EPS15

EPS15
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	1C07, 1EH2, 1F8H, 1FF1, 2IV9, 2JXC, 4RH5, 4RH9, 4RHG, 4S0G, 5JP2
Identifikatori
Aliasi	EPS15
Vanjski ID-jevi	OMIM: 600051 MGI: 104583 HomoloGene: 128359 GeneCards: EPS15
Lokacija gena (čovjek)
Hrom.	Hromosom 1 (čovjek)
Kraj	51,519,266 bp
Lokacija gena (miš)
Hrom.	Hromosom 4 (miš)
Kraj	109,245,014 bp
Obrazac RNK ekspresije
	; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• calcium ion binding; • SH3 domain binding; • vezivanje iona metala; • polyubiquitin modification-dependent protein binding; • GO:0001948, GO:0016582 vezivanje za proteine; • cadherin binding; • vezivanje identičnih proteina; • cargo receptor activity;
Ćelijska komponenta	• endozom; • clathrin coat of coated pit; • early endosome membrane; • membrana; • intracellular membrane-bounded organelle; • ćelijska membrana; • aggresome; • ciliary membrane; • clathrin-coated pit; • AP-2 adaptor complex; • clathrin-coated vesicle; • basal plasma membrane; • apical plasma membrane; • early endosome; • citoplazma; • citosol; • sinapsa; • postsynapse; • glutamatergic synapse;
Biološki proces	• negative regulation of epidermal growth factor receptor signaling pathway; • Endocitoza; • epidermal growth factor receptor signaling pathway; • vesicle organization; • Golgi to endosome transport; • clathrin coat assembly; • protein transport; • viral entry into host cell; • receptor-mediated endocytosis of virus by host cell; • Ćelijska proliferacija; • positive regulation of receptor recycling; • regulation of cell population proliferation; • endocytic recycling; • membrane organization; • GO:0022415 viral process; • GO:0015915 transport; • postsynaptic neurotransmitter receptor internalization;
	Izvori:Amigo / QuickGO
Ortolozi
	2060
	13858
	ENSG00000085832
	ENSMUSG00000028552
	P42566
	P42567
	NM_001159969; NM_001981
	NM_001159964; NM_007943
	NP_001153441; NP_001972
	NP_001153436; NP_031969
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

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]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

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]

Fenotip *Eps15* nokaut-miševa
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 Mtrf1l^{tm1a(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.

Vanjski linkovi[uredi | uredi izvor]

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000085832 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000028552 - 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.

[pmid8183552-5] 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-6] "UniProt, P42566" (jezik: engleski). Pristupljeno 25. 11. 2021.

[entrez-7] "Entrez Gene: EPS15 epidermal growth factor receptor pathway substrate 15".

[Clinical_chemistry-8] "Clinical chemistry data for Mtrf1l". Wellcome Trust Sanger Institute.

[''Salmonella''_infection-9] "Salmonella infection data for Mtrf1l". Wellcome Trust Sanger Institute.

[''Citrobacter''_infection-10] "Citrobacter infection data for Mtrf1l". Wellcome Trust Sanger Institute.

[mgp_reference-11] 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.

[12] Mouse Resources Portal, Wellcome Trust Sanger Institute.

[allele_ref-13] "International Knockout Mouse Consortium". Arhivirano s originala, 2. 6. 2012. Pristupljeno 25. 11. 2021.

[mgi_allele_ref-14] "Mouse Genome Informatics".

[pmid21722353-15] 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.

[pmid7797522-16] 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.

[pmid9723620-17] 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.

[pmid10809762-18] 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.

[pmid12551915-19] 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.

[pmid10613896-20] 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.

[pmid10393179-21] 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.

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