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Target not currently curated in GtoImmuPdb
Target id: 609
Nomenclature: Hepatocyte nuclear factor-4-γ
Systematic Nomenclature: NR2A2
Gene and Protein Information  |
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| Species | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 408 | 8q21.13 | HNF4G | hepatocyte nuclear factor 4 gamma | 3 |
| Mouse | 408 | 3 A1 | Hnf4g | hepatocyte nuclear factor 4, gamma | 6 |
| Rat | - | 2q24 | Hnf4g | hepatocyte nuclear factor 4, gamma | |
| Previous and Unofficial Names |
| hepatocyte nuclear factor 4 |
| Database Links |
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| Alphafold | Q14541 (Hs), Q9WUU6 (Mm) |
| CATH/Gene3D | 3.30.50.10 |
| ChEMBL Target | CHEMBL1961786 (Hs) |
| Ensembl Gene | ENSG00000164749 (Hs), ENSMUSG00000017688 (Mm), ENSRNOG00000008971 (Rn) |
| Entrez Gene | 3174 (Hs), 30942 (Mm), 365744 (Rn) |
| Human Protein Atlas | ENSG00000164749 (Hs) |
| KEGG Gene | hsa:3174 (Hs), mmu:30942 (Mm), rno:365744 (Rn) |
| OMIM | 605966 (Hs) |
| Pharos | Q14541 (Hs) |
| RefSeq Nucleotide | NM_004133 (Hs), NM_013920 (Mm), NM_001108939 (Rn) |
| RefSeq Protein | NP_004124 (Hs), NP_038948 (Mm), NP_001102409 (Rn) |
| UniProtKB | Q14541 (Hs), Q9WUU6 (Mm) |
| Wikipedia | HNF4G (Hs) |
| Selected 3D Structures |
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| Natural/Endogenous Ligands |
| Comments: Orphan |
| Agonist Comments | ||
| Fatty acids originating from bacteria were found in crystalized HNF4γ LBD. Authors showed that these fatty acids were not exchangeable without prior denaturation of the protein and suggested that fatty acids act as co-factors, rather than exchangeable ligands. Recent work on HNF4α in mammalian cells by the groups of Forman and Sladek, however, suggest that the bacterially expressed protein may not be an accurate representation of HNF4 in vivo [7]. |
| DNA Binding |
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| DNA Binding Comments | |||||||
| The HNF4γ DBD is nearly identical to that of HNF4α (62/66 amino acids with the remaining four being conservative changes) and shares at least some of the same response elements with HNF4α. On the one element where HNF4α and γ were compared side-by-side, they displayed similar DNA binding affinities. Despite the fact that HNF4γ contains the same signature motif which directs dimerization in HNF4α, other groups have not found evidence of HNF4γ and HNF4α heterodimers [1-2]. | |||||||
| Main Target Genes |
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| Name | Species | Effect | Technique | Comments | References |
| Apoc3 | Mouse | Activated | Transient transfection | 6 | |
| Apoa4 | Mouse | Activated | Transient transfection, EMSA, Footprint | 1,5 | |
| Tat | Mouse | Activated | Transient transfection | 6 | |
| HNF1α | Human | Activated | Transient transfection | 3 | |
| AKR1C4 | Human | Activated | EMSA, Footprint | HNF-4alpha, HNF-4gamma and HNF-1alpha regulate co-operatively the transcription of the human DD4 gene in HepG2 cells | 4 |
| Tissue Distribution Comments | |
| HNF4γ was detected as a 6.0 kb species in endocrine pancreas, kidney, small intestine and testis, but, strikingly, not in liver and only very weakly in colon. HNF4γ is expressed only in the villus while HNF4α is expressed in the entire length of the crypt-to-villus axis. In general HNF4γ is more than 10 fold less abundant than HNF4α. It was detected in, human, mouse and rat studies [5-6]. |
| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||
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1. Archer A, Sauvaget D, Chauffeton V, Bouchet PE, Chambaz J, Pinçon-Raymond M, Cardot P, Ribeiro A, Lacasa M. (2005) Intestinal apolipoprotein A-IV gene transcription is controlled by two hormone-responsive elements: a role for hepatic nuclear factor-4 isoforms. Mol Endocrinol, 19 (9): 2320-34. [PMID:15928313]
2. Bogan AA, Dallas-Yang Q, Ruse MD, Maeda Y, Jiang G, Nepomuceno L, Scanlan TS, Cohen FE, Sladek FM. (2000) Analysis of protein dimerization and ligand binding of orphan receptor HNF4alpha. J Mol Biol, 302 (4): 831-51. [PMID:10993727]
3. Drewes T, Senkel S, Holewa B, Ryffel GU. (1996) Human hepatocyte nuclear factor 4 isoforms are encoded by distinct and differentially expressed genes. Mol Cell Biol, 16 (3): 925-31. [PMID:8622695]
4. Ozeki T, Takahashi Y, Kume T, Nakayama K, Yokoi T, Nunoya K, Hara A, Kamataki T. (2001) Co-operative regulation of the transcription of human dihydrodiol dehydrogenase (DD)4/aldo-keto reductase (AKR)1C4 gene by hepatocyte nuclear factor (HNF)-4alpha/gamma and HNF-1alpha. Biochem J, 355 (Pt 2): 537-44. [PMID:11284743]
5. Sauvaget D, Chauffeton V, Citadelle D, Chatelet FP, Cywiner-Golenzer C, Chambaz J, Pinçon-Raymond M, Cardot P, Le Beyec J, Ribeiro A. (2002) Restriction of apolipoprotein A-IV gene expression to the intestine villus depends on a hormone-responsive element and parallels differential expression of the hepatic nuclear factor 4alpha and gamma isoforms. J Biol Chem, 277 (37): 34540-8. [PMID:12105231]
6. Taraviras S, Mantamadiotis T, Dong-Si T, Mincheva A, Lichter P, Drewes T, Ryffel GU, Monaghan AP, Schütz G. (2000) Primary structure, chromosomal mapping, expression and transcriptional activity of murine hepatocyte nuclear factor 4gamma. Biochim Biophys Acta, 1490 (1-2): 21-32. [PMID:10786614]
7. Wisely GB, Miller AB, Davis RG, Thornquest AD, Johnson R, Spitzer T, Sefler A, Shearer B, Moore JT, Miller AB, Willson TM, Williams SP. (2002) Hepatocyte nuclear factor 4 is a transcription factor that constitutively binds fatty acids. Structure, 10 (9): 1225-34. [PMID:12220494]
