ADAM15
Protein 15 koji sadrži domen dezintegrina i metaloproteinaze je enzim koji je kod ljudi [[kodon|kodiran genom ADAM15.[5]
Aminokiselinska sekvenca
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MRLALLWALG | LLGAGSPLPS | WPLPNIGGTE | EQQAESEKAP | REPLEPQVLQ | ||||
| DDLPISLKKV | LQTSLPEPLR | IKLELDGDSH | ILELLQNREL | VPGRPTLVWY | ||||
| QPDGTRVVSE | GHTLENCCYQ | GRVRGYAGSW | VSICTCSGLR | GLVVLTPERS | ||||
| YTLEQGPGDL | QGPPIISRIQ | DLHLPGHTCA | LSWRESVHTQ | KPPEHPLGQR | ||||
| HIRRRRDVVT | ETKTVELVIV | ADHSEAQKYR | DFQHLLNRTL | EVALLLDTFF | ||||
| RPLNVRVALV | GLEAWTQRDL | VEISPNPAVT | LENFLHWRRA | HLLPRLPHDS | ||||
| AQLVTGTSFS | GPTVGMAIQN | SICSPDFSGG | VNMDHSTSIL | GVASSIAHEL | ||||
| GHSLGLDHDL | PGNSCPCPGP | APAKTCIMEA | STDFLPGLNF | SNCSRRALEK | ||||
| ALLDGMGSCL | FERLPSLPPM | AAFCGNMFVE | PGEQCDCGFL | DDCVDPCCDS | ||||
| LTCQLRPGAQ | CASDGPCCQN | CQLRPSGWQC | RPTRGDCDLP | EFCPGDSSQC | ||||
| PPDVSLGDGE | PCAGGQAVCM | HGRCASYAQQ | CQSLWGPGAQ | PAAPLCLQTA | ||||
| NTRGNAFGSC | GRNPSGSYVS | CTPRDAICGQ | LQCQTGRTQP | LLGSIRDLLW | ||||
| ETIDVNGTEL | NCSWVHLDLG | SDVAQPLLTL | PGTACGPGLV | CIDHRCQRVD | ||||
| LLGAQECRSK | CHGHGVCDSN | RHCYCEEGWA | PPDCTTQLKA | TSSLTTGLLL | ||||
| SLLVLLVLVM | LGASYWYRAR | LHQRLCQLKG | PTCQYRAAQS | GPSERPGPPQ | ||||
| RALLARGTKQ | ASALSFPAPP | SRPLPPDPVS | KRLQAELADR | PNPPTRPLPA | ||||
| DPVVRSPKSQ | GPAKPPPPRK | PLPADPQGRC | PSGDLPGPGA | GIPPLVVPSR | ||||
| PAPPPPTVSS | LYL |
Funkcija
Protein kodiran ovim genom je član porodice proteina ADAM (disintegrin i metaloproteinaza). Članovi porodice ADAM su transmembranski glikoproteini tipa I za koje se zna da su uključeni u adheziju ćelija i proteolitaku ektodomensku obradu citokina i molekula adhezije. Ovaj protein sadrži više funkcionalnih domena, uključujući domen metaloproteinaze koji veže cink, domen sličan disintegrinu, kao i domen sličan EGF-u. Putem svog disintegrinolikog domena, ovaj protein specifično interraguje sa lancem integrina beta, beta 3. Također interraguje sa protein-tirozin-kinazama iz porodiceSrc na način koji zavisi o fosforilaciji, što ukazuje na to da ovaj protein može funkcionisati u ćelijskoj adheziji, kao i u ćelijskoj signalizaciji. Uočeno je više alternativno prerađennih varijanti transkripta koje kodiraju različite izoforme.[6]
Klinički značaj
Artritis
ADAM15 je povezan s nizom bolesti, a najnovije s reumatoidnim artritisom gdje je potreban za aktivaciju puteva FAK i Src za stvaranje otpornosti na apoptozu kao odgovor na apoptotičku signalizaciju ili stanični stres ref name="pmid23918525">Böhm BB, Freund I, Krause K, Kinne RW, Burkhardt H (novembar 2013). "ADAM15 adds to apoptosis resistance of synovial fibroblasts by modulating focal adhesion kinase signaling". Arthritis Rheum. 65 (11): 2826–34. doi:10.1002/art.38109. PMID 23918525.</ref> ADAM15 također ima antiapoptotozni učinak kod osteoartritisnih hondrocita.[7]
Precizna uloga ADAM15 u raku još uvijek nije jasna, ali metalloprotein je povezan s nizom različitih kancerogenih bolesti kao što je rak dojke gdje je ekspresija proteina povećana u tkivima karcinoma in situ, invazivnog karcinoma i metastatskog raka dojke.[8] Pored toga, alternativne splajsing varijantne forme ADAM15 su također bile povezane s različitom prognozom kod 48 pacijenata oboljelih od raka dojke na osnovu njihovih nivoa ekspresije.[9] Također je pokazano da ADAM15 ima ulogu u raku prostate ponovo kroz povećanu ekspresiju u neoplastičnim i metastatskim tkivima u poređenju s normalnim tkivom prostate[8], a također i kroz modulaciju interakcija epitelnih ćelija i tumorskih ćelija.[10]
Interakcije
Pokazano je da ADAM15 interraguje sa:
Također je pokazano da alternativno prerađene izoforme pokazuju različite preferencijalne interakcije s proteinima koji sadrže SH3 domen.[9][13]
Reference
- ^ a b c GRCh38: Ensembl release 89: ENSG00000143537 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028041 - 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.
- ^ Zhang XP, Kamata T, Yokoyama K, Puzon-McLaughlin W, Takada Y (april 1998). "Specific interaction of the recombinant disintegrin-like domain of MDC-15 (metargidin, ADAM-15) with integrin alphavbeta3". J Biol Chem. 273 (13): 7345–50. doi:10.1074/jbc.273.13.7345. PMID 9516430.
- ^ "Entrez Gene: ADAM15 ADAM metallopeptidase domain 15 (metargidin)".
- ^ Böhm B, Hess S, Krause K, Schirner A, Ewald W, Aigner T, Burkhardt H (maj 2010). "ADAM15 exerts an antiapoptotic effect on osteoarthritic chondrocytes via up-regulation of the X-linked inhibitor of apoptosis". Arthritis Rheum. 62 (5): 1372–82. doi:10.1002/art.27387. PMID 20213810.
- ^ a b Kuefer R, Day KC, Kleer CG, Sabel MS, Hofer MD, Varambally S, Zorn CS, Chinnaiyan AM, Rubin MA, Day ML (april 2006). "ADAM15 disintegrin is associated with aggressive prostate and breast cancer disease". Neoplasia. 8 (4): 319–29. doi:10.1593/neo.05682. PMC 1600681. PMID 16756724.
- ^ a b Zhong JL, Poghosyan Z, Pennington CJ, Scott X, Handsley MM, Warn A, Gavrilovic J, Honert K, Krüger A, Span PN, Sweep FC, Edwards DR (mart 2008). "Distinct functions of natural ADAM-15 cytoplasmic domain variants in human mammary carcinoma". Mol. Cancer Res. 6 (3): 383–94. doi:10.1158/1541-7786.MCR-07-2028. PMID 18296648.
- ^ Najy AJ, Day KC, Day ML (februar 2008). "ADAM15 supports prostate cancer metastasis by modulating tumor cell-endothelial cell interaction". Cancer Res. 68 (4): 1092–9. doi:10.1158/0008-5472.CAN-07-2432. PMID 18281484.
- ^ a b c Poghosyan Z, Robbins SM, Houslay MD, Webster A, Murphy G, Edwards DR (februar 2002). "Phosphorylation-dependent interactions between ADAM15 cytoplasmic domain and Src family protein-tyrosine kinases". J. Biol. Chem. 277 (7): 4999–5007. doi:10.1074/jbc.M107430200. PMID 11741929.
- ^ a b Howard L, Nelson KK, Maciewicz RA, Blobel CP (oktobar 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.
- ^ Kleino I, Ortiz RM, Yritys M, Huovila AP, Saksela K (novembar 2009). "Alternative splicing of ADAM15 regulates its interactions with cellular SH3 proteins". J. Cell. Biochem. 108 (4): 877–85. doi:10.1002/jcb.22317. PMID 19718658. S2CID 25997734.
Dodatni izvori
- Primakoff P, Myles DG (2000). "The ADAM gene family: surface proteins with adhesion and protease activity". Trends Genet. 16 (2): 83–7. doi:10.1016/S0168-9525(99)01926-5. PMID 10652535.
- Takagi J (2002). "[First atomic view of alpha V beta 3 integrin extracellular domain]". Tanpakushitsu Kakusan Koso. 47 (2): 153–9. PMID 11840679.
- Krätzschmar J, Lum L, Blobel CP (1996). "Metargidin, a membrane-anchored metalloprotease-disintegrin protein with an RGD integrin binding sequence". J. Biol. Chem. 271 (9): 4593–6. doi:10.1074/jbc.271.9.4593. PMID 8617717.
- Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
- McKie N, Edwards T, Dallas DJ, et al. (1997). "Expression of members of a novel membrane linked metalloproteinase family (ADAM) in human articular chondrocytes". Biochem. Biophys. Res. Commun. 230 (2): 335–9. Bibcode:1997BBRC..230..335M. doi:10.1006/bbrc.1996.5957. PMID 9016778.
- Herren B, Raines EW, Ross R (1997). "Expression of a disintegrin-like protein in cultured human vascular cells and in vivo". FASEB J. 11 (2): 173–80. doi:10.1096/fasebj.11.2.9039960. PMID 9039960. S2CID 9206855.
- Nath D, Slocombe PM, Stephens PE, et al. (1999). "Interaction of metargidin (ADAM-15) with alphavbeta3 and alpha5beta1 integrins on different haemopoietic cells". J. Cell Sci. 112 (4): 579–87. doi:10.1242/jcs.112.4.579. PMID 9914169.
- 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.
- Kärkkäinen I, Karhu R, Huovila AP (2000). "Assignment of the ADAM15 gene to human chromosome band 1q21.3 by in situ hybridization". Cytogenet. Cell Genet. 88 (3–4): 206–7. doi:10.1159/000015549. PMID 10828588. S2CID 42541340.
- Seldin MF, Hirohata S, Apte SS (2000). "Chromosomal mapping of Adam9, Adam15 and Adam21". Matrix Biol. 19 (2): 185–7. doi:10.1016/S0945-053X(00)00062-7. PMID 10842103.
- Poghosyan Z, Robbins SM, Houslay MD, et al. (2002). "Phosphorylation-dependent interactions between ADAM15 cytoplasmic domain and Src family protein-tyrosine kinases". J. Biol. Chem. 277 (7): 4999–5007. doi:10.1074/jbc.M107430200. PMID 11741929.
- Arndt M, Lendeckel U, Röcken C, et al. (2002). "Altered expression of ADAMs (A Disintegrin And Metalloproteinase) in fibrillating human atria". Circulation. 105 (6): 720–5. doi:10.1161/hc0602.103639. PMID 11839628.
- Eto K, Huet C, Tarui T, et al. (2002). "Functional classification of ADAMs based on a conserved motif for binding to integrin alpha 9beta 1: implications for sperm-egg binding and other cell interactions". J. Biol. Chem. 277 (20): 17804–10. doi:10.1074/jbc.M200086200. PMID 11882657.
- Martin J, Eynstone LV, Davies M, et al. (2002). "The role of ADAM 15 in glomerular mesangial cell migration". J. Biol. Chem. 277 (37): 33683–9. doi:10.1074/jbc.M200988200. PMID 12091380.
- Ham C, Levkau B, Raines EW, Herren B (2002). "ADAM15 is an adherens junction molecule whose surface expression can be driven by VE-cadherin". Exp. Cell Res. 279 (2): 239–47. doi:10.1006/excr.2002.5606. PMID 12243749.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Abram CL, Seals DF, Pass I, et al. (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.
Vanjski linkovi
- The MEROPS online database for peptidases and their inhibitors: M12.215[mrtav link]
- Lokacija ljudskog genoma ADAM15 i stranica sa detaljima o genu ADAM15 u UCSC Genome Browseru.
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