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P41235

- HNF4A_HUMAN

UniProt

P41235 - HNF4A_HUMAN

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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

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 homodimerization activity Source: BHF-UCL
  5. receptor binding Source: BHF-UCL
  6. RNA polymerase II activating transcription factor binding Source: BHF-UCL
  7. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: BHF-UCL
  8. RNA polymerase II core promoter sequence-specific DNA binding Source: Ensembl
  9. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: Ensembl
  10. sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  11. steroid hormone receptor activity Source: InterPro
  12. transcription regulatory region DNA binding Source: BHF-UCL
  13. 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
Complete GO annotation...

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
Complete GO annotation...

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 – 1421Phosphoserine1 Publication
Modified residuei166 – 1661Phosphothreonine1 Publication
Modified residuei167 – 1671Phosphoserine1 Publication
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 AMPK1 Publication
Modified residuei429 – 4291PhosphothreonineBy similarity
Modified residuei432 – 4321Phosphothreonine1 Publication
Modified residuei436 – 4361Phosphoserine1 Publication
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

BgeeiP41235.
ExpressionAtlasiP41235. baseline and differential.
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.
GeneTreeiENSGT00760000118948.
HOVERGENiHBG005606.
InParanoidiP41235.
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

        10         20         30         40         50
MRLSKTLVDM DMADYSAALD PAYTTLEFEN VQVLTMGNDT SPSEGTNLNA
60 70 80 90 100
PNSLGVSALC AICGDRATGK HYGASSCDGC KGFFRRSVRK NHMYSCRFSR
110 120 130 140 150
QCVVDKDKRN QCRYCRLKKC FRAGMKKEAV QNERDRISTR RSSYEDSSLP
160 170 180 190 200
SINALLQAEV LSRQITSPVS GINGDIRAKK IASIADVCES MKEQLLVLVE
210 220 230 240 250
WAKYIPAFCE LPLDDQVALL RAHAGEHLLL GATKRSMVFK DVLLLGNDYI
260 270 280 290 300
VPRHCPELAE MSRVSIRILD ELVLPFQELQ IDDNEYAYLK AIIFFDPDAK
310 320 330 340 350
GLSDPGKIKR LRSQVQVSLE DYINDRQYDS RGRFGELLLL LPTLQSITWQ
360 370 380 390 400
MIEQIQFIKL FGMAKIDNLL QEMLLGGSPS DAPHAHHPLH PHLMQEHMGT
410 420 430 440 450
NVIVANTMPT HLSNGQMCEW PRPRGQAATP ETPQPSPPGG SGSEPYKLLP
460 470
GAVATIVKPL SAIPQPTITK QEVI

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.
GeneTreei ENSGT00760000118948.
HOVERGENi HBG005606.
InParanoidi P41235.
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

Bgeei P41235.
ExpressionAtlasi P41235. baseline and differential.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 175 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