand-binding domain of HNF-4alpha resulting in either activation or inhibition of its transcriptional activity as a function of chain length and the degree of saturation [9];
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IN T05778 ASC-2; human, Homo sapiens.
IN T21342 FOXO6; human, Homo sapiens.
IN T04498 FXR-isoform4; human, Homo sapiens.
IN T05076 GR; human, Homo sapiens.
IN T01610 HIF-1alpha; human, Homo sapiens.
IN T03828 HNF-4alpha; human, Homo sapiens.
IN T02430 HNF-4gamma; human, Homo sapiens.
IN T05295 PGC-1-isoform1; human, Homo sapiens.
IN T05296 PGC-1; mouse, Mus musculus.
IN T04922 Prox-1; human, Homo sapiens.
IN T02738 SHP; human, Homo sapiens.
IN T05271 Smad3-isoform1:Smad4; human, Homo sapiens.
IN T04096 Smad3-isoform1; human, Homo sapiens.
IN T04292 Smad4; human, Homo sapiens.
IN T21552 SRC-1; Mammalia.
IN T01560 SREBP-2; human, Homo sapiens.
XX
MX M00158 V$COUP_01.
MX M00762 V$DR1_Q3.
MX M00638 V$HNF4ALPHA_Q6.
MX M02220 V$HNF4A_03.
MX M04808 V$HNF4A_09.
MX M04903 V$HNF4A_10.
MX M07215 V$HNF4A_11.
MX M07321 V$HNF4A_Q3.
MX M02016 V$HNF4A_Q6_01.
MX M00764 V$HNF4DR1_Q3.
MX M00134 V$HNF4_01.
MX M00411 V$HNF4_01_B.
MX M00967 V$HNF4_Q6.
MX M01031 V$HNF4_Q6_01.
MX M01032 V$HNF4_Q6_02.
MX M01033 V$HNF4_Q6_03.
MX M03828 V$HNF4_Q6_04.
XX
BS R22738.
BS R41908.
BS R00114.
BS R23135.
BS R28424.
BS R28425.
BS R28426.
BS R28428.
BS R28429.
BS R26637.
BS R26635.
BS R34331.
BS R34332.
BS R34330.
BS R34329.
BS R23138.
BS R13037.
BS R36556.
BS R22701.
BS R32351.
BS R15850.
BS R15854.
BS R20250.
BS R12993.
BS R21453.
BS R74034.
BS R16063.
BS R26194.
BS R26195.
BS R27570.
BS R01612.
BS R23136.
BS R20717.
BS R36554.
BS R74027.
BS R02657.
BS R31228.
BS R33063.
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BS R66154.
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BS R40011.
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BS R15917.
BS R19630.
BS R31213.
BS R36014.
BS R32756.
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BS R35002.
BS R15905.
BS R32755.
BS R15898.
BS R15907.
BS R15908.
BS R19198.
BS R32875.
BS R15916.
BS R40036.
BS R73921.
BS R73922.
BS R15918.
BS R13034.
BS R13059.
BS R23146.
BS R08885.
BS R31041.
BS R15921.
BS R62829.
BS R62830.
BS R15922.
BS R23481.
BS R31438.
BS R40035.
BS R20937.
BS R20940.
BS R62684.
BS R15925.
BS R68618.
BS R72887.
BS R40009.
BS R31645.
BS R63133.
BS R63134.
BS R63135.
BS R23140.
BS R23142.
BS R23143.
BS R40008.
BS R36555.
BS R28982.
BS R63098.
BS R39190.
BS R23144.
BS R23145.
BS R63807.
BS R30909.
BS R40030.
BS R22735.
BS R23521.
BS R32001.
BS R62264.
BS R62811.
BS R62812.
BS R62826.
BS R62827.
BS R36162.
BS R19255.
BS R28979.
BS R40010.
BS R40056.
BS R36226.
BS R28981.
BS R27924.
BS R28435.
BS R28437.
BS R25967.
BS R20585.
BS R56408.
BS R28222.
BS R62990.
BS R62991.
BS R25936.
BS R26316.
BS R56419.
BS R57890.
BS R57898.
BS R57902.
BS R70411.
BS R70412.
BS R03034.
BS R56753.
BS R28432.
BS R28433.
BS R28434.
BS R13070.
BS R03881.
BS R36557.
BS R13035.
BS R31207.
BS R28985.
BS R26750.
BS R28984.
BS R74037.
XX
DR TRANSPATH: MO000027755.
DR TRANSCOMPEL: C00123.
DR TRANSCOMPEL: C00124.
DR TRANSCOMPEL: C00125.
DR TRANSCOMPEL: C00283.
DR TRANSCOMPEL: C00284.
DR TRANSCOMPEL: C00285.
DR TRANSCOMPEL: C00286.
DR TRANSCOMPEL: C00288.
DR TRANSCOMPEL: C00290.
DR TRANSCOMPEL: C00368.
DR TRANSCOMPEL: C00370.
DR PATHODB: MT010546.
DR PATHODB: MT010547.
DR PATHODB: MT010548.
DR PATHODB: MT010549.
DR PATHODB: MT010550.
DR PATHODB: MT010552.
DR PATHODB: MT010553.
DR PATHODB: MT010554.
DR EMBL: Z49825;
DR UniProtKB: P41235;
XX
RN [1]; RE0004693.
RX PUBMED: 1734282.
RA Kuo C. J., Conley P. B., Chen L., Sladek F. M., Darnell J. E., Crabtree G. R.
RT A transcriptional hierarchy involved in mammalian cell-type specification
RL Nature 355:457-461 (1992).
RN [2]; RE0006831.
RX PUBMED: 8622695.
RA Drewes T., Senkel S., Holewa B., Ryffel G. U.
RT Human hepatocyte nuclear factor 4 isoforms are encoded by distinct and differentially expressed genes
RL Mol. Cell. Biol. 16:925-931 (1996).
RN [3]; RE0015072.
RX PUBMED: 9313765.
RA Furuta H., Iwasaki N., Oda N., Hinokio Y., Horikawa Y., Yamagata K., Yano N., Sugahiro J., Ogata M., Ohgawara H., Omori Y., Iwamoto Y., Bell G. I.
RT Organization and partial sequence of the hepatocyte nuclear factor-4 alpha/MODY1 gene and identification of a missense mutation, R127W, in a Japanese family with MODY
RL Diabetes 46:1652-1657 (1997).
RN [4]; RE0015077.
RX PUBMED: 9371825.
RA Stoffel M., Duncan S. A.
RT The maturity-onset diabetes of the young (MODY1) transcription factor HNF4alpha regulates expression of genes required for glucose transport and metabolism
RL Proc. Natl. Acad. Sci. USA 94:13209-13214 (1997).
RN [5]; RE0015099.
RX PUBMED: 8995424.
RA Jiang G., Sladek F. M.
RT The DNA binding domain of hepatocyte nuclear factor 4 mediates cooperative, specific binding to DNA and heterodimerization with the retinoid X receptor alpha
RL J. Biol. Chem. 272:1218-1225 (1997).
RN [6]; RE0015100.
RX PUBMED: 8641560.
RA Cereghini S.
RT Liver-enriched transcription factors and hepatocyte differentiation
RL FASEB J. 10:267-282 (1996).
RN [7]; RE0015106.
RX PUBMED: 10905494.
RA Shih D. Q., Dansky H. M., Fleisher M., Assmann G., Fajans S. S., Stoffel M.
RT Genotype/phenotype relationships in HNF-4alpha/MODY1: haploinsufficiency is associated with reduced apolipoprotein (AII), apolipoprotein (CIII), lipoprotein(a), and triglyceride levels
RL Diabetes 49:832-837 (2000).
RN [8]; RE0015135.
RX PUBMED: 8995295.
RA Hadzopoulou-Cladaras M., Kistanova E., Evagelopoulou C., Zeng S., Cladaras C., Ladias J. A.
RT Functional domains of the nuclear receptor hepatocyte nuclear factor 4
RL J. Biol. Chem. 272:539-550 (1997).
RN [9]; RE0018052.
RX PUBMED: 9548258.
RA Hertz R., Magenheim J., Berman I., Bar-Tana J.
RT Fatty acyl-CoA thioesters are ligands of hepatic nuclear factor-4alpha.
RL Nature 392:512-516 (1998).
RN [10]; RE0018069.
RX PUBMED: 10995777.
RA Kardassis D., Pardali K., Zannis V. I.
RT SMAD proteins transactivate the human ApoCIII promoter by interacting physically and functionally with hepatocyte nuclear factor 4.
RL J. Biol. Chem. 275:41405-41414 (2000).
RN [11]; RE0018079.
RX PUBMED: 11557972.
RA Yoon J. C., Puigserver P., Chen G., Donovan J., Wu Z., Rhee J., Adelmant G., Stafford J., Kahn C. R., Granner D. K., Newgard C. B., Spiegelman B. M.
RT Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1.
RL Nature 413:131-138 (2001).
RN [12]; RE0023998.
RX PUBMED: 14988562.
RA Odom D. T., Zizlsperger N., Gordon D. B., Bell G. W., Rinaldi N. J., Murray H. L., Volkert T. L., Schreiber J., Rolfe P. A., Gifford D. K., Fraenkel E., Bell G. I., Young R. A.
RT Control of pancreas and liver gene expression by HNF transcription factors.
RL Science 303:1378-1381 (2004).
RN [13]; RE0033615.
RX PUBMED: 14741200.
RA Sanchez-Elsner T., Ramirez J. R., Sanz-Rodriguez F., Varela E., Bernabeu C., Botella L. M.
RT A cross-talk between hypoxia and TGF-beta orchestrates erythropoietin gene regulation through SP1 and Smads.
RL J. Mol. Biol. 336:9-24 (2004).
RN [14]; RE0050456.
RX PUBMED: 11752221.
RA Hara H., Adachi T.
RT Contribution of hepatocyte nuclear factor-4 to down-regulation of CYP2D6 gene expression by nitric oxide.
RL Mol. Pharmacol. 61:194-200 (2002).
RN [15]; RE0051630.
RX PUBMED: 12193589.
RA Dhe-Paganon S., Duda K., Iwamoto M., Chi Y. I., Shoelson S. E.
RT Crystal structure of the HNF4 alpha ligand binding domain in complex with endogenous fatty acid ligand.
RL J. Biol. Chem. 277:37973-37976 (2002).
RN [16]; RE0053156.
RX PUBMED: 12220494.
RA Wisely G. B., Miller A. B., Davis R. G., Thornquest AD J. r., Johnson R., Spitzer T., Sefler A., Shearer B., Moore J. T., Miller A. B., Willson T. M., Williams S. P.
RT Hepatocyte nuclear factor 4 is a transcription factor that constitutively binds fatty acids.
RL Structure 10:1225-1234 (2002).
RN [17]; RE0053638.
RX PUBMED: 16488887.
RA Song K. H., Li T., Chiang J. Y.
RT A Prospero-related homeodomain protein is a novel co-regulator of hepatocyte nuclear factor 4alpha that regulates the cholesterol 7alpha-hydroxylase gene.
RL J. Biol. Chem. 281:10081-10088 (2006).
RN [18]; RE0054989.
RX PUBMED: 15604093.
RA Albers M., Kranz H., Kober I., Kaiser C., Klink M., Suckow J., Kern R., Koegl M.
RT Automated yeast two-hybrid screening for nuclear receptor-interacting proteins.
RL Mol. Cell. Proteomics 4:205-213 (2005).
RN [19]; RE0055387.
RX PUBMED: 17403900.
RA Sumi K., Tanaka T., Uchida A., Magoori K., Urashima Y., Ohashi R., Ohguchi H., Okamura M., Kudo H., Daigo K., Maejima T., Kojima N., Sakakibara I., Jiang S., Hasegawa G., Kim I., Osborne T. F., Naito M., Gonzalez F. J., Hamakubo T., Kodama T., Sakai J.
RT Cooperative interaction between hepatocyte nuclear factor 4 alpha and GATA transcription factors regulates ATP-binding cassette sterol transporters ABCG5 and ABCG8.
RL Mol. Cell. Biol. 27:4248-4260 (2007).
RN [20]; RE0065107.
RX PUBMED: 18845576.
RA Kajiwara M., Terada T., Asaka J., Aoki M., Katsura T., Ikai I., Inui K.
RT Regulation of basal core promoter activity of human organic cation transporter 1 (OCT1/SLC22A1).
RL Am. J. Physiol. Gastrointest. Liver Physiol. 295:G1211-6 (2008).
RN [21]; RE0066471.
RX PUBMED: 18513187.
RA Guo D., Dong L. Y., Wu Y., Yang L., An W.
RT Down-regulation of hepatic nuclear factor 4alpha on expression of human hepatic stimulator substance via its action on the proximal promoter in HepG2 cells.
RL Biochem. J. 415:111-121 (2008).
RN [22]; RE0068245.
RX PUBMED: 18765665.
RA Ungaro P., Teperino R., Mirra P., Cassese A., Fiory F., Perruolo G., Miele C., Laakso M., Formisano P., Beguinot F.
RT Molecular cloning and characterization of the human PED/PEA-15 gene promoter reveal antagonistic regulation by hepatocyte nuclear factor 4alpha and chicken ovalbumin upstream promoter transcription factor II.
RL J. Biol. Chem. 283:30970-30979 (2008).
RN [23]; RE0068251.
RX PUBMED: 16895524.
RA Maeda Y., Hwang-Verslues W. W., Wei G., Fukazawa T., Durbin M. L., Owen L. B., Liu X., Sladek F. M.
RT Tumour suppressor p53 down-regulates the expression of the human hepatocyte nuclear factor 4alpha (HNF4alpha) gene.
RL Biochem. J. 400:303-313 (2006).
RN [24]; RE0038571.
RX PUBMED: 12855700.
RA Misawa K., Horiba T., Arimura N., Hirano Y., Inoue J., Emoto N., Shimano H., Shimizu M., Sato R.
RT Sterol regulatory element-binding protein-2 interacts with hepatocyte nuclear factor-4 to enhance sterol isomerase gene expression in hepatocytes
RL J. Biol. Chem. 278:36176-82 (2003).
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