EPS15
Substrat 15 receptora epidermnog faktora rasta jest protein koji je kod ljudi kodiran genom EPS15 sa hromosoma 1.[5]
Amiokiselininska sekvenca
[uredi | uredi izvor]Dužina polipeptidnog lanca je 896 aminokiselina, a molekulska težina 98.656 Da.[6]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MAAAAQLSLT | QLSSGNPVYE | KYYRQVDTGN | TGRVLASDAA | AFLKKSGLPD | ||||
| LILGKIWDLA | DTDGKGILNK | QEFFVALRLV | ACAQNGLEVS | LSSLNLAVPP | ||||
| PRFHDTSSPL | LISGTSAAEL | PWAVKPEDKA | KYDAIFDSLS | PVNGFLSGDK | ||||
| VKPVLLNSKL | PVDILGRVWE | LSDIDHDGML | DRDEFAVAMF | LVYCALEKEP | ||||
| VPMSLPPALV | PPSKRKTWVV | SPAEKAKYDE | IFLKTDKDMD | GFVSGLEVRE | ||||
| IFLKTGLPST | LLAHIWSLCD | TKDCGKLSKD | QFALAFHLIS | QKLIKGIDPP | ||||
| HVLTPEMIPP | SDRASLQKNI | IGSSPVADFS | AIKELDTLNN | EIVDLQREKN | ||||
| NVEQDLKEKE | DTIKQRTSEV | QDLQDEVQRE | NTNLQKLQAQ | KQQVQELLDE | ||||
| LDEQKAQLEE | QLKEVRKKCA | EEAQLISSLK | AELTSQESQI | STYEEELAKA | ||||
| REELSRLQQE | TAELEESVES | GKAQLEPLQQ | HLQDSQQEIS | SMQMKLMEMK | ||||
| DLENHNSQLN | WCSSPHSILV | NGATDYCSLS | TSSSETANLN | EHVEGQSNLE | ||||
| SEPIHQESPA | RSSPELLPSG | VTDENEVTTA | VTEKVCSELD | NNRHSKEEDP | ||||
| FNVDSSSLTG | PVADTNLDFF | QSDPFVGSDP | FKDDPFGKID | PFGGDPFKGS | ||||
| DPFASDCFFR | QSTDPFATSS | TDPFSAANNS | SITSVETLKH | NDPFAPGGTV | ||||
| VAASDSATDP | FASVFGNESF | GGGFADFSTL | SKVNNEDPFR | SATSSSVSNV | ||||
| VITKNVFEET | SVKSEDEPPA | LPPKIGTPTR | PCPLPPGKRS | INKLDSPDPF | ||||
| KLNDPFQPFP | GNDSPKEKDP | EIFCDPFTSA | TTTTNKEADP | SNFANFSAYP | ||||
| SEEDMIEWAK | RESEREEEQR | LARLNQQEQE | DLELAIALSK | SEISEA |
Funkcija
[uredi | uredi izvor]Ovaj gen kodira protein koji je dio EGFR puta. Protein je prisutan u jamicama obloženim klatrinom i uključen je u endocitozu EGF posredovanu receptorima. Značajno je da je ovaj gen preuređen sa HRX/ALL/MLL genom u akutnoj mijeloidnoj leukemiji. Uočene su alternativne transkripcijske varijante transkripta ovog gena, ali nisu detaljno okarakterisane.[7]
Modelni organizmi
[uredi | uredi izvor]| Svojstvo | Fenotip |
|---|---|
| Vijabilnost homozigota | Normalan |
| Studija recesivne letalnosti | Normalan |
| Plodnost | Normalan |
| Tjelesnsna težina | Normalan |
| Anksioznost otvorenog polja | Normalan |
| Neurološka procjena | Normalan |
| Snaga stiska | Normalan |
| Test vruće ploče | Normalan |
| Dismorfologija | Normalan |
| Indirektna kalorimetrija | Normalan |
| Test tolerancije glukoze | Normalan |
| Slušni odgovor moždanog stabla | Normalan |
| DEXA | Normalan |
| Radiografija | Normalan |
| Tjelesna temperatura | Normalan |
| Morfologija oka | Normalan |
| Klinička hemija | Normalan[8] |
| Hematologija | Nenormalan |
| Limfociti periferne krvi | Normalan |
| Mikronukleus test | Normalan |
| Težina srca | Normalan |
| Cjelovitost repne epiderme | Normalan |
| Histopatologija kože | Normalan |
| Histopatologija mozga | Normalan |
| Salmonella infekcija | Normalan[9] |
| Citrobacter infekcija | Normalan[10] |
| Svi testovi i alalize su prema:[11][12] |
Modelni organizmi bili su iz linije nokaut-miševa zvane Mtrf1ltm1a(KOMP)Wtsi[13][14] generirani po programu Međunarodnog konzorcija za nokaut-miševe — visokopropusnog projekta za mutagenezu, generiranje životinjskih modela, na Institutu Wellcome Trust Sanger, zainteresiranim naučnicima Mužjaci i ženke podvrgniti su standardiziranom fenotipskom pregledu za određivanje efekata delecija.[11][15] U studiji funkcije EPS15 korišteni su modelni organizmi. Provedeno je 26 testova na mutantnim miševima i uočena je jedna značajna abnormalnost: homozigotne mutantne životinje su imale smanjenu srednju korpuskularnu koncentraciju hemoglobina.
Interakcije
[uredi | uredi izvor]Pokazalo se da je EPS15 u interakciji sa:
Reference
[uredi | uredi izvor]- ^ a b c GRCh38: Ensembl release 89: ENSG00000085832 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028552 - 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.
- ^ Wong WT, Kraus MH, Carlomagno F, Zelano A, Druck T, Croce CM, Huebner K, Di Fiore PP (Jun 1994). "The human eps15 gene, encoding a tyrosine kinase substrate, is conserved in evolution and maps to 1p31-p32". Oncogene. 9 (6): 1591–7. PMID 8183552.
- ^ "UniProt, P42566" (jezik: engleski). Pristupljeno 25. 11. 2021.
- ^ "Entrez Gene: EPS15 epidermal growth factor receptor pathway substrate 15".
- ^ "Clinical chemistry data for Mtrf1l". Wellcome Trust Sanger Institute.
- ^ "Salmonella infection data for Mtrf1l". Wellcome Trust Sanger Institute.
- ^ "Citrobacter infection data for Mtrf1l". Wellcome Trust Sanger Institute.
- ^ a b Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88 (S248). doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
- ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
- ^ "International Knockout Mouse Consortium". Arhivirano s originala, 2. 6. 2012. Pristupljeno 25. 11. 2021.
- ^ "Mouse Genome Informatics".
- ^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
- ^ Schumacher C, Knudsen BS, Ohuchi T, Di Fiore PP, Glassman RH, Hanafusa H (juni 1995). "The SH3 domain of Crk binds specifically to a conserved proline-rich motif in Eps15 and Eps15R". J. Biol. Chem. 270 (25): 15341–7. doi:10.1074/jbc.270.25.15341. PMID 7797522.
- ^ Chen H, Fre S, Slepnev VI, Capua MR, Takei K, Butler MH, Di Fiore PP, De Camilli P (august 1998). "Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis". Nature. 394 (6695): 793–7. Bibcode:1998Natur.394..793C. doi:10.1038/29555. PMID 9723620. S2CID 4430975.
- ^ Bean AJ, Davanger S, Chou MF, Gerhardt B, Tsujimoto S, Chang Y (maj 2000). "Hrs-2 regulates receptor-mediated endocytosis via interactions with Eps15". J. Biol. Chem. 275 (20): 15271–8. doi:10.1074/jbc.275.20.15271. PMID 10809762.
- ^ Bache KG, Raiborg C, Mehlum A, Stenmark H (april 2003). "STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on early endosomes". J. Biol. Chem. 278 (14): 12513–21. doi:10.1074/jbc.M210843200. PMID 12551915.
- ^ Doria M, Salcini AE, Colombo E, Parslow TG, Pelicci PG, Di Fiore PP (decembar 1999). "The eps15 homology (EH) domain-based interaction between eps15 and hrb connects the molecular machinery of endocytosis to that of nucleocytosolic transport". J. Cell Biol. 147 (7): 1379–84. doi:10.1083/jcb.147.7.1379. PMC 2174238. PMID 10613896.
- ^ Nakashima S, Morinaka K, Koyama S, Ikeda M, Kishida M, Okawa K, Iwamatsu A, Kishida S, Kikuchi A (juli 1999). "Small G protein Ral and its downstream molecules regulate endocytosis of EGF and insulin receptors". EMBO J. 18 (13): 3629–42. doi:10.1093/emboj/18.13.3629. PMC 1171441. PMID 10393179.
Dopunska literatura
[uredi | uredi izvor]- Schumacher C, Knudsen BS, Ohuchi T, Di Fiore PP, Glassman RH, Hanafusa H (1995). "The SH3 domain of Crk binds specifically to a conserved proline-rich motif in Eps15 and Eps15R". J. Biol. Chem. 270 (25): 15341–7. doi:10.1074/jbc.270.25.15341. PMID 7797522.
- Bernard OA, Mauchauffe M, Mecucci C, Van den Berghe H, Berger R (1994). "A novel gene, AF-1p, fused to HRX in t(1;11)(p32;q23), is not related to AF-4, AF-9 nor ENL". Oncogene. 9 (4): 1039–45. PMID 8134107.
- Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (1996). "A "double adaptor" method for improved shotgun library construction". Anal. Biochem. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
- Benmerah A, Bégue B, Dautry-Varsat A, Cerf-Bensussan N (1996). "The ear of alpha-adaptin interacts with the COOH-terminal domain of the Eps 15 protein". J. Biol. Chem. 271 (20): 12111–6. doi:10.1074/jbc.271.20.12111. PMID 8662627.
- Matsuda M, Ota S, Tanimura R, Nakamura H, Matuoka K, Takenawa T, Nagashima K, Kurata T (1996). "Interaction between the amino-terminal SH3 domain of CRK and its natural target proteins". J. Biol. Chem. 271 (24): 14468–72. doi:10.1074/jbc.271.24.14468. PMID 8662907.
- van Delft S, Schumacher C, Hage W, Verkleij AJ, van Bergen en Henegouwen PM (1997). "Association and colocalization of Eps15 with adaptor protein-2 and clathrin". J. Cell Biol. 136 (4): 811–21. doi:10.1083/jcb.136.4.811. PMC 2132490. PMID 9049247.
- Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA (1997). "Large-scale concatenation cDNA sequencing". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
- Tebar F, Confalonieri S, Carter RE, Di Fiore PP, Sorkin A (1997). "Eps15 is constitutively oligomerized due to homophilic interaction of its coiled-coil region". J. Biol. Chem. 272 (24): 15413–8. doi:10.1074/jbc.272.24.15413. PMID 9182572.
- Salcini AE, Confalonieri S, Doria M, Santolini E, Tassi E, Minenkova O, Cesareni G, Pelicci PG, Di Fiore PP (1997). "Binding specificity and in vivo targets of the EH domain, a novel protein-protein interaction module". Genes Dev. 11 (17): 2239–49. doi:10.1101/gad.11.17.2239. PMC 275390. PMID 9303539.
- Cupers P, ter Haar E, Boll W, Kirchhausen T (1998). "Parallel dimers and anti-parallel tetramers formed by epidermal growth factor receptor pathway substrate clone 15". J. Biol. Chem. 272 (52): 33430–4. doi:10.1074/jbc.272.52.33430. PMID 9407139.
- Haffner C, Takei K, Chen H, Ringstad N, Hudson A, Butler MH, Salcini AE, Di Fiore PP, De Camilli P (1998). "Synaptojanin 1: localization on coated endocytic intermediates in nerve terminals and interaction of its 170 kDa isoform with Eps15". FEBS Lett. 419 (2–3): 175–80. doi:10.1016/S0014-5793(97)01451-8. PMID 9428629. S2CID 45186831.
- Benmerah A, Lamaze C, Bègue B, Schmid SL, Dautry-Varsat A, Cerf-Bensussan N (1998). "AP-2/Eps15 interaction is required for receptor-mediated endocytosis". J. Cell Biol. 140 (5): 1055–62. doi:10.1083/jcb.140.5.1055. PMC 2132690. PMID 9490719.
- de Beer T, Carter RE, Lobel-Rice KE, Sorkin A, Overduin M (1998). "Structure and Asn-Pro-Phe binding pocket of the Eps15 homology domain". Science. 281 (5381): 1357–60. Bibcode:1998Sci...281.1357D. doi:10.1126/science.281.5381.1357. PMID 9721102.
- Chen H, Fre S, Slepnev VI, Capua MR, Takei K, Butler MH, Di Fiore PP, De Camilli P (1998). "Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis". Nature. 394 (6695): 793–7. Bibcode:1998Natur.394..793C. doi:10.1038/29555. PMID 9723620. S2CID 4430975.
- Lewin DA, Sheff D, Ooi CE, Whitney JA, Yamamoto E, Chicione LM, Webster P, Bonifacino JS, Mellman I (1998). "Cloning, expression, and localization of a novel gamma-adaptin-like molecule". FEBS Lett. 435 (2–3): 263–8. doi:10.1016/S0014-5793(98)01083-7. PMID 9762922. S2CID 83518205.
- Sengar AS, Wang W, Bishay J, Cohen S, Egan SE (1999). "The EH and SH3 domain Ese proteins regulate endocytosis by linking to dynamin and Eps15". EMBO J. 18 (5): 1159–71. doi:10.1093/emboj/18.5.1159. PMC 1171207. PMID 10064583.
- Poupon V, Bègue B, Gagnon J, Dautry-Varsat A, Cerf-Bensussan N, Benmerah A (1999). "Molecular cloning and characterization of MT-ACT48, a novel mitochondrial acyl-CoA thioesterase". J. Biol. Chem. 274 (27): 19188–94. doi:10.1074/jbc.274.27.19188. PMID 10383425.
- Nakashima S, Morinaka K, Koyama S, Ikeda M, Kishida M, Okawa K, Iwamatsu A, Kishida S, Kikuchi A (1999). "Small G protein Ral and its downstream molecules regulate endocytosis of EGF and insulin receptors". EMBO J. 18 (13): 3629–42. doi:10.1093/emboj/18.13.3629. PMC 1171441. PMID 10393179.
- Stephens DJ, Banting G (1999). "Direct interaction of the trans-Golgi network membrane protein, TGN38, with the F-actin binding protein, neurabin". J. Biol. Chem. 274 (42): 30080–6. doi:10.1074/jbc.274.42.30080. PMID 10514494.