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SELE
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	1ESL, 1G1T, 4C16, 4CSY
Identifikatori
Aliasi	SELE
Vanjski ID-jevi	OMIM: 131210 MGI: 98278 HomoloGene: 389 GeneCards: SELE
Lokacija gena (čovjek)
Hrom.	Hromosom 1 (čovjek)
Kraj	169,764,705 bp
Lokacija gena (miš)
Hrom.	Hromosom 1 (miš)
Kraj	163,885,246 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• phospholipase binding; • oligosaccharide binding; • GO:0001948, GO:0016582 vezivanje za proteine; • transmembrane signaling receptor activity; • carbohydrate binding; • sialic acid binding; • vezivanje iona metala;
Ćelijska komponenta	• integral component of membrane; • membrana; • cortical cytoskeleton; • ćelijska membrana; • perinuklearno područje citoplazme; • Kaveole; • Lipidni splav; • clathrin-coated pit; • Vanćelijsko; • integral component of plasma membrane;
Biološki proces	• leukocyte cell-cell adhesion; • heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; • response to interleukin-1; • positive regulation of receptor internalization; • actin filament-based process; • leukocyte migration involved in inflammatory response; • activation of phospholipase C activity; • response to tumor necrosis factor; • response to lipopolysaccharide; • Ćelijska adhezija; • regulation of inflammatory response; • leukocyte tethering or rolling; • inflammatory response; • leukocyte migration; • calcium-mediated signaling;
	Izvori:Amigo / QuickGO
Ortolozi
	6401
	20339
	ENSG00000007908
	ENSMUSG00000026582
	P16581
	Q00690
	NM_000450
	NM_011345
	NP_000441
	NP_035475
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

E-selektin, znan i kao član E antigenolikih proteina porodice CD62 (CD62E), molekula 1 endotelno leukocitne adhhezije (ELAM-1) ili molekula 2 endolelnoleukocitnw ćelijske adhezuije (LECAM2), jest protein koji je kod ljudi kodiran genom SELE sa hromosoma 1. To je selektinska molekula ćelijske adhezije eksprimirana samo na endotelnim ćelijama aktiviranim citokinima. Kao i drugi selektini, ima važnu ulogu u upalama.^[5]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 610 aminokiselina, a molekulska težina 66.655 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
MIASQFLSAL	TLVLLIKESG	AWSYNTSTEA	MTYDEASAYC	QQRYTHLVAI
QNKEEIEYLN	SILSYSPSYY	WIGIRKVNNV	WVWVGTQKPL	TEEAKNWAPG
EPNNRQKDED	CVEIYIKREK	DVGMWNDERC	SKKKLALCYT	AACTNTSCSG
HGECVETINN	YTCKCDPGFS	GLKCEQIVNC	TALESPEHGS	LVCSHPLGNF
SYNSSCSISC	DRGYLPSSME	TMQCMSSGEW	SAPIPACNVV	ECDAVTNPAN
GFVECFQNPG	SFPWNTTCTF	DCEEGFELMG	AQSLQCTSSG	NWDNEKPTCK
AVTCRAVRQP	QNGSVRCSHS	PAGEFTFKSS	CNFTCEEGFM	LQGPAQVECT
TQGQWTQQIP	VCEAFQCTAL	SNPERGYMNC	LPSASGSFRY	GSSCEFSCEQ
GFVLKGSKRL	QCGPTGEWDN	EKPTCEAVRC	DAVHQPPKGL	VRCAHSPIGE
FTYKSSCAFS	CEEGFELHGS	TQLECTSQGQ	WTEEVPSCQV	VKCSSLAVPG
KINMSCSGEP	VFGTVCKFAC	PEGWTLNGSA	ARTCGATGHW	SGLLPTCEAP
TESNIPLVAG	LSAAGLSLLT	LAPFLLWLRK	CLRKAKKFVP	ASSCQSLESD
GSYQKPSYIL

Struktura

E selektin ima kasetnu strukturu: N-terminal, C-tip lektinskog domena, EGF (epidermni faktor rasta) sličan domen, šest jedinica Sushi domena (SCR ponavljanje), transmembranski domen (TM) i unutarćelijski citoplazmatski rep . Trodimenzijska struktura regiona koji se vezuje za ligand ljudskog E-selektina određena je pri rezoluciji 2,0 Å, 1994.^[7] Struktura otkriva ograničen kontakt između dva domena i koordinaciju Ca²⁺, koji nije predviđen kod ostalih lektina C-tipa. Analiza strukture/funkcije ukazuje na definiranu regiju i specifične bočne lance aminokiselina koji mogu biti uključeni u vezivanje liganda. E-selektin vezan za sialil-Lewis^X (SLe^X; NeuNAcα2,3Galβ1,4[Fucα1,3]GlcNAc) tetrasaharid riješen je u 2000.^[8]

Ligandi

E-selektin prepoznaje i vezuje se za sijaliirane ugljikohidrate na površinskim proteinima određenih leukocita. E-selektinske ligande eksprimiraju neutrofili, monociti, eozinofili, limfociti slični T-efektoru memorije i prirodne ćelije ubice. Svaki od ovih tipova ćelija nalazi se u akutnim i hroničnim upalnim mestima u vezi sa ekspresijom E-selektina, što implicira E-selektin u regrutaciji ovih ćelija na takva mesta upala. Ovi ugljikohidrati uključuju članove porodica Lewis X i Lewis A koji se nalaze na monocitiima, granulocitima, i T-limfocitima.^[9]

Glikoprotein ESL-1, na neutrofilima i mijeloidnim ćelijama, bio je prvi opisan kontrareceptor za E-selektin. To je varijanta FGF glikorceptora tirozin kinaze, što povećava mogućnost da je njegovo vezivanje za E-selektin uključeno u iniciranje signalizacije u vezanim ćelijama.

P-selektinski glikoproteinski ligand-1 (PSGL-1) izveden iz ljudskih neutrofila je također visoko efikasan ligand za E-selektin eksprimiran u endotelu pod protokom.^[10] Posreduje u kotrlanju leukocita na aktiviranom endotelu koji okružuje upaljeno tkivo.

I ESL-1 i PSGL-1 bi trebali nositi sialil Lewis a/x da bi vezali E/P-selektine.^[11]

Funkcija

Uloga u upalama

Tokom upala, E-selektin ima važnu ulogu u premještanja leukocita na mesto povrede. Lokalno oslobađanje citokina IL-1 i TNF-α it makrofaga u upaljenom tkivu indukuje prekomjernu ekspresiju E-selektina na endotelnim ćelijama obližnjih krvnih sudova. Leukociti u krvi koji eksprimiraju ispravan ligand će se vezati sa niskim afinitetom za E-selektin, također pod pritiskom stresa na smicanje protoka krvi, uzrokujući da se leukociti "kotrljaju" duž unutrašnje površine krvnog suda kako se stvaraju i prekidaju privremene interakcije.

Kako upalni odgovor napreduje, hemokini koje oslobađa oštećeno tkivo ulaze u krvne sudove i ktiviraju kotrljajuće leukocite, koji su sada u stanju da se čvrsto vežu za površinu endotela i počnu ulaziti u tkivo. P-selectin ima sličnu funkciju, ali se eksprimira na površini endotelne ćelije u roku od nekoliko minuta jer se pohranjuje unutar ćelije, a ne proizvodi po potrebi.^[9]

Uloga u kanceru

E-selektin je prvi put otkriven kao transmembranski receptor induciran u endotelnim ćelijama nakon upalne stimulacije koja je posredovala adheziju monocitnih ili HL60 leukemijskih ćelija.^[12]^[13] Ovo je dovelo do hipoteze da ćelije raka luče upalne citokine kao što su IL-1β ili TNFα da induciraju E-selektin na udaljenim metastatskim mjestima . Ova indukcija bi omogućila cirkulirajućim tumorskim ćelijama da se zaustave na stimuliranim mjestima, kotrljaju duž aktiviranog endotela, ekstravazatiraju i formiraju metastaze.^[14] Istraživanja su pokazala da vezivanje E-selektina za ćelije raka debelog crijeva korelira s povećanjem metastatskog potencijala,^[15] i da ćelije raka multiplih tipova tumora vezuju E-selektin, koristeći glikoprotein ili glikolipidne ligande koji se normalno eksprimiraju na imunskim ćelijama.^[16]^[17]^[18]^[19]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000007908 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000026582 - 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.
^ Collins T, Williams A, Johnston GI, Kim J, Eddy R, Shows T, Gimbrone MA, Bevilacqua MP (februar 1991). "Structure and chromosomal location of the gene for endothelial-leukocyte adhesion molecule 1". The Journal of Biological Chemistry. 266 (4): 2466–73. doi:10.1016/S0021-9258(18)52267-5. PMID 1703529.
^ "UniProt, P16581" (jezik: engleski). Pristupljeno 18. 12. 2021.
^ Graves BJ, Crowther RL, Chandran C, Rumberger JM, Li S, Huang KS, Presky DH, Familletti PC, Wolitzky BA, Burns DK (februar 1994). "Insight into E-selectin/ligand interaction from the crystal structure and mutagenesis of the lec/EGF domains". Nature. 367 (6463): 532–8. Bibcode:1994Natur.367..532G. doi:10.1038/367532a0. PMID 7509040. S2CID 4338500.
^ Somers WS, Tang J, Shaw GD, Camphausen RT (oktobar 2000). "Insights into the molecular basis of leukocyte tethering and rolling revealed by structures of P- and E-selectin bound to SLe(X) and PSGL-1". Cell. 103 (3): 467–79. doi:10.1016/S0092-8674(00)00138-0. PMID 11081633. S2CID 12719907.
^ ^a ^b Robbins SL, Cotran RS, Kumar V, Collins T (1999). Robbins pathologic basis of disease. Philadelphia: WB Saunders. ISBN 0-7216-7335-X.
^ Zou X, Shinde Patil VR, Dagia NM, Smith LA, Wargo MJ, Interliggi KA, Lloyd CM, Tees DF, Walcheck B, Lawrence MB, Goetz DJ (august 2005). "PSGL-1 derived from human neutrophils is a high-efficiency ligand for endothelium-expressed E-selectin under flow". American Journal of Physiology. Cell Physiology. 289 (2): C415-24. doi:10.1152/ajpcell.00289.2004. PMID 15814589.
^ Kannagi R, Izawa M, Koike T, Miyazaki K, Kimura N (maj 2004). "Carbohydrate-mediated cell adhesion in cancer metastasis and angiogenesis". Cancer Science. 95 (5): 377–84. doi:10.1111/j.1349-7006.2004.tb03219.x. PMID 15132763. S2CID 27761640.
^ Bevilacqua MP, Pober JS, Mendrick DL, Cotran RS, Gimbrone MA (decembar 1987). "Identification of an inducible endothelial-leukocyte adhesion molecule". Proceedings of the National Academy of Sciences of the United States of America. 84 (24): 9238–42. Bibcode:1987PNAS...84.9238B. doi:10.1073/pnas.84.24.9238. PMC 299728. PMID 2827173.
^ Walz G, Aruffo A, Kolanus W, Bevilacqua M, Seed B (novembar 1990). "Recognition by ELAM-1 of the sialyl-Lex determinant on myeloid and tumor cells". Science. 250 (4984): 1132–5. Bibcode:1990Sci...250.1132W. doi:10.1126/science.1701275. PMID 1701275.
^ Khatib AM, Kontogiannea M, Fallavollita L, Jamison B, Meterissian S, Brodt P (mart 1999). "Rapid induction of cytokine and E-selectin expression in the liver in response to metastatic tumor cells". Cancer Research. 59 (6): 1356–61. PMID 10096570.
^ Sawada R, Tsuboi S, Fukuda M (januar 1994). "Differential E-selectin-dependent adhesion efficiency in sublines of a human colon cancer exhibiting distinct metastatic potentials". The Journal of Biological Chemistry. 269 (2): 1425–31. doi:10.1016/S0021-9258(17)42275-7. PMID 7507108.
^ Dimitroff CJ, Lechpammer M, Long-Woodward D, Kutok JL (august 2004). "Rolling of human bone-metastatic prostate tumor cells on human bone marrow endothelium under shear flow is mediated by E-selectin". Cancer Research. 64 (15): 5261–9. doi:10.1158/0008-5472.CAN-04-0691. PMID 15289332. S2CID 11632075.
^ Laferrière J, Houle F, Huot J (2004). "Adhesion of HT-29 colon carcinoma cells to endothelial cells requires sequential events involving E-selectin and integrin beta4". Clinical & Experimental Metastasis. 21 (3): 257–64. doi:10.1023/B:CLIN.0000037708.09420.9a. PMID 15387376. S2CID 22354589.
^ Barthel SR, Hays DL, Yazawa EM, Opperman M, Walley KC, Nimrichter L, et al. (januar 2013). "Definition of molecular determinants of prostate cancer cell bone extravasation". Cancer Research. 73 (2): 942–52. doi:10.1158/0008-5472.CAN-12-3264. PMC 3548951. PMID 23149920.
^ Esposito M, Kang Y (februar 2014). "Targeting tumor-stromal interactions in bone metastasis". Pharmacology & Therapeutics. 141 (2): 222–33. doi:10.1016/j.pharmthera.2013.10.006. PMC 3947254. PMID 24140083.

Vanjski linkovi

E-Selectin na US National Library of Medicine Medical Subject Headings (MeSH)

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000007908 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000026582 - 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.

[pmid1703529-5] Collins T, Williams A, Johnston GI, Kim J, Eddy R, Shows T, Gimbrone MA, Bevilacqua MP (februar 1991). "Structure and chromosomal location of the gene for endothelial-leukocyte adhesion molecule 1". The Journal of Biological Chemistry. 266 (4): 2466–73. doi:10.1016/S0021-9258(18)52267-5. PMID 1703529.

[UniProt-6] "UniProt, P16581" (jezik: engleski). Pristupljeno 18. 12. 2021.

[pmid7509040-7] Graves BJ, Crowther RL, Chandran C, Rumberger JM, Li S, Huang KS, Presky DH, Familletti PC, Wolitzky BA, Burns DK (februar 1994). "Insight into E-selectin/ligand interaction from the crystal structure and mutagenesis of the lec/EGF domains". Nature. 367 (6463): 532–8. Bibcode:1994Natur.367..532G. doi:10.1038/367532a0. PMID 7509040. S2CID 4338500.

[pmid11081633-8] Somers WS, Tang J, Shaw GD, Camphausen RT (oktobar 2000). "Insights into the molecular basis of leukocyte tethering and rolling revealed by structures of P- and E-selectin bound to SLe(X) and PSGL-1". Cell. 103 (3): 467–79. doi:10.1016/S0092-8674(00)00138-0. PMID 11081633. S2CID 12719907.

[robspath-9] Robbins SL, Cotran RS, Kumar V, Collins T (1999). Robbins pathologic basis of disease. Philadelphia: WB Saunders. ISBN 0-7216-7335-X.

[pmid15814589-10] Zou X, Shinde Patil VR, Dagia NM, Smith LA, Wargo MJ, Interliggi KA, Lloyd CM, Tees DF, Walcheck B, Lawrence MB, Goetz DJ (august 2005). "PSGL-1 derived from human neutrophils is a high-efficiency ligand for endothelium-expressed E-selectin under flow". American Journal of Physiology. Cell Physiology. 289 (2): C415-24. doi:10.1152/ajpcell.00289.2004. PMID 15814589.

[pmid15132763-11] Kannagi R, Izawa M, Koike T, Miyazaki K, Kimura N (maj 2004). "Carbohydrate-mediated cell adhesion in cancer metastasis and angiogenesis". Cancer Science. 95 (5): 377–84. doi:10.1111/j.1349-7006.2004.tb03219.x. PMID 15132763. S2CID 27761640.

[12] Bevilacqua MP, Pober JS, Mendrick DL, Cotran RS, Gimbrone MA (decembar 1987). "Identification of an inducible endothelial-leukocyte adhesion molecule". Proceedings of the National Academy of Sciences of the United States of America. 84 (24): 9238–42. Bibcode:1987PNAS...84.9238B. doi:10.1073/pnas.84.24.9238. PMC 299728. PMID 2827173.

[13] Walz G, Aruffo A, Kolanus W, Bevilacqua M, Seed B (novembar 1990). "Recognition by ELAM-1 of the sialyl-Lex determinant on myeloid and tumor cells". Science. 250 (4984): 1132–5. Bibcode:1990Sci...250.1132W. doi:10.1126/science.1701275. PMID 1701275.

[14] Khatib AM, Kontogiannea M, Fallavollita L, Jamison B, Meterissian S, Brodt P (mart 1999). "Rapid induction of cytokine and E-selectin expression in the liver in response to metastatic tumor cells". Cancer Research. 59 (6): 1356–61. PMID 10096570.

[15] Sawada R, Tsuboi S, Fukuda M (januar 1994). "Differential E-selectin-dependent adhesion efficiency in sublines of a human colon cancer exhibiting distinct metastatic potentials". The Journal of Biological Chemistry. 269 (2): 1425–31. doi:10.1016/S0021-9258(17)42275-7. PMID 7507108.

[16] Dimitroff CJ, Lechpammer M, Long-Woodward D, Kutok JL (august 2004). "Rolling of human bone-metastatic prostate tumor cells on human bone marrow endothelium under shear flow is mediated by E-selectin". Cancer Research. 64 (15): 5261–9. doi:10.1158/0008-5472.CAN-04-0691. PMID 15289332. S2CID 11632075.

[17] Laferrière J, Houle F, Huot J (2004). "Adhesion of HT-29 colon carcinoma cells to endothelial cells requires sequential events involving E-selectin and integrin beta4". Clinical & Experimental Metastasis. 21 (3): 257–64. doi:10.1023/B:CLIN.0000037708.09420.9a. PMID 15387376. S2CID 22354589.

[18] Barthel SR, Hays DL, Yazawa EM, Opperman M, Walley KC, Nimrichter L, et al. (januar 2013). "Definition of molecular determinants of prostate cancer cell bone extravasation". Cancer Research. 73 (2): 942–52. doi:10.1158/0008-5472.CAN-12-3264. PMC 3548951. PMID 23149920.

[19] Esposito M, Kang Y (februar 2014). "Targeting tumor-stromal interactions in bone metastasis". Pharmacology & Therapeutics. 141 (2): 222–33. doi:10.1016/j.pharmthera.2013.10.006. PMC 3947254. PMID 24140083.

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p r u Proteini: Klasteri diferencijacije (također pogledati Lista ljudskih klastera diferencijacije)
1–50	CD1 a-c 1A 1B 1D 1E CD2 CD3 γ δ ε CD4 CD5 CD6 CD7 CD8 a CD9 CD10 CD11 a b c d CD13 CD14 CD15 CD16 A B CD18 CD19 CD20 CD21 CD22 CD23 CD24 CD25 CD26 CD27 CD28 CD29 CD30 CD31 CD32 A B CD33 CD34 CD35 CD36 CD37 CD38 CD39 CD40 CD41 CD42 a b c d CD43 CD44 CD45 CD46 CD47 CD48 CD49 a b c d e f CD50
51–100	CD51 CD52 CD53 CD54 CD55 CD56 CD57 CD58 CD59 CD61 CD62 E L P CD63 CD64 A B C CD66 a b c d e f CD68 CD69 CD70 CD71 CD72 CD73 CD74 CD78 CD79 a b CD80 CD81 CD82 CD83 CD84 CD85 a d e h j k CD86 CD87 CD88 CD89 CD90 CD91 - CD92 CD93 CD94 CD95 CD96 CD97 CD98 CD99 CD100
101–150	CD101 CD102 CD103 CD104 CD105 CD106 CD107 a b CD108 CD109 CD110 CD111 CD112 CD113 CD114 CD115 CD116 CD117 CD118 CD119 CD120 a b CD121 a b CD122 CD123 CD124 CD125 CD126 CD127 CD129 CD130 CD131 CD132 CD133 CD134 CD135 CD136 CD137 CD138 CD140b CD141 CD142 CD143 CD144 CD146 CD147 CD148 CD150
151–200	CD151 CD152 CD153 CD154 CD155 CD156 a b c CD157 CD158 (a d e i k) CD159 a c CD160 CD161 CD162 CD163 CD164 CD166 CD167 a b CD168 CD169 CD170 CD171 CD172 a b g CD174 CD177 CD178 CD179 a b CD180 CD181 CD182 CD183 CD184 CD185 CD186 CD191 CD192 CD193 CD194 CD195 CD196 CD197 CDw198 CDw199 CD200
201–250	CD201 CD202b CD204 CD205 CD206 CD207 CD208 CD209 CDw210 a b CD212 CD213a 1 2 CD217 CD218 (a b) CD220 CD221 CD222 CD223 CD224 CD225 CD226 CD227 CD228 CD229 CD230 CD233 CD234 CD235 a b CD236 CD238 CD239 CD240CE CD240D CD241 CD243 CD244 CD246 CD247 - CD248 CD249
251–300	CD252 CD253 CD254 CD256 CD257 CD258 CD261 CD262 CD263 CD264 CD265 CD266 CD267 CD268 CD269 CD271 CD272 CD273 CD274 CD275 CD276 CD278 CD279 CD280 CD281 CD282 CD283 CD284 CD286 CD288 CD289 CD290 CD292 CDw293 CD294 CD295 CD297 CD298 CD299
301–350	CD300A CD301 CD302 CD303 CD304 CD305 CD306 CD307 CD309 CD312 CD314 CD315 CD316 CD317 CD318 CD320 CD321 CD322 CD324 CD325 CD326 CD328 CD329 CD331 CD332 CD333 CD334 CD335 CD336 CD337 CD338 CD339 CD340 CD344 CD349 CD350

SELE