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P41235 (HNF4A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 172. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Hepatocyte nuclear factor 4-alpha

Short name=HNF-4-alpha
Alternative name(s):
Nuclear receptor subfamily 2 group A member 1
Transcription factor 14
Short name=TCF-14
Transcription factor HNF-4
Gene names
Name:HNF4A
Synonyms:HNF4, NR2A1, TCF14
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length474 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcriptionally controlled transcription factor. Binds to DNA sites required for the transcription of alpha 1-antitrypsin, apolipoprotein CIII, transthyretin genes and HNF1-alpha. May be essential for development of the liver, kidney and intestine.

Subunit structure

Homodimerization is required for HNF4-alpha to bind to its recognition site. Interacts with PER2.

Subcellular location

Nucleus.

Post-translational modification

Phosphorylated on tyrosine residue(s); phosphorylation is important for its DNA-binding activity. Phosphorylation may directly or indirectly play a regulatory role in the subnuclear distribution. Phosphorylation at Ser-313 by AMPK reduces the ability to form homodimers and bind DNA. Ref.10 Ref.11 Ref.12

Acetylation at Lys-458 lowers transcriptional activation by about two-fold. Ref.12

Involvement in disease

Maturity-onset diabetes of the young 1 (MODY1) [MIM:125850]: A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14 Ref.15 Ref.18

Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
Note: Disease susceptibility may be associated with variations affecting the gene represented in this entry. Ref.17

Miscellaneous

Binds fatty acids.

Sequence similarities

Belongs to the nuclear hormone receptor family. NR2 subfamily.

Contains 1 nuclear receptor DNA-binding domain.

Sequence caution

The sequence AAB48082.1 differs from that shown. Reason: Erroneous gene model prediction.

The sequence CAA54248.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence CAA61133.1 differs from that shown. Reason: Frameshift at positions 2 and 7.

The sequence CAA61134.1 differs from that shown. Reason: Frameshift at positions 2 and 7.

The sequence CAA61135.1 differs from that shown. Reason: Frameshift at positions 2 and 7.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative promoter usage
Alternative splicing
Polymorphism
   DiseaseDiabetes mellitus
Disease mutation
   DomainZinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionReceptor
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processSMAD protein signal transduction

Inferred from electronic annotation. Source: Ensembl

blood coagulation

Inferred from direct assay PubMed 12911579. Source: BHF-UCL

endocrine pancreas development

Traceable author statement. Source: Reactome

gene expression

Traceable author statement. Source: Reactome

glucose homeostasis

Inferred from sequence or structural similarity. Source: BHF-UCL

lipid homeostasis

Inferred from mutant phenotype PubMed 17827783. Source: BHF-UCL

lipid metabolic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell growth

Inferred from mutant phenotype PubMed 18163890. Source: BHF-UCL

negative regulation of cell proliferation

Inferred from mutant phenotype PubMed 18163890. Source: BHF-UCL

ornithine metabolic process

Inferred from mutant phenotype PubMed 17827783. Source: BHF-UCL

phospholipid homeostasis

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of cholesterol homeostasis

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 17827783. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 16488887. Source: BHF-UCL

regulation of gastrulation

Inferred from electronic annotation. Source: Ensembl

regulation of growth hormone receptor signaling pathway

Non-traceable author statement PubMed 17991764PubMed 17991764. Source: BHF-UCL

regulation of insulin secretion

Inferred from sequence or structural similarity. Source: BHF-UCL

regulation of lipid metabolic process

Inferred from direct assay PubMed 10551874. Source: BHF-UCL

regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 10330009PubMed 12911579. Source: BHF-UCL

response to glucose

Inferred from sequence or structural similarity. Source: BHF-UCL

sex differentiation

Inferred from electronic annotation. Source: Ensembl

signal transduction involved in regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

transcription initiation from RNA polymerase II promoter

Traceable author statement. Source: Reactome

triglyceride homeostasis

Inferred from sequence or structural similarity. Source: BHF-UCL

xenobiotic metabolic process

Inferred from mutant phenotype PubMed 17827783. Source: BHF-UCL

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 14563941. Source: BHF-UCL

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay PubMed 14563941. Source: BHF-UCL

   Molecular_functionDNA binding

Inferred from direct assay PubMed 10551874. Source: BHF-UCL

RNA polymerase II activating transcription factor binding

Inferred from sequence or structural similarity. Source: BHF-UCL

RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription

Inferred from sequence or structural similarity. Source: BHF-UCL

RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

fatty acid binding

Inferred from direct assay PubMed 12220494. Source: BHF-UCL

ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity

Inferred from electronic annotation. Source: InterPro

protein binding

Inferred from physical interaction PubMed 19549071PubMed 21532585. Source: UniProtKB

protein homodimerization activity

Inferred from direct assay PubMed 12220494. Source: BHF-UCL

receptor binding

Inferred from direct assay PubMed 12220494. Source: BHF-UCL

sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 10330009PubMed 12911579PubMed 16488887. Source: BHF-UCL

steroid hormone receptor activity

Inferred from electronic annotation. Source: InterPro

transcription regulatory region DNA binding

Inferred from direct assay PubMed 16488887. Source: BHF-UCL

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CITED2Q999673EBI-1049011,EBI-937732
FOXO6A8MYZ62EBI-1049011,EBI-8531039

Alternative products

This entry describes 7 isoforms produced by alternative promoter usage and alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform HNF4-Alpha-1 (identifier: P41235-1)

Also known as: HNF-4B;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Note: Produced by alternative promoter usage.
Isoform HNF4-Alpha-2 (identifier: P41235-2)

Also known as: HNF4-A;

The sequence of this isoform differs from the canonical sequence as follows:
     418-428: CEWPRPRGQAA → S
Note: Produced by alternative splicing of isoform HNF4-Alpha-1.
Isoform HNF4-Alpha-3 (identifier: P41235-3)

Also known as: HNF4-C;

The sequence of this isoform differs from the canonical sequence as follows:
     378-474: SPSDAPHAHH...QPTITKQEVI → PCQAQEGRGW...SPLCRFGQVA
Note: Produced by alternative splicing of isoform HNF4-Alpha-1.
Isoform HNF4-Alpha-4 (identifier: P41235-4)

The sequence of this isoform differs from the canonical sequence as follows:
     38-38: N → NDLLPLRLARLRHPLRHHWSISGGVDSSPQG
Note: Produced by alternative splicing of isoform HNF4-Alpha-1.
Isoform HNF4-Alpha-7 (identifier: P41235-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-38: MRLSKTLVDMDMADYSAALDPAYTTLEFENVQVLTMGN → MVSVNAPLGAPVESSY
Note: Produced by alternative promoter usage.
Isoform HNF4-Alpha-8 (identifier: P41235-6)

The sequence of this isoform differs from the canonical sequence as follows:
     1-38: MRLSKTLVDMDMADYSAALDPAYTTLEFENVQVLTMGN → MVSVNAPLGAPVESSY
     418-428: CEWPRPRGQAA → S
Note: Produced by alternative splicing of isoform HNF4-Alpha-7.
Isoform HNF4-Alpha-9 (identifier: P41235-7)

The sequence of this isoform differs from the canonical sequence as follows:
     1-38: MRLSKTLVDMDMADYSAALDPAYTTLEFENVQVLTMGN → MVSVNAPLGAPVESSY
     378-474: SPSDAPHAHH...QPTITKQEVI → PCQAQEGRGW...SPLCRFGQVA
Note: Produced by alternative splicing of isoform HNF4-Alpha-7.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 474474Hepatocyte nuclear factor 4-alpha
PRO_0000053558

Regions

DNA binding57 – 13276Nuclear receptor
Zinc finger60 – 8021NR C4-type
Zinc finger96 – 12025NR C4-type

Amino acid modifications

Modified residue1421Phosphoserine Ref.12
Modified residue1661Phosphothreonine Ref.12
Modified residue1671Phosphoserine Ref.12
Modified residue3131Phosphoserine; by AMPK Ref.11
Modified residue4291Phosphothreonine By similarity
Modified residue4321Phosphothreonine Ref.12
Modified residue4361Phosphoserine Ref.12
Modified residue4581N6-acetyllysine Ref.12
Cross-link234Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.12
Cross-link307Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.12

Natural variations

Alternative sequence1 – 3838MRLSK…LTMGN → MVSVNAPLGAPVESSY in isoform HNF4-Alpha-7, isoform HNF4-Alpha-8 and isoform HNF4-Alpha-9.
VSP_026030
Alternative sequence381N → NDLLPLRLARLRHPLRHHWS ISGGVDSSPQG in isoform HNF4-Alpha-4.
VSP_003673
Alternative sequence378 – 47497SPSDA…KQEVI → PCQAQEGRGWSGDSPGDRPH TVSSPLSSLASPLCRFGQVA in isoform HNF4-Alpha-3 and isoform HNF4-Alpha-9.
VSP_003675
Alternative sequence418 – 42811CEWPRPRGQAA → S in isoform HNF4-Alpha-2 and isoform HNF4-Alpha-8.
VSP_003674
Natural variant1361R → W in MODY1. Ref.14
Corresponds to variant rs137853336 [ dbSNP | Ensembl ].
VAR_004668
Natural variant1391T → I. Ref.5 Ref.16
Corresponds to variant rs1800961 [ dbSNP | Ensembl ].
VAR_004669
Natural variant2641V → M Rare polymorphism found in a patient with non-insulin-dependent diabetes mellitus; does not affect activity. Ref.16 Ref.18
Corresponds to variant rs139779712 [ dbSNP | Ensembl ].
VAR_010600
Natural variant2851E → Q in MODY1; results in loss of function. Ref.15 Ref.18
VAR_010601
Natural variant4021V → I in NIDDM; reduced transactivation activity. Ref.17
Corresponds to variant rs137853337 [ dbSNP | Ensembl ].
VAR_004670
Natural variant4451P → S. Ref.1
Corresponds to variant rs1063239 [ dbSNP | Ensembl ].
VAR_011785
Natural variant4531V → I. Ref.5
VAR_062267

Experimental info

Mutagenesis3131S → A: Abolishes AMPK-mediated phosphorylation. Ref.11
Mutagenesis3131S → D: Phosphomimetic mutant that leads to reduced ability to bind DNA. Ref.11
Sequence conflict4401G → A in CAA54248. Ref.9

Secondary structure

.................................................. 474
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform HNF4-Alpha-1 (HNF-4B) [UniParc].

Last modified May 29, 2007. Version 3.
Checksum: 5F1309B89D95DCAF

FASTA47452,785
        10         20         30         40         50         60 
MRLSKTLVDM DMADYSAALD PAYTTLEFEN VQVLTMGNDT SPSEGTNLNA PNSLGVSALC 

        70         80         90        100        110        120 
AICGDRATGK HYGASSCDGC KGFFRRSVRK NHMYSCRFSR QCVVDKDKRN QCRYCRLKKC 

       130        140        150        160        170        180 
FRAGMKKEAV QNERDRISTR RSSYEDSSLP SINALLQAEV LSRQITSPVS GINGDIRAKK 

       190        200        210        220        230        240 
IASIADVCES MKEQLLVLVE WAKYIPAFCE LPLDDQVALL RAHAGEHLLL GATKRSMVFK 

       250        260        270        280        290        300 
DVLLLGNDYI VPRHCPELAE MSRVSIRILD ELVLPFQELQ IDDNEYAYLK AIIFFDPDAK 

       310        320        330        340        350        360 
GLSDPGKIKR LRSQVQVSLE DYINDRQYDS RGRFGELLLL LPTLQSITWQ MIEQIQFIKL 

       370        380        390        400        410        420 
FGMAKIDNLL QEMLLGGSPS DAPHAHHPLH PHLMQEHMGT NVIVANTMPT HLSNGQMCEW 

       430        440        450        460        470 
PRPRGQAATP ETPQPSPPGG SGSEPYKLLP GAVATIVKPL SAIPQPTITK QEVI 

« Hide

Isoform HNF4-Alpha-2 (HNF4-A) [UniParc].

Checksum: FF0A4FB233ADCC56
Show »

FASTA46451,619
Isoform HNF4-Alpha-3 (HNF4-C) [UniParc].

Checksum: DE7D9F4F6436EFE2
Show »

FASTA41746,623
Isoform HNF4-Alpha-4 [UniParc].

Checksum: F291EFDE331E9338
Show »

FASTA50456,139
Isoform HNF4-Alpha-7 [UniParc].

Checksum: 96854D18F389B0F9
Show »

FASTA45250,150
Isoform HNF4-Alpha-8 [UniParc].

Checksum: 8FD1619FC51F7217
Show »

FASTA44248,984
Isoform HNF4-Alpha-9 [UniParc].

Checksum: DC25511938ED9EF0
Show »

FASTA39543,988

References

« Hide 'large scale' references
[1]"Isolation and characterization of a third isoform of human hepatocyte nuclear factor 4."
Kritis A.A., Argyrokastritis A., Moschonas N.K., Power S., Katrakili N., Zannis V.I., Cereghini S., Talianidis I.
Gene 173:275-280(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS HNF4-ALPHA-1; HNF4-ALPHA-2 AND HNF4-ALPHA-3), VARIANT SER-445.
Tissue: Liver.
[2]"Human hepatocyte nuclear factor 4 isoforms are encoded by distinct and differentially expressed genes."
Drewes T., Senkel S., Holewa B., Ryffel G.U.
Mol. Cell. Biol. 16:925-931(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING.
Tissue: Kidney.
[3]"Mutations in the hepatocyte nuclear factor-4alpha gene in maturity-onset diabetes of the young (MODY1)."
Yamagata K., Furuta H., Oda N., Kaisaki P.J., Menzel S., Cox N.J., Fajans S.S., Signorini S., Stoffel M., Bell G.I.
Nature 384:458-460(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Variation in P1 and P2 promoter-driven hepatocyte nuclear factor-4a (HNF4a) expression in human tissues: implications for carcinogenesis."
Tanaka T., Jiang S., Hotta H., Takano K., Iwanari H., Hirayama Y., Midorikawa Y., Hippo Y., Watanabe A., Yamashita H., Kumakura J., Uchiyama Y., Hasegawa G., Aburatani H., Hamakubo T., Naito M., Sakai J., Kodama T.
Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE PROMOTER USAGE (ISOFORMS HNF4-ALPHA-7; HNF4-ALPHA-8 AND HNF4-ALPHA-9).
[5]SeattleSNPs variation discovery resource
Submitted (MAY-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ILE-139 AND ILE-453.
[6]"The DNA sequence and comparative analysis of human chromosome 20."
Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. expand/collapse author list , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM HNF4-ALPHA-3).
[9]"Cloning and sequencing of cDNAs encoding the human hepatocyte nuclear factor 4 indicate the presence of two isoforms in human liver."
Chartier F.L., Bossu J.-P., Laudet V., Fruchart J.-C., Laine B.
Gene 147:269-272(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 4-474, ALTERNATIVE SPLICING.
Tissue: Liver.
[10]"Recruitment of hepatocyte nuclear factor 4 into specific intranuclear compartments depends on tyrosine phosphorylation that affects its DNA-binding and transactivation potential."
Ktistaki E., Ktistakis N.T., Papadogeorgaki E., Talianidis I.
Proc. Natl. Acad. Sci. U.S.A. 92:9876-9880(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION.
[11]"AMP-activated protein kinase regulates HNF4alpha transcriptional activity by inhibiting dimer formation and decreasing protein stability."
Hong Y.H., Varanasi U.S., Yang W., Leff T.
J. Biol. Chem. 278:27495-27501(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-313, MUTAGENESIS OF SER-313.
[12]"Multiple post-translational modifications in hepatocyte nuclear factor 4alpha."
Yokoyama A., Katsura S., Ito R., Hashiba W., Sekine H., Fujiki R., Kato S.
Biochem. Biophys. Res. Commun. 410:749-753(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-142; THR-166; SER-167; THR-432 AND SER-436, UBIQUITINATION AT LYS-234 AND LYS-307, ACETYLATION AT LYS-458.
[13]"Structural basis for HNF-4alpha activation by ligand and coactivator binding."
Duda K., Chi Y.-I., Shoelson S.E.
J. Biol. Chem. 279:23311-23316(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 142-378, FATTY ACID BINDING.
[14]"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."
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.
Diabetes 46:1652-1657(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MODY1 TRP-136.
[15]"A missense mutation in the hepatocyte nuclear factor 4 alpha gene in a UK pedigree with maturity-onset diabetes of the young."
Bulman M.P., Dronsfield M.J., Frayling T.M., Appleton M., Bain S.C., Ellard S., Hattersley A.T.
Diabetologia 40:859-862(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MODY1 GLN-285.
[16]"Studies of the genetic variability of the coding region of the hepatocyte nuclear factor-4alpha in Caucasians with maturity onset NIDDM."
Moeller A.M., Urhammer S.A., Dalgaard L.T., Reneland R., Berglund L., Hansen T., Clausen J.O., Lithell H., Pedersen O.
Diabetologia 40:980-983(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ILE-139 AND MET-264.
[17]"A missense mutation in hepatocyte nuclear factor-4-alpha, resulting in a reduced transactivation activity, in human late-onset non-insulin-dependent diabetes mellitus."
Hani E.H., Suaud L., Boutin P., Chevre J.-C., Durand E., Philippi A., Demenais F., Vionnet N., Furuta H., Velho G., Bell G.I., Laine B., Froguel P.
J. Clin. Invest. 101:521-526(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NIDDM ILE-402.
[18]"Functional characterization of the MODY1 gene mutations HNF4(R127W), HNF4(V255M), and HNF4(E276Q)."
Navas M.A., Munoz-Elias E.J., Kim J., Shih D., Stoffel M.
Diabetes 48:1459-1465(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF MET-264, CHARACTERIZATION OF VARIANT MODY1 GLN-285.
+Additional computationally mapped references.

Web resources

Wikipedia

Hepatocyte nuclear factors entry

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X87870 mRNA. Translation: CAA61133.1. Frameshift.
X87871 mRNA. Translation: CAA61134.1. Frameshift.
X87872 mRNA. Translation: CAA61135.1. Frameshift.
Z49825 mRNA. Translation: CAA89989.1.
AY680696 mRNA. Translation: AAT91237.1.
AY680697 mRNA. Translation: AAT91238.1.
AY680698 mRNA. Translation: AAT91239.1.
U72969 expand/collapse EMBL AC list , U72959, U72961, U72962, U72963, U72964, U72965, U72966, U72967, U72968 Genomic DNA. Translation: AAB48082.1. Sequence problems.
U72967 expand/collapse EMBL AC list , U72959, U72961, U72962, U72963, U72964, U72965, U72966 Genomic DNA. Translation: AAB48083.1.
EF591040 Genomic DNA. Translation: ABQ52204.1.
AL132772 Genomic DNA. Translation: CAC01303.1.
AL132772 Genomic DNA. Translation: CAI18856.1.
CH471077 Genomic DNA. Translation: EAW75924.1.
CH471077 Genomic DNA. Translation: EAW75925.1.
BC137539 mRNA. Translation: AAI37540.1.
BC137540 mRNA. Translation: AAI37541.1.
X76930 mRNA. Translation: CAA54248.1. Different initiation.
CCDSCCDS13330.1. [P41235-1]
CCDS13331.1. [P41235-3]
CCDS42876.1. [P41235-5]
CCDS46604.1. [P41235-6]
CCDS46605.1. [P41235-2]
CCDS68131.1. [P41235-7]
PIRJC4937.
JC4938.
JC6096.
RefSeqNP_000448.3. NM_000457.4. [P41235-1]
NP_001025174.1. NM_001030003.2. [P41235-6]
NP_001025175.1. NM_001030004.2. [P41235-7]
NP_001245284.1. NM_001258355.1.
NP_001274111.1. NM_001287182.1.
NP_001274112.1. NM_001287183.1.
NP_001274113.1. NM_001287184.1.
NP_787110.2. NM_175914.4. [P41235-5]
NP_849181.1. NM_178850.2. [P41235-3]
UniGeneHs.116462.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1PZLX-ray2.10A142-378[»]
3CBBX-ray2.00A/B58-135[»]
3FS1X-ray2.20A148-377[»]
4B7WX-ray4.00A/B/C/D142-377[»]
4IQRX-ray2.90A/B/E/F55-377[»]
ProteinModelPortalP41235.
SMRP41235. Positions 58-377.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109414. 65 interactions.
DIPDIP-499N.
IntActP41235. 3 interactions.
MINTMINT-269829.

Chemistry

BindingDBP41235.
ChEMBLCHEMBL5398.
GuidetoPHARMACOLOGY608.

PTM databases

PhosphoSiteP41235.

Polymorphism databases

DMDM148886624.

Proteomic databases

MaxQBP41235.
PaxDbP41235.
PRIDEP41235.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000316099; ENSP00000312987; ENSG00000101076. [P41235-1]
ENST00000316673; ENSP00000315180; ENSG00000101076. [P41235-5]
ENST00000415691; ENSP00000412111; ENSG00000101076. [P41235-2]
ENST00000443598; ENSP00000410911; ENSG00000101076. [P41235-3]
ENST00000457232; ENSP00000396216; ENSG00000101076. [P41235-6]
ENST00000609795; ENSP00000476609; ENSG00000101076. [P41235-7]
GeneID3172.
KEGGhsa:3172.
UCSCuc002xlt.3. human. [P41235-7]
uc002xlu.4. human. [P41235-6]
uc002xly.4. human. [P41235-3]
uc002xma.4. human. [P41235-1]

Organism-specific databases

CTD3172.
GeneCardsGC20P042984.
GeneReviewsHNF4A.
HGNCHGNC:5024. HNF4A.
HPACAB019417.
HPA004712.
MIM125850. phenotype.
125853. phenotype.
600281. gene.
606391. phenotype.
neXtProtNX_P41235.
Orphanet263455. Hyperinsulinism due to HNF4A deficiency.
552. MODY syndrome.
PharmGKBPA29349.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG241134.
HOVERGENHBG005606.
KOK07292.
OMAANTMPSH.
OrthoDBEOG7K3TKX.
PhylomeDBP41235.
TreeFamTF352097.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_71. Gene Expression.
SignaLinkP41235.

Gene expression databases

ArrayExpressP41235.
BgeeP41235.
GenevestigatorP41235.

Family and domain databases

Gene3D1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProIPR003068. COUP_TF.
IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSPR01282. COUPTNFACTOR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMSSF48508. SSF48508. 1 hit.
PROSITEPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP41235.
GeneWikiHepatocyte_nuclear_factor_4_alpha.
GenomeRNAi3172.
NextBio12578.
PROP41235.
SOURCESearch...

Entry information

Entry nameHNF4A_HUMAN
AccessionPrimary (citable) accession number: P41235
Secondary accession number(s): A5JW41 expand/collapse secondary AC list , B2RPP8, O00659, O00723, Q14540, Q5QPB8, Q6B4V5, Q6B4V6, Q6B4V7, Q92653, Q92654, Q92655, Q99864, Q9NQH0
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: May 29, 2007
Last modified: July 9, 2014
This is version 172 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM