CASP6_CHICK
ID CASP6_CHICK Reviewed; 304 AA.
AC A0A1D5PPP7; O93415;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 10-APR-2019, sequence version 2.
DT 03-AUG-2022, entry version 27.
DE RecName: Full=Caspase-6 {ECO:0000303|PubMed:10684799};
DE Short=CASP-6;
DE EC=3.4.22.59 {ECO:0000250|UniProtKB:P55212};
DE Contains:
DE RecName: Full=Caspase-6 subunit p18 {ECO:0000250|UniProtKB:P55212};
DE Contains:
DE RecName: Full=Caspase-6 subunit p11 {ECO:0000250|UniProtKB:P55212};
GN Name=CASP6 {ECO:0000250|UniProtKB:P55212};
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=10684799; DOI=10.1095/biolreprod62.3.589;
RA Johnson A.L., Bridgham J.T.;
RT "Caspase-3 and -6 expression and enzyme activity in hen granulosa cells.";
RL Biol. Reprod. 62:589-598(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RX PubMed=11953316; DOI=10.1093/emboj/21.8.1967;
RA Ruchaud S., Korfali N., Villa P., Kottke T.J., Dingwall C., Kaufmann S.H.,
RA Earnshaw W.C.;
RT "Caspase-6 gene disruption reveals a requirement for lamin A cleavage in
RT apoptotic chromatin condensation.";
RL EMBO J. 21:1967-1977(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Red jungle fowl;
RX PubMed=15592404; DOI=10.1038/nature03154;
RA Hillier L.W., Miller W., Birney E., Warren W., Hardison R.C., Ponting C.P.,
RA Bork P., Burt D.W., Groenen M.A.M., Delany M.E., Dodgson J.B.,
RA Chinwalla A.T., Cliften P.F., Clifton S.W., Delehaunty K.D., Fronick C.,
RA Fulton R.S., Graves T.A., Kremitzki C., Layman D., Magrini V.,
RA McPherson J.D., Miner T.L., Minx P., Nash W.E., Nhan M.N., Nelson J.O.,
RA Oddy L.G., Pohl C.S., Randall-Maher J., Smith S.M., Wallis J.W.,
RA Yang S.-P., Romanov M.N., Rondelli C.M., Paton B., Smith J., Morrice D.,
RA Daniels L., Tempest H.G., Robertson L., Masabanda J.S., Griffin D.K.,
RA Vignal A., Fillon V., Jacobbson L., Kerje S., Andersson L.,
RA Crooijmans R.P., Aerts J., van der Poel J.J., Ellegren H., Caldwell R.B.,
RA Hubbard S.J., Grafham D.V., Kierzek A.M., McLaren S.R., Overton I.M.,
RA Arakawa H., Beattie K.J., Bezzubov Y., Boardman P.E., Bonfield J.K.,
RA Croning M.D.R., Davies R.M., Francis M.D., Humphray S.J., Scott C.E.,
RA Taylor R.G., Tickle C., Brown W.R.A., Rogers J., Buerstedde J.-M.,
RA Wilson S.A., Stubbs L., Ovcharenko I., Gordon L., Lucas S., Miller M.M.,
RA Inoko H., Shiina T., Kaufman J., Salomonsen J., Skjoedt K., Wong G.K.-S.,
RA Wang J., Liu B., Wang J., Yu J., Yang H., Nefedov M., Koriabine M.,
RA Dejong P.J., Goodstadt L., Webber C., Dickens N.J., Letunic I., Suyama M.,
RA Torrents D., von Mering C., Zdobnov E.M., Makova K., Nekrutenko A.,
RA Elnitski L., Eswara P., King D.C., Yang S.-P., Tyekucheva S.,
RA Radakrishnan A., Harris R.S., Chiaromonte F., Taylor J., He J.,
RA Rijnkels M., Griffiths-Jones S., Ureta-Vidal A., Hoffman M.M., Severin J.,
RA Searle S.M.J., Law A.S., Speed D., Waddington D., Cheng Z., Tuzun E.,
RA Eichler E., Bao Z., Flicek P., Shteynberg D.D., Brent M.R., Bye J.M.,
RA Huckle E.J., Chatterji S., Dewey C., Pachter L., Kouranov A.,
RA Mourelatos Z., Hatzigeorgiou A.G., Paterson A.H., Ivarie R., Brandstrom M.,
RA Axelsson E., Backstrom N., Berlin S., Webster M.T., Pourquie O.,
RA Reymond A., Ucla C., Antonarakis S.E., Long M., Emerson J.J., Betran E.,
RA Dupanloup I., Kaessmann H., Hinrichs A.S., Bejerano G., Furey T.S.,
RA Harte R.A., Raney B., Siepel A., Kent W.J., Haussler D., Eyras E.,
RA Castelo R., Abril J.F., Castellano S., Camara F., Parra G., Guigo R.,
RA Bourque G., Tesler G., Pevzner P.A., Smit A., Fulton L.A., Mardis E.R.,
RA Wilson R.K.;
RT "Sequence and comparative analysis of the chicken genome provide unique
RT perspectives on vertebrate evolution.";
RL Nature 432:695-716(2004).
CC -!- FUNCTION: Cysteine protease that plays essential roles in programmed
CC cell death, development and innate immunity (PubMed:11953316). Acts as
CC a non-canonical executioner caspase during apoptosis: localizes in the
CC nucleus and cleaves the nuclear structural protein lamin-A/LMNA thereby
CC inducing nuclear shrinkage and fragmentation (PubMed:11953316). Lamin-
CC A/LMNA cleavage is required for chromatin condensation and nuclear
CC disassembly during apoptotic execution (PubMed:11953316). Plays an
CC essential role in defense against viruses by acting as a central
CC mediator of the ZBP1-mediated pyroptosis, apoptosis, and necroptosis
CC (PANoptosis), independently of its cysteine protease activity.
CC PANoptosis is a unique inflammatory programmed cell death, which
CC provides a molecular scaffold that allows the interactions and
CC activation of machinery required for inflammasome/pyroptosis, apoptosis
CC and necroptosis (By similarity). {ECO:0000250|UniProtKB:P55212,
CC ECO:0000269|PubMed:11953316}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Strict requirement for Asp at position P1 and has a preferred
CC cleavage sequence of Val-Glu-His-Asp-|-.; EC=3.4.22.59;
CC Evidence={ECO:0000250|UniProtKB:P55212};
CC -!- ACTIVITY REGULATION: During activation, the N-terminal prodomain is
CC removed by cleavage (By similarity). Concomitantly, double cleavage
CC gives rise to a large 18-kDa and a small 11-kDa subunit (By
CC similarity). The two large and two small subunits then assemble to form
CC the active CASP6 complex (By similarity). Intramolecular cleavage at
CC Asp-191 is a prerequisite for CASP6 self-activation (By similarity).
CC {ECO:0000250|UniProtKB:P55212}.
CC -!- SUBUNIT: Heterotetramer that consists of two anti-parallel arranged
CC heterodimers, each one formed by a 18 kDa (p18) and a 11 kDa (p11)
CC subunit. {ECO:0000250|UniProtKB:P55212}.
CC -!- SUBUNIT: [Caspase-6 subunit p18]: Heterotetramer that consists of two
CC anti-parallel arranged heterodimers, each one formed by a 18 kDa
CC (Caspase-6 subunit p18) and a 11 kDa (Caspase-6 subunit p11) subunit.
CC {ECO:0000250|UniProtKB:P55212}.
CC -!- SUBUNIT: [Caspase-6 subunit p11]: Heterotetramer that consists of two
CC anti-parallel arranged heterodimers, each one formed by a 18 kDa
CC (Caspase-6 subunit p18) and a 11 kDa (Caspase-6 subunit p11) subunit.
CC {ECO:0000250|UniProtKB:P55212}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P55212}. Nucleus
CC {ECO:0000250|UniProtKB:P55212}.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:10684799}.
CC -!- DOMAIN: The N-terminal disordered prodomain is required to prevent
CC self-activation. {ECO:0000250|UniProtKB:P55212}.
CC -!- DOMAIN: The Tri-arginine exosite is required to recruit substrates for
CC hydrolysis. {ECO:0000250|UniProtKB:P55212}.
CC -!- DOMAIN: Undergoes helix-strand structural transitions upon substrate-
CC binding: the 130's region interconverts between an inactive helical
CC state and the canonically active strand state. Other caspases rest
CC constitutively in the strand conformation before and after substrate-
CC binding. {ECO:0000250|UniProtKB:P55212}.
CC -!- SIMILARITY: Belongs to the peptidase C14A family. {ECO:0000305}.
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DR EMBL; AF082329; AAC32378.1; -; mRNA.
DR EMBL; AF469049; AAL82386.1; -; Genomic_DNA.
DR EMBL; AADN05000017; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_990057.1; NM_204726.1.
DR MEROPS; C14.005; -.
DR Ensembl; ENSGALT00000057584; ENSGALP00000054851; ENSGALG00000012186.
DR GeneID; 395477; -.
DR KEGG; gga:395477; -.
DR CTD; 839; -.
DR VEuPathDB; HostDB:geneid_395477; -.
DR GeneTree; ENSGT00940000155140; -.
DR OrthoDB; 984395at2759; -.
DR Proteomes; UP000000539; Chromosome 4.
DR Bgee; ENSGALG00000012186; Expressed in kidney and 13 other tissues.
DR ExpressionAtlas; A0A1D5PPP7; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IMP:AgBase.
DR GO; GO:0097153; F:cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0097200; F:cysteine-type endopeptidase activity involved in execution phase of apoptosis; IEA:InterPro.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IDA:AgBase.
DR GO; GO:0002218; P:activation of innate immune response; ISS:UniProtKB.
DR GO; GO:0030263; P:apoptotic chromosome condensation; IGI:AgBase.
DR GO; GO:0006309; P:apoptotic DNA fragmentation; IGI:AgBase.
DR GO; GO:0030262; P:apoptotic nuclear changes; IGI:AgBase.
DR GO; GO:0006915; P:apoptotic process; IMP:AgBase.
DR GO; GO:0097284; P:hepatocyte apoptotic process; ISS:UniProtKB.
DR GO; GO:0072332; P:intrinsic apoptotic signaling pathway by p53 class mediator; ISS:UniProtKB.
DR GO; GO:0070306; P:lens fiber cell differentiation; TAS:AgBase.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0060545; P:positive regulation of necroptotic process; ISS:UniProtKB.
DR GO; GO:0016540; P:protein autoprocessing; ISS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IGI:AgBase.
DR GO; GO:0070269; P:pyroptosis; ISS:UniProtKB.
DR CDD; cd00032; CASc; 1.
DR InterPro; IPR029030; Caspase-like_dom_sf.
DR InterPro; IPR037554; Caspase_6.
DR InterPro; IPR033139; Caspase_cys_AS.
DR InterPro; IPR002398; Pept_C14.
DR InterPro; IPR002138; Pept_C14_p10.
DR InterPro; IPR001309; Pept_C14_p20.
DR InterPro; IPR015917; Pept_C14A.
DR PANTHER; PTHR10454; PTHR10454; 1.
DR PANTHER; PTHR10454:SF206; PTHR10454:SF206; 1.
DR PRINTS; PR00376; IL1BCENZYME.
DR SMART; SM00115; CASc; 1.
DR SUPFAM; SSF52129; SSF52129; 1.
DR PROSITE; PS01122; CASPASE_CYS; 1.
DR PROSITE; PS50207; CASPASE_P10; 1.
DR PROSITE; PS50208; CASPASE_P20; 1.
PE 2: Evidence at transcript level;
KW Apoptosis; Autocatalytic cleavage; Cytoplasm; Hydrolase; Nucleus; Protease;
KW Reference proteome; Thiol protease; Zymogen.
FT CHAIN 1..304
FT /note="Caspase-6"
FT /id="PRO_0000454577"
FT PROPEP 1..35
FT /evidence="ECO:0000303|PubMed:10684799"
FT /id="PRO_0000454578"
FT CHAIN 36..191
FT /note="Caspase-6 subunit p18"
FT /evidence="ECO:0000250|UniProtKB:P55212"
FT /id="PRO_0000454579"
FT PROPEP 192..204
FT /evidence="ECO:0000250|UniProtKB:P55212"
FT /id="PRO_0000454580"
FT CHAIN 205..304
FT /note="Caspase-6 subunit p11"
FT /evidence="ECO:0000250|UniProtKB:P55212"
FT /id="PRO_0000454581"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 54..56
FT /note="Tri-arginine exosite"
FT /evidence="ECO:0000250|UniProtKB:P55212"
FT REGION 137..154
FT /note="130's region"
FT /evidence="ECO:0000250|UniProtKB:P55212"
FT ACT_SITE 133
FT /evidence="ECO:0000250|UniProtKB:P55212"
FT ACT_SITE 175
FT /evidence="ECO:0000250|UniProtKB:P55212"
FT CONFLICT 41
FT /note="Q -> R (in Ref. 1; AAC32378 and 2; AAL82386)"
FT /evidence="ECO:0000305"
FT CONFLICT 47
FT /note="V -> E (in Ref. 1; AAC32378 and 2; AAL82386)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 304 AA; 34476 MW; AEFB3B7A68303C83 CRC64;
MSGAERRPAA GRVQLDSKPT PTTTADGNQN ITEVDAFDKR QTFDPAVQYK MNHQRRGVAL
IFNHEHFFWH LRLPDRRGTL ADRNNLKRSL TDLGFEVRIF DDLKAEDVLK KVFEASRDDY
SNADCFVCVF LSHGENDHVY AYDAQIKIET ITNMFRGDKC QSLVGKPKIF IIQACRGDKH
DDPVLVQDSV DSKDETTVNQ TEVDAAGVYT LPAGADFIMC YSVAQGYFSH RETVNGSWYI
QDLCEALGKH GSSLEFTELL TVVNRKVSHR KVDICRDINA IGKKQIPCFA SMLTKKLYFH
PKSK
