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
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

2OO4

Identifikatori
AliasiNOTCH2
Vanjski ID-jeviOMIM: 600275 MGI: 97364 HomoloGene: 7865 GeneCards: NOTCH2
Lokacija gena (čovjek)
Hromosom 1 (čovjek)
Hrom.Hromosom 1 (čovjek)[1]
Hromosom 1 (čovjek)
Genomska lokacija za NOTCH2
Genomska lokacija za NOTCH2
Bend1p12Početak119,911,553 bp[1]
Kraj120,100,779 bp[1]
Lokacija gena (miš)
Hromosom 3 (miš)
Hrom.Hromosom 3 (miš)[2]
Hromosom 3 (miš)
Genomska lokacija za NOTCH2
Genomska lokacija za NOTCH2
Bend3 F2.2|3 42.42 cMPočetak97,920,843 bp[2]
Kraj98,057,677 bp[2]
Obrazac RNK ekspresije




Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija calcium ion binding
GO:0001948, GO:0016582 protein binding
signaling receptor activity
Ćelijska komponenta citoplazma
integral component of membrane
endoplasmic reticulum membrane
membrana
Golđijeva membrana
receptor complex
Ćelijska membrana
integral component of plasma membrane
Nukleoplazma
extracellular region
cell surface
Jedro
Biološki proces Notch signaling pathway
Ćelijska diferencijacija
Hematopoeza
pulmonary valve morphogenesis
GO:0009373 regulation of transcription, DNA-templated
positive regulation of Ras protein signal transduction
negative regulation of apoptotic process
marginal zone B cell differentiation
transcription, DNA-templated
nervous system development
stem cell population maintenance
multicellular organism development
atrial septum morphogenesis
GO:0090343, GO:0090342 regulation of developmental process
bone remodeling
animal organ morphogenesis
transcription initiation from RNA polymerase II promoter
Notch signaling involved in heart development
GO:0097285 Apoptoza
cell fate determination
intracellular receptor signaling pathway
negative regulation of gene expression
negative regulation of growth rate
positive regulation of ERK1 and ERK2 cascade
regulation of osteoclast development
positive regulation of keratinocyte proliferation
regulation of actin cytoskeleton reorganization
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_001200001
NM_024408

NM_010928

RefSeq (bjelančevina)

NP_001186930
NP_077719

NP_035058

Lokacija (UCSC)Chr 1: 119.91 – 120.1 MbChr 3: 97.92 – 98.06 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

NOTCH2 vezan je za Alagilleov[6] i Hajdu-Cheneyev sindrom.[7]

Aminokiselinska sekvenca uredi

Dužina polipeptidnog lanca je 2.471 aminokiselina, a molekulska težina 265.405 Da.[8]

1020304050
MPALRPALLWALLALWLCCAAPAHALQCRDGYEPCVNEGMCVTYHNGTGY
CKCPEGFLGEYCQHRDPCEKNRCQNGGTCVAQAMLGKATCRCASGFTGED
CQYSTSHPCFVSRPCLNGGTCHMLSRDTYECTCQVGFTGKECQWTDACLS
HPCANGSTCTTVANQFSCKCLTGFTGQKCETDVNECDIPGHCQHGGTCLN
LPGSYQCQCPQGFTGQYCDSLYVPCAPSPCVNGGTCRQTGDFTFECNCLP
GFEGSTCERNIDDCPNHRCQNGGVCVDGVNTYNCRCPPQWTGQFCTEDVD
ECLLQPNACQNGGTCANRNGGYGCVCVNGWSGDDCSENIDDCAFASCTPG
STCIDRVASFSCMCPEGKAGLLCHLDDACISNPCHKGALCDTNPLNGQYI
CTCPQGYKGADCTEDVDECAMANSNPCEHAGKCVNTDGAFHCECLKGYAG
PRCEMDINECHSDPCQNDATCLDKIGGFTCLCMPGFKGVHCELEINECQS
NPCVNNGQCVDKVNRFQCLCPPGFTGPVCQIDIDDCSSTPCLNGAKCIDH
PNGYECQCATGFTGVLCEENIDNCDPDPCHHGQCQDGIDSYTCICNPGYM
GAICSDQIDECYSSPCLNDGRCIDLVNGYQCNCQPGTSGVNCEINFDDCA
SNPCIHGICMDGINRYSCVCSPGFTGQRCNIDIDECASNPCRKGATCING
VNGFRCICPEGPHHPSCYSQVNECLSNPCIHGNCTGGLSGYKCLCDAGWV
GINCEVDKNECLSNPCQNGGTCDNLVNGYRCTCKKGFKGYNCQVNIDECA
SNPCLNQGTCFDDISGYTCHCVLPYTGKNCQTVLAPCSPNPCENAAVCKE
SPNFESYTCLCAPGWQGQRCTIDIDECISKPCMNHGLCHNTQGSYMCECP
PGFSGMDCEEDIDDCLANPCQNGGSCMDGVNTFSCLCLPGFTGDKCQTDM
NECLSEPCKNGGTCSDYVNSYTCKCQAGFDGVHCENNINECTESSCFNGG
TCVDGINSFSCLCPVGFTGSFCLHEINECSSHPCLNEGTCVDGLGTYRCS
CPLGYTGKNCQTLVNLCSRSPCKNKGTCVQKKAESQCLCPSGWAGAYCDV
PNVSCDIAASRRGVLVEHLCQHSGVCINAGNTHYCQCPLGYTGSYCEEQL
DECASNPCQHGATCSDFIGGYRCECVPGYQGVNCEYEVDECQNQPCQNGG
TCIDLVNHFKCSCPPGTRGLLCEENIDDCARGPHCLNGGQCMDRIGGYSC
RCLPGFAGERCEGDINECLSNPCSSEGSLDCIQLTNDYLCVCRSAFTGRH
CETFVDVCPQMPCLNGGTCAVASNMPDGFICRCPPGFSGARCQSSCGQVK
CRKGEQCVHTASGPRCFCPSPRDCESGCASSPCQHGGSCHPQRQPPYYSC
QCAPPFSGSRCELYTAPPSTPPATCLSQYCADKARDGVCDEACNSHACQW
DGGDCSLTMENPWANCSSPLPCWDYINNQCDELCNTVECLFDNFECQGNS
KTCKYDKYCADHFKDNHCDQGCNSEECGWDGLDCAADQPENLAEGTLVIV
VLMPPEQLLQDARSFLRALGTLLHTNLRIKRDSQGELMVYPYYGEKSAAM
KKQRMTRRSLPGEQEQEVAGSKVFLEIDNRQCVQDSDHCFKNTDAAAALL
ASHAIQGTLSYPLVSVVSESLTPERTQLLYLLAVAVVIILFIILLGVIMA
KRKRKHGSLWLPEGFTLRRDASNHKRREPVGQDAVGLKNLSVQVSEANLI
GTGTSEHWVDDEGPQPKKVKAEDEALLSEEDDPIDRRPWTQQHLEAADIR
RTPSLALTPPQAEQEVDVLDVNVRGPDGCTPLMLASLRGGSSDLSDEDED
AEDSSANIITDLVYQGASLQAQTDRTGEMALHLAARYSRADAAKRLLDAG
ADANAQDNMGRCPLHAAVAADAQGVFQILIRNRVTDLDARMNDGTTPLIL
AARLAVEGMVAELINCQADVNAVDDHGKSALHWAAAVNNVEATLLLLKNG
ANRDMQDNKEETPLFLAAREGSYEAAKILLDHFANRDITDHMDRLPRDVA
RDRMHHDIVRLLDEYNVTPSPPGTVLTSALSPVICGPNRSFLSLKHTPMG
KKSRRPSAKSTMPTSLPNLAKEAKDAKGSRRKKSLSEKVQLSESSVTLSP
VDSLESPHTYVSDTTSSPMITSPGILQASPNPMLATAAPPAPVHAQHALS
FSNLHEMQPLAHGASTVLPSVSQLLSHHHIVSPGSGSAGSLSRLHPVPVP
ADWMNRMEVNETQYNEMFGMVLAPAEGTHPGIAPQSRPPEGKHITTPREP
LPPIVTFQLIPKGSIAQPAGAPQPQSTCPPAVAGPLPTMYQIPEMARLPS
VAFPTAMMPQQDGQVAQTILPAYHPFPASVGKYPTPPSQHSYASSNAAER
TPSHSGHLQGEHPYLTPSPESPDQWSSSSPHSASDWSDVTTSPTPGGAGG
GQRGPGTHMSEPPHNNMQVYA

Funkcija uredi

Notch 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 uredi

Pokazalo se da NOTCH2 ima interakcije sa:

Reference uredi

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000134250 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027878 - Ensembl, maj 2017
  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.
  5. ^ 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.
  6. ^ 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.
  7. ^ 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.
  8. ^ "UniProt, Q04721" (jezik: eng.). Pristupljeno 3. 12. 2021.CS1 održavanje: nepoznati jezik (link)
  9. ^ "Entrez Gene: NOTCH2 Notch homolog 2 (Drosophila)".
  10. ^ 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.
  11. ^ 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.
  12. ^ 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.
  13. ^ 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.
  14. ^ 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.
  15. ^ 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.
  16. ^ 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.
  17. ^ 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

Vanjski linkovi uredi

Šablon:Notch signalni put