Kaspaza-8 Dostupne strukture PDB Pretraga ortologa:PDBe RCSB Spisak PDB ID kodova 1F9E ,1I4E ,1QDU ,1QTN ,2C2Z ,2FUN ,2K7Z ,2Y1L ,3H11 ,3KJN ,3KJQ ,4JJ7 ,4PRZ ,4PS1 ,4ZBW
Identifikatori Aliasi CASP8 Vanjski ID-jevi OMIM :601763 MGI :1261423 HomoloGene :7657 GeneCards :CASP8 Ortolozi Vrste Čovjek Miš Entrez Ensembl UniProt RefSeq (mRNK) RefSeq (bjelančevina) Lokacija (UCSC) Chr 2: 201.23 – 201.29 Mb Chr 1: 58.83 – 58.89 Mb PubMed pretraga[ 3] [ 4] Wikipodaci
Kaspaza-8 jekaspazni protein, kodiranCASP8 genom. To jestproteinski enzim koji je kodljudi kodiran genom sahromosoma 2 . Najvjerovatnije djeluje nakaspazu-3 .
CASP8 ortolozi [ 5] sisara za koje su dostupni potpuni podaci ogenomu . Ovi jedinstveni ortolozi su takođe prisutni upticama .
Dužinapolipeptidnog lanca je 479aminokiselina , amolekulska težina 55.391Da .ref name="OrthoMaM"/>
10 20 30 40 50 MDFSRNLYDI GEQLDSEDLA SLKFLSLDYI PQRKQEPIKD ALMLFQRLQE KRMLEESNLS FLKELLFRIN RLDLLITYLN TRKEEMEREL QTPGRAQISA YRVMLYQISE EVSRSELRSF KFLLQEEISK CKLDDDMNLL DIFIEMEKRV ILGEGKLDIL KRVCAQINKS LLKIINDYEE FSKERSSSLE GSPDEFSNGE ELCGVMTISD SPREQDSESQ TLDKVYQMKS KPRGYCLIIN NHNFAKAREK VPKLHSIRDR NGTHLDAGAL TTTFEELHFE IKPHDDCTVE QIYEILKIYQ LMDHSNMDCF ICCILSHGDK GIIYGTDGQE APIYELTSQF TGLKCPSLAG KPKVFFIQAC QGDNYQKGIP VETDSEEQPY LEMDLSSPQT RYIPDEADFL LGMATVNNCV SYRNPAEGTW YIQSLCQSLR ERCPRGDDIL TILTEVNYEV SNKDDKKNMG KQMPQPTFTL RKKLVFPSD
GenCASP8 kodira člana porodiceproteaza cistein -asparaginska kiselina (kaspaza ). Sekvencna aktivacija kaspaza ima centralnu ulogu u fazi izvršenja ćelijskihapoptoza . Kaspaze postoje kao neaktivniproenzimi sastavljeni odprodomena , velike i maled proteaznepodjedinice . Aktivacija kaspaza zahtijevaproteolitsku obradu konzerviranih unutrašnjih asparaginskih ostataka da bi se dobioheterodimerni enzim koji se sastoji od velike i male podjedinice. Ovaj protein je uključen uprogramiranu smrt ćelije izazvanuFas-om i raznim apoptotskim stimulansima. Domen efektora smrti nalikN-terminalnom FADD ovog proteina sugerira da on može stupiti u interakciju sa proteinom FADD koji djeluje na Fas. Ovaj protein je otkriven u nerastvorljivoj frakciji zahvaćene regije mozga kod pacijenata saHuntingtonovom bolešću , ali ne i kod onih iz normalne kontrole, što implicira ulogu uneurodegenerativnim bolestima . Opisane su mnoge alternativno sprerađenevarijante transkripta koje kodiraju različiteizoforme , iako za sve varijante nisu određene sekvence pune dužine..[ 6]
Vrlo rijedakgenetički poremećaj imunskog sistema također može biti uzrokovan mutacijama ovog gena. Ova bolest, nazvana CEDS, znači "stanje nedostatka kaspaze osam". CEDS ima karakteristike sličneALPS , još jednu genetičku bolestapoptoze , uz dodatakimunodeficijentnog fenotipa . Dakle, kliničke manifestacije uključujusplenomegaliju ilimfadenopatiju , pored rekurentnih sinopulmonalnihinfekcija , rekurentnemukokutane herpesvirusne , uporne bradavice i infekcijemolluscum contagiosum hipogamaglobulinemija . Ponekad postoji limfocitna infiltrativna bolest uparenhimskim organima, aliautoimunost je minimalna ilimfom nije uočen kod pacijenata sa CEDS-om. CEDS se nasljeđuje na autosomno recesivan način.[ 7] paradoks jer se kaspaza-8 smatrala uglavnomproapoptotskom proteazom , koja je uglavnom bila uključena u transdukciju signala izreceptora faktora nekroze tumora porodične receptore smrti kao što je Fas. Defekt u aktivaciji limfocita i zaštitnoi imunosti sugerira da kaspaza-8 ima dodatnu signalnu ulogu ulimfocitima . Dalji rad je otkrio da je kaspaza-8 neophodna za indukcijufaktora transkripcije „jedarni faktor κB” (NF-κB ), nakon stimulacije prekoantigenog receptora, Fc receptora ili Toll-likog receptora 4 u T, B iprirodne ćelije ubice .[ 7]
Biohemijski je utvrđeno da kaspaza-8 ulazi u kompleks inhibitoraNF-κB kinaza (IKK) sa uzvodnim adapterskim kompleksom Bcl10-MALT1 (mukoza-povezano limfno tkivo) koji su bili ključni za indukcija jedarne translokacije NF-κB. Štaviše, biohemijski oblik kaspaze-8 razlikovao se u dva puta. Za put smrti,zimogen kaspaze-8 cijepa se na podjedinice koje se sastavljaju kako bi formirale zreli, visoko aktivni kaspazni heterotetramer, dok se za put aktivacije čini da zimogen ostaje netaknut možda da bi ograničio njegovu proteolitsku funkciju, ali poboljšao njegovu sposobnost kao adapter proteina.[ 7]
Pokazalo se da kaspaza-8reaguje sa:
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Šablon:Fas apoptozni signalni put
