HNF4A

HNF4A
PDBに登録とうろくされている構造こうぞう
PDB	オルソログ検索けんさく: RCSB PDBe PDBj
PDBのIDコード一覧いちらん
	1PZL, 3CBB, 3FS1, 4B7W, 4IQR
識別子しきべつし
記号きごう	HNF4A, HNF4, HNF4a7, HNF4a8, HNF4a9, HNF4alpha, MODY, MODY1, NR2A1, NR2A21, TCF, TCF14, FRTS4, Hepatocyte nuclear factor 4 alpha, TCF-14
外部がいぶID	OMIM: 600281 MGI: 109128 HomoloGene: 395 GeneCards: HNF4A
遺伝子いでんしの位置いち (ヒト)
染色せんしょく体たい	20番ばん染色せんしょく体たい (ヒト)
終点しゅうてん	44,432,845 bp
遺伝子いでんしの位置いち (マウス)
染色せんしょく体たい	2番ばん染色せんしょく体たい (マウス)
終点しゅうてん	163,414,830 bp
RNA発現はつげんパターン
	; ; ; ;
	さらなる参照さんしょう発現はつげんデータ
遺伝子いでんしオントロジー
分子ぶんし機能きのう	• DNA結合けつごう; • sequence-specific DNA binding; • DNA-binding transcription factor activity; • DNA-binding transcription activator activity, RNA polymerase II-specific; • zinc ion binding; • 金属きんぞくイオン結合けつごう; • steroid hormone receptor activity; • nuclear receptor activity; • 血漿けっしょうタンパク結合けつごう; • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding; • 受容じゅよう体たい結合けつごう; • fatty acid binding; • protein homodimerization activity; • RNA polymerase II cis-regulatory region sequence-specific DNA binding; • DNA-binding transcription factor activity, RNA polymerase II-specific;
細胞さいぼうの構成こうせい要素ようそ	• 細胞さいぼう核かく; • 細胞さいぼう質しつ; • 核質かくしつ;
生物せいぶつ学がく的てきプロセス	• triglyceride homeostasis; • ornithine metabolic process; • phospholipid homeostasis; • regulation of transcription, DNA-templated; • SMAD protein signal transduction; • glucose homeostasis; • regulation of insulin secretion; • 脂質ししつ代謝たいしゃ; • regulation of transcription by RNA polymerase II; • signal transduction involved in regulation of gene expression; • sex differentiation; • 凝固ぎょうこ・線せん溶系; • response to glucose; • transcription, DNA-templated; • positive regulation of transcription, DNA-templated; • regulation of lipid metabolic process; • intracellular receptor signaling pathway; • regulation of growth hormone receptor signaling pathway; • negative regulation of cell growth; • lipid homeostasis; • 生体せいたい異物いぶつの代謝たいしゃプロセス; • transcription initiation from RNA polymerase II promoter; • regulation of gastrulation; • steroid hormone mediated signaling pathway; • positive regulation of transcription by RNA polymerase II; • negative regulation of cell population proliferation; • cholesterol homeostasis; • type B pancreatic cell development; • hepatocyte differentiation; • regulation of circadian rhythm; • negative regulation of transcription, DNA-templated; • 周期しゅうき的てきプロセス;
	出典しゅってん:Amigo / QuickGO
オルソログ
	3172
	15378
	ENSG00000101076
	ENSMUSG00000017950
	P41235
	P49698
NM_000457; NM_001030003; NM_001030004; NM_001258355; NM_001287182;
	NM_001287183; NM_001287184; NM_175914; NM_178849; NM_178850
	NM_008261; NM_001312906; NM_001312907
NP_000448; NP_001025174; NP_001025175; NP_001245284; NP_001274111;
	NP_001274112; NP_001274113; NP_787110; NP_849180; NP_849181
	NP_001299835; NP_001299836; NP_032287
	ウィキデータ
閲覧えつらん/編集へんしゅうヒト	閲覧えつらん/編集へんしゅうマウス

HNF4AまたはHNF4αあるふぁ（hepatocyte nuclear factor 4 alpha）、NR2A1（nuclear receptor subfamily 2, group A, member 1）は、ヒトではHNF4A遺伝子いでんしにコードされる核かく内ない受容じゅよう体たいである^[5]^[6]。

機能きのう

HNF4αあるふぁはホモ二に量りょう体たいとしてDNAに結合けつごうする転写てんしゃ因子いんしであり、肝臓かんぞう遺伝子いでんしの発現はつげんを調節ちょうせつする転写てんしゃ因子いんしであるHNF1αあるふぁなど、いくつかの遺伝子いでんしの発現はつげんを制御せいぎょする。HNF4αあるふぁは肝臓かんぞう、腎臓じんぞう、腸ちょうの発生はっせいに関与かんよしている。HNF4A遺伝子いでんしからは選択せんたく的てきスプライシングにより、複数ふくすうの転写てんしゃバリアントが生しょうじる^[7]。

HNF4AはPXRとCAR（英語えいご版ばん）を介かいしたCYP3A4の転写てんしゃ活性かっせい化かに必要ひつようである^[8]。HNF4A遺伝子いでんしの変異へんいは、CYP2D6などHNF4αあるふぁの下流かりゅうのタンパク質たんぱくしつの活性かっせいに影響えいきょうを与あたえる^[9]^[10]。

アルカロイドの1種しゅであるベルベリンは、HNF4Aの発現はつげんをアップレギュレーションする。

臨床りんしょう的てき意義いぎ

HNF4A遺伝子いでんしの変異へんいは、若年じゃくねん発症はっしょう成人せいじん型がた糖尿とうにょう病びょう（英語えいご版ばん）（MODY）^[11]、特とくにMODY 1（英語えいご版ばん）と関係かんけいしている。少すくなくとも56種類しゅるいの疾患しっかん原因げんいん変異へんいがこの遺伝子いでんしには発見はっけんされている^[12]。

大腸だいちょうがんではHNF4αあるふぁの増幅ぞうふくが観察かんさつされる^[13]。

HNF4A遺伝子いでんしのミスセンス変異へんいは、ファンコーニ症候群しょうこうぐんの表現ひょうげん型がたの出現しゅつげんとも関係かんけいしている^[14]。

相互そうご作用さよう

HNF4αあるふぁは次つぎに挙あげる因子いんしと相互そうご作用さようすることが示しめされている。

βべーた-カテニン^[15]
CREB結合けつごうタンパク質たんぱくしつ（英語えいご版ばん）^[16]^[17]
MED1（英語えいご版ばん）^[18]^[19]
MED14（英語えいご版ばん）^[18]^[19]
SHP（英語えいご版ばん）^[20]
TR4（英語えいご版ばん）^[21]

出典しゅってん

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000101076 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000017950 - Ensembl, May 2017
^ Human PubMed Reference:
^ Mouse PubMed Reference:
^ “Cloning and sequencing of cDNAs encoding the human hepatocyte nuclear factor 4 indicate the presence of two isoforms in human liver”. Gene 147 (2): 269–72. (Sep 1994). doi:10.1016/0378-1119(94)90079-5. PMID 7926813.
^ “Human hepatocyte nuclear factor-4 (hHNF-4) gene maps to 20q12-q13.1 between PLCG1 and D20S17”. Human Genetics 99 (2): 233–6. (Feb 1997). doi:10.1007/s004390050345. PMID 9048927.
^ “Entrez Gene: HNF4A hepatocyte nuclear factor 4, alpha”. 2023年ねん6月がつ7日にち閲覧えつらん。
^ “The orphan nuclear receptor HNF4alpha determines PXR- and CAR-mediated xenobiotic induction of CYP3A4”. Nature Medicine 9 (2): 220–4. (Feb 2003). doi:10.1038/nm815. PMID 12514743.
^ “Genetic polymorphism of hepatocyte nuclear factor-4alpha influences human cytochrome P450 2D6 activity”. Hepatology 48 (2): 635–45. (2008). doi:10.1002/hep.22396. PMID 18666237.
^ “Effect of HNF4αあるふぁ genetic polymorphism G60D on the pharmacokinetics of CYP2D6 substrate tolterodine in healthy Korean individuals”. Pharmacogenetics and Genomics 23 (3): 175–9. (2013). doi:10.1097/FPC.0b013e32835de25e. PMID 23292115.
^ “Roles of HNF1αあるふぁ and HNF4αあるふぁ in pancreatic βべーた-cells: lessons from a monogenic form of diabetes (MODY)”. Vitamins and Hormones 95: 407–23. (2014). doi:10.1016/B978-0-12-800174-5.00016-8. PMID 24559927.
^ “Refinement of evolutionary medicine predictions based on clinical evidence for the manifestations of Mendelian diseases”. Scientific Reports 9 (1): 18577. (December 2019). Bibcode: 2019NatSR...918577S. doi:10.1038/s41598-019-54976-4. PMC 6901466. PMID 31819097.
^ “Proteogenomic characterization of human colon and rectal cancer”. Nature 513 (7518): 382–7. (2014). Bibcode: 2014Natur.513..382.. doi:10.1038/nature13438. PMC 4249766. PMID 25043054.
^ “Proximal renal tubular acidosis with and without Fanconi syndrome”. Kidney Research and Clinical Practice 38 (3): 267–281. (September 2019). doi:10.23876/j.krcp.19.056. PMC 6727890. PMID 31474092.
^ “Functional localization and competition between the androgen receptor and T-cell factor for nuclear beta-catenin: a means for inhibition of the Tcf signaling axis”. Oncogene 22 (36): 5602–13. (Aug 2003). doi:10.1038/sj.onc.1206802. PMID 12944908.
^ “Functional association between CBP and HNF4 in trans-activation”. Biochemical and Biophysical Research Communications 241 (3): 664–9. (Dec 1997). doi:10.1006/bbrc.1997.7871. PMID 9434765.
^ “CREB-binding protein is a transcriptional coactivator for hepatocyte nuclear factor-4 and enhances apolipoprotein gene expression”. The Journal of Biological Chemistry 274 (13): 9013–21. (Mar 1999). doi:10.1074/jbc.274.13.9013. PMID 10085149.
^ ^a ^b “Polyamines modulate the interaction between nuclear receptors and vitamin D receptor-interacting protein 205”. Molecular Endocrinology 16 (7): 1502–10. (Jul 2002). doi:10.1210/mend.16.7.0883. PMID 12089346.
^ ^a ^b “TRAP/SMCC/mediator-dependent transcriptional activation from DNA and chromatin templates by orphan nuclear receptor hepatocyte nuclear factor 4”. Molecular and Cellular Biology 22 (15): 5626–37. (Aug 2002). doi:10.1128/MCB.22.15.5626-5637.2002. PMC 133960. PMID 12101254.
^ “The orphan nuclear receptor SHP inhibits hepatocyte nuclear factor 4 and retinoid X receptor transactivation: two mechanisms for repression”. Molecular and Cellular Biology 20 (1): 187–95. (Jan 2000). doi:10.1128/MCB.20.1.187-195.2000. PMC 85074. PMID 10594021.
^ “Suppression of hepatitis B virus core promoter by the nuclear orphan receptor TR4”. The Journal of Biological Chemistry 278 (11): 9353–60. (Mar 2003). doi:10.1074/jbc.M205944200. PMID 12522137.

外部がいぶリンク

FactorBook HNF4A

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000101076 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000017950 - Ensembl, May 2017

[3] Human PubMed Reference:

[4] Mouse PubMed Reference:

[pmid7926813-5] “Cloning and sequencing of cDNAs encoding the human hepatocyte nuclear factor 4 indicate the presence of two isoforms in human liver”. Gene 147 (2): 269–72. (Sep 1994). doi:10.1016/0378-1119(94)90079-5. PMID 7926813.

[pmid9048927-6] “Human hepatocyte nuclear factor-4 (hHNF-4) gene maps to 20q12-q13.1 between PLCG1 and D20S17”. Human Genetics 99 (2): 233–6. (Feb 1997). doi:10.1007/s004390050345. PMID 9048927.

[entrez-7] “Entrez Gene: HNF4A hepatocyte nuclear factor 4, alpha”. 2023年ねん6月がつ7日にち閲覧えつらん。

[pmid12514743-8] “The orphan nuclear receptor HNF4alpha determines PXR- and CAR-mediated xenobiotic induction of CYP3A4”. Nature Medicine 9 (2): 220–4. (Feb 2003). doi:10.1038/nm815. PMID 12514743.

[pmid18666237-9] “Genetic polymorphism of hepatocyte nuclear factor-4alpha influences human cytochrome P450 2D6 activity”. Hepatology 48 (2): 635–45. (2008). doi:10.1002/hep.22396. PMID 18666237.

[pmid23292115-10] “Effect of HNF4αあるふぁ genetic polymorphism G60D on the pharmacokinetics of CYP2D6 substrate tolterodine in healthy Korean individuals”. Pharmacogenetics and Genomics 23 (3): 175–9. (2013). doi:10.1097/FPC.0b013e32835de25e. PMID 23292115.

[pmid24559927-11] “Roles of HNF1αあるふぁ and HNF4αあるふぁ in pancreatic βべーた-cells: lessons from a monogenic form of diabetes (MODY)”. Vitamins and Hormones 95: 407–23. (2014). doi:10.1016/B978-0-12-800174-5.00016-8. PMID 24559927.

[Šimčíková_2019_-_supplementary_table_S7-12] “Refinement of evolutionary medicine predictions based on clinical evidence for the manifestations of Mendelian diseases”. Scientific Reports 9 (1): 18577. (December 2019). Bibcode: 2019NatSR...918577S. doi:10.1038/s41598-019-54976-4. PMC 6901466. PMID 31819097.

[pmid25043054-13] “Proteogenomic characterization of human colon and rectal cancer”. Nature 513 (7518): 382–7. (2014). Bibcode: 2014Natur.513..382.. doi:10.1038/nature13438. PMC 4249766. PMID 25043054.

[pmid31474092-14] “Proximal renal tubular acidosis with and without Fanconi syndrome”. Kidney Research and Clinical Practice 38 (3): 267–281. (September 2019). doi:10.23876/j.krcp.19.056. PMC 6727890. PMID 31474092.

[pmid12944908-15] “Functional localization and competition between the androgen receptor and T-cell factor for nuclear beta-catenin: a means for inhibition of the Tcf signaling axis”. Oncogene 22 (36): 5602–13. (Aug 2003). doi:10.1038/sj.onc.1206802. PMID 12944908.

[pmid9434765-16] “Functional association between CBP and HNF4 in trans-activation”. Biochemical and Biophysical Research Communications 241 (3): 664–9. (Dec 1997). doi:10.1006/bbrc.1997.7871. PMID 9434765.

[pmid10085149-17] “CREB-binding protein is a transcriptional coactivator for hepatocyte nuclear factor-4 and enhances apolipoprotein gene expression”. The Journal of Biological Chemistry 274 (13): 9013–21. (Mar 1999). doi:10.1074/jbc.274.13.9013. PMID 10085149.

[pmid12089346-18] “Polyamines modulate the interaction between nuclear receptors and vitamin D receptor-interacting protein 205”. Molecular Endocrinology 16 (7): 1502–10. (Jul 2002). doi:10.1210/mend.16.7.0883. PMID 12089346.

[pmid12101254-19] “TRAP/SMCC/mediator-dependent transcriptional activation from DNA and chromatin templates by orphan nuclear receptor hepatocyte nuclear factor 4”. Molecular and Cellular Biology 22 (15): 5626–37. (Aug 2002). doi:10.1128/MCB.22.15.5626-5637.2002. PMC 133960. PMID 12101254.

[pmid10594021-20] “The orphan nuclear receptor SHP inhibits hepatocyte nuclear factor 4 and retinoid X receptor transactivation: two mechanisms for repression”. Molecular and Cellular Biology 20 (1): 187–95. (Jan 2000). doi:10.1128/MCB.20.1.187-195.2000. PMC 85074. PMID 10594021.

[pmid12522137-21] “Suppression of hepatitis B virus core promoter by the nuclear orphan receptor TR4”. The Journal of Biological Chemistry 278 (11): 9353–60. (Mar 2003). doi:10.1074/jbc.M205944200. PMID 12522137.

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