Kaspaza-2

Kaspaza-2
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	1PYO, 2P2C, 3R5J, 3R6G, 3R6L, 3R7B, 3R7N, 3R7S, 3RJM
Identifikatori
Aliasi	CASP2
Vanjski ID-jevi	OMIM: 600639 MGI: 97295 HomoloGene: 7254 GeneCards: CASP2
Lokacija gena (čovjek)
Hrom.	Hromosom 7 (čovjek)
Kraj	143,307,696 bp
Lokacija gena (miš)
Hrom.	Hromosom 6 (miš)
Kraj	42,259,442 bp
Obrazac RNK ekspresije
	; ; ; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• cysteine-type peptidase activity; • protein domain specific binding; • GO:0070122 peptidase activity; • GO:0001948, GO:0016582 vezivanje za proteine; • vezivanje enzima; • hydrolase activity; • vezivanje identičnih proteina; • cysteine-type endopeptidase activity involved in apoptotic process; • cysteine-type endopeptidase activity; • cysteine-type endopeptidase activity involved in execution phase of apoptosis;
Ćelijska komponenta	• citoplazma; • citosol; • membrana; • mitohondrija; • jedro;
Biološki proces	• DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; • execution phase of apoptosis; • protein processing; • GO:0010260 Starenje; • positive regulation of apoptotic signaling pathway; • luteolysis; • cellular response to mechanical stimulus; • positive regulation of neuron apoptotic process; • brain development; • intrinsic apoptotic signaling pathway in response to DNA damage; • extrinsic apoptotic signaling pathway in absence of ligand; • positive regulation of apoptotic process; • ectopic germ cell programmed cell death; • apoptotic signaling pathway; • neural retina development; • GO:0097285 apoptoza; • regulation of apoptotic process; • Proteoliza; • negative regulation of apoptotic process;
	Izvori:Amigo / QuickGO
Ortolozi
	835
	12366
	ENSG00000106144
	ENSMUSG00000029863
	P42575
	P29594
	NM_032983; NM_001224; NM_032982; NM_032984
	NM_007610
	NP_001215; NP_116764; NP_116765
	NP_031636
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Kaspaza 2, znana i kao CASP2 je enzim koji je kod ljudi kodiran genom CASP2 sa hromosoma 7.^[5] Ortolozi CASP2^[6] identificirani su kod gotovo svih sisara za koje su dostupni potpuni podaci o genomu. Jedinstveni ortolozi su također prisutni u ptica, gušterova, Lissamphibia i košljoriba.

Aminokiselinska sekvenca[uredi | uredi izvor]

Dužina polipeptidnog lanca je 452 aminokiseline, a molekulska težina 50.685 Da.^[7]

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
MAAPSAGSWS	TFQHKELMAA	DRGRRILGVC	GMHPHHQETL	KKNRVVLAKQ
LLLSELLEHL	LEKDIITLEM	RELIQAKVGS	FSQNVELLNL	LPKRGPQAFD
AFCEALRETK	QGHLEDMLLT	TLSGLQHVLP	PLSCDYDLSL	PFPVCESCPL
YKKLRLSTDT	VEHSLDNKDG	PVCLQVKPCT	PEFYQTHFQL	AYRLQSRPRG
LALVLSNVHF	TGEKELEFRS	GGDVDHSTLV	TLFKLLGYDV	HVLCDQTAQE
MQEKLQNFAQ	LPAHRVTDSC	IVALLSHGVE	GAIYGVDGKL	LQLQEVFQLF
DNANCPSLQN	KPKMFFIQAC	RGDETDRGVD	QQDGKNHAGS	PGCEESDAGK
EKLPKMRLPT	RSDMICGYAC	LKGTAAMRNT	KRGSWYIEAL	AQVFSERACD
MHVADMLVKV	NALIKDREGY	APGTEFHRCK	EMSEYCSTLC	RHLYLFPGHP
PT

Funkcija[uredi | uredi izvor]

Sekvencna aktivacija kaspaza ima centralnu ulogu u fazi izvršenja ćelijskih apoptoza. Kaspaze postoje kao neaktivni proenzimi koji se podvrgavaju proteolitskoj obradi na konzerviranim ostacima aspartata da bi se dobile dvije podjedinice, velike i male, koje se dimeriziraju i formiraju aktivni enzim. Proteolitsko cijepanje ovog proteina inducirano je raznim apoptotskim stimulansima.^[7]

Kaspaza 2 proteolitski cijepa druge proteine. Pripada porodici cistein-proteaza zvanih kaspaze koje cijepaju proteine samo na aminokiselinama nakon ostatka asperaginske kiseline. Unutar ove porodice, kaspaza 2 je dio potporodice ICH-1. To je jedna od najkonzerviranijih kaspaza kod različitih vrsta životinja. Kaspaza-2 ima sličnu sekvencu aminokiselina kao inicijator kaspaza, uključujući kaspazu-1, kaspazu-4, kaspazu 5, i kaspazu-9. Proizveden je kao zimogen, koji sadrži dugi prodomen koji je sličan onom kod kaspaze 9 i sadrži domen interakcije proteina poznat kao CARD domen. Prokaspaza-2 sadrži dvije podjedinice, p19 i p12.

Pokazalo se da se povezuje sa nekoliko proteina uključenih u apoptozu, koristeći svoj CARD domen, uključujući RIP-povezani Ich-1/Ced-3-homologni protein sa domenom smrti (RAIDD), apoptozni represor sa domenom regrutacije kaspaze (ARC) i protein apoptoze koji formira filamente nalik Ced-4 (DEFCAP).^[8] Zajedno sa RAIDD-om i proteinom izazvanim p53 sa domenom smrti ([PIDD])(LRDD), pokazalo se da kaspaza 2 formira tzv. PIDDosome,^[9] koji može poslužiti kao aktivacijska platforma za proteazu, iako se također može aktivirati u odsustvu PIDD-a.^[10] Sve u svemu, čini se da je kaspaza-2 vrlo svestrana kaspaza s višestrukim funkcijama izvan indukcije ćelijske smrti.^[11]^[12]

Interakcije[uredi | uredi izvor]

Pokazalo se da kaspaza 2 reaguje sa:

BH3,^[13]^[14]
CRADD,^[9]^[15]^[16] i
Kaspaza-8.^[13]^[17]

Također pogledajte[uredi | uredi izvor]

References[uredi | uredi izvor]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000106144 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000029863 - 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.
^ Kumar S, White DL, Takai S, Turczynowicz S, Juttner CA, Hughes TP (juni 1995). "Apoptosis regulatory gene NEDD2 maps to human chromosome segment 7q34-35, a region frequently affected in haematological neoplasms". Hum. Genet. 95 (6): 641–4. doi:10.1007/bf00209480. PMID 7789948. S2CID 22813779.
^ "OrthoMaM phylogenetic marker: CASP2 coding sequence". Arhivirano s originala, 24. 9. 2015. Pristupljeno 20. 12. 2009.
^ ^a ^b "Entrez Gene: CASP2".
^ Zhivotovsky B, Orrenius S (2005). "Caspase-2 function in response to DNA damage". Biochem. Biophys. Res. Commun. 331 (3): 859–67. doi:10.1016/j.bbrc.2005.03.191. PMID 15865942.
^ ^a ^b Tinel A, Tschopp J (maj 2004). "The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic stress". Science. 304 (5672): 843–6. Bibcode:2004Sci...304..843T. doi:10.1126/science.1095432. PMID 15073321. S2CID 6583298.
^ Manzl C, Krumschnabel G, Bock F, Sohm B, Labi V, Baumgartner F, Logette E, Tschopp J, Villunger A (april 2009). "Caspase-2 activation in the absence of PIDDosome formation". J. Cell Biol. 185 (2): 291–303. doi:10.1083/jcb.200811105. PMC 2700374. PMID 19364921.
^ Krumschnabel G, Manzl C, Villunger A (septembar 2009). "Caspase-2: killer, savior and safeguard--emerging versatile roles for an ill-defined caspase". Oncogene. 28 (35): 3093–6. doi:10.1038/onc.2009.173. PMC 3272399. PMID 19581929.
^ Krumschnabel G, Sohm B, Bock F, Manzl C, Villunger A (februar 2009). "The enigma of caspase-2: the laymen's view". Cell Death Differ. 16 (2): 195–207. doi:10.1038/cdd.2008.170. PMC 3272397. PMID 19023332.
^ ^a ^b Guo Y, Srinivasula SM, Druilhe A, Fernandes-Alnemri T, Alnemri ES (april 2002). "Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria". J. Biol. Chem. 277 (16): 13430–7. doi:10.1074/jbc.M108029200. PMID 11832478.
^ Paroni G, Henderson C, Schneider C, Brancolini C (juni 2001). "Caspase-2-induced apoptosis is dependent on caspase-9, but its processing during UV- or tumor necrosis factor-dependent cell death requires caspase-3". J. Biol. Chem. 276 (24): 21907–15. doi:10.1074/jbc.M011565200. PMID 11399776.
^ Droin N, Beauchemin M, Solary E, Bertrand R (decembar 2000). "Identification of a caspase-2 isoform that behaves as an endogenous inhibitor of the caspase cascade". Cancer Res. 60 (24): 7039–47. PMID 11156409.
^ Duan H, Dixit VM (januar 1997). "RAIDD is a new 'death' adaptor molecule" (PDF). Nature. 385 (6611): 86–9. Bibcode:1997Natur.385...86D. doi:10.1038/385086a0. hdl:2027.42/62739. PMID 8985253. S2CID 4317538.
^ Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Litwack G, Alnemri ES (decembar 1996). "Molecular ordering of the Fas-apoptotic pathway: the Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases". Proc. Natl. Acad. Sci. U.S.A. 93 (25): 14486–91. Bibcode:1996PNAS...9314486S. doi:10.1073/pnas.93.25.14486. PMC 26159. PMID 8962078.

Vanjski linkovi[uredi | uredi izvor]

The MEROPS online database for peptidases and their inhibitors: C14.006^{[mrtav link]}
P42575

Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.

Portal Biologija

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000106144 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000029863 - 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.

[pmid7789948-5] Kumar S, White DL, Takai S, Turczynowicz S, Juttner CA, Hughes TP (juni 1995). "Apoptosis regulatory gene NEDD2 maps to human chromosome segment 7q34-35, a region frequently affected in haematological neoplasms". Hum. Genet. 95 (6): 641–4. doi:10.1007/bf00209480. PMID 7789948. S2CID 22813779.

[OrthoMaM-6] "OrthoMaM phylogenetic marker: CASP2 coding sequence". Arhivirano s originala, 24. 9. 2015. Pristupljeno 20. 12. 2009.

[entrez-7] "Entrez Gene: CASP2".

[8] Zhivotovsky B, Orrenius S (2005). "Caspase-2 function in response to DNA damage". Biochem. Biophys. Res. Commun. 331 (3): 859–67. doi:10.1016/j.bbrc.2005.03.191. PMID 15865942.

[pmid15073321-9] Tinel A, Tschopp J (maj 2004). "The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic stress". Science. 304 (5672): 843–6. Bibcode:2004Sci...304..843T. doi:10.1126/science.1095432. PMID 15073321. S2CID 6583298.

[pmid19364921-10] Manzl C, Krumschnabel G, Bock F, Sohm B, Labi V, Baumgartner F, Logette E, Tschopp J, Villunger A (april 2009). "Caspase-2 activation in the absence of PIDDosome formation". J. Cell Biol. 185 (2): 291–303. doi:10.1083/jcb.200811105. PMC 2700374. PMID 19364921.

[pmid19581929-11] Krumschnabel G, Manzl C, Villunger A (septembar 2009). "Caspase-2: killer, savior and safeguard--emerging versatile roles for an ill-defined caspase". Oncogene. 28 (35): 3093–6. doi:10.1038/onc.2009.173. PMC 3272399. PMID 19581929.

[pmid19023332-12] Krumschnabel G, Sohm B, Bock F, Manzl C, Villunger A (februar 2009). "The enigma of caspase-2: the laymen's view". Cell Death Differ. 16 (2): 195–207. doi:10.1038/cdd.2008.170. PMC 3272397. PMID 19023332.

[pmid11832478-13] Guo Y, Srinivasula SM, Druilhe A, Fernandes-Alnemri T, Alnemri ES (april 2002). "Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria". J. Biol. Chem. 277 (16): 13430–7. doi:10.1074/jbc.M108029200. PMID 11832478.

[pmid11399776-14] Paroni G, Henderson C, Schneider C, Brancolini C (juni 2001). "Caspase-2-induced apoptosis is dependent on caspase-9, but its processing during UV- or tumor necrosis factor-dependent cell death requires caspase-3". J. Biol. Chem. 276 (24): 21907–15. doi:10.1074/jbc.M011565200. PMID 11399776.

[pmid11156409-15] Droin N, Beauchemin M, Solary E, Bertrand R (decembar 2000). "Identification of a caspase-2 isoform that behaves as an endogenous inhibitor of the caspase cascade". Cancer Res. 60 (24): 7039–47. PMID 11156409.

[pmid8985253-16] Duan H, Dixit VM (januar 1997). "RAIDD is a new 'death' adaptor molecule" (PDF). Nature. 385 (6611): 86–9. Bibcode:1997Natur.385...86D. doi:10.1038/385086a0. hdl:2027.42/62739. PMID 8985253. S2CID 4317538.

[pmid8962078-17] Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Litwack G, Alnemri ES (decembar 1996). "Molecular ordering of the Fas-apoptotic pathway: the Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases". Proc. Natl. Acad. Sci. U.S.A. 93 (25): 14486–91. Bibcode:1996PNAS...9314486S. doi:10.1073/pnas.93.25.14486. PMC 26159. PMID 8962078.

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p r u Proteaza: Cisteinska proteaza (EC 3.4.22)
Kaspaza	Kaspaza-1 Kaspaza-2 Kaspaza-3 Kaspaza-4 Kaspaza-5 Kaspaza-6 Kaspaza-7 Kaspaza-8 Kaspaza-9 Kaspaza-10 Kaspaza-12 Kaspaza-13 Kaspaza-14
Izvedene iz plodova	Papain Fikain Bromelain Aktinidain
Kalpain	CAPN1 CAPN2 CAPN3 CAPN5 CAPN6 CAPN7 CAPN8 CAPN9 CAPN10 CAPN11 CAPN12 CAPN13 CAPN14 CAPNS1 CAPNS2
Katepsin	B C F H K L1/L2 O S W Z
Ostale	Klostripain Kancerski prokoagulant Separaza Autofagin Kruzipain 3C-lika proteaza

p r u Enzimi
Teme	Aktivno mjesto Alosterna regulacija Difuzijski limitirani enzim EC broj Enzimska kataliza Inhibicija enzimskih reakcija Kinetika enzima Koenzim Kooperativnost Lineweaver–Burkov dijagram Michaelis–Mentenova kinetika Mjesto vezanja Spisak enzima
Tipovi	EC1 Oksidoreduktaze/spisak EC2 Transferaze/spisak EC3 Hidrolaze/spisak EC4 Lijaze/spisak EC5 Izomeraze/spisak EC6 Ligaze/spisak