HNF4A_HUMAN
ID HNF4A_HUMAN Reviewed; 474 AA.
AC P41235; A5JW41; B2RPP8; O00659; O00723; Q14540; Q5QPB8; Q6B4V5; Q6B4V6;
AC Q6B4V7; Q92653; Q92654; Q92655; Q99864; Q9NQH0;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 29-MAY-2007, sequence version 3.
DT 03-AUG-2022, entry version 241.
DE RecName: Full=Hepatocyte nuclear factor 4-alpha;
DE Short=HNF-4-alpha;
DE AltName: Full=Nuclear receptor subfamily 2 group A member 1;
DE AltName: Full=Transcription factor 14;
DE Short=TCF-14;
DE AltName: Full=Transcription factor HNF-4;
GN Name=HNF4A; Synonyms=HNF4, NR2A1, TCF14;
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] (ISOFORMS HNF4-ALPHA-1; HNF4-ALPHA-2 AND
RP HNF4-ALPHA-3), AND VARIANT SER-445.
RC TISSUE=Liver;
RX PubMed=8964514; DOI=10.1016/0378-1119(96)00183-7;
RA Kritis A.A., Argyrokastritis A., Moschonas N.K., Power S., Katrakili N.,
RA Zannis V.I., Cereghini S., Talianidis I.;
RT "Isolation and characterization of a third isoform of human hepatocyte
RT nuclear factor 4.";
RL Gene 173:275-280(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE SPLICING.
RC TISSUE=Kidney;
RX PubMed=8622695; DOI=10.1128/mcb.16.3.925;
RA Drewes T., Senkel S., Holewa B., Ryffel G.U.;
RT "Human hepatocyte nuclear factor 4 isoforms are encoded by distinct and
RT differentially expressed genes.";
RL Mol. Cell. Biol. 16:925-931(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8945471; DOI=10.1038/384458a0;
RA Yamagata K., Furuta H., Oda N., Kaisaki P.J., Menzel S., Cox N.J.,
RA Fajans S.S., Signorini S., Stoffel M., Bell G.I.;
RT "Mutations in the hepatocyte nuclear factor-4alpha gene in maturity-onset
RT diabetes of the young (MODY1).";
RL Nature 384:458-460(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE PROMOTER USAGE (ISOFORMS
RP HNF4-ALPHA-7; HNF4-ALPHA-8 AND HNF4-ALPHA-9).
RA Tanaka T., Jiang S., Hotta H., Takano K., Iwanari H., Hirayama Y.,
RA Midorikawa Y., Hippo Y., Watanabe A., Yamashita H., Kumakura J.,
RA Uchiyama Y., Hasegawa G., Aburatani H., Hamakubo T., Naito M., Sakai J.,
RA Kodama T.;
RT "Variation in P1 and P2 promoter-driven hepatocyte nuclear factor-4a
RT (HNF4a) expression in human tissues: implications for carcinogenesis.";
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ILE-139 AND ILE-453.
RG SeattleSNPs variation discovery resource;
RL Submitted (MAY-2007) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [7]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM HNF4-ALPHA-3).
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 [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4-474, AND ALTERNATIVE SPLICING.
RC TISSUE=Liver;
RX PubMed=7926813; DOI=10.1016/0378-1119(94)90079-5;
RA Chartier F.L., Bossu J.-P., Laudet V., Fruchart J.-C., Laine B.;
RT "Cloning and sequencing of cDNAs encoding the human hepatocyte nuclear
RT factor 4 indicate the presence of two isoforms in human liver.";
RL Gene 147:269-272(1994).
RN [10]
RP PHOSPHORYLATION.
RX PubMed=7568236; DOI=10.1073/pnas.92.21.9876;
RA Ktistaki E., Ktistakis N.T., Papadogeorgaki E., Talianidis I.;
RT "Recruitment of hepatocyte nuclear factor 4 into specific intranuclear
RT compartments depends on tyrosine phosphorylation that affects its DNA-
RT binding and transactivation potential.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:9876-9880(1995).
RN [11]
RP PHOSPHORYLATION AT SER-313, AND MUTAGENESIS OF SER-313.
RX PubMed=12740371; DOI=10.1074/jbc.m304112200;
RA Hong Y.H., Varanasi U.S., Yang W., Leff T.;
RT "AMP-activated protein kinase regulates HNF4alpha transcriptional activity
RT by inhibiting dimer formation and decreasing protein stability.";
RL J. Biol. Chem. 278:27495-27501(2003).
RN [12]
RP PHOSPHORYLATION AT SER-142; THR-166; SER-167; THR-432 AND SER-436,
RP UBIQUITINATION AT LYS-234 AND LYS-307, AND ACETYLATION AT LYS-458.
RX PubMed=21708125; DOI=10.1016/j.bbrc.2011.06.033;
RA Yokoyama A., Katsura S., Ito R., Hashiba W., Sekine H., Fujiki R., Kato S.;
RT "Multiple post-translational modifications in hepatocyte nuclear factor
RT 4alpha.";
RL Biochem. Biophys. Res. Commun. 410:749-753(2011).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-144; THR-429; THR-432 AND
RP SER-436, AND 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 [14]
RP INTERACTION WITH DDX3X AND NR0B2.
RX PubMed=28128295; DOI=10.1038/srep41452;
RA Tsai T.Y., Wang W.T., Li H.K., Chen W.J., Tsai Y.H., Chao C.H.,
RA Wu Lee Y.H.;
RT "RNA helicase DDX3 maintains lipid homeostasis through upregulation of the
RT microsomal triglyceride transfer protein by interacting with HNF4 and
RT SHP.";
RL Sci. Rep. 7:41452-41452(2017).
RN [15]
RP 9AATAD MOTIF.
RX PubMed=30468856; DOI=10.1016/j.jsbmb.2018.11.008;
RA Piskacek M., Havelka M., Jendruchova K., Knight A.;
RT "Nuclear hormone receptors: Ancient 9aaTAD and evolutionally gained NCoA
RT activation pathways.";
RL J. Steroid Biochem. Mol. Biol. 187:118-123(2019).
RN [16]
RP FUNCTION.
RX PubMed=30597922; DOI=10.3390/genes10010021;
RA DeLaForest A., Di Furio F., Jing R., Ludwig-Kubinski A., Twaroski K.,
RA Urick A., Pulakanti K., Rao S., Duncan S.A.;
RT "HNF4A regulates the formation of hepatic progenitor cells from human iPSC-
RT Derived endoderm by facilitating efficient recruitment of RNA Pol II.";
RL Genes (Basel) 10:0-0(2018).
RN [17]
RP FUNCTION, AND INTERACTION WITH CLOCK; ARNTL; CRY1; CRY2; PER1 AND PER2.
RX PubMed=30530698; DOI=10.1073/pnas.1816411115;
RA Qu M., Duffy T., Hirota T., Kay S.A.;
RT "Nuclear receptor HNF4A transrepresses CLOCK:BMAL1 and modulates tissue-
RT specific circadian networks.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:E12305-E12312(2018).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 142-378, FATTY ACID BINDING, AND
RP SUBUNIT.
RX PubMed=14982928; DOI=10.1074/jbc.m400864200;
RA Duda K., Chi Y.-I., Shoelson S.E.;
RT "Structural basis for HNF-4alpha activation by ligand and coactivator
RT binding.";
RL J. Biol. Chem. 279:23311-23316(2004).
RN [19]
RP VARIANT MODY1 TRP-136.
RX PubMed=9313765; DOI=10.2337/diacare.46.10.1652;
RA Furuta H., Iwasaki N., Oda N., Hinokio Y., Horikawa Y., Yamagata K.,
RA Yano N., Sugahiro J., Ogata M., Ohgawara H., Omori Y., Iwamoto Y.,
RA Bell G.I.;
RT "Organization and partial sequence of the hepatocyte nuclear factor-4-
RT alpha/MODY1 gene and identification of a missense mutation, R127W, in a
RT Japanese family with MODY.";
RL Diabetes 46:1652-1657(1997).
RN [20]
RP VARIANT MODY1 GLN-285.
RX PubMed=9243109; DOI=10.1007/s001250050760;
RA Bulman M.P., Dronsfield M.J., Frayling T.M., Appleton M., Bain S.C.,
RA Ellard S., Hattersley A.T.;
RT "A missense mutation in the hepatocyte nuclear factor 4 alpha gene in a UK
RT pedigree with maturity-onset diabetes of the young.";
RL Diabetologia 40:859-862(1997).
RN [21]
RP VARIANTS ILE-139 AND MET-264.
RX PubMed=9267996; DOI=10.1007/s001250050778;
RA Moeller A.M., Urhammer S.A., Dalgaard L.T., Reneland R., Berglund L.,
RA Hansen T., Clausen J.O., Lithell H., Pedersen O.;
RT "Studies of the genetic variability of the coding region of the hepatocyte
RT nuclear factor-4alpha in Caucasians with maturity onset NIDDM.";
RL Diabetologia 40:980-983(1997).
RN [22]
RP VARIANT NIDDM ILE-402.
RX PubMed=9449683; DOI=10.1172/jci1403;
RA Hani E.H., Suaud L., Boutin P., Chevre J.-C., Durand E., Philippi A.,
RA Demenais F., Vionnet N., Furuta H., Velho G., Bell G.I., Laine B.,
RA Froguel P.;
RT "A missense mutation in hepatocyte nuclear factor-4-alpha, resulting in a
RT reduced transactivation activity, in human late-onset non-insulin-dependent
RT diabetes mellitus.";
RL J. Clin. Invest. 101:521-526(1998).
RN [23]
RP CHARACTERIZATION OF VARIANT MET-264, AND CHARACTERIZATION OF VARIANT MODY1
RP GLN-285.
RX PubMed=10389854; DOI=10.2337/diabetes.48.7.1459;
RA Navas M.A., Munoz-Elias E.J., Kim J., Shih D., Stoffel M.;
RT "Functional characterization of the MODY1 gene mutations HNF4(R127W),
RT HNF4(V255M), and HNF4(E276Q).";
RL Diabetes 48:1459-1465(1999).
RN [24]
RP VARIANT MODY1 ARG-373.
RX PubMed=17407387; DOI=10.1371/journal.pmed.0040118;
RA Pearson E.R., Boj S.F., Steele A.M., Barrett T., Stals K., Shield J.P.,
RA Ellard S., Ferrer J., Hattersley A.T.;
RT "Macrosomia and hyperinsulinaemic hypoglycaemia in patients with
RT heterozygous mutations in the HNF4A gene.";
RL PLoS Med. 4:E118-E118(2007).
RN [25]
RP INVOLVEMENT IN FRTS4, AND VARIANT FRTS4 TRP-85.
RX PubMed=22802087; DOI=10.1210/jc.2012-1356;
RA Stanescu D.E., Hughes N., Kaplan B., Stanley C.A., De Leon D.D.;
RT "Novel presentations of congenital hyperinsulinism due to mutations in the
RT MODY genes: HNF1A and HNF4A.";
RL J. Clin. Endocrinol. Metab. 97:E2026-2030(2012).
RN [26]
RP VARIANT FRTS4 TRP-85.
RX PubMed=24285859; DOI=10.1136/jmedgenet-2013-102066;
RA Hamilton A.J., Bingham C., McDonald T.J., Cook P.R., Caswell R.C.,
RA Weedon M.N., Oram R.A., Shields B.M., Shepherd M., Inward C.D.,
RA Hamilton-Shield J.P., Kohlhase J., Ellard S., Hattersley A.T.;
RT "The HNF4A R76W mutation causes atypical dominant Fanconi syndrome in
RT addition to a beta cell phenotype.";
RL J. Med. Genet. 51:165-169(2014).
CC -!- FUNCTION: Transcriptional regulator which controls the expression of
CC hepatic genes during the transition of endodermal cells to hepatic
CC progenitor cells, facilitating the recruitment of RNA pol II to the
CC promoters of target genes (PubMed:30597922). Activates the
CC transcription of CYP2C38 (By similarity). Represses the CLOCK-
CC ARNTL/BMAL1 transcriptional activity and is essential for circadian
CC rhythm maintenance and period regulation in the liver and colon cells
CC (PubMed:30530698). {ECO:0000250|UniProtKB:P49698,
CC ECO:0000269|PubMed:30530698, ECO:0000269|PubMed:30597922}.
CC -!- SUBUNIT: Homodimerization is required for HNF4-alpha to bind to its
CC recognition site (PubMed:14982928). Interacts with CLOCK, ARNTL, CRY1,
CC CRY2, PER1 and PER2 (PubMed:30530698). Interacts with NR0B2/SHP; the
CC resulting heterodimer is transcriptionnally inactive (PubMed:28128295).
CC Interacts with DDX3X; this interaction disrupts the interaction between
CC HNF4 and NR0B2 that forms inactive heterodimers and enhances the
CC formation of active HNF4 homodimers (PubMed:28128295).
CC {ECO:0000269|PubMed:14982928, ECO:0000269|PubMed:28128295,
CC ECO:0000269|PubMed:30530698}.
CC -!- INTERACTION:
CC P41235; Q99967: CITED2; NbExp=3; IntAct=EBI-1049011, EBI-937732;
CC P41235; A8MYZ6: FOXO6; NbExp=2; IntAct=EBI-1049011, EBI-8531039;
CC P41235; P04150: NR3C1; NbExp=2; IntAct=EBI-1049011, EBI-493507;
CC P41235; Q9UBK2: PPARGC1A; NbExp=4; IntAct=EBI-1049011, EBI-765486;
CC P41235; Q92786: PROX1; NbExp=3; IntAct=EBI-1049011, EBI-3912635;
CC P41235; P23246: SFPQ; NbExp=2; IntAct=EBI-1049011, EBI-355453;
CC P41235; Q12772: SREBF2; NbExp=2; IntAct=EBI-1049011, EBI-465059;
CC P41235-3; P11532: DMD; NbExp=3; IntAct=EBI-12690684, EBI-295827;
CC P41235-3; O14602: EIF1AY; NbExp=3; IntAct=EBI-12690684, EBI-286439;
CC P41235-3; O43688: PLPP2; NbExp=3; IntAct=EBI-12690684, EBI-722017;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=7;
CC Comment=Additional isoforms seem to exist.;
CC Name=HNF4-Alpha-1; Synonyms=HNF-4B;
CC IsoId=P41235-1; Sequence=Displayed;
CC Name=HNF4-Alpha-2; Synonyms=HNF4-A;
CC IsoId=P41235-2; Sequence=VSP_003674;
CC Name=HNF4-Alpha-3; Synonyms=HNF4-C;
CC IsoId=P41235-3; Sequence=VSP_003675;
CC Name=HNF4-Alpha-4;
CC IsoId=P41235-4; Sequence=VSP_003673;
CC Name=HNF4-Alpha-7;
CC IsoId=P41235-5; Sequence=VSP_026030;
CC Name=HNF4-Alpha-8;
CC IsoId=P41235-6; Sequence=VSP_026030, VSP_003674;
CC Name=HNF4-Alpha-9;
CC IsoId=P41235-7; Sequence=VSP_026030, VSP_003675;
CC -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large
CC number of yeast and animal transcription factors.
CC {ECO:0000305|PubMed:30468856}.
CC -!- PTM: Phosphorylated on tyrosine residue(s); phosphorylation is
CC important for its DNA-binding activity. Phosphorylation may directly or
CC indirectly play a regulatory role in the subnuclear distribution.
CC Phosphorylation at Ser-313 by AMPK reduces the ability to form
CC homodimers and bind DNA. {ECO:0000269|PubMed:12740371,
CC ECO:0000269|PubMed:21708125, ECO:0000269|PubMed:7568236}.
CC -!- PTM: Acetylation at Lys-458 lowers transcriptional activation by about
CC two-fold. {ECO:0000269|PubMed:21708125}.
CC -!- DISEASE: Maturity-onset diabetes of the young 1 (MODY1) [MIM:125850]: 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:10389854, ECO:0000269|PubMed:17407387,
CC ECO:0000269|PubMed:9243109, ECO:0000269|PubMed:9313765}. 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:9449683}. Note=Disease susceptibility may be
CC associated with variants affecting the gene represented in this entry.
CC -!- DISEASE: Fanconi renotubular syndrome 4 with maturity-onset diabetes of
CC the young (FRTS4) [MIM:616026]: An autosomal dominant disease
CC characterized by Fanconi syndrome associated with a beta cell phenotype
CC of neonatal hyperinsulinism with macrosomia and young onset diabetes.
CC Fanconi syndrome is a proximal tubulopathy resulting in generalized
CC aminoaciduria, low molecular weight proteinuria, glycosuria,
CC hyperphosphaturia and hypouricemia. Some FRTS4 patients have
CC nephrocalcinosis, renal impairment, hypercalciuria with relative
CC hypocalcemia, and hypermagnesemia. {ECO:0000269|PubMed:22802087,
CC ECO:0000269|PubMed:24285859}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Binds fatty acids.
CC -!- MISCELLANEOUS: [Isoform HNF4-Alpha-1]: Produced by alternative promoter
CC usage.
CC -!- MISCELLANEOUS: [Isoform HNF4-Alpha-2]: Produced by alternative splicing
CC of isoform HNF4-Alpha-1. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform HNF4-Alpha-3]: Produced by alternative splicing
CC of isoform HNF4-Alpha-1. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform HNF4-Alpha-4]: Produced by alternative splicing
CC of isoform HNF4-Alpha-1. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform HNF4-Alpha-7]: Produced by alternative promoter
CC usage. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform HNF4-Alpha-8]: Produced by alternative splicing
CC of isoform HNF4-Alpha-7. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform HNF4-Alpha-9]: Produced by alternative splicing
CC of isoform HNF4-Alpha-7. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR2
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB48082.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=CAA54248.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAA61133.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAA61134.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAA61135.1; Type=Frameshift; Evidence={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/hnf4a/";
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DR EMBL; X87870; CAA61133.1; ALT_FRAME; mRNA.
DR EMBL; X87871; CAA61134.1; ALT_FRAME; mRNA.
DR EMBL; X87872; CAA61135.1; ALT_FRAME; mRNA.
DR EMBL; Z49825; CAA89989.1; -; mRNA.
DR EMBL; AY680696; AAT91237.1; -; mRNA.
DR EMBL; AY680697; AAT91238.1; -; mRNA.
DR EMBL; AY680698; AAT91239.1; -; mRNA.
DR EMBL; U72969; AAB48082.1; ALT_SEQ; Genomic_DNA.
DR EMBL; U72959; AAB48082.1; JOINED; Genomic_DNA.
DR EMBL; U72961; AAB48082.1; JOINED; Genomic_DNA.
DR EMBL; U72962; AAB48082.1; JOINED; Genomic_DNA.
DR EMBL; U72963; AAB48082.1; JOINED; Genomic_DNA.
DR EMBL; U72964; AAB48082.1; JOINED; Genomic_DNA.
DR EMBL; U72965; AAB48082.1; JOINED; Genomic_DNA.
DR EMBL; U72966; AAB48082.1; JOINED; Genomic_DNA.
DR EMBL; U72967; AAB48082.1; JOINED; Genomic_DNA.
DR EMBL; U72968; AAB48082.1; JOINED; Genomic_DNA.
DR EMBL; U72967; AAB48083.1; -; Genomic_DNA.
DR EMBL; U72959; AAB48083.1; JOINED; Genomic_DNA.
DR EMBL; U72961; AAB48083.1; JOINED; Genomic_DNA.
DR EMBL; U72962; AAB48083.1; JOINED; Genomic_DNA.
DR EMBL; U72963; AAB48083.1; JOINED; Genomic_DNA.
DR EMBL; U72964; AAB48083.1; JOINED; Genomic_DNA.
DR EMBL; U72965; AAB48083.1; JOINED; Genomic_DNA.
DR EMBL; U72966; AAB48083.1; JOINED; Genomic_DNA.
DR EMBL; EF591040; ABQ52204.1; -; Genomic_DNA.
DR EMBL; AL132772; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW75924.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW75925.1; -; Genomic_DNA.
DR EMBL; BC137539; AAI37540.1; -; mRNA.
DR EMBL; BC137540; AAI37541.1; -; mRNA.
DR EMBL; X76930; CAA54248.1; ALT_INIT; mRNA.
DR CCDS; CCDS13330.1; -. [P41235-1]
DR CCDS; CCDS13331.1; -. [P41235-3]
DR CCDS; CCDS42876.1; -. [P41235-5]
DR CCDS; CCDS46604.1; -. [P41235-6]
DR CCDS; CCDS46605.1; -. [P41235-2]
DR CCDS; CCDS68131.1; -. [P41235-7]
DR PIR; JC4937; JC4937.
DR PIR; JC4938; JC4938.
DR PIR; JC6096; JC6096.
DR RefSeq; NP_000448.3; NM_000457.4. [P41235-1]
DR RefSeq; NP_001025174.1; NM_001030003.2. [P41235-6]
DR RefSeq; NP_001025175.1; NM_001030004.2. [P41235-7]
DR RefSeq; NP_001245284.1; NM_001258355.1.
DR RefSeq; NP_001274111.1; NM_001287182.1.
DR RefSeq; NP_001274112.1; NM_001287183.1.
DR RefSeq; NP_001274113.1; NM_001287184.1.
DR RefSeq; NP_787110.2; NM_175914.4. [P41235-5]
DR RefSeq; NP_849181.1; NM_178850.2. [P41235-3]
DR PDB; 1PZL; X-ray; 2.10 A; A=142-378.
DR PDB; 3CBB; X-ray; 2.00 A; A/B=58-135.
DR PDB; 3FS1; X-ray; 2.20 A; A=148-377.
DR PDB; 4B7W; X-ray; 4.00 A; A/B/C/D=142-377.
DR PDB; 4IQR; X-ray; 2.90 A; A/B/E/F=55-377.
DR PDB; 6CHT; X-ray; 3.17 A; A/B/D/E/G/H/J/K/M/N/P/Q/S/T/V/W=148-391.
DR PDBsum; 1PZL; -.
DR PDBsum; 3CBB; -.
DR PDBsum; 3FS1; -.
DR PDBsum; 4B7W; -.
DR PDBsum; 4IQR; -.
DR PDBsum; 6CHT; -.
DR AlphaFoldDB; P41235; -.
DR SMR; P41235; -.
DR BioGRID; 109414; 270.
DR CORUM; P41235; -.
DR DIP; DIP-499N; -.
DR IntAct; P41235; 213.
DR MINT; P41235; -.
DR STRING; 9606.ENSP00000312987; -.
DR BindingDB; P41235; -.
DR ChEMBL; CHEMBL5398; -.
DR DrugBank; DB05447; AVI-4557.
DR DrugBank; DB03017; Lauric acid.
DR DrugBank; DB08231; Myristic acid.
DR iPTMnet; P41235; -.
DR PhosphoSitePlus; P41235; -.
DR BioMuta; HNF4A; -.
DR DMDM; 148886624; -.
DR jPOST; P41235; -.
DR MassIVE; P41235; -.
DR MaxQB; P41235; -.
DR PaxDb; P41235; -.
DR PeptideAtlas; P41235; -.
DR PRIDE; P41235; -.
DR ProteomicsDB; 55441; -. [P41235-1]
DR ProteomicsDB; 55442; -. [P41235-2]
DR ProteomicsDB; 55443; -. [P41235-3]
DR ProteomicsDB; 55444; -. [P41235-4]
DR ProteomicsDB; 55445; -. [P41235-5]
DR ProteomicsDB; 55446; -. [P41235-6]
DR ProteomicsDB; 55447; -. [P41235-7]
DR ABCD; P41235; 1 sequenced antibody.
DR Antibodypedia; 1326; 996 antibodies from 43 providers.
DR DNASU; 3172; -.
DR Ensembl; ENST00000316099.10; ENSP00000312987.3; ENSG00000101076.19. [P41235-1]
DR Ensembl; ENST00000316673.8; ENSP00000315180.4; ENSG00000101076.19. [P41235-5]
DR Ensembl; ENST00000415691.2; ENSP00000412111.1; ENSG00000101076.19. [P41235-2]
DR Ensembl; ENST00000443598.6; ENSP00000410911.2; ENSG00000101076.19. [P41235-3]
DR Ensembl; ENST00000457232.5; ENSP00000396216.1; ENSG00000101076.19. [P41235-6]
DR Ensembl; ENST00000609795.5; ENSP00000476609.1; ENSG00000101076.19. [P41235-7]
DR GeneID; 3172; -.
DR KEGG; hsa:3172; -.
DR MANE-Select; ENST00000316673.9; ENSP00000315180.4; NM_175914.5; NP_787110.2. [P41235-5]
DR UCSC; uc002xlt.4; human. [P41235-1]
DR CTD; 3172; -.
DR DisGeNET; 3172; -.
DR GeneCards; HNF4A; -.
DR GeneReviews; HNF4A; -.
DR HGNC; HGNC:5024; HNF4A.
DR HPA; ENSG00000101076; Tissue enhanced (intestine, kidney, liver).
DR MalaCards; HNF4A; -.
DR MIM; 125850; phenotype.
DR MIM; 125853; phenotype.
DR MIM; 600281; gene.
DR MIM; 606391; phenotype.
DR MIM; 616026; phenotype.
DR neXtProt; NX_P41235; -.
DR OpenTargets; ENSG00000101076; -.
DR Orphanet; 544628; Atypical Fanconi syndrome-neonatal hyperinsulinism syndrome.
DR Orphanet; 263455; Hyperinsulinism due to HNF4A deficiency.
DR Orphanet; 552; MODY.
DR PharmGKB; PA29349; -.
DR VEuPathDB; HostDB:ENSG00000101076; -.
DR eggNOG; KOG4215; Eukaryota.
DR GeneTree; ENSGT00940000157965; -.
DR HOGENOM; CLU_007368_5_2_1; -.
DR InParanoid; P41235; -.
DR OMA; PVMILRD; -.
DR PhylomeDB; P41235; -.
DR TreeFam; TF352097; -.
DR PathwayCommons; P41235; -.
DR Reactome; R-HSA-210745; Regulation of gene expression in beta cells.
DR Reactome; R-HSA-383280; Nuclear Receptor transcription pathway.
DR SignaLink; P41235; -.
DR SIGNOR; P41235; -.
DR BioGRID-ORCS; 3172; 39 hits in 1094 CRISPR screens.
DR ChiTaRS; HNF4A; human.
DR EvolutionaryTrace; P41235; -.
DR GeneWiki; Hepatocyte_nuclear_factor_4_alpha; -.
DR GenomeRNAi; 3172; -.
DR Pharos; P41235; Tchem.
DR PRO; PR:P41235; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; P41235; protein.
DR Bgee; ENSG00000101076; Expressed in right lobe of liver and 93 other tissues.
DR ExpressionAtlas; P41235; baseline and differential.
DR Genevisible; P41235; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0003677; F:DNA binding; IDA:BHF-UCL.
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:BHF-UCL.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0005504; F:fatty acid binding; IDA:BHF-UCL.
DR GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISS:BHF-UCL.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0005102; F:signaling receptor binding; IDA:BHF-UCL.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:BHF-UCL.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0048856; P:anatomical structure development; IBA:GO_Central.
DR GO; GO:0007596; P:blood coagulation; IDA:BHF-UCL.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0042632; P:cholesterol homeostasis; ISS:BHF-UCL.
DR GO; GO:0042593; P:glucose homeostasis; ISS:BHF-UCL.
DR GO; GO:0070365; P:hepatocyte differentiation; IEA:InterPro.
DR GO; GO:0055088; P:lipid homeostasis; IMP:BHF-UCL.
DR GO; GO:0006629; P:lipid metabolic process; IEA:Ensembl.
DR GO; GO:0030308; P:negative regulation of cell growth; IMP:BHF-UCL.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0006591; P:ornithine metabolic process; IMP:BHF-UCL.
DR GO; GO:0055091; P:phospholipid homeostasis; ISS:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-UCL.
DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB.
DR GO; GO:0010470; P:regulation of gastrulation; IEA:Ensembl.
DR GO; GO:0060398; P:regulation of growth hormone receptor signaling pathway; NAS:BHF-UCL.
DR GO; GO:0050796; P:regulation of insulin secretion; ISS:BHF-UCL.
DR GO; GO:0019216; P:regulation of lipid metabolic process; IDA:BHF-UCL.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0009749; P:response to glucose; ISS:BHF-UCL.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0007548; P:sex differentiation; IEA:Ensembl.
DR GO; GO:0023019; P:signal transduction involved in regulation of gene expression; IEA:Ensembl.
DR GO; GO:0060395; P:SMAD protein signal transduction; IEA:Ensembl.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0070328; P:triglyceride homeostasis; ISS:BHF-UCL.
DR GO; GO:0003323; P:type B pancreatic cell development; IEA:InterPro.
DR GO; GO:0006805; P:xenobiotic metabolic process; IMP:BHF-UCL.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR IDEAL; IID00045; -.
DR InterPro; IPR039067; HNF4A.
DR InterPro; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR InterPro; IPR001628; Znf_hrmn_rcpt.
DR InterPro; IPR013088; Znf_NHR/GATA.
DR PANTHER; PTHR24083:SF41; PTHR24083:SF41; 1.
DR Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF00105; zf-C4; 1.
DR PRINTS; PR00398; STRDHORMONER.
DR PRINTS; PR00047; STROIDFINGER.
DR SMART; SM00430; HOLI; 1.
DR SMART; SM00399; ZnF_C4; 1.
DR SUPFAM; SSF48508; SSF48508; 1.
DR PROSITE; PS51843; NR_LBD; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Alternative promoter usage;
KW Alternative splicing; Biological rhythms; Diabetes mellitus;
KW Disease variant; DNA-binding; Isopeptide bond; Metal-binding; Nucleus;
KW Phosphoprotein; Receptor; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..474
FT /note="Hepatocyte nuclear factor 4-alpha"
FT /id="PRO_0000053558"
FT DOMAIN 147..377
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 57..132
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 60..80
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 96..120
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 419..447
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 368..376
FT /note="9aaTAD"
FT /evidence="ECO:0000269|PubMed:30468856"
FT MOD_RES 142
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21708125"
FT MOD_RES 143
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P22449"
FT MOD_RES 144
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 166
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:21708125"
FT MOD_RES 167
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21708125"
FT MOD_RES 313
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000269|PubMed:12740371"
FT MOD_RES 429
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 432
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:21708125,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 436
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21708125,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 458
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:21708125"
FT CROSSLNK 234
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:21708125"
FT CROSSLNK 307
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:21708125"
FT VAR_SEQ 1..38
FT /note="MRLSKTLVDMDMADYSAALDPAYTTLEFENVQVLTMGN -> MVSVNAPLGA
FT PVESSY (in isoform HNF4-Alpha-7, isoform HNF4-Alpha-8 and
FT isoform HNF4-Alpha-9)"
FT /evidence="ECO:0000305"
FT /id="VSP_026030"
FT VAR_SEQ 38
FT /note="N -> NDLLPLRLARLRHPLRHHWSISGGVDSSPQG (in isoform
FT HNF4-Alpha-4)"
FT /evidence="ECO:0000305"
FT /id="VSP_003673"
FT VAR_SEQ 378..474
FT /note="SPSDAPHAHHPLHPHLMQEHMGTNVIVANTMPTHLSNGQMCEWPRPRGQAAT
FT PETPQPSPPGGSGSEPYKLLPGAVATIVKPLSAIPQPTITKQEVI -> PCQAQEGRGW
FT SGDSPGDRPHTVSSPLSSLASPLCRFGQVA (in isoform HNF4-Alpha-3 and
FT isoform HNF4-Alpha-9)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:8964514"
FT /id="VSP_003675"
FT VAR_SEQ 418..428
FT /note="CEWPRPRGQAA -> S (in isoform HNF4-Alpha-2 and
FT isoform HNF4-Alpha-8)"
FT /evidence="ECO:0000303|PubMed:8964514"
FT /id="VSP_003674"
FT VARIANT 85
FT /note="R -> W (in FRTS4; dbSNP:rs587777732)"
FT /evidence="ECO:0000269|PubMed:22802087,
FT ECO:0000269|PubMed:24285859"
FT /id="VAR_071951"
FT VARIANT 136
FT /note="R -> W (in MODY1; dbSNP:rs137853336)"
FT /evidence="ECO:0000269|PubMed:9313765"
FT /id="VAR_004668"
FT VARIANT 139
FT /note="T -> I (in dbSNP:rs1800961)"
FT /evidence="ECO:0000269|PubMed:9267996, ECO:0000269|Ref.5"
FT /id="VAR_004669"
FT VARIANT 264
FT /note="V -> M (found in a patient with non-insulin-
FT dependent diabetes mellitus; does not affect activity;
FT dbSNP:rs139779712)"
FT /evidence="ECO:0000269|PubMed:10389854,
FT ECO:0000269|PubMed:9267996"
FT /id="VAR_010600"
FT VARIANT 285
FT /note="E -> Q (in MODY1; results in loss of function)"
FT /evidence="ECO:0000269|PubMed:10389854,
FT ECO:0000269|PubMed:9243109"
FT /id="VAR_010601"
FT VARIANT 373
FT /note="M -> R (in MODY1; dbSNP:rs137853338)"
FT /evidence="ECO:0000269|PubMed:17407387"
FT /id="VAR_071952"
FT VARIANT 402
FT /note="V -> I (in NIDDM; reduced transactivation activity;
FT dbSNP:rs137853337)"
FT /evidence="ECO:0000269|PubMed:9449683"
FT /id="VAR_004670"
FT VARIANT 445
FT /note="P -> S (in dbSNP:rs1063239)"
FT /evidence="ECO:0000269|PubMed:8964514"
FT /id="VAR_011785"
FT VARIANT 453
FT /note="V -> I (in dbSNP:rs776824742)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_062267"
FT MUTAGEN 313
FT /note="S->A: Abolishes AMPK-mediated phosphorylation."
FT /evidence="ECO:0000269|PubMed:12740371"
FT MUTAGEN 313
FT /note="S->D: Phosphomimetic mutant that leads to reduced
FT ability to bind DNA."
FT /evidence="ECO:0000269|PubMed:12740371"
FT CONFLICT 440
FT /note="G -> A (in Ref. 9; CAA54248)"
FT /evidence="ECO:0000305"
FT TURN 61..63
FT /evidence="ECO:0007829|PDB:3CBB"
FT STRAND 64..66
FT /evidence="ECO:0007829|PDB:3CBB"
FT STRAND 69..71
FT /evidence="ECO:0007829|PDB:3CBB"
FT HELIX 78..89
FT /evidence="ECO:0007829|PDB:3CBB"
FT STRAND 97..100
FT /evidence="ECO:0007829|PDB:4IQR"
FT TURN 106..111
FT /evidence="ECO:0007829|PDB:3CBB"
FT HELIX 113..123
FT /evidence="ECO:0007829|PDB:3CBB"
FT HELIX 127..129
FT /evidence="ECO:0007829|PDB:3CBB"
FT HELIX 149..153
FT /evidence="ECO:0007829|PDB:1PZL"
FT HELIX 155..163
FT /evidence="ECO:0007829|PDB:1PZL"
FT TURN 176..178
FT /evidence="ECO:0007829|PDB:1PZL"
FT HELIX 184..202
FT /evidence="ECO:0007829|PDB:1PZL"
FT HELIX 206..209
FT /evidence="ECO:0007829|PDB:1PZL"
FT HELIX 213..222
FT /evidence="ECO:0007829|PDB:1PZL"
FT HELIX 224..236
FT /evidence="ECO:0007829|PDB:1PZL"
FT STRAND 239..244
FT /evidence="ECO:0007829|PDB:1PZL"
FT STRAND 250..254
FT /evidence="ECO:0007829|PDB:1PZL"
FT HELIX 256..261
FT /evidence="ECO:0007829|PDB:1PZL"
FT HELIX 262..271
FT /evidence="ECO:0007829|PDB:1PZL"
FT HELIX 273..279
FT /evidence="ECO:0007829|PDB:1PZL"
FT HELIX 283..294
FT /evidence="ECO:0007829|PDB:1PZL"
FT HELIX 305..324
FT /evidence="ECO:0007829|PDB:1PZL"
FT STRAND 325..328
FT /evidence="ECO:0007829|PDB:1PZL"
FT HELIX 333..338
FT /evidence="ECO:0007829|PDB:1PZL"
FT HELIX 340..360
FT /evidence="ECO:0007829|PDB:1PZL"
FT HELIX 368..374
FT /evidence="ECO:0007829|PDB:1PZL"
SQ SEQUENCE 474 AA; 52785 MW; 5F1309B89D95DCAF CRC64;
MRLSKTLVDM DMADYSAALD PAYTTLEFEN VQVLTMGNDT SPSEGTNLNA PNSLGVSALC
AICGDRATGK HYGASSCDGC KGFFRRSVRK NHMYSCRFSR QCVVDKDKRN QCRYCRLKKC
FRAGMKKEAV QNERDRISTR RSSYEDSSLP SINALLQAEV LSRQITSPVS GINGDIRAKK
IASIADVCES MKEQLLVLVE WAKYIPAFCE LPLDDQVALL RAHAGEHLLL GATKRSMVFK
DVLLLGNDYI VPRHCPELAE MSRVSIRILD ELVLPFQELQ IDDNEYAYLK AIIFFDPDAK
GLSDPGKIKR LRSQVQVSLE DYINDRQYDS RGRFGELLLL LPTLQSITWQ MIEQIQFIKL
FGMAKIDNLL QEMLLGGSPS DAPHAHHPLH PHLMQEHMGT NVIVANTMPT HLSNGQMCEW
PRPRGQAATP ETPQPSPPGG SGSEPYKLLP GAVATIVKPL SAIPQPTITK QEVI
