간세포핵인자4α

HNF4A
사용 가능한 구조
PDB	Ortholog 검색: PDBe RCSB
PDB ID 코드 목록
	1PZL, 3CBB, 3FS1, 4B7W, 4IQR
식별자
에일리어스	HNF4A, HNF4, HNF4a7, HNF4a8, HNF4a9, HNF4alpha, MODY, MODY1, NR2A21, TCF, HEP14, FRTS
외부 ID	OMIM : 600281 MGI : 109128 HomoloGene : 395 GenCard : HNF4A
유전자 위치(인간)
크르.	20번 염색체(인간)
끝.	44,432,845 bp
유전자 위치(마우스)
크르.	2번 염색체(마우스)
끝.	163,414,830 bp
RNA발현패턴
	상단 표시 위치:
	간우엽; ; 십이지장; ; 직장; ; 제주날 점막; ; 신장; ; 랑게르한스 섬; ; 췌장체; ; 췌상피세포; ; 망막 색소 상피; ; 담낭;
	상단 표시 위치:
	파네스 세포; ; 좌결장; ; jejunum; ; 소장의 리베르쿤 지하실; ; 간좌엽; ; 신장; ; 십이지장; ; 노른자낭; ; 유문성 항문; ; 회장;
	추가 참조 표현식 데이터
	; ; ; ;
	추가 참조 표현식 데이터
유전자 존재론
분자 함수	DNA결합; 배열특이적 DNA결합; DNA결합전사인자활성; DNA결합전사활성화제, RNA중합효소II 특이적; 아연 이온 결합; 금속 이온 결합; 스테로이드 호르몬 수용체 활성; 핵수용체활성; 단백질 결합; 전사인자활성, RNA중합효소II 원위증강제배열특이결합; 신호수용체결합; 지방산 결합; 단백질 호모다이머화; RNA중합효소II 시스조절영역배열특이적 DNA결합; DNA결합전사인자활성, RNA중합효소II 특이적;
셀룰러 컴포넌트	핵; 세포질; 핵소체;
생물학적 과정	트리글리세리드 항상성; 오르니틴 대사 과정; 인지질 항상성; 전사조절, DNA템플릿화; SMAD단백질신호전달; 포도당 항상성; 인슐린 분비 조절; 지질대사; RNA중합효소II에 의한 전사조절; 유전자 발현 조절에 관여하는 신호 전달; 성차별화; 혈액 응고; 포도당에 대한 반응; 전사, DNA 템플릿; 전사의 양성 조절, DNA 템플릿화; 지질대사과정조절; 세포내수용체신호경로; 성장호르몬수용체신호경로조절; 세포 증식의 음성 조절; 지질 항상성; 이종 생물 대사 과정; RNA중합효소II 프로모터로부터의 전사 개시; 위조절 조절; 스테로이드 호르몬 매개 신호 경로; RNA중합효소II에 의한 전사의 양성 조절; 세포군 증식의 음성 조절; 콜레스테롤 항상성; B형 췌장 세포 발달; 간세포분화; 일주기 리듬 조절; 전사 음성 조절, DNA 템플릿; 율동 과정;
	출처:아미고 / QuickGO
맞춤법
	3172
	15378
	ENSG000001076
	ENSMUSG000017950
	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
	위키데이터
인간 보기/편집	마우스 표시/편집

NR2A1(핵수용체 서브패밀리 2, 그룹 A, 멤버 1)이라고도 하는 간세포 핵인자 4 알파(HNF4A)는 인체에서 HNF4A ^[5]^[6]유전자에 의해 암호화되는 핵수용체이다.

기능.

HNF-4α는 DNA를 호모디머로 결합하는 핵전사인자다.암호화된 단백질은 여러 간 유전자의 발현을 조절하는 전사 인자인 간세포 핵 인자 1 알파를 포함한 여러 유전자의 발현을 조절합니다.이 유전자는 간, 신장, 장의 발달에 역할을 한다.이 유전자의 대체 스플라이싱은 다중 전사 ^[7]변형을 일으킨다.

HNF4A는 CYP3A4의 ^[8]PXR 및 CAR 매개 전사 활성화에 필요하다.HNF4A 유전자의 유전자 돌연변이는 CYP2D6, 체외 및 ^[9]^[10]체내와 같은 HNF4α의 하류 단백질의 활성에 영향을 미칠 수 있다.

알칼로이드 베르베린은 HNF4A의 ^[11]발현을 상향 조절한다.

이 유전자는 또한 주로 간에서 만들어지는 중요한 당단백질인 SHBG의 발현과 합성에 중추적인 역할을 하며, 이는 인슐린 저항성을 낮추는 것 외에도 ^{[citation needed]}테스토스테론의 반감기를 연장시키는 데에도 도움이 됩니다.

HNF4A 유전자의 기능을 독립적 ^[12]검증에 기초한 siRNA 녹다운에 의해 효과적으로 검사할 수 있다.

임상적 의의

HNF4A 유전자의 돌연변이는 젊은이의 성숙기 당뇨병이라고 불리는 당뇨병, 특히 MODY ^[13]1과 관련이 있다. 이 유전자의 질병을 유발하는 돌연변이는 최소 56개이다.^[14]

대장암에서 ^[15]간세포 핵인자 4α의 증폭이 관찰되었다.

그것은 또한 유전자의 ^[16]미센스 돌연변이로 인해 발생하는 판코니 증후군 표현형의 출현과도 관련이 있다.

상호 작용

간세포 핵인자 4 알파는 다음과 상호작용하는 것으로 나타났다.

「」를 참조해 주세요.

레퍼런스

^ ^a ^b ^c GRCh38: 앙상블 릴리즈 89: ENSG000001076 - 앙상블, 2017년 5월
^ ^a ^b ^c GRCm38: 앙상블 릴리즈 89: ENSMUSG000017950 - 앙상블, 2017년 5월
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Chartier FL, Bossu JP, Laudet V, Fruchart JC, Laine B (Sep 1994). "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. doi:10.1016/0378-1119(94)90079-5. PMID 7926813.
^ Argyrokastritis A, Kamakari S, Kapsetaki M, Kritis A, Talianidis I, Moschonas NK (Feb 1997). "Human hepatocyte nuclear factor-4 (hHNF-4) gene maps to 20q12-q13.1 between PLCG1 and D20S17". Human Genetics. 99 (2): 233–6. doi:10.1007/s004390050345. PMID 9048927. S2CID 10943721.
^ "Entrez Gene: HNF4A hepatocyte nuclear factor 4, alpha".
^ Tirona RG, Lee W, Leake BF, Lan LB, Cline CB, Lamba V, Parviz F, Duncan SA, Inoue Y, Gonzalez FJ, Schuetz EG, Kim RB (Feb 2003). "The orphan nuclear receptor HNF4alpha determines PXR- and CAR-mediated xenobiotic induction of CYP3A4". Nature Medicine. 9 (2): 220–4. doi:10.1038/nm815. PMID 12514743. S2CID 8925996.
^ Lee SS, Cha EY, Jung HJ, Shon JH, Kim EY, Yeo CW, Shin JG (2008). "Genetic polymorphism of hepatocyte nuclear factor-4alpha influences human cytochrome P450 2D6 activity". Hepatology. 48 (2): 635–45. doi:10.1002/hep.22396. PMID 18666237. S2CID 205866107.
^ Jiang F, Yeo CW, Lee SS, Oh MK, Ghim JL, Shon JH, Kim HS, Kim EY, Kim DH, Shin JG (2013). "Effect of HNF4α genetic polymorphism G60D on the pharmacokinetics of CYP2D6 substrate tolterodine in healthy Korean individuals". Pharmacogenetics and Genomics. 23 (3): 175–9. doi:10.1097/FPC.0b013e32835de25e. PMID 23292115. S2CID 19230792.
^ Wang ZQ, Lu FE, Leng SH, Fang XS, Chen G, Wang ZS, Dong LP, Yan ZQ (Oct 2008). "Facilitating effects of berberine on rat pancreatic islets through modulating hepatic nuclear factor 4 alpha expression and glucokinase activity". World Journal of Gastroenterology. 14 (39): 6004–11. doi:10.3748/wjg.14.6004. PMC 2760199. PMID 18932278.
^ Munkácsy, Gyöngyi; Sztupinszki, Zsófia; Herman, Péter; Bán, Bence; Pénzváltó, Zsófia; Szarvas, Nóra; Győrffy, Balázs (2016-01-01). "Validation of RNAi Silencing Efficiency Using Gene Array Data shows 18.5% Failure Rate across 429 Independent Experiments". Molecular Therapy: Nucleic Acids. 5 (9): e366. doi:10.1038/mtna.2016.66. ISSN 2162-2531. PMC 5056990. PMID 27673562.
^ Yamagata K (2014). "Roles of HNF1α and HNF4α in pancreatic β-cells: lessons from a monogenic form of diabetes (MODY)". Vitamins and Hormones. 95: 407–23. doi:10.1016/B978-0-12-800174-5.00016-8. PMID 24559927.
^ Šimčíková D, Heneberg P (December 2019). "Refinement of evolutionary medicine predictions based on clinical evidence for the manifestations of Mendelian diseases". Scientific Reports. 9 (1): 18577. doi:10.1038/s41598-019-54976-4. PMC 6901466. PMID 31819097.
^ Zhang B, Wang J, Wang X, Zhu J, Liu Q, Shi Z, et al. (2014). "Proteogenomic characterization of human colon and rectal cancer". Nature. 513 (7518): 382–7. Bibcode:2014Natur.513..382.. doi:10.1038/nature13438. PMC 4249766. PMID 25043054.
^ Kashoor I, Batlle D (September 2019). "Proximal renal tubular acidosis with and without Fanconi syndrome". Kidney Research and Clinical Practice. 38 (3): 267–281. doi:10.23876/j.krcp.19.056. PMC 6727890. PMID 31474092.
^ Mulholland DJ, Read JT, Rennie PS, Cox ME, Nelson CC (Aug 2003). "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. doi:10.1038/sj.onc.1206802. PMID 12944908.
^ Yoshida E, Aratani S, Itou H, Miyagishi M, Takiguchi M, Osumu T, Murakami K, Fukamizu A (Dec 1997). "Functional association between CBP and HNF4 in trans-activation". Biochemical and Biophysical Research Communications. 241 (3): 664–9. doi:10.1006/bbrc.1997.7871. PMID 9434765.
^ Dell H, Hadzopoulou-Cladaras M (Mar 1999). "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. doi:10.1074/jbc.274.13.9013. PMID 10085149.
^ ^a ^b Maeda Y, Rachez C, Hawel L, Byus CV, Freedman LP, Sladek FM (Jul 2002). "Polyamines modulate the interaction between nuclear receptors and vitamin D receptor-interacting protein 205". Molecular Endocrinology. 16 (7): 1502–10. doi:10.1210/mend.16.7.0883. PMID 12089346.
^ ^a ^b Malik S, Wallberg AE, Kang YK, Roeder RG (Aug 2002). "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. doi:10.1128/MCB.22.15.5626-5637.2002. PMC 133960. PMID 12101254.
^ Lee YK, Dell H, Dowhan DH, Hadzopoulou-Cladaras M, Moore DD (Jan 2000). "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. doi:10.1128/MCB.20.1.187-195.2000. PMC 85074. PMID 10594021.
^ Lin WJ, Li J, Lee YF, Yeh SD, Altuwaijri S, Ou JH, Chang C (Mar 2003). "Suppression of hepatitis B virus core promoter by the nuclear orphan receptor TR4". The Journal of Biological Chemistry. 278 (11): 9353–60. doi:10.1074/jbc.M205944200. PMID 12522137.

추가 정보

Winter WE, Nakamura M, House DV (Dec 1999). "Monogenic diabetes mellitus in youth. The MODY syndromes". Endocrinology and Metabolism Clinics of North America. 28 (4): 765–85. doi:10.1016/S0889-8529(05)70101-8. PMID 10609119.
Zannis VI, Kan HY, Kritis A, Zanni E, Kardassis D (Mar 2001). "Transcriptional regulation of the human apolipoprotein genes". Frontiers in Bioscience. 6: D456-504. doi:10.2741/Zannis. PMID 11229886.
Gupta RK, Kaestner KH (Nov 2004). "HNF-4alpha: from MODY to late-onset type 2 diabetes". Trends in Molecular Medicine. 10 (11): 521–4. doi:10.1016/j.molmed.2004.09.004. PMID 15519277.
Mohlke KL, Boehnke M (Apr 2005). "The role of HNF4A variants in the risk of type 2 diabetes". Current Diabetes Reports. 5 (2): 149–56. doi:10.1007/s11892-005-0043-y. PMID 15794920. S2CID 1661923.
Love-Gregory L, Permutt MA (Jul 2007). "HNF4A genetic variants: role in diabetes". Current Opinion in Clinical Nutrition and Metabolic Care. 10 (4): 397–402. doi:10.1097/MCO.0b013e3281e3888d. PMID 17563455. S2CID 10318597.
Bell GI, Xiang KS, Newman MV, Wu SH, Wright LG, Fajans SS, Spielman RS, Cox NJ (Feb 1991). "Gene for non-insulin-dependent diabetes mellitus (maturity-onset diabetes of the young subtype) is linked to DNA polymorphism on human chromosome 20q". Proceedings of the National Academy of Sciences of the United States of America. 88 (4): 1484–8. Bibcode:1991PNAS...88.1484B. doi:10.1073/pnas.88.4.1484. PMC 51043. PMID 1899928.
Ktistaki E, Ktistakis NT, Papadogeorgaki E, Talianidis I (Oct 1995). "Recruitment of hepatocyte nuclear factor 4 into specific intranuclear compartments depends on tyrosine phosphorylation that affects its DNA-binding and transactivation potential". Proceedings of the National Academy of Sciences of the United States of America. 92 (21): 9876–80. Bibcode:1995PNAS...92.9876K. doi:10.1073/pnas.92.21.9876. PMC 40905. PMID 7568236.
Ginsburg GS, Ozer J, Karathanasis SK (Jul 1995). "Intestinal apolipoprotein AI gene transcription is regulated by multiple distinct DNA elements and is synergistically activated by the orphan nuclear receptor, hepatocyte nuclear factor 4". The Journal of Clinical Investigation. 96 (1): 528–38. doi:10.1172/JCI118065. PMC 185227. PMID 7615825.
Jiang G, Nepomuceno L, Hopkins K, Sladek FM (Sep 1995). "Exclusive homodimerization of the orphan receptor hepatocyte nuclear factor 4 defines a new subclass of nuclear receptors". Molecular and Cellular Biology. 15 (9): 5131–43. doi:10.1128/mcb.15.9.5131. PMC 230760. PMID 7651430.
Chartier FL, Bossu JP, Laudet V, Fruchart JC, Laine B (Sep 1994). "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. doi:10.1016/0378-1119(94)90079-5. PMID 7926813.
Drewes T, Senkel S, Holewa B, Ryffel GU (Mar 1996). "Human hepatocyte nuclear factor 4 isoforms are encoded by distinct and differentially expressed genes". Molecular and Cellular Biology. 16 (3): 925–31. doi:10.1128/mcb.16.3.925. PMC 231074. PMID 8622695.
Yamagata K, Furuta H, Oda N, Kaisaki PJ, Menzel S, Cox NJ, Fajans SS, Signorini S, Stoffel M, Bell GI (Dec 1996). "Mutations in the hepatocyte nuclear factor-4alpha gene in maturity-onset diabetes of the young (MODY1)". Nature. 384 (6608): 458–60. Bibcode:1996Natur.384..458Y. doi:10.1038/384458a0. hdl:2027.42/62605. PMID 8945471. S2CID 4253951.
Kritis AA, Argyrokastritis A, Moschonas NK, Power S, Katrakili N, Zannis VI, Cereghini S, Talianidis I (Sep 1996). "Isolation and characterization of a third isoform of human hepatocyte nuclear factor 4". Gene. 173 (2): 275–80. doi:10.1016/0378-1119(96)00183-7. PMID 8964514.
Argyrokastritis A, Kamakari S, Kapsetaki M, Kritis A, Talianidis I, Moschonas NK (Feb 1997). "Human hepatocyte nuclear factor-4 (hHNF-4) gene maps to 20q12-q13.1 between PLCG1 and D20S17". Human Genetics. 99 (2): 233–6. doi:10.1007/s004390050345. PMID 9048927. S2CID 10943721.
Thénot S, Henriquet C, Rochefort H, Cavaillès V (May 1997). "Differential interaction of nuclear receptors with the putative human transcriptional coactivator hTIF1". The Journal of Biological Chemistry. 272 (18): 12062–8. doi:10.1074/jbc.272.18.12062. PMID 9115274.
Bulman MP, Dronsfield MJ, Frayling T, Appleton M, Bain SC, Ellard S, Hattersley AT (Jul 1997). "A missense mutation in the hepatocyte nuclear factor 4 alpha gene in a UK pedigree with maturity-onset diabetes of the young". Diabetologia. 40 (7): 859–62. doi:10.1007/s001250050760. PMID 9243109.
Møller AM, Urhammer SA, Dalgaard LT, Reneland R, Berglund L, Hansen T, Clausen JO, Lithell H, Pedersen O (Aug 1997). "Studies of the genetic variability of the coding region of the hepatocyte nuclear factor-4alpha in Caucasians with maturity onset NIDDM". Diabetologia. 40 (8): 980–3. doi:10.1007/s001250050778. PMID 9267996.
Lindner T, Gragnoli C, Furuta H, Cockburn BN, Petzold C, Rietzsch H, Weiss U, Schulze J, Bell GI (Sep 1997). "Hepatic function in a family with a nonsense mutation (R154X) in the hepatocyte nuclear factor-4alpha/MODY1 gene". The Journal of Clinical Investigation. 100 (6): 1400–5. doi:10.1172/JCI119660. PMC 508318. PMID 9294105.
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 GI (Oct 1997). "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". Diabetes. 46 (10): 1652–7. doi:10.2337/diabetes.46.10.1652. PMID 9313765.
Stoffel M, Duncan SA (Nov 1997). "The maturity-onset diabetes of the young (MODY1) transcription factor HNF4alpha regulates expression of genes required for glucose transport and metabolism". Proceedings of the National Academy of Sciences of the United States of America. 94 (24): 13209–14. Bibcode:1997PNAS...9413209S. doi:10.1073/pnas.94.24.13209. PMC 24288. PMID 9371825.

외부 링크

팩터북 HNF4A

이 기사에는 미국 국립 의학 도서관(미국 국립 의학 도서관)의 공공 도메인 텍스트가 포함되어 있습니다.

[refGRCh38Ensembl-1] GRCh38: 앙상블 릴리즈 89: ENSG000001076 - 앙상블, 2017년 5월

[refGRCm38Ensembl-2] GRCm38: 앙상블 릴리즈 89: ENSMUSG000017950 - 앙상블, 2017년 5월

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid7926813-5] Chartier FL, Bossu JP, Laudet V, Fruchart JC, Laine B (Sep 1994). "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. doi:10.1016/0378-1119(94)90079-5. PMID 7926813.

[pmid9048927-6] Argyrokastritis A, Kamakari S, Kapsetaki M, Kritis A, Talianidis I, Moschonas NK (Feb 1997). "Human hepatocyte nuclear factor-4 (hHNF-4) gene maps to 20q12-q13.1 between PLCG1 and D20S17". Human Genetics. 99 (2): 233–6. doi:10.1007/s004390050345. PMID 9048927. S2CID 10943721.

[entrez-7] "Entrez Gene: HNF4A hepatocyte nuclear factor 4, alpha".

[pmid12514743-8] Tirona RG, Lee W, Leake BF, Lan LB, Cline CB, Lamba V, Parviz F, Duncan SA, Inoue Y, Gonzalez FJ, Schuetz EG, Kim RB (Feb 2003). "The orphan nuclear receptor HNF4alpha determines PXR- and CAR-mediated xenobiotic induction of CYP3A4". Nature Medicine. 9 (2): 220–4. doi:10.1038/nm815. PMID 12514743. S2CID 8925996.

[pmid18666237-9] Lee SS, Cha EY, Jung HJ, Shon JH, Kim EY, Yeo CW, Shin JG (2008). "Genetic polymorphism of hepatocyte nuclear factor-4alpha influences human cytochrome P450 2D6 activity". Hepatology. 48 (2): 635–45. doi:10.1002/hep.22396. PMID 18666237. S2CID 205866107.

[pmid23292115-10] Jiang F, Yeo CW, Lee SS, Oh MK, Ghim JL, Shon JH, Kim HS, Kim EY, Kim DH, Shin JG (2013). "Effect of HNF4α genetic polymorphism G60D on the pharmacokinetics of CYP2D6 substrate tolterodine in healthy Korean individuals". Pharmacogenetics and Genomics. 23 (3): 175–9. doi:10.1097/FPC.0b013e32835de25e. PMID 23292115. S2CID 19230792.

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