ADAM12
Protein 12 koji sadrži domen dezintegrina i metaloproteinaze (ranije Meltrin) je enzim koji je kod ljudi kodiran genom ADAM12.[5][6] ADAM12 ima dvije splajs varijante: ADAM12-L, dugi oblik, ima transmembransku regiju i ADAM12-S, kraća varijanta, je rastvorljiva i nema transmembranski i citoplazmatski domen.[7]
Funkcija
Ovaj gen kodira člana proteinske porodice ADAM (dizintegrin i metaloproteinaza). Članovi ove porodice su proteini usidreni u membrani, strukturno srodni zmijskim otrovima disintegrin, i uključeni su u različite biološke procese koji uključuju interakcije ćelija-ćelija i ćelija-matriks, uključujući oplodnju, razvoj mišića i neurogenezu. Ovaj gen ima dva alternativno spojena transkripta: kraći sekretovani oblik i duži membranski vezan oblik. Utvrđeno je da kraći oblik stimuliše miogenezu.[8]
Klinički značaj
ADAM 12, metaloproteinaza koja veže protein-3 koji veže faktor rasta inzulina (IGFBP-3), čini se da je efikasan rani marker Downovog sindroma. Smanjeni nivoi ADAM 12 mogu se otkriti u slučajevima trisomije 21 već u 8. do 10. sedmici trudnoće. Nivoi ADAM 12 i PAPP-A u majčinom serumu u 8. do 9. sedmici trudnoće u kombinaciji s dobi majke dali su stopu detekcije Downovog sindroma od 91% uz stopu lažno pozitivnih rezultata od 5%. Kada su dodani podaci o njušnoj translucenciji iz približno 12. sedmice trudnoće, ovo je povećalo stopu detekcije na 97%.[9]
ADAM12 je također povezan s razvojem patoloških promjena kod različitih kancera, hipertenzije, jetrene fibrogeneze i astme.[10] Kod astme, ADAM12 je pojačano izražen u plućnom epitelu kao odgovor na TNF-alfa.[11]
U studiji provedenoj na oko 1200 osoba s izuzetno visokom inteligencijom (IQ oko 170), varijante gena bile su povezane s visokim IQ-om u usporedbi s općom populacijom.[12]
Interakcije
Pokazano je da je ADAM12 u interakciji sa:
Reference
- ^ a b c GRCh38: Ensembl release 89: ENSG00000148848 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000054555 - Ensembl, maj 2017
- ^ "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.
- ^ Gilpin BJ, Loechel F, Mattei MG, Engvall E, Albrechtsen R, Wewer UM (Feb 1998). "A novel, secreted form of human ADAM 12 (meltrin alpha) provokes myogenesis in vivo". J. Biol. Chem. 273 (1): 157–66. doi:10.1074/jbc.273.1.157. PMID 9417060.
- ^ Kveiborg M, Albrechtsen R, Couchman JR, Wewer UM (Jun 2008). "Cellular roles of ADAM12 in health and disease". Int. J. Biochem. Cell Biol. 40 (9): 1685–702. doi:10.1016/j.biocel.2008.01.025. PMID 18342566.
- ^ Yagami-Hiromasa T, Sato T, Kurisaki T, Kamijo K, Nabeshima Y, Fujisawa-Sehara A (1995). "A metalloprotease-disintegrin participating in myoblast fusion". Nature. 377 (6550): 652–6. Bibcode:1995Natur.377..652Y. doi:10.1038/377652a0. PMID 7566181. S2CID 4348744.
- ^ "Entrez Gene: ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha)".
- ^ Danforth's Obstetrics and Gynecology, 10th Edition; Copyright ©2008 Lippincott Williams & Wilkins; Chapter 7: Prenatal Diagnosis, Page 113
- ^ Nyren-Erickson EK, Jones JM, Srivastava DK, Mallik S (2013). "A disintegrin and metalloproteinase-12 (ADAM12): function, roles in disease progression, and clinical implications". Biochim. Biophys. Acta. 1830 (10): 4445–55. doi:10.1016/j.bbagen.2013.05.011. PMC 3740046. PMID 23680494.
- ^ Estrella C, Rocks N, Paulissen G, Quesada-Calvo F, Noel A, Vilain E, Lassalle P, Tillie-Leblond I, Cataldo D, Gosset P (2009). "Role of a disintegrin and metalloprotease-12 in neutrophil recruitment induced by airway epithelium". Am. J. Respir. Cell Mol. Biol. 41 (4): 449–58. doi:10.1165/rcmb.2008-0124OC. hdl:2268/5767. PMID 19213876.
- ^ Dzirasa, Kafui (2. 8. 2017). "A brilliant approach to study the basis of intelligence?". Science Translational Medicine (jezik: engleski). 9 (401). doi:10.1126/scitranslmed.aao0978. ISSN 1946-6234. S2CID 44125138.
- ^ Galliano MF, Huet C, Frygelius J, Polgren A, Wewer UM, Engvall E (maj 2000). "Binding of ADAM12, a marker of skeletal muscle regeneration, to the muscle-specific actin-binding protein, alpha -actinin-2, is required for myoblast fusion". J. Biol. Chem. 275 (18): 13933–9. doi:10.1074/jbc.275.18.13933. PMID 10788519.
- ^ Shi Z, Xu W, Loechel F, Wewer UM, Murphy LJ (Jun 2000). "ADAM 12, a disintegrin metalloprotease, interacts with insulin-like growth factor-binding protein-3". J. Biol. Chem. 275 (24): 18574–80. doi:10.1074/jbc.M002172200. PMID 10849447.
- ^ Loechel F, Fox JW, Murphy G, Albrechtsen R, Wewer UM (Nov 2000). "ADAM 12-S cleaves IGFBP-3 and IGFBP-5 and is inhibited by TIMP-3". Biochem. Biophys. Res. Commun. 278 (3): 511–5. Bibcode:2000BBRC..278..511L. doi:10.1006/bbrc.2000.3835. PMID 11095942.
- ^ Kang Q, Cao Y, Zolkiewska A (Jul 2001). "Direct interaction between the cytoplasmic tail of ADAM 12 and the Src homology 3 domain of p85alpha activates phosphatidylinositol 3-kinase in C2C12 cells". J. Biol. Chem. 276 (27): 24466–72. doi:10.1074/jbc.M101162200. PMID 11313349.
Dodatno štivo
- Kang Q, Cao Y, Zolkiewska A (2001). "Direct interaction between the cytoplasmic tail of ADAM 12 and the Src homology 3 domain of p85alpha activates phosphatidylinositol 3-kinase in C2C12 cells". J. Biol. Chem. 276 (27): 24466–72. doi:10.1074/jbc.M101162200. PMID 11313349.
- Loechel F, Gilpin BJ, Engvall E, Albrechtsen R, Wewer UM (1998). "Human ADAM 12 (meltrin alpha) is an active metalloprotease". J. Biol. Chem. 273 (27): 16993–7. doi:10.1074/jbc.273.27.16993. PMID 9642263.
- Howard L, Nelson KK, Maciewicz RA, Blobel CP (1999). "Interaction of the metalloprotease disintegrins MDC9 and MDC15 with two SH3 domain-containing proteins, endophilin I and SH3PX1". J. Biol. Chem. 274 (44): 31693–9. doi:10.1074/jbc.274.44.31693. PMID 10531379.
- Galliano MF, Huet C, Frygelius J, Polgren A, Wewer UM, Engvall E (2000). "Binding of ADAM12, a marker of skeletal muscle regeneration, to the muscle-specific actin-binding protein, alpha -actinin-2, is required for myoblast fusion". J. Biol. Chem. 275 (18): 13933–9. doi:10.1074/jbc.275.18.13933. PMID 10788519.
- Iba K, Albrechtsen R, Gilpin B, Fröhlich C, Loechel F, Zolkiewska A, Ishiguro K, Kojima T, Liu W, Langford JK, Sanderson RD, Brakebusch C, Fässler R, Wewer UM (2000). "The cysteine-rich domain of human ADAM 12 supports cell adhesion through syndecans and triggers signaling events that lead to beta1 integrin-dependent cell spreading". J. Cell Biol. 149 (5): 1143–56. doi:10.1083/jcb.149.5.1143. PMC 2174829. PMID 10831617.
- Shi Z, Xu W, Loechel F, Wewer UM, Murphy LJ (2000). "ADAM 12, a disintegrin metalloprotease, interacts with insulin-like growth factor-binding protein-3". J. Biol. Chem. 275 (24): 18574–80. doi:10.1074/jbc.M002172200. PMID 10849447.
- Eto K, Puzon-McLaughlin W, Sheppard D, Sehara-Fujisawa A, Zhang XP, Takada Y (2001). "RGD-independent binding of integrin alpha9beta1 to the ADAM-12 and -15 disintegrin domains mediates cell-cell interaction". J. Biol. Chem. 275 (45): 34922–30. doi:10.1074/jbc.M001953200. PMID 10944520.
- Loechel F, Fox JW, Murphy G, Albrechtsen R, Wewer UM (2001). "ADAM 12-S cleaves IGFBP-3 and IGFBP-5 and is inhibited by TIMP-3". Biochem. Biophys. Res. Commun. 278 (3): 511–5. Bibcode:2000BBRC..278..511L. doi:10.1006/bbrc.2000.3835. PMID 11095942.
- Suzuki A, Kadota N, Hara T, Nakagami Y, Izumi T, Takenawa T, Sabe H, Endo T (2000). "Meltrin alpha cytoplasmic domain interacts with SH3 domains of Src and Grb2 and is phosphorylated by v-Src". Oncogene. 19 (51): 5842–50. doi:10.1038/sj.onc.1203986. PMID 11127814.
- Kawaguchi N, Xu X, Tajima R, Kronqvist P, Sundberg C, Loechel F, Albrechtsen R, Wewer UM (2002). "ADAM 12 protease induces adipogenesis in transgenic mice". Am. J. Pathol. 160 (5): 1895–903. doi:10.1016/S0002-9440(10)61136-4. PMC 1850877. PMID 12000741.
- Cao Y, Kang Q, Zhao Z, Zolkiewska A (2002). "Intracellular processing of metalloprotease disintegrin ADAM12". J. Biol. Chem. 277 (29): 26403–11. doi:10.1074/jbc.M110814200. PMID 12000744.
- Abram CL, Seals DF, Pass I, Salinsky D, Maurer L, Roth TM, Courtneidge SA (2003). "The adaptor protein fish associates with members of the ADAMs family and localizes to podosomes of Src-transformed cells". J. Biol. Chem. 278 (19): 16844–51. doi:10.1074/jbc.M300267200. PMID 12615925.
- Le Pabic H, Bonnier D, Wewer UM, Coutand A, Musso O, Baffet G, Clément B, Théret N (2003). "ADAM12 in human liver cancers: TGF-beta-regulated expression in stellate cells is associated with matrix remodeling". Hepatology. 37 (5): 1056–66. doi:10.1053/jhep.2003.50205. PMID 12717386. S2CID 32722392.
- Kawaguchi N, Sundberg C, Kveiborg M, Moghadaszadeh B, Asmar M, Dietrich N, Thodeti CK, Nielsen FC, Möller P, Mercurio AM, Albrechtsen R, Wewer UM (2004). "ADAM12 induces actin cytoskeleton and extracellular matrix reorganization during early adipocyte differentiation by regulating beta1 integrin function". J. Cell Sci. 116 (Pt 19): 3893–904. doi:10.1242/jcs.00699. PMID 12915587.
- Mori S, Tanaka M, Nanba D, Nishiwaki E, Ishiguro H, Higashiyama S, Matsuura N (2003). "PACSIN3 binds ADAM12/meltrin alpha and up-regulates ectodomain shedding of heparin-binding epidermal growth factor-like growth factor". J. Biol. Chem. 278 (46): 46029–34. doi:10.1074/jbc.M306393200. PMID 12952982.
- Laigaard J, Sørensen T, Fröhlich C, Pedersen BN, Christiansen M, Schiøtt K, Uldbjerg N, Albrechtsen R, Clausen HV, Ottesen B, Wewer UM (2004). "ADAM12: a novel first-trimester maternal serum marker for Down syndrome". Prenat. Diagn. 23 (13): 1086–91. doi:10.1002/pd.762. PMID 14691998. S2CID 32888570.
Vanjski linkovi
- The MEROPS online database for peptidases and their inhibitors: M12.212[mrtav link]
- ADAM12 on the [Atlas of Genetics and Cytogenetics in Oncology and Haematology
- Lokacija ljudskog genoma ADAM12 i stranica sa detaljima o genu ADAM12 u UCSC Genome Browseru.
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