ACVRL1
ACVRL1
세린/트레오닌-단백질인산화효소 수용체 R3은 ACVRL1 [5][6][7]유전자에 의해 인체 내에서 암호화되는 효소이다.
ACVRL1은 TGF 베타 시그널링 경로에 있는 수용체이다.또한 액티빈 수용체 유사 키나제 1 또는 ALK1로도 알려져 있다.
기능.
이 유전자는 리간드의 TGF-β 슈퍼패밀리에 대한 타입 I 세포 표면 수용체를 코드한다.그것은 다른 타입 I 수용체들과 세린-트레오닌 키나아제 서브도메인, 키나아제 도메인 앞의 글리신 및 세린이 풍부한 영역(GS 도메인이라고 함), 짧은 C 말단 꼬리에서 높은 유사성을 공유한다.때때로 ALK1이라고 불리는 암호화된 단백질은 수용체 세린/트레오닌 키나제의 하위 패밀리를 형성하는 다른 밀접하게 관련된 ALK 또는 액티빈 수용체 유사 키나제 단백질과 유사한 도메인 구조를 공유한다.이 유전자의 돌연변이는 Rendu-Osler-Weber 증후군 [7]2로도 알려진 유전성 출혈성 Telangioctasia(HHT) 타입 2와 관련이 있다.
병리학
ACVRL1의 생식선 돌연변이는 다음과 관련이 있습니다.
ACVRL1의 체세포 모자이즘은 심각한 폐동맥 [10]고혈압과 관련이 있다.
ACVRL1은 저밀도 지질단백질(LDL)과 직접 상호작용하며, 이는 아테롬성 [11]동맥경화의 초기 단계를 시작할 수 있음을 암시한다.
ACVRL1의 비정상적인 활동은 특발성 폐동맥 고혈압과 밀접한 관련이 있는 것으로 밝혀졌다.
약물 표적으로서
(무형성 림프종 키나제(ALK)와 혼동하지 말 것)
ALK4는 ACVR1B, ALK7은 ACVR1C, ALK5는 TGF-β형 I [13]수용체의 일부이다.
「 」를 참조해 주세요.
- TGF 베타 시그널링 경로, ALK에 대한 요약표 참조*
레퍼런스
- ^ a b c GRCh38: 앙상블 릴리즈 89: ENSG00000139567 - 앙상블, 2017년 5월
- ^ a b c GRCm38: 앙상블 릴리즈 89: ENSMUSG000000530 - 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.
- ^ ten Dijke P, Ichijo H, Franzén P, Schulz P, Saras J, Toyoshima H, Heldin CH, Miyazono K (October 1993). "Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity". Oncogene. 8 (10): 2879–87. PMID 8397373.
- ^ Johnson DW, Berg JN, Baldwin MA, Gallione CJ, Marondel I, Yoon SJ, Stenzel TT, Speer M, Pericak-Vance MA, Diamond A, Guttmacher AE, Jackson CE, Attisano L, Kucherlapati R, Porteous ME, Marchuk DA (June 1996). "Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2". Nature Genetics. 13 (2): 189–95. doi:10.1038/ng0696-189. PMID 8640225. S2CID 21379604.
- ^ a b "Entrez Gene: ACVRL1 activin A receptor type II-like 1".
- ^ Olivieri C, Mira E, Delù G, Pagella F, Zambelli A, Malvezzi L, Buscarini E, Danesino C (July 2002). "Identification of 13 new mutations in the ACVRL1 gene in a group of 52 unselected Italian patients affected by hereditary haemorrhagic telangiectasia". Journal of Medical Genetics. 39 (7): 39e–39. doi:10.1136/jmg.39.7.e39. PMC 1735165. PMID 12114496.
- ^ Vandenbriele C, Peerlinck K, de Ravel T, Verhamme P, Vanassche T (April 2014). "Pulmonary arterio-venous malformations in a patient with a novel mutation in exon 10 of the ACVRL1 gene". Acta Clinica Belgica. 69 (2): 139–41. doi:10.1179/0001551213Z.00000000012. PMID 24724759. S2CID 35264961.
- ^ Jones G, Robertson L, Harrison R, Ridout C, Vasudevan P (August 2014). "Somatic mosaicism in ACVRL1 with transmission to several offspring affected with severe pulmonary arterial hypertension". American Journal of Medical Genetics. Part A. 164A (8): 2121–3. doi:10.1002/ajmg.a.36568. PMID 24753439. S2CID 5417225.
- ^ Kraehling JR, Chidlow JH, Rajagopal C, Sugiyama MG, Fowler JW, Lee MY, Zhang X, Ramírez CM, Park EJ, Tao B, Chen K, Kuruvilla L, Larriveé B, Folta-Stogniew E, Ola R, Rotllan N, Zhou W, Nagle MW, Herz J, Williams KJ, Eichmann A, Lee WL, Fernández-Hernando C, Sessa WC (November 2016). "Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells". Nature Communications. 7: 13516. Bibcode:2016NatCo...713516K. doi:10.1038/ncomms13516. PMC 5121336. PMID 27869117.
- ^ Gupta S, Gill D, Pal SK, Agarwal N (2015). "Activin receptor inhibitors--dalantercept". Current Oncology Reports. 17 (4): 14. doi:10.1007/s11912-015-0441-5. PMID 25708802. S2CID 22676858.
- ^ Laping NJ, Grygielko E, Mathur A, Butter S, Bomberger J, Tweed C, Martin W, Fornwald J, Lehr R, Harling J, Gaster L, Callahan JF, Olson BA (July 2002). "Inhibition of transforming growth factor (TGF)-beta1-induced extracellular matrix with a novel inhibitor of the TGF-beta type I receptor kinase activity: SB-431542". Molecular Pharmacology. 62 (1): 58–64. doi:10.1124/mol.62.1.58. PMID 12065755.
추가 정보
- Attisano L, Cárcamo J, Ventura F, Weis FM, Massagué J, Wrana JL (November 1993). "Identification of human activin and TGF beta type I receptors that form heteromeric kinase complexes with type II receptors". Cell. 75 (4): 671–80. doi:10.1016/0092-8674(93)90488-C. PMID 8242742. S2CID 25408172.
- Johnson DW, Berg JN, Gallione CJ, McAllister KA, Warner JP, Helmbold EA, Markel DS, Jackson CE, Porteous ME, Marchuk DA (August 1995). "A second locus for hereditary hemorrhagic telangiectasia maps to chromosome 12". Genome Research. 5 (1): 21–8. doi:10.1101/gr.5.1.21. PMID 8717052.
- Panchenko MP, Williams MC, Brody JS, Yu Q (April 1996). "Type I receptor serine-threonine kinase preferentially expressed in pulmonary blood vessels". The American Journal of Physiology. 270 (4 Pt 1): L547-58. doi:10.1152/ajplung.1996.270.4.L547. PMID 8928814.
- Berg JN, Gallione CJ, Stenzel TT, Johnson DW, Allen WP, Schwartz CE, Jackson CE, Porteous ME, Marchuk DA (July 1997). "The activin receptor-like kinase 1 gene: genomic structure and mutations in hereditary hemorrhagic telangiectasia type 2". American Journal of Human Genetics. 61 (1): 60–7. doi:10.1086/513903. PMC 1715857. PMID 9245985.
- Stockwell BR, Schreiber SL (June 1998). "Probing the role of homomeric and heteromeric receptor interactions in TGF-beta signaling using small molecule dimerizers". Current Biology. 8 (13): 761–70. doi:10.1016/S0960-9822(98)70299-4. PMID 9651680. S2CID 93779.
- Lux A, Attisano L, Marchuk DA (April 1999). "Assignment of transforming growth factor beta1 and beta3 and a third new ligand to the type I receptor ALK-1". The Journal of Biological Chemistry. 274 (15): 9984–92. doi:10.1074/jbc.274.15.9984. PMID 10187774.
- Klaus DJ, Gallione CJ, Anthony K, Yeh EY, Yu J, Lux A, Johnson DW, Marchuk DA (2000). "Novel missense and frameshift mutations in the activin receptor-like kinase-1 gene in hereditary hemorrhagic telangiectasia. Mutations in brief no. 164. Online". Human Mutation. 12 (2): 137–138. doi:10.1002/(SICI)1098-1004(1998)12:2<137::AID-HUMU16>3.0.CO;2-J. PMID 10694922.
- Oh SP, Seki T, Goss KA, Imamura T, Yi Y, Donahoe PK, Li L, Miyazono K, ten Dijke P, Kim S, Li E (March 2000). "Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis". Proceedings of the National Academy of Sciences of the United States of America. 97 (6): 2626–31. Bibcode:2000PNAS...97.2626O. doi:10.1073/pnas.97.6.2626. PMC 15979. PMID 10716993.
- Abdalla SA, Pece-Barbara N, Vera S, Tapia E, Paez E, Bernabeu C, Letarte M (May 2000). "Analysis of ALK-1 and endoglin in newborns from families with hereditary hemorrhagic telangiectasia type 2". Human Molecular Genetics. 9 (8): 1227–37. doi:10.1093/hmg/9.8.1227. PMID 10767348.
- Kjeldsen AD, Brusgaard K, Poulsen L, Kruse T, Rasmussen K, Green A, Vase P (February 2001). "Mutations in the ALK-1 gene and the phenotype of hereditary hemorrhagic telangiectasia in two large Danish families". American Journal of Medical Genetics. 98 (4): 298–302. doi:10.1002/1096-8628(20010201)98:4<298::AID-AJMG1093>3.0.CO;2-K. PMID 11170071.
- Wurthner JU, Frank DB, Felici A, Green HM, Cao Z, Schneider MD, McNally JG, Lechleider RJ, Roberts AB (June 2001). "Transforming growth factor-beta receptor-associated protein 1 is a Smad4 chaperone". The Journal of Biological Chemistry. 276 (22): 19495–502. doi:10.1074/jbc.M006473200. PMID 11278302.
- Parks WT, Frank DB, Huff C, Renfrew Haft C, Martin J, Meng X, de Caestecker MP, McNally JG, Reddi A, Taylor SI, Roberts AB, Wang T, Lechleider RJ (June 2001). "Sorting nexin 6, a novel SNX, interacts with the transforming growth factor-beta family of receptor serine-threonine kinases". The Journal of Biological Chemistry. 276 (22): 19332–9. doi:10.1074/jbc.M100606200. PMID 11279102.
- Birkey Reffey S, Wurthner JU, Parks WT, Roberts AB, Duckett CS (July 2001). "X-linked inhibitor of apoptosis protein functions as a cofactor in transforming growth factor-beta signaling". The Journal of Biological Chemistry. 276 (28): 26542–9. doi:10.1074/jbc.M100331200. PMID 11356828.
- Trembath RC, Thomson JR, Machado RD, Morgan NV, Atkinson C, Winship I, Simonneau G, Galie N, Loyd JE, Humbert M, Nichols WC, Morrell NW, Berg J, Manes A, McGaughran J, Pauciulo M, Wheeler L (August 2001). "Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia" (PDF). The New England Journal of Medicine. 345 (5): 325–34. doi:10.1056/NEJM200108023450503. hdl:2381/35988. PMID 11484689.
- Inman GJ, Nicolás FJ, Callahan JF, Harling JD, Gaster LM, Reith AD, Laping NJ, Hill CS (July 2002). "SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7". Molecular Pharmacology. 62 (1): 65–74. doi:10.1124/mol.62.1.65. PMID 12065756.
- Olivieri C, Mira E, Delù G, Pagella F, Zambelli A, Malvezzi L, Buscarini E, Danesino C (July 2002). "Identification of 13 new mutations in the ACVRL1 gene in a group of 52 unselected Italian patients affected by hereditary haemorrhagic telangiectasia". Journal of Medical Genetics. 39 (7): 39e–39. doi:10.1136/jmg.39.7.e39. PMC 1735165. PMID 12114496.
- Mo J, Fang SJ, Chen W, Blobe GC (December 2002). "Regulation of ALK-1 signaling by the nuclear receptor LXRbeta". The Journal of Biological Chemistry. 277 (52): 50788–94. doi:10.1074/jbc.M210376200. PMID 12393874.
- Lamouille S, Mallet C, Feige JJ, Bailly S (December 2002). "Activin receptor-like kinase 1 is implicated in the maturation phase of angiogenesis". Blood. 100 (13): 4495–501. doi:10.1182/blood.V100.13.4495. PMID 12453878.
- Mitchell D, Pobre EG, Mulivor AW, Grinberg AV, Castonguay R, Monnell TE, Solban N, Ucran JA, Pearsall RS, Underwood KW, Seehra J, Kumar R (February 2010). "ALK1-Fc inhibits multiple mediators of angiogenesis and suppresses tumor growth". Molecular Cancer Therapeutics. 9 (2): 379–88. doi:10.1158/1535-7163.MCT-09-0650. PMID 20124460.
외부 링크
- 유전성 출혈성 Telangioctasia에 대한 GeneReviews/NCBI/NIH/UW 엔트리
- UCSC Genome Browser의 인간 ACVRL1 게놈 위치 및 ACVRL1 유전자 세부 정보 페이지.
이 기사에는 미국 국립 의학 도서관(미국 국립 의학 도서관)의 공공 도메인 텍스트가 포함되어 있습니다.
