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P41235

- HNF4A_HUMAN

UniProt

P41235 - HNF4A_HUMAN

Protein

Hepatocyte nuclear factor 4-alpha

Gene

HNF4A

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 174 (01 Oct 2014)
      Sequence version 3 (29 May 2007)
      Previous versions | rss
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    Functioni

    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.

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi57 – 13276Nuclear receptorPROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri60 – 8021NR C4-typePROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri96 – 12025NR C4-typePROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. DNA binding Source: BHF-UCL
    2. fatty acid binding Source: BHF-UCL
    3. ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity Source: InterPro
    4. protein binding Source: UniProtKB
    5. protein homodimerization activity Source: BHF-UCL
    6. receptor binding Source: BHF-UCL
    7. RNA polymerase II activating transcription factor binding Source: BHF-UCL
    8. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: BHF-UCL
    9. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: Ensembl
    10. sequence-specific DNA binding Source: Ensembl
    11. sequence-specific DNA binding transcription factor activity Source: BHF-UCL
    12. steroid hormone receptor activity Source: InterPro
    13. transcription regulatory region DNA binding Source: BHF-UCL
    14. zinc ion binding Source: InterPro

    GO - Biological processi

    1. blood coagulation Source: BHF-UCL
    2. endocrine pancreas development Source: Reactome
    3. gene expression Source: Reactome
    4. glucose homeostasis Source: BHF-UCL
    5. lipid homeostasis Source: BHF-UCL
    6. lipid metabolic process Source: Ensembl
    7. negative regulation of cell growth Source: BHF-UCL
    8. negative regulation of cell proliferation Source: BHF-UCL
    9. ornithine metabolic process Source: BHF-UCL
    10. phospholipid homeostasis Source: BHF-UCL
    11. positive regulation of cholesterol homeostasis Source: BHF-UCL
    12. positive regulation of transcription, DNA-templated Source: BHF-UCL
    13. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
    14. regulation of gastrulation Source: Ensembl
    15. regulation of growth hormone receptor signaling pathway Source: BHF-UCL
    16. regulation of insulin secretion Source: BHF-UCL
    17. regulation of lipid metabolic process Source: BHF-UCL
    18. regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
    19. response to glucose Source: BHF-UCL
    20. sex differentiation Source: Ensembl
    21. signal transduction involved in regulation of gene expression Source: Ensembl
    22. SMAD protein signal transduction Source: Ensembl
    23. transcription initiation from RNA polymerase II promoter Source: Reactome
    24. triglyceride homeostasis Source: BHF-UCL
    25. xenobiotic metabolic process Source: BHF-UCL

    Keywords - Molecular functioni

    Receptor

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding, Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_13819. Regulation of gene expression in beta cells.
    REACT_15525. Nuclear Receptor transcription pathway.
    SignaLinkiP41235.

    Names & Taxonomyi

    Protein namesi
    Recommended 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 namesi
    Name:HNF4A
    Synonyms:HNF4, NR2A1, TCF14
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 20

    Organism-specific databases

    HGNCiHGNC:5024. HNF4A.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: BHF-UCL
    2. nucleoplasm Source: Reactome
    3. nucleus Source: BHF-UCL

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    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.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti136 – 1361R → W in MODY1. 1 Publication
    Corresponds to variant rs137853336 [ dbSNP | Ensembl ].
    VAR_004668
    Natural varianti285 – 2851E → Q in MODY1; results in loss of function. 1 Publication
    VAR_010601
    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.1 Publication
    Note: Disease susceptibility may be associated with variations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti402 – 4021V → I in NIDDM; reduced transactivation activity. 1 Publication
    Corresponds to variant rs137853337 [ dbSNP | Ensembl ].
    VAR_004670

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi313 – 3131S → A: Abolishes AMPK-mediated phosphorylation. 1 Publication
    Mutagenesisi313 – 3131S → D: Phosphomimetic mutant that leads to reduced ability to bind DNA. 1 Publication

    Keywords - Diseasei

    Diabetes mellitus, Disease mutation

    Organism-specific databases

    MIMi125850. phenotype.
    125853. phenotype.
    606391. phenotype.
    Orphaneti263455. Hyperinsulinism due to HNF4A deficiency.
    552. MODY syndrome.
    PharmGKBiPA29349.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 474474Hepatocyte nuclear factor 4-alphaPRO_0000053558Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei142 – 1421Phosphoserine2 Publications
    Modified residuei166 – 1661Phosphothreonine2 Publications
    Modified residuei167 – 1671Phosphoserine2 Publications
    Cross-linki234 – 234Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Cross-linki307 – 307Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Modified residuei313 – 3131Phosphoserine; by AMPK2 Publications
    Modified residuei429 – 4291PhosphothreonineBy similarity
    Modified residuei432 – 4321Phosphothreonine2 Publications
    Modified residuei436 – 4361Phosphoserine2 Publications
    Modified residuei458 – 4581N6-acetyllysine1 Publication

    Post-translational modificationi

    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.3 Publications
    Acetylation at Lys-458 lowers transcriptional activation by about two-fold.1 Publication

    Keywords - PTMi

    Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP41235.
    PaxDbiP41235.
    PRIDEiP41235.

    PTM databases

    PhosphoSiteiP41235.

    Expressioni

    Gene expression databases

    ArrayExpressiP41235.
    BgeeiP41235.
    GenevestigatoriP41235.

    Organism-specific databases

    HPAiCAB019417.
    HPA004712.

    Interactioni

    Subunit structurei

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

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CITED2Q999673EBI-1049011,EBI-937732
    FOXO6A8MYZ62EBI-1049011,EBI-8531039

    Protein-protein interaction databases

    BioGridi109414. 65 interactions.
    DIPiDIP-499N.
    IntActiP41235. 5 interactions.
    MINTiMINT-269829.

    Structurei

    Secondary structure

    1
    474
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Turni61 – 633
    Beta strandi64 – 663
    Beta strandi69 – 713
    Helixi78 – 8912
    Beta strandi97 – 1004
    Turni106 – 1116
    Helixi113 – 12311
    Helixi127 – 1293
    Helixi149 – 1535
    Helixi155 – 1639
    Turni176 – 1783
    Helixi184 – 20219
    Helixi206 – 2094
    Helixi213 – 22210
    Helixi224 – 23613
    Beta strandi239 – 2446
    Beta strandi250 – 2545
    Helixi256 – 2616
    Helixi262 – 27110
    Helixi273 – 2797
    Helixi283 – 29412
    Helixi305 – 32420
    Beta strandi325 – 3284
    Helixi333 – 3386
    Helixi340 – 36021
    Helixi368 – 3747

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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[»]
    ProteinModelPortaliP41235.
    SMRiP41235. Positions 58-377.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP41235.

    Family & Domainsi

    Sequence similaritiesi

    Contains 1 nuclear receptor DNA-binding domain.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri60 – 8021NR C4-typePROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri96 – 12025NR C4-typePROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Zinc-finger

    Phylogenomic databases

    eggNOGiNOG241134.
    HOVERGENiHBG005606.
    KOiK07292.
    OMAiANTMPSH.
    OrthoDBiEOG7K3TKX.
    PhylomeDBiP41235.
    TreeFamiTF352097.

    Family and domain databases

    Gene3Di1.10.565.10. 1 hit.
    3.30.50.10. 1 hit.
    InterProiIPR003068. 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]
    PfamiPF00104. Hormone_recep. 1 hit.
    PF00105. zf-C4. 1 hit.
    [Graphical view]
    PRINTSiPR01282. COUPTNFACTOR.
    PR00398. STRDHORMONER.
    PR00047. STROIDFINGER.
    SMARTiSM00430. HOLI. 1 hit.
    SM00399. ZnF_C4. 1 hit.
    [Graphical view]
    SUPFAMiSSF48508. SSF48508. 1 hit.
    PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
    PS51030. NUCLEAR_REC_DBD_2. 1 hit.
    [Graphical view]

    Sequences (7)i

    Sequence statusi: Complete.

    This entry describes 7 isoformsi produced by alternative promoter usage and alternative splicing. Align

    Note: Additional isoforms seem to exist.

    Isoform HNF4-Alpha-1 (identifier: P41235-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MRLSKTLVDM DMADYSAALD PAYTTLEFEN VQVLTMGNDT SPSEGTNLNA    50
    PNSLGVSALC AICGDRATGK HYGASSCDGC KGFFRRSVRK NHMYSCRFSR 100
    QCVVDKDKRN QCRYCRLKKC FRAGMKKEAV QNERDRISTR RSSYEDSSLP 150
    SINALLQAEV LSRQITSPVS GINGDIRAKK IASIADVCES MKEQLLVLVE 200
    WAKYIPAFCE LPLDDQVALL RAHAGEHLLL GATKRSMVFK DVLLLGNDYI 250
    VPRHCPELAE MSRVSIRILD ELVLPFQELQ IDDNEYAYLK AIIFFDPDAK 300
    GLSDPGKIKR LRSQVQVSLE DYINDRQYDS RGRFGELLLL LPTLQSITWQ 350
    MIEQIQFIKL FGMAKIDNLL QEMLLGGSPS DAPHAHHPLH PHLMQEHMGT 400
    NVIVANTMPT HLSNGQMCEW PRPRGQAATP ETPQPSPPGG SGSEPYKLLP 450
    GAVATIVKPL SAIPQPTITK QEVI 474

    Note: Produced by alternative promoter usage.

    Length:474
    Mass (Da):52,785
    Last modified:May 29, 2007 - v3
    Checksum:i5F1309B89D95DCAF
    GO
    Isoform HNF4-Alpha-2 (identifier: P41235-2) [UniParc]FASTAAdd to Basket

    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.

    Show »
    Length:464
    Mass (Da):51,619
    Checksum:iFF0A4FB233ADCC56
    GO
    Isoform HNF4-Alpha-3 (identifier: P41235-3) [UniParc]FASTAAdd to Basket

    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.

    Show »
    Length:417
    Mass (Da):46,623
    Checksum:iDE7D9F4F6436EFE2
    GO
    Isoform HNF4-Alpha-4 (identifier: P41235-4) [UniParc]FASTAAdd to Basket

    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.

    Show »
    Length:504
    Mass (Da):56,139
    Checksum:iF291EFDE331E9338
    GO
    Isoform HNF4-Alpha-7 (identifier: P41235-5) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-38: MRLSKTLVDMDMADYSAALDPAYTTLEFENVQVLTMGN → MVSVNAPLGAPVESSY

    Note: Produced by alternative promoter usage.

    Show »
    Length:452
    Mass (Da):50,150
    Checksum:i96854D18F389B0F9
    GO
    Isoform HNF4-Alpha-8 (identifier: P41235-6) [UniParc]FASTAAdd to Basket

    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.

    Show »
    Length:442
    Mass (Da):48,984
    Checksum:i8FD1619FC51F7217
    GO
    Isoform HNF4-Alpha-9 (identifier: P41235-7) [UniParc]FASTAAdd to Basket

    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.

    Show »
    Length:395
    Mass (Da):43,988
    Checksum:iDC25511938ED9EF0
    GO

    Sequence cautioni

    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.
    The sequence CAA54248.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.
    The sequence AAB48082.1 differs from that shown. Reason: Erroneous gene model prediction.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti440 – 4401G → A in CAA54248. (PubMed:7926813)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti136 – 1361R → W in MODY1. 1 Publication
    Corresponds to variant rs137853336 [ dbSNP | Ensembl ].
    VAR_004668
    Natural varianti139 – 1391T → I.2 Publications
    Corresponds to variant rs1800961 [ dbSNP | Ensembl ].
    VAR_004669
    Natural varianti264 – 2641V → M Rare polymorphism found in a patient with non-insulin-dependent diabetes mellitus; does not affect activity. 1 Publication
    Corresponds to variant rs139779712 [ dbSNP | Ensembl ].
    VAR_010600
    Natural varianti285 – 2851E → Q in MODY1; results in loss of function. 1 Publication
    VAR_010601
    Natural varianti402 – 4021V → I in NIDDM; reduced transactivation activity. 1 Publication
    Corresponds to variant rs137853337 [ dbSNP | Ensembl ].
    VAR_004670
    Natural varianti445 – 4451P → S.1 Publication
    Corresponds to variant rs1063239 [ dbSNP | Ensembl ].
    VAR_011785
    Natural varianti453 – 4531V → I.1 Publication
    VAR_062267

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 3838MRLSK…LTMGN → MVSVNAPLGAPVESSY in isoform HNF4-Alpha-7, isoform HNF4-Alpha-8 and isoform HNF4-Alpha-9. CuratedVSP_026030Add
    BLAST
    Alternative sequencei38 – 381N → NDLLPLRLARLRHPLRHHWS ISGGVDSSPQG in isoform HNF4-Alpha-4. CuratedVSP_003673
    Alternative sequencei378 – 47497SPSDA…KQEVI → PCQAQEGRGWSGDSPGDRPH TVSSPLSSLASPLCRFGQVA in isoform HNF4-Alpha-3 and isoform HNF4-Alpha-9. 2 PublicationsVSP_003675Add
    BLAST
    Alternative sequencei418 – 42811CEWPRPRGQAA → S in isoform HNF4-Alpha-2 and isoform HNF4-Alpha-8. 1 PublicationVSP_003674Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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
    , U72959, U72961, U72962, U72963, U72964, U72965, U72966, U72967, U72968 Genomic DNA. Translation: AAB48082.1. Sequence problems.
    U72967
    , 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.
    CCDSiCCDS13330.1. [P41235-1]
    CCDS13331.1. [P41235-3]
    CCDS42876.1. [P41235-5]
    CCDS46604.1. [P41235-6]
    CCDS46605.1. [P41235-2]
    CCDS68131.1. [P41235-7]
    PIRiJC4937.
    JC4938.
    JC6096.
    RefSeqiNP_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]
    UniGeneiHs.116462.

    Genome annotation databases

    EnsembliENST00000316099; 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]
    GeneIDi3172.
    KEGGihsa:3172.
    UCSCiuc002xlt.3. human. [P41235-7]
    uc002xlu.4. human. [P41235-6]
    uc002xly.4. human. [P41235-3]
    uc002xma.4. human. [P41235-1]

    Polymorphism databases

    DMDMi148886624.

    Keywords - Coding sequence diversityi

    Alternative promoter usage, Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Wikipedia

    Hepatocyte nuclear factors entry

    SeattleSNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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
    , U72959 , U72961 , U72962 , U72963 , U72964 , U72965 , U72966 , U72967 , U72968 Genomic DNA. Translation: AAB48082.1 . Sequence problems.
    U72967
    , 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.
    CCDSi CCDS13330.1. [P41235-1 ]
    CCDS13331.1. [P41235-3 ]
    CCDS42876.1. [P41235-5 ]
    CCDS46604.1. [P41235-6 ]
    CCDS46605.1. [P41235-2 ]
    CCDS68131.1. [P41235-7 ]
    PIRi JC4937.
    JC4938.
    JC6096.
    RefSeqi NP_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 ]
    UniGenei Hs.116462.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1PZL X-ray 2.10 A 142-378 [» ]
    3CBB X-ray 2.00 A/B 58-135 [» ]
    3FS1 X-ray 2.20 A 148-377 [» ]
    4B7W X-ray 4.00 A/B/C/D 142-377 [» ]
    4IQR X-ray 2.90 A/B/E/F 55-377 [» ]
    ProteinModelPortali P41235.
    SMRi P41235. Positions 58-377.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109414. 65 interactions.
    DIPi DIP-499N.
    IntActi P41235. 5 interactions.
    MINTi MINT-269829.

    Chemistry

    BindingDBi P41235.
    ChEMBLi CHEMBL5398.
    GuidetoPHARMACOLOGYi 608.

    PTM databases

    PhosphoSitei P41235.

    Polymorphism databases

    DMDMi 148886624.

    Proteomic databases

    MaxQBi P41235.
    PaxDbi P41235.
    PRIDEi P41235.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000316099 ; 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 ]
    GeneIDi 3172.
    KEGGi hsa:3172.
    UCSCi uc002xlt.3. human. [P41235-7 ]
    uc002xlu.4. human. [P41235-6 ]
    uc002xly.4. human. [P41235-3 ]
    uc002xma.4. human. [P41235-1 ]

    Organism-specific databases

    CTDi 3172.
    GeneCardsi GC20P042984.
    GeneReviewsi HNF4A.
    HGNCi HGNC:5024. HNF4A.
    HPAi CAB019417.
    HPA004712.
    MIMi 125850. phenotype.
    125853. phenotype.
    600281. gene.
    606391. phenotype.
    neXtProti NX_P41235.
    Orphaneti 263455. Hyperinsulinism due to HNF4A deficiency.
    552. MODY syndrome.
    PharmGKBi PA29349.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG241134.
    HOVERGENi HBG005606.
    KOi K07292.
    OMAi ANTMPSH.
    OrthoDBi EOG7K3TKX.
    PhylomeDBi P41235.
    TreeFami TF352097.

    Enzyme and pathway databases

    Reactomei REACT_13819. Regulation of gene expression in beta cells.
    REACT_15525. Nuclear Receptor transcription pathway.
    SignaLinki P41235.

    Miscellaneous databases

    EvolutionaryTracei P41235.
    GeneWikii Hepatocyte_nuclear_factor_4_alpha.
    GenomeRNAii 3172.
    NextBioi 12578.
    PROi P41235.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P41235.
    Bgeei P41235.
    Genevestigatori P41235.

    Family and domain databases

    Gene3Di 1.10.565.10. 1 hit.
    3.30.50.10. 1 hit.
    InterProi IPR003068. 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 ]
    Pfami PF00104. Hormone_recep. 1 hit.
    PF00105. zf-C4. 1 hit.
    [Graphical view ]
    PRINTSi PR01282. COUPTNFACTOR.
    PR00398. STRDHORMONER.
    PR00047. STROIDFINGER.
    SMARTi SM00430. HOLI. 1 hit.
    SM00399. ZnF_C4. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48508. SSF48508. 1 hit.
    PROSITEi PS00031. NUCLEAR_REC_DBD_1. 1 hit.
    PS51030. NUCLEAR_REC_DBD_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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. 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.

    Entry informationi

    Entry nameiHNF4A_HUMAN
    AccessioniPrimary (citable) accession number: P41235
    Secondary accession number(s): A5JW41
    , B2RPP8, O00659, O00723, Q14540, Q5QPB8, Q6B4V5, Q6B4V6, Q6B4V7, Q92653, Q92654, Q92655, Q99864, Q9NQH0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1995
    Last sequence update: May 29, 2007
    Last modified: October 1, 2014
    This is version 174 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Miscellaneous

    Binds fatty acids.

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 20
      Human chromosome 20: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3