NOTCH2
Homologni protein 2 neurogenog lokusa notch znan i kao notch 2 jest protein koji je kod ljudi kodiran genom NOTCH2 sa hromosoma 1.[5]
NOTCH2 vezan je za Alagilleov[6] i Hajdu-Cheneyev sindrom.[7]
Aminokiselinska sekvenca
urediDužina polipeptidnog lanca je 2.471 aminokiselina, a molekulska težina 265.405 Da.[8]
10 | 20 | 30 | 40 | 50 | ||||
---|---|---|---|---|---|---|---|---|
MPALRPALLW | ALLALWLCCA | APAHALQCRD | GYEPCVNEGM | CVTYHNGTGY | ||||
CKCPEGFLGE | YCQHRDPCEK | NRCQNGGTCV | AQAMLGKATC | RCASGFTGED | ||||
CQYSTSHPCF | VSRPCLNGGT | CHMLSRDTYE | CTCQVGFTGK | ECQWTDACLS | ||||
HPCANGSTCT | TVANQFSCKC | LTGFTGQKCE | TDVNECDIPG | HCQHGGTCLN | ||||
LPGSYQCQCP | QGFTGQYCDS | LYVPCAPSPC | VNGGTCRQTG | DFTFECNCLP | ||||
GFEGSTCERN | IDDCPNHRCQ | NGGVCVDGVN | TYNCRCPPQW | TGQFCTEDVD | ||||
ECLLQPNACQ | NGGTCANRNG | GYGCVCVNGW | SGDDCSENID | DCAFASCTPG | ||||
STCIDRVASF | SCMCPEGKAG | LLCHLDDACI | SNPCHKGALC | DTNPLNGQYI | ||||
CTCPQGYKGA | DCTEDVDECA | MANSNPCEHA | GKCVNTDGAF | HCECLKGYAG | ||||
PRCEMDINEC | HSDPCQNDAT | CLDKIGGFTC | LCMPGFKGVH | CELEINECQS | ||||
NPCVNNGQCV | DKVNRFQCLC | PPGFTGPVCQ | IDIDDCSSTP | CLNGAKCIDH | ||||
PNGYECQCAT | GFTGVLCEEN | IDNCDPDPCH | HGQCQDGIDS | YTCICNPGYM | ||||
GAICSDQIDE | CYSSPCLNDG | RCIDLVNGYQ | CNCQPGTSGV | NCEINFDDCA | ||||
SNPCIHGICM | DGINRYSCVC | SPGFTGQRCN | IDIDECASNP | CRKGATCING | ||||
VNGFRCICPE | GPHHPSCYSQ | VNECLSNPCI | HGNCTGGLSG | YKCLCDAGWV | ||||
GINCEVDKNE | CLSNPCQNGG | TCDNLVNGYR | CTCKKGFKGY | NCQVNIDECA | ||||
SNPCLNQGTC | FDDISGYTCH | CVLPYTGKNC | QTVLAPCSPN | PCENAAVCKE | ||||
SPNFESYTCL | CAPGWQGQRC | TIDIDECISK | PCMNHGLCHN | TQGSYMCECP | ||||
PGFSGMDCEE | DIDDCLANPC | QNGGSCMDGV | NTFSCLCLPG | FTGDKCQTDM | ||||
NECLSEPCKN | GGTCSDYVNS | YTCKCQAGFD | GVHCENNINE | CTESSCFNGG | ||||
TCVDGINSFS | CLCPVGFTGS | FCLHEINECS | SHPCLNEGTC | VDGLGTYRCS | ||||
CPLGYTGKNC | QTLVNLCSRS | PCKNKGTCVQ | KKAESQCLCP | SGWAGAYCDV | ||||
PNVSCDIAAS | RRGVLVEHLC | QHSGVCINAG | NTHYCQCPLG | YTGSYCEEQL | ||||
DECASNPCQH | GATCSDFIGG | YRCECVPGYQ | GVNCEYEVDE | CQNQPCQNGG | ||||
TCIDLVNHFK | CSCPPGTRGL | LCEENIDDCA | RGPHCLNGGQ | CMDRIGGYSC | ||||
RCLPGFAGER | CEGDINECLS | NPCSSEGSLD | CIQLTNDYLC | VCRSAFTGRH | ||||
CETFVDVCPQ | MPCLNGGTCA | VASNMPDGFI | CRCPPGFSGA | RCQSSCGQVK | ||||
CRKGEQCVHT | ASGPRCFCPS | PRDCESGCAS | SPCQHGGSCH | PQRQPPYYSC | ||||
QCAPPFSGSR | CELYTAPPST | PPATCLSQYC | ADKARDGVCD | EACNSHACQW | ||||
DGGDCSLTME | NPWANCSSPL | PCWDYINNQC | DELCNTVECL | FDNFECQGNS | ||||
KTCKYDKYCA | DHFKDNHCDQ | GCNSEECGWD | GLDCAADQPE | NLAEGTLVIV | ||||
VLMPPEQLLQ | DARSFLRALG | TLLHTNLRIK | RDSQGELMVY | PYYGEKSAAM | ||||
KKQRMTRRSL | PGEQEQEVAG | SKVFLEIDNR | QCVQDSDHCF | KNTDAAAALL | ||||
ASHAIQGTLS | YPLVSVVSES | LTPERTQLLY | LLAVAVVIIL | FIILLGVIMA | ||||
KRKRKHGSLW | LPEGFTLRRD | ASNHKRREPV | GQDAVGLKNL | SVQVSEANLI | ||||
GTGTSEHWVD | DEGPQPKKVK | AEDEALLSEE | DDPIDRRPWT | QQHLEAADIR | ||||
RTPSLALTPP | QAEQEVDVLD | VNVRGPDGCT | PLMLASLRGG | SSDLSDEDED | ||||
AEDSSANIIT | DLVYQGASLQ | AQTDRTGEMA | LHLAARYSRA | DAAKRLLDAG | ||||
ADANAQDNMG | RCPLHAAVAA | DAQGVFQILI | RNRVTDLDAR | MNDGTTPLIL | ||||
AARLAVEGMV | AELINCQADV | NAVDDHGKSA | LHWAAAVNNV | EATLLLLKNG | ||||
ANRDMQDNKE | ETPLFLAARE | GSYEAAKILL | DHFANRDITD | HMDRLPRDVA | ||||
RDRMHHDIVR | LLDEYNVTPS | PPGTVLTSAL | SPVICGPNRS | FLSLKHTPMG | ||||
KKSRRPSAKS | TMPTSLPNLA | KEAKDAKGSR | RKKSLSEKVQ | LSESSVTLSP | ||||
VDSLESPHTY | VSDTTSSPMI | TSPGILQASP | NPMLATAAPP | APVHAQHALS | ||||
FSNLHEMQPL | AHGASTVLPS | VSQLLSHHHI | VSPGSGSAGS | LSRLHPVPVP | ||||
ADWMNRMEVN | ETQYNEMFGM | VLAPAEGTHP | GIAPQSRPPE | GKHITTPREP | ||||
LPPIVTFQLI | PKGSIAQPAG | APQPQSTCPP | AVAGPLPTMY | QIPEMARLPS | ||||
VAFPTAMMPQ | QDGQVAQTIL | PAYHPFPASV | GKYPTPPSQH | SYASSNAAER | ||||
TPSHSGHLQG | EHPYLTPSPE | SPDQWSSSSP | HSASDWSDVT | TSPTPGGAGG | ||||
GQRGPGTHMS | EPPHNNMQVY | A |
Funkcija
urediNotch 2 je član porodice notch. Članovi ove porodice transmembranskih proteina tipa 1 dijele strukturne karakteristike, uključujući vanćelijski domen koji se sastoji od višestrukih ponavljanja sličnih epidermnim faktorima rasta (EGF) i unutarćelijski domen koji se sastoji od više različitih tipova domena. Članovi porodice Notch imaju ulogu u raznim razvojnim procesima, kontrolišućirješenja o sudbini ćelije. Notch signalna mreža je evolucijski konzervirani međućelijski signalni put koji regulira interakcije između fizički susjednih ćelija. Kod Drosophila, interakcija Notch-a sa svojim ćelijskim ligandima (delta, serat) uspostavlja međućelijski signalni put koji ima ključnu ulogu u razvoju. Homolozi notch-liganda su također identifikovani kod ljudi, ali precizne interakcije između ovih liganada i ljudsjih homologa ostaju da se utvrde. Ovaj protein se cijepa u trans-Golgi mreži i edksprimira na površini ćelije kao heterodimer. Ovaj protein funkcionira kao receptor za ligande vezane za membranu i može imati ulogu u razvoju vaskularne mreže, bubrega i jetre.[9]
Pokazalo se da su mutacije unutar posljednjeg kodirajućeg egzona Notch2 koje uklanjaju PEST domen i izbjegavaju nonsens posredovani raspad iRNK glavni uzrok Hajdu–Cheneyevog sindroma.[10][11][12]
Interakcije
urediPokazalo se da NOTCH2 ima interakcije sa:
Reference
uredi- ^ a b c GRCh38: Ensembl release 89: ENSG00000134250 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027878 - 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.
- ^ Larsson C, Lardelli M, White I, Lendahl U (maj 1995). "The human NOTCH1, 2, and 3 genes are located at chromosome positions 9q34, 1p13-p11, and 19p13.2-p13.1 in regions of neoplasia-associated translocation". Genomics. 24 (2): 253–8. doi:10.1006/geno.1994.1613. PMID 7698746.
- ^ Samejima H, Torii C, Kosaki R, Kurosawa K, Yoshihashi H, Muroya K, Okamoto N, Watanabe Y, Kosho T, Kubota M, Matsuda O, Goto M, Izumi K, Takahashi T, Kosaki K (2007). "Screening for Alagille syndrome mutations in the JAG1 and NOTCH2 genes using denaturing high-performance liquid chromatography". Genet. Test. 11 (3): 216–27. doi:10.1089/gte.2006.0519. PMID 17949281.
- ^ Simpson MA, Irving MD, Asilmaz E, Gray MJ, Dafou D, Elmslie FV, Mansour S, Holder SE, Brain CE, Burton BK, Kim KH, Pauli RM, Aftimos S, Stewart H, Kim CA, Holder-Espinasse M, Robertson SP, Drake WM, Trembath RC (6. 3. 2011). "Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss". Nature Genetics. 43 (4): 303–5. doi:10.1038/ng.779. PMID 21378985. S2CID 205357391.
- ^ "UniProt, Q04721" (jezik: eng.). Pristupljeno 3. 12. 2021.CS1 održavanje: nepoznati jezik (link)
- ^ "Entrez Gene: NOTCH2 Notch homolog 2 (Drosophila)".
- ^ Simpson MA, Irving MD, Asilmaz E, Gray MJ, Dafou D, Elmslie FV, Mansour S, Holder SE, et al. (2011). "Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss". Nature Genetics. 43 (4): 303–305. doi:10.1038/ng.779. PMID 21378985. S2CID 205357391.
- ^ Isidor B, Lindenbaum P, Pichon O, Bézieau S, Dina C, Jacquemont S, Martin-Coignard D, Thauvin-Robinet C, Le Merrer M, Mandel JL, David A, Faivre L, Cormier-Daire V, Redon R, Le Caignec C (2011). "Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis". Nature Genetics. 43 (4): 306–8. doi:10.1038/ng.778. PMID 21378989. S2CID 205357384.
- ^ Majewski J, Schwartzentruber JA, Caqueret A, Patry L, Marcadier J, Fryns JP, Boycott KM, Ste-Marie LG, McKiernan FE, Marik I, Van Esch H, Michaud JL, Samuels ME (2011). "Mutations in NOTCH2 in families with Hajdu-Cheney syndrome". Hum Mutat. 32 (10): 1114–7. doi:10.1002/humu.21546. PMID 21681853. S2CID 39342783.
- ^ a b Shimizu K, Chiba S, Saito T, Kumano K, Takahashi T, Hirai H (juli 2001). "Manic fringe and lunatic fringe modify different sites of the Notch2 extracellular region, resulting in different signaling modulation". J. Biol. Chem. 276 (28): 25753–8. doi:10.1074/jbc.M103473200. PMID 11346656.
- ^ a b c Shimizu K, Chiba S, Hosoya N, Kumano K, Saito T, Kurokawa M, Kanda Y, Hamada Y, Hirai H (septembar 2000). "Binding of Delta1, Jagged1, and Jagged2 to Notch2 rapidly induces cleavage, nuclear translocation, and hyperphosphorylation of Notch2". Mol. Cell. Biol. 20 (18): 6913–22. doi:10.1128/mcb.20.18.6913-6922.2000. PMC 88767. PMID 10958687.
- ^ Blaumueller CM, Qi H, Zagouras P, Artavanis-Tsakonas S (juli 1997). "Intracellular cleavage of Notch leads to a heterodimeric receptor on the plasma membrane". Cell. 90 (2): 281–91. doi:10.1016/s0092-8674(00)80336-0. PMID 9244302. S2CID 16544864.
- ^ Espinosa L, Inglés-Esteve J, Aguilera C, Bigas A (august 2003). "Phosphorylation by glycogen synthase kinase-3 beta down-regulates Notch activity, a link for Notch and Wnt pathways". J. Biol. Chem. 278 (34): 32227–35. doi:10.1074/jbc.M304001200. PMID 12794074.
- ^ Shimizu K, Chiba S, Kumano K, Hosoya N, Takahashi T, Kanda Y, Hamada Y, Yazaki Y, Hirai H (novembar 1999). "Mouse jagged1 physically interacts with notch2 and other notch receptors. Assessment by quantitative methods". J. Biol. Chem. 274 (46): 32961–9. doi:10.1074/jbc.274.46.32961. PMID 10551863.
Dopunska literatura
uredi- Artavanis-Tsakonas S, Rand MD, Lake RJ (1999). "Notch signaling: cell fate control and signal integration in development". Science. 284 (5415): 770–6. Bibcode:1999Sci...284..770A. doi:10.1126/science.284.5415.770. PMID 10221902. S2CID 16790253.
- Kojika S, Griffin JD (2001). "Notch receptors and hematopoiesis". Exp. Hematol. 29 (9): 1041–52. doi:10.1016/S0301-472X(01)00676-2. PMID 11532344.
- Schwarzmeier JD, Hubmann R, Düchler M, Jäger U, Shehata M (2005). "Regulation of CD23 expression by Notch2 in B-cell chronic lymphocytic leukemia". Leuk. Lymphoma. 46 (2): 157–65. doi:10.1080/10428190400010742. PMID 15621797. S2CID 36863790.
- Stifani S, Blaumueller CM, Redhead NJ, Hill RE, Artavanis-Tsakonas S (1993). "Human homologs of a Drosophila Enhancer of split gene product define a novel family of nuclear proteins". Nat. Genet. 2 (2): 119–27. doi:10.1038/ng1092-119. PMID 1303260. S2CID 32142845.
- Katsanis N, Fitzgibbon J, Fisher EM (1996). "Paralogy mapping: identification of a region in the human MHC triplicated onto human chromosomes 1 and 9 allows the prediction and isolation of novel PBX and NOTCH loci". Genomics. 35 (1): 101–8. doi:10.1006/geno.1996.0328. PMID 8661110.
- Hsieh JJ, Nofziger DE, Weinmaster G, Hayward SD (1997). "Epstein-Barr virus immortalization: Notch2 interacts with CBF1 and blocks differentiation". J. Virol. 71 (3): 1938–45. doi:10.1128/JVI.71.3.1938-1945.1997. PMC 191274. PMID 9032325.
- Blaumueller CM, Qi H, Zagouras P, Artavanis-Tsakonas S (1997). "Intracellular cleavage of Notch leads to a heterodimeric receptor on the plasma membrane". Cell. 90 (2): 281–91. doi:10.1016/S0092-8674(00)80336-0. PMID 9244302. S2CID 16544864.
- Bigas A, Martin DI, Milner LA (1998). "Notch1 and Notch2 inhibit myeloid differentiation in response to different cytokines". Mol. Cell. Biol. 18 (4): 2324–33. doi:10.1128/mcb.18.4.2324. PMC 121486. PMID 9528802.
- Berezovska O, Xia MQ, Hyman BT (1998). "Notch is expressed in adult brain, is coexpressed with presenilin-1, and is altered in Alzheimer disease". J. Neuropathol. Exp. Neurol. 57 (8): 738–45. doi:10.1097/00005072-199808000-00003. PMID 9720489.
- Gray GE, Mann RS, Mitsiadis E, Henrique D, Carcangiu ML, Banks A, Leiman J, Ward D, Ish-Horowitz D, Artavanis-Tsakonas S (1999). "Human ligands of the Notch receptor". Am. J. Pathol. 154 (3): 785–94. doi:10.1016/S0002-9440(10)65325-4. PMC 1866435. PMID 10079256.
- Shimizu K, Chiba S, Kumano K, Hosoya N, Takahashi T, Kanda Y, Hamada Y, Yazaki Y, Hirai H (2000). "Mouse jagged1 physically interacts with notch2 and other notch receptors. Assessment by quantitative methods". J. Biol. Chem. 274 (46): 32961–9. doi:10.1074/jbc.274.46.32961. PMID 10551863.
- Shimizu K, Chiba S, Hosoya N, Kumano K, Saito T, Kurokawa M, Kanda Y, Hamada Y, Hirai H (2000). "Binding of Delta1, Jagged1, and Jagged2 to Notch2 rapidly induces cleavage, nuclear translocation, and hyperphosphorylation of Notch2". Mol. Cell. Biol. 20 (18): 6913–22. doi:10.1128/MCB.20.18.6913-6922.2000. PMC 88767. PMID 10958687.
- Wu L, Aster JC, Blacklow SC, Lake R, Artavanis-Tsakonas S, Griffin JD (2001). "MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors". Nat. Genet. 26 (4): 484–9. doi:10.1038/82644. PMID 11101851. S2CID 23335042.
- Sriuranpong V, Borges MW, Ravi RK, Arnold DR, Nelkin BD, Baylin SB, Ball DW (2001). "Notch signaling induces cell cycle arrest in small cell lung cancer cells". Cancer Res. 61 (7): 3200–5. PMID 11306509.
- Shimizu K, Chiba S, Saito T, Kumano K, Takahashi T, Hirai H (2001). "Manic fringe and lunatic fringe modify different sites of the Notch2 extracellular region, resulting in different signaling modulation". J. Biol. Chem. 276 (28): 25753–8. doi:10.1074/jbc.M103473200. PMID 11346656.
- Saxena MT, Schroeter EH, Mumm JS, Kopan R (2001). "Murine notch homologs (N1-4) undergo presenilin-dependent proteolysis". J. Biol. Chem. 276 (43): 40268–73. doi:10.1074/jbc.M107234200. PMID 11518718.
- Inglés-Esteve J, Espinosa L, Milner LA, Caelles C, Bigas A (2002). "Phosphorylation of Ser2078 modulates the Notch2 function in 32D cell differentiation". J. Biol. Chem. 276 (48): 44873–80. doi:10.1074/jbc.M104703200. PMID 11577080.