Kaspaza-8

S Wikipedije, slobodne enciklopedije
Kaspaza-8
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

1F9E, 1I4E, 1QDU, 1QTN, 2C2Z, 2FUN, 2K7Z, 2Y1L, 3H11, 3KJN, 3KJQ, 4JJ7, 4PRZ, 4PS1, 4ZBW

Identifikatori
AliasiCASP8
Vanjski ID-jeviOMIM: 601763 MGI: 1261423 HomoloGene: 7657 GeneCards: CASP8
Lokacija gena (čovjek)
Hromosom 2 (čovjek)
Hrom.Hromosom 2 (čovjek)[1]
Hromosom 2 (čovjek)
Genomska lokacija za Kaspaza-8
Genomska lokacija za Kaspaza-8
Bend2q33.1Početak201,233,443 bp[1]
Kraj201,287,711 bp[1]
Lokacija gena (miš)
Hromosom 1 (miš)
Hrom.Hromosom 1 (miš)[2]
Hromosom 1 (miš)
Genomska lokacija za Kaspaza-8
Genomska lokacija za Kaspaza-8
Bend1 C1.3|1 29.19 cMPočetak58,834,533 bp[2]
Kraj58,886,662 bp[2]
Obrazac RNK ekspresije


Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija• death effector domain binding
• cysteine-type peptidase activity
• cysteine-type endopeptidase activity involved in apoptotic signaling pathway
• scaffold protein binding
• GO:0001948, GO:0016582 vezivanje za proteine
• vezivanje identičnih proteina
• cysteine-type endopeptidase activity involved in apoptotic process
• cysteine-type endopeptidase activity
• hydrolase activity
• ubiquitin protein ligase binding
• GO:0070122 peptidase activity
• cysteine-type endopeptidase activity involved in execution phase of apoptosis
• death receptor binding
• tumor necrosis factor receptor binding
• GO:0032403 protein-containing complex binding
Ćelijska komponenta• cell body
• citosol
• CD95 death-inducing signaling complex
• ripoptosome
• nukleoplazma
• mitochondrial outer membrane
• death-inducing signaling complex
• Lipidni splav
• neuron projection
• citoskelet
• citoplazma
• mitohondrija
• jedro
• GO:0009327 makromolekulani kompleks
Biološki proces• regulation of apoptotic process
• response to estradiol
• activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
• GO:1904576 response to antibiotic
• regulation of tumor necrosis factor-mediated signaling pathway
• positive regulation of macrophage differentiation
• GO:1904579 cellular response to organic cyclic compound
• natural killer cell activation
• negative regulation of I-kappaB kinase/NF-kappaB signaling
• TRAIL-activated apoptotic signaling pathway
• Proteoliza
• macrophage differentiation
• TRIF-dependent toll-like receptor signaling pathway
• response to tumor necrosis factor
• B cell activation
• cell surface receptor signaling pathway
• response to lipopolysaccharide
• cellular response to mechanical stimulus
• activation of cysteine-type endopeptidase activity
• positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
• death-inducing signaling complex assembly
• positive regulation of proteolysis
• positive regulation of I-kappaB kinase/NF-kappaB signaling
• apoptotic signaling pathway
• response to cold
• regulation of extrinsic apoptotic signaling pathway via death domain receptors
• GO:0022415 viral process
• response to ethanol
• response to cobalt ion
• activation of cysteine-type endopeptidase activity involved in apoptotic process
• proteolysis involved in cellular protein catabolic process
• syncytiotrophoblast cell differentiation involved in labyrinthine layer development
• nucleotide-binding oligomerization domain containing signaling pathway
• T cell activation
• suppression by virus of host cysteine-type endopeptidase activity involved in apoptotic process
• GO:0097285 apoptoza
• extrinsic apoptotic signaling pathway
• negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
• regulation of necroptotic process
• execution phase of apoptosis
• toll-like receptor 3 signaling pathway
• positive regulation of neuron death
• extrinsic apoptotic signaling pathway via death domain receptors
• positive regulation of interleukin-1 beta production
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez

841

12370

Ensembl

ENSG00000064012

ENSMUSG00000026029

UniProt

Q14790

O89110

RefSeq (mRNK)
NM_001080124
NM_001080125
NM_001228
NM_033355
NM_033356

NM_033357
NM_033358
NM_001372051

NM_001080126
NM_001277926
NM_009812

RefSeq (bjelančevina)
NP_001073593
NP_001073594
NP_001219
NP_203519
NP_203520

NP_203522
NP_001358980

NP_001073595
NP_001264855
NP_033942

Lokacija (UCSC)Chr 2: 201.23 – 201.29 MbChr 1: 58.83 – 58.89 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Kaspaza-8 je kaspazni protein, kodiran CASP8 genom. To jest proteinski enzim koji je kod ljudi kodiran genom sa hromosoma 2. Najvjerovatnije djeluje na kaspazu-3.

CASP8 ortolozi[5] identificirani su kod brojnih sisara za koje su dostupni potpuni podaci o genomu. Ovi jedinstveni ortolozi su takođe prisutni u pticama.

Aminokiselinska sekvenca[uredi | uredi izvor]

Dužina polipeptidnog lanca je 479 aminokiselina, a molekulska težina 55.391 Da.ref name="OrthoMaM"/>

1020304050
MDFSRNLYDIGEQLDSEDLASLKFLSLDYIPQRKQEPIKDALMLFQRLQE
KRMLEESNLSFLKELLFRINRLDLLITYLNTRKEEMERELQTPGRAQISA
YRVMLYQISEEVSRSELRSFKFLLQEEISKCKLDDDMNLLDIFIEMEKRV
ILGEGKLDILKRVCAQINKSLLKIINDYEEFSKERSSSLEGSPDEFSNGE
ELCGVMTISDSPREQDSESQTLDKVYQMKSKPRGYCLIINNHNFAKAREK
VPKLHSIRDRNGTHLDAGALTTTFEELHFEIKPHDDCTVEQIYEILKIYQ
LMDHSNMDCFICCILSHGDKGIIYGTDGQEAPIYELTSQFTGLKCPSLAG
KPKVFFIQACQGDNYQKGIPVETDSEEQPYLEMDLSSPQTRYIPDEADFL
LGMATVNNCVSYRNPAEGTWYIQSLCQSLRERCPRGDDILTILTEVNYEV
SNKDDKKNMGKQMPQPTFTLRKKLVFPSD

Funkcija[uredi | uredi izvor]

Gen CASP8 kodira člana porodice proteaza cistein-asparaginska kiselina (kaspaza). Sekvencna aktivacija kaspaza ima centralnu ulogu u fazi izvršenja ćelijskih apoptoza. Kaspaze postoje kao neaktivni proenzimi sastavljeni od prodomena, velike i maled proteazne podjedinice. Aktivacija kaspaza zahtijeva proteolitsku obradu konzerviranih unutrašnjih asparaginskih ostataka da bi se dobio heterodimerni enzim koji se sastoji od velike i male podjedinice. Ovaj protein je uključen u programiranu smrt ćelije izazvanu Fas-om i raznim apoptotskim stimulansima. Domen efektora smrti nalik N-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 sa Huntingtonovom bolešću, ali ne i kod onih iz normalne kontrole, što implicira ulogu u neurodegenerativnim bolestima. Opisane su mnoge alternativno sprerađene varijante transkripta koje kodiraju različite izoforme, iako za sve varijante nisu određene sekvence pune dužine..[6]

Klinički značaj[uredi | uredi izvor]

Vrlo rijedak genetički poremećaj imunskog sistema također može biti uzrokovan mutacijama ovog gena. Ova bolest, nazvana CEDS, znači "stanje nedostatka kaspaze osam". CEDS ima karakteristike slične ALPS, još jednu genetičku bolest apoptoze, uz dodatak imunodeficijentnog fenotipa. Dakle, kliničke manifestacije uključuju splenomegaliju i limfadenopatiju, pored rekurentnih sinopulmonalnih infekcija, rekurentne mukokutane herpesvirusne, uporne bradavice i infekcije molluscum contagiosum i hipogamaglobulinemija. Ponekad postoji limfocitna infiltrativna bolest u parenhimskim organima, ali autoimunost je minimalna i limfom nije uočen kod pacijenata sa CEDS-om. CEDS se nasljeđuje na autosomno recesivan način.[7] Klinički fenotip pacijenata sa CEDS-om predstavlja paradoks jer se kaspaza-8 smatrala uglavnom proapoptotskom proteazom, koja je uglavnom bila uključena u transdukciju signala iz receptora 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 u limfocitima. Dalji rad je otkrio da je kaspaza-8 neophodna za indukciju faktora transkripcije „jedarni faktor κB” (NF-κB), nakon stimulacije preko antigenog receptora, Fc receptora ili Toll-likog receptora 4 u T, B i prirodne ćelije ubice.[7]

Biohemijski je utvrđeno da kaspaza-8 ulazi u kompleks inhibitora NF-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]

Interakcije[uredi | uredi izvor]

Pokazalo se da kaspaza-8 reaguje sa:

Dopunske slike[uredi | uredi izvor]

Signalni put TNF-R1. Isprekidane sive linije predstavljaju više koraka
Pregled puteva transdukcija signala uključenih u apoptozu.

Također pogledajte[uredi | uredi izvor]

Reference[uredi | uredi izvor]

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Dopunska literatura[uredi | uredi izvor]

Vanjsk linkovi[uredi | uredi izvor]

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