CFLAR_HUMAN
ID CFLAR_HUMAN Reviewed; 480 AA.
AC O15519; B4DJE0; B7Z9F9; O14673; O14674; O14675; O15137; O15138; O15356;
AC O15510; O43618; O43619; O43620; O60458; O60459; Q53TS6; Q54AF1; Q96TE4;
AC Q9UEW1;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 212.
DE RecName: Full=CASP8 and FADD-like apoptosis regulator;
DE AltName: Full=Caspase homolog;
DE Short=CASH;
DE AltName: Full=Caspase-eight-related protein;
DE Short=Casper;
DE AltName: Full=Caspase-like apoptosis regulatory protein;
DE Short=CLARP;
DE AltName: Full=Cellular FLICE-like inhibitory protein;
DE Short=c-FLIP;
DE AltName: Full=FADD-like antiapoptotic molecule 1;
DE Short=FLAME-1;
DE AltName: Full=Inhibitor of FLICE;
DE Short=I-FLICE;
DE AltName: Full=MACH-related inducer of toxicity;
DE Short=MRIT;
DE AltName: Full=Usurpin;
DE Contains:
DE RecName: Full=CASP8 and FADD-like apoptosis regulator subunit p43;
DE Contains:
DE RecName: Full=CASP8 and FADD-like apoptosis regulator subunit p12;
DE Flags: Precursor;
GN Name=CFLAR; Synonyms=CASH, CASP8AP1, CLARP, MRIT;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 13 AND 14), MUTAGENESIS OF TYR-360,
RP AND INTERACTION WITH FADD; CASP8; CASP3; TRAF1 AND TRAF2.
RC TISSUE=Embryonic kidney, and Umbilical vein endothelial cell;
RX PubMed=9208847; DOI=10.1016/s1074-7613(00)80450-1;
RA Shu H.-B., Halpin D.R., Goeddel D.V.;
RT "Casper is a FADD- and caspase-related inducer of apoptosis.";
RL Immunity 6:751-763(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), AND INTERACTION WITH
RP FADD; CASP8; CASP3 AND BCL-X(L).
RX PubMed=9326610; DOI=10.1073/pnas.94.21.11333;
RA Han D.K.M., Chaudhary P.M., Wright M.E., Friedman C., Trask B.J.,
RA Riedel R.T., Baskin D.G., Schwartz S.M., Hood L.;
RT "MRIT, a novel death-effector domain-containing protein, interacts with
RT caspases and BclXL and initiates cell death.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:11333-11338(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Peripheral blood lymphocyte;
RX PubMed=9217161; DOI=10.1038/40657;
RA Irmler M., Thome M., Hahne M., Schneider P., Hofmann K., Steiner V.,
RA Bodmer J.-L., Schroeter M., Burns K., Mattmann C., Rimoldi D., French L.E.,
RA Tschopp J.;
RT "Inhibition of death receptor signals by cellular FLIP.";
RL Nature 388:190-195(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 8; 9 AND 10), MUTAGENESIS OF
RP ASP-376, PROTEOLYTIC PROCESSING, AND SITE.
RC TISSUE=T-cell;
RX PubMed=9228018; DOI=10.1074/jbc.272.30.18542;
RA Srinivasula S.M., Ahmad M., Ottilie S., Bullrich F., Banks S., Wang Y.,
RA Fernandes-Alnemri T., Croce C.M., Litwack G., Tomaselli K.J.,
RA Armstrong R.C., Alnemri E.S.;
RT "FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates
RT Fas/TNFR1-induced apoptosis.";
RL J. Biol. Chem. 272:18542-18545(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Umbilical vein endothelial cell;
RX PubMed=9211860; DOI=10.1074/jbc.272.28.17255;
RA Hu S., Vincenz C., Ni J., Gentz R., Dixit V.M.;
RT "I-FLICE, a novel inhibitor of tumor necrosis factor receptor-1- and CD-95-
RT induced apoptosis.";
RL J. Biol. Chem. 272:17255-17257(1997).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4; 5; 6 AND 7).
RA Hu S., Dixit V.M.;
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Skin fibroblast;
RX PubMed=9289491; DOI=10.1074/jbc.272.32.19641;
RA Goltsev Y.V., Kovalenko A.V., Arnold E., Varfolomeev E.E.,
RA Brodianskii V.M., Wallach D.;
RT "CASH, a novel caspase homologue with death effector domains.";
RL J. Biol. Chem. 272:19641-19644(1997).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Colon carcinoma;
RX PubMed=9380701; DOI=10.1073/pnas.94.20.10717;
RA Inohara N., Koseki T., Hu Y., Chen S., Nunez G.;
RT "CLARP, a death effector domain-containing protein interacts with caspase-8
RT and regulates apoptosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:10717-10722(1997).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 11 AND 12).
RC TISSUE=Kidney;
RX PubMed=10200473; DOI=10.1038/sj.cdd.4400370;
RA Rasper D.M., Vaillancourt J.P., Hadano S., Houtzager V.M., Seiden I.,
RA Keen S.L.C., Tawa P., Xanthoudakis S., Nasir J., Martindale D., Koop B.F.,
RA Peterson E.P., Thornberry N.A., Huang J., MacPherson D.P., Black S.C.,
RA Hornung F., Lenardo M.J., Hayden M.R., Roy S., Nicholson D.W.;
RT "Cell death attenuation by 'Usurpin', a mammalian DED-caspase homologue
RT that precludes caspase-8 recruitment and activation by the CD-95 (Fas, APO-
RT 1) receptor complex.";
RL Cell Death Differ. 5:271-288(1998).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11161814; DOI=10.1006/geno.2000.6392;
RA Hadano S., Yanagisawa Y., Skaug J., Fichter K., Nasir J., Martindale D.,
RA Koop B.F., Scherer S.W., Nicholson D.W., Rouleau G.A., Ikeda J.-E.,
RA Hayden M.R.;
RT "Cloning and characterization of three novel genes, ALS2CR1, ALS2CR2, and
RT ALS2CR3, in the juvenile amyotrophic lateral sclerosis (ALS2) critical
RT region at chromosome 2q33-q34: candidate genes for ALS2.";
RL Genomics 71:200-213(2001).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 15).
RC TISSUE=Cerebellum, Corpus callosum, and Subthalamic nucleus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [13]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [14]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [15]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [16]
RP FUNCTION, AND ASSOCIATION WITH DISC.
RX PubMed=9880531; DOI=10.1074/jbc.274.3.1541;
RA Scaffidi C., Schmitz I., Krammer P.H., Peter M.E.;
RT "The role of c-FLIP in modulation of CD95-induced apoptosis.";
RL J. Biol. Chem. 274:1541-1548(1999).
RN [17]
RP INDUCTION.
RX PubMed=10227994;
RA Algeciras-Schimnich A., Griffith T.S., Lynch D.H., Paya C.V.;
RT "Cell cycle-dependent regulation of FLIP levels and susceptibility to Fas-
RT mediated apoptosis.";
RL J. Immunol. 162:5205-5211(1999).
RN [18]
RP INTERACTION WITH HBV PROTEIN X (MICROBIAL INFECTION).
RX PubMed=12727877; DOI=10.1093/emboj/cdg210;
RA Kim K.H., Seong B.L.;
RT "Pro-apoptotic function of HBV X protein is mediated by interaction with c-
RT FLIP and enhancement of death-inducing signal.";
RL EMBO J. 22:2104-2116(2003).
RN [19]
RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA Hillman R.T., Green R.E., Brenner S.E.;
RT "An unappreciated role for RNA surveillance.";
RL Genome Biol. 5:R8.1-R8.16(2004).
CC -!- FUNCTION: Apoptosis regulator protein which may function as a crucial
CC link between cell survival and cell death pathways in mammalian cells.
CC Acts as an inhibitor of TNFRSF6 mediated apoptosis. A proteolytic
CC fragment (p43) is likely retained in the death-inducing signaling
CC complex (DISC) thereby blocking further recruitment and processing of
CC caspase-8 at the complex. Full length and shorter isoforms have been
CC shown either to induce apoptosis or to reduce TNFRSF-triggered
CC apoptosis. Lacks enzymatic (caspase) activity.
CC {ECO:0000269|PubMed:9880531}.
CC -!- SUBUNIT: TNFRSF6 stimulation triggers recruitment to the death-inducing
CC signaling complex (DISC) formed by TNFRSF6, FADD and CASP8
CC (PubMed:9880531). A proteolytic fragment (p43) stays associated with
CC the DISC (PubMed:9880531). Also interacts with FADD, CASP8, CASP3,
CC TRAF1, TRAF2 and Bcl-X(L) (in vitro) (PubMed:9326610, PubMed:9208847).
CC Interacts with RIPK1 (By similarity) (PubMed:9326610, PubMed:9208847,
CC PubMed:9880531). {ECO:0000250|UniProtKB:O35732,
CC ECO:0000269|PubMed:9208847, ECO:0000269|PubMed:9326610,
CC ECO:0000269|PubMed:9880531}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HBV protein X.
CC {ECO:0000269|PubMed:12727877}.
CC -!- INTERACTION:
CC O15519; Q92851: CASP10; NbExp=3; IntAct=EBI-514941, EBI-495095;
CC O15519; Q14790: CASP8; NbExp=9; IntAct=EBI-514941, EBI-78060;
CC O15519; Q13077: TRAF1; NbExp=6; IntAct=EBI-514941, EBI-359224;
CC O15519-1; Q14790: CASP8; NbExp=2; IntAct=EBI-4567563, EBI-78060;
CC O15519-1; Q14790-2: CASP8; NbExp=3; IntAct=EBI-4567563, EBI-15777741;
CC O15519-1; Q02750: MAP2K1; NbExp=3; IntAct=EBI-4567563, EBI-492564;
CC O15519-1; O14733: MAP2K7; NbExp=2; IntAct=EBI-4567563, EBI-492605;
CC PRO_0000004678; Q92851-4: CASP10; NbExp=3; IntAct=EBI-4478097, EBI-6621134;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=15;
CC Name=1; Synonyms=FLIP-L, CLARP1, MRIT alpha-1, CASH alpha, I-FLICE 1,
CC FLAME-1 gamma, Usurpin alpha;
CC IsoId=O15519-1; Sequence=Displayed;
CC Name=2; Synonyms=FLIP-S, CLARP2, MRIT beta-1, CASH beta;
CC IsoId=O15519-2; Sequence=VSP_000828, VSP_000829;
CC Name=3; Synonyms=MRIT alpha-2;
CC IsoId=O15519-3; Sequence=VSP_000824, VSP_000838;
CC Name=4; Synonyms=I-FLICE 2;
CC IsoId=O15519-4; Sequence=VSP_000825;
CC Name=5; Synonyms=I-FLICE 3;
CC IsoId=O15519-5; Sequence=VSP_000840;
CC Name=6; Synonyms=I-FLICE 4;
CC IsoId=O15519-6; Sequence=VSP_000826, VSP_000841;
CC Name=7; Synonyms=I-FLICE 5;
CC IsoId=O15519-7; Sequence=VSP_000824, VSP_000827, VSP_000838;
CC Name=8; Synonyms=FLAME-1 alpha;
CC IsoId=O15519-8; Sequence=VSP_000830;
CC Name=9; Synonyms=FLAME-1 beta;
CC IsoId=O15519-9; Sequence=VSP_000830, VSP_000836, VSP_000837;
CC Name=10; Synonyms=FLAME-1 delta;
CC IsoId=O15519-10; Sequence=VSP_000834, VSP_000835;
CC Name=11; Synonyms=Usurpin beta;
CC IsoId=O15519-11; Sequence=VSP_000838;
CC Name=12; Synonyms=Usurpin gamma;
CC IsoId=O15519-12; Sequence=VSP_000832, VSP_000833;
CC Name=13;
CC IsoId=O15519-13; Sequence=VSP_000831;
CC Name=14;
CC IsoId=O15519-14; Sequence=VSP_000839;
CC Name=15;
CC IsoId=O15519-15; Sequence=VSP_000824;
CC -!- TISSUE SPECIFICITY: Widely expressed. Higher expression in skeletal
CC muscle, pancreas, heart, kidney, placenta, and peripheral blood
CC leukocytes. Also detected in diverse cell lines. Isoform 8 is
CC predominantly expressed in testis and skeletal muscle.
CC -!- INDUCTION: Repressed by IL2/interleukin-2 after TCR stimulation, during
CC progression to the S phase of the cell cycle.
CC {ECO:0000269|PubMed:10227994}.
CC -!- DOMAIN: The caspase domain lacks the active site residues involved in
CC catalysis.
CC -!- PTM: Proteolytically processed by CASP8 generating subunit p43 and p12.
CC {ECO:0000269|PubMed:9228018}.
CC -!- MISCELLANEOUS: [Isoform 9]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the peptidase C14A family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CFLARID40065ch2q33.html";
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DR EMBL; AF010127; AAB64110.1; -; mRNA.
DR EMBL; U85059; AAB82648.1; -; mRNA.
DR EMBL; U97074; AAC51622.1; -; mRNA.
DR EMBL; U97075; AAC51623.1; -; mRNA.
DR EMBL; AF009616; AAB70909.1; -; mRNA.
DR EMBL; AF009617; AAB70910.1; -; mRNA.
DR EMBL; AF009618; AAB70911.1; -; mRNA.
DR EMBL; AF009619; AAB70912.1; -; mRNA.
DR EMBL; AF041458; AAB99790.1; -; mRNA.
DR EMBL; AF041459; AAB99791.1; -; mRNA.
DR EMBL; AF041462; AAB99794.1; -; mRNA.
DR EMBL; AF041461; AAB99793.1; -; mRNA.
DR EMBL; AF041460; AAB99792.1; -; mRNA.
DR EMBL; Y14039; CAA74366.1; -; mRNA.
DR EMBL; Y14040; CAA74367.1; -; mRNA.
DR EMBL; AF005774; AAC15825.1; -; mRNA.
DR EMBL; AF005775; AAC15826.1; -; mRNA.
DR EMBL; AF015450; AAC16439.1; -; mRNA.
DR EMBL; AF015451; AAC16440.1; -; mRNA.
DR EMBL; AF015452; AAC16441.1; -; mRNA.
DR EMBL; AB038972; BAB32551.1; -; Genomic_DNA.
DR EMBL; AB038972; BAB32552.1; -; Genomic_DNA.
DR EMBL; BT006751; AAP35397.1; -; mRNA.
DR EMBL; AK289913; BAF82602.1; -; mRNA.
DR EMBL; AK296036; BAG58802.1; -; mRNA.
DR EMBL; AK315208; BAG37645.1; -; mRNA.
DR EMBL; AK315924; BAH14295.1; -; mRNA.
DR EMBL; AC007283; AAY24290.1; -; Genomic_DNA.
DR EMBL; CH471063; EAW70237.1; -; Genomic_DNA.
DR EMBL; CH471063; EAW70244.1; -; Genomic_DNA.
DR EMBL; BC001602; AAH01602.1; -; mRNA.
DR CCDS; CCDS2337.1; -. [O15519-1]
DR CCDS; CCDS46487.1; -. [O15519-2]
DR CCDS; CCDS56157.1; -. [O15519-8]
DR CCDS; CCDS56158.1; -. [O15519-15]
DR CCDS; CCDS59436.1; -. [O15519-3]
DR CCDS; CCDS77505.1; -. [O15519-11]
DR RefSeq; NP_001120655.1; NM_001127183.2. [O15519-1]
DR RefSeq; NP_001120656.1; NM_001127184.2. [O15519-2]
DR RefSeq; NP_001189444.1; NM_001202515.1. [O15519-4]
DR RefSeq; NP_001189445.1; NM_001202516.1. [O15519-8]
DR RefSeq; NP_001189446.1; NM_001202517.1. [O15519-15]
DR RefSeq; NP_001189447.1; NM_001202518.1. [O15519-3]
DR RefSeq; NP_001189448.1; NM_001202519.1. [O15519-3]
DR RefSeq; NP_001294971.1; NM_001308042.1. [O15519-11]
DR RefSeq; NP_003870.4; NM_003879.5. [O15519-1]
DR RefSeq; XP_016860679.1; XM_017005190.1. [O15519-1]
DR RefSeq; XP_016860680.1; XM_017005191.1. [O15519-1]
DR RefSeq; XP_016860681.1; XM_017005192.1.
DR RefSeq; XP_016860682.1; XM_017005193.1. [O15519-11]
DR RefSeq; XP_016860683.1; XM_017005194.1.
DR RefSeq; XP_016860684.1; XM_017005195.1. [O15519-15]
DR RefSeq; XP_016860685.1; XM_017005196.1.
DR RefSeq; XP_016860686.1; XM_017005197.1.
DR RefSeq; XP_016860687.1; XM_017005198.1.
DR PDB; 2N5R; NMR; -; A=62-73.
DR PDB; 3H11; X-ray; 1.90 A; A=209-480.
DR PDB; 3H13; X-ray; 2.20 A; A=209-480.
DR PDB; 6M6O; NMR; -; A=2-173.
DR PDB; 7DEE; NMR; -; A=2-173.
DR PDBsum; 2N5R; -.
DR PDBsum; 3H11; -.
DR PDBsum; 3H13; -.
DR PDBsum; 6M6O; -.
DR PDBsum; 7DEE; -.
DR AlphaFoldDB; O15519; -.
DR SMR; O15519; -.
DR BioGRID; 114364; 63.
DR CORUM; O15519; -.
DR DIP; DIP-27629N; -.
DR IntAct; O15519; 31.
DR MINT; O15519; -.
DR STRING; 9606.ENSP00000312455; -.
DR ChEMBL; CHEMBL1955713; -.
DR MEROPS; C14.971; -.
DR iPTMnet; O15519; -.
DR PhosphoSitePlus; O15519; -.
DR BioMuta; CFLAR; -.
DR EPD; O15519; -.
DR jPOST; O15519; -.
DR MassIVE; O15519; -.
DR MaxQB; O15519; -.
DR PaxDb; O15519; -.
DR PeptideAtlas; O15519; -.
DR PRIDE; O15519; -.
DR ProteomicsDB; 4369; -.
DR ProteomicsDB; 48707; -. [O15519-1]
DR ProteomicsDB; 48708; -. [O15519-10]
DR ProteomicsDB; 48709; -. [O15519-11]
DR ProteomicsDB; 48710; -. [O15519-12]
DR ProteomicsDB; 48711; -. [O15519-13]
DR ProteomicsDB; 48712; -. [O15519-14]
DR ProteomicsDB; 48713; -. [O15519-2]
DR ProteomicsDB; 48714; -. [O15519-3]
DR ProteomicsDB; 48715; -. [O15519-4]
DR ProteomicsDB; 48716; -. [O15519-5]
DR ProteomicsDB; 48717; -. [O15519-6]
DR ProteomicsDB; 48718; -. [O15519-7]
DR ProteomicsDB; 48719; -. [O15519-8]
DR ProteomicsDB; 48720; -. [O15519-9]
DR Antibodypedia; 19934; 977 antibodies from 43 providers.
DR DNASU; 8837; -.
DR Ensembl; ENST00000309955.8; ENSP00000312455.2; ENSG00000003402.21. [O15519-1]
DR Ensembl; ENST00000341222.10; ENSP00000339335.6; ENSG00000003402.21. [O15519-2]
DR Ensembl; ENST00000341582.10; ENSP00000345807.6; ENSG00000003402.21. [O15519-8]
DR Ensembl; ENST00000342795.9; ENSP00000342809.5; ENSG00000003402.21. [O15519-12]
DR Ensembl; ENST00000423241.6; ENSP00000399420.2; ENSG00000003402.21. [O15519-1]
DR Ensembl; ENST00000440180.5; ENSP00000406775.1; ENSG00000003402.21. [O15519-2]
DR Ensembl; ENST00000443227.5; ENSP00000413270.1; ENSG00000003402.21. [O15519-15]
DR Ensembl; ENST00000457277.5; ENSP00000411535.1; ENSG00000003402.21. [O15519-11]
DR Ensembl; ENST00000479953.6; ENSP00000471805.1; ENSG00000003402.21. [O15519-3]
DR GeneID; 8837; -.
DR KEGG; hsa:8837; -.
DR MANE-Select; ENST00000309955.8; ENSP00000312455.2; NM_003879.7; NP_003870.4.
DR UCSC; uc002uwz.4; human. [O15519-1]
DR CTD; 8837; -.
DR DisGeNET; 8837; -.
DR GeneCards; CFLAR; -.
DR HGNC; HGNC:1876; CFLAR.
DR HPA; ENSG00000003402; Low tissue specificity.
DR MIM; 603599; gene.
DR neXtProt; NX_O15519; -.
DR OpenTargets; ENSG00000003402; -.
DR PharmGKB; PA26425; -.
DR VEuPathDB; HostDB:ENSG00000003402; -.
DR eggNOG; KOG3573; Eukaryota.
DR GeneTree; ENSGT00530000064199; -.
DR HOGENOM; CLU_1030405_0_0_1; -.
DR InParanoid; O15519; -.
DR OMA; HIPEERY; -.
DR OrthoDB; 939331at2759; -.
DR PhylomeDB; O15519; -.
DR TreeFam; TF352765; -.
DR PathwayCommons; O15519; -.
DR Reactome; R-HSA-3371378; Regulation by c-FLIP. [O15519-1]
DR Reactome; R-HSA-5213460; RIPK1-mediated regulated necrosis.
DR Reactome; R-HSA-5218900; CASP8 activity is inhibited.
DR Reactome; R-HSA-5357905; Regulation of TNFR1 signaling. [O15519-1]
DR Reactome; R-HSA-69416; Dimerization of procaspase-8. [O15519-2]
DR Reactome; R-HSA-75158; TRAIL signaling.
DR SignaLink; O15519; -.
DR SIGNOR; O15519; -.
DR BioGRID-ORCS; 8837; 338 hits in 1084 CRISPR screens.
DR ChiTaRS; CFLAR; human.
DR EvolutionaryTrace; O15519; -.
DR GeneWiki; CFLAR; -.
DR GenomeRNAi; 8837; -.
DR Pharos; O15519; Tbio.
DR PRO; PR:O15519; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; O15519; protein.
DR Bgee; ENSG00000003402; Expressed in right lung and 209 other tissues.
DR ExpressionAtlas; O15519; baseline and differential.
DR Genevisible; O15519; HS.
DR GO; GO:0031265; C:CD95 death-inducing signaling complex; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031264; C:death-inducing signaling complex; IDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0097342; C:ripoptosome; IDA:UniProtKB.
DR GO; GO:0097153; F:cysteine-type endopeptidase activity involved in apoptotic process; IBA:GO_Central.
DR GO; GO:0097199; F:cysteine-type endopeptidase activity involved in apoptotic signaling pathway; IBA:GO_Central.
DR GO; GO:0097200; F:cysteine-type endopeptidase activity involved in execution phase of apoptosis; IBA:GO_Central.
DR GO; GO:0005123; F:death receptor binding; IEA:Ensembl.
DR GO; GO:0008047; F:enzyme activator activity; IDA:UniProtKB.
DR GO; GO:0002020; F:protease binding; IPI:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IMP:UniProtKB.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IEA:Ensembl.
DR GO; GO:0071392; P:cellular response to estradiol stimulus; IEA:Ensembl.
DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEA:Ensembl.
DR GO; GO:0071732; P:cellular response to nitric oxide; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:ProtInc.
DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IEA:Ensembl.
DR GO; GO:1903845; P:negative regulation of cellular response to transforming growth factor beta stimulus; IEA:Ensembl.
DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IDA:UniProtKB.
DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; IDA:MGI.
DR GO; GO:1903944; P:negative regulation of hepatocyte apoptotic process; IEA:Ensembl.
DR GO; GO:1901740; P:negative regulation of myoblast fusion; ISS:BHF-UCL.
DR GO; GO:1903427; P:negative regulation of reactive oxygen species biosynthetic process; IEA:Ensembl.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:1903055; P:positive regulation of extracellular matrix organization; IEA:Ensembl.
DR GO; GO:0072126; P:positive regulation of glomerular mesangial cell proliferation; IEA:Ensembl.
DR GO; GO:2000347; P:positive regulation of hepatocyte proliferation; IEA:Ensembl.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEP:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IEA:Ensembl.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:BHF-UCL.
DR GO; GO:0006508; P:proteolysis; IEA:InterPro.
DR GO; GO:0060544; P:regulation of necroptotic process; IDA:UniProtKB.
DR GO; GO:0014842; P:regulation of skeletal muscle satellite cell proliferation; ISS:BHF-UCL.
DR GO; GO:0033574; P:response to testosterone; IEA:Ensembl.
DR GO; GO:0014732; P:skeletal muscle atrophy; ISS:BHF-UCL.
DR GO; GO:0007519; P:skeletal muscle tissue development; ISS:BHF-UCL.
DR GO; GO:0043403; P:skeletal muscle tissue regeneration; ISS:BHF-UCL.
DR GO; GO:0014866; P:skeletal myofibril assembly; ISS:BHF-UCL.
DR GO; GO:0042060; P:wound healing; ISS:BHF-UCL.
DR CDD; cd00032; CASc; 1.
DR Gene3D; 1.10.533.10; -; 2.
DR InterPro; IPR029030; Caspase-like_dom_sf.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR001875; DED_dom.
DR InterPro; IPR002398; Pept_C14.
DR InterPro; IPR001309; Pept_C14_p20.
DR InterPro; IPR015917; Pept_C14A.
DR PANTHER; PTHR10454; PTHR10454; 1.
DR Pfam; PF01335; DED; 2.
DR SMART; SM00115; CASc; 1.
DR SMART; SM00031; DED; 2.
DR SUPFAM; SSF47986; SSF47986; 2.
DR SUPFAM; SSF52129; SSF52129; 1.
DR PROSITE; PS50208; CASPASE_P20; 1.
DR PROSITE; PS50168; DED; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Host-virus interaction;
KW Reference proteome; Repeat.
FT CHAIN 1..376
FT /note="CASP8 and FADD-like apoptosis regulator subunit p43"
FT /id="PRO_0000004678"
FT CHAIN 377..480
FT /note="CASP8 and FADD-like apoptosis regulator subunit p12"
FT /evidence="ECO:0000269|PubMed:9228018"
FT /id="PRO_0000004679"
FT DOMAIN 1..73
FT /note="DED 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00065"
FT DOMAIN 92..170
FT /note="DED 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00065"
FT REGION 1..435
FT /note="Not proteolytically processed and involved in
FT apoptosis inhibition"
FT REGION 1..305
FT /note="Interaction with CASP8 propeptide"
FT /evidence="ECO:0000269|PubMed:9208847,
FT ECO:0000269|PubMed:9326610"
FT REGION 1..227
FT /note="Interaction with FADD"
FT /evidence="ECO:0000269|PubMed:9208847,
FT ECO:0000269|PubMed:9326610"
FT REGION 1..195
FT /note="Interaction with CASP8"
FT /evidence="ECO:0000269|PubMed:9208847,
FT ECO:0000269|PubMed:9326610"
FT REGION 192..480
FT /note="Interaction with TRAF1 and TRAF2"
FT /evidence="ECO:0000269|PubMed:9208847"
FT REGION 192..435
FT /note="Interaction with CASP3"
FT /evidence="ECO:0000269|PubMed:9208847,
FT ECO:0000269|PubMed:9326610"
FT REGION 217..480
FT /note="Interaction with CASP8 subunits p18 and p10"
FT /evidence="ECO:0000269|PubMed:9208847,
FT ECO:0000269|PubMed:9326610"
FT REGION 263..358
FT /note="Caspase"
FT REGION 370..480
FT /note="Interaction with CASP8"
FT /evidence="ECO:0000269|PubMed:9208847,
FT ECO:0000269|PubMed:9326610"
FT SITE 369..370
FT /note="Cleavage; by CASP8"
FT /evidence="ECO:0000250|UniProtKB:O35732"
FT SITE 376..377
FT /note="Cleavage; by CASP8"
FT /evidence="ECO:0000269|PubMed:9228018"
FT VAR_SEQ 1..245
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.6"
FT /id="VSP_000825"
FT VAR_SEQ 1..96
FT /note="Missing (in isoform 3, isoform 7 and isoform 15)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:9326610, ECO:0000303|Ref.6"
FT /id="VSP_000824"
FT VAR_SEQ 2..30
FT /note="SAEVIHQVEEALDTDEKEMLLFLCRDVAI -> LERPPVCSKV (in
FT isoform 6)"
FT /evidence="ECO:0000303|Ref.6"
FT /id="VSP_000826"
FT VAR_SEQ 203..480
FT /note="Missing (in isoform 13)"
FT /evidence="ECO:0000303|PubMed:9208847"
FT /id="VSP_000831"
FT VAR_SEQ 203..237
FT /note="Missing (in isoform 8 and isoform 9)"
FT /evidence="ECO:0000303|PubMed:9228018"
FT /id="VSP_000830"
FT VAR_SEQ 203..221
FT /note="LHNGRSKEQRLKEQLGAQQ -> MITPYAHCPDLKILGNCSM (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:9217161,
FT ECO:0000303|PubMed:9289491, ECO:0000303|PubMed:9326610,
FT ECO:0000303|PubMed:9380701"
FT /id="VSP_000828"
FT VAR_SEQ 203..221
FT /note="LHNGRSKEQRLKEQLGAQQ -> E (in isoform 7)"
FT /evidence="ECO:0000303|Ref.6"
FT /id="VSP_000827"
FT VAR_SEQ 222..480
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9217161,
FT ECO:0000303|PubMed:9289491, ECO:0000303|PubMed:9326610,
FT ECO:0000303|PubMed:9380701"
FT /id="VSP_000829"
FT VAR_SEQ 265..292
FT /note="ELLRDTFTSLGYEVQKFLHLSMHGISQI -> GWSAMAQSQLTAISTSQVQA
FT ILLPQPPE (in isoform 12)"
FT /evidence="ECO:0000303|PubMed:10200473"
FT /id="VSP_000832"
FT VAR_SEQ 266..300
FT /note="LLRDTFTSLGYEVQKFLHLSMHGISQILGQFACMP -> NAHSWIFTLNSMA
FT TCMIGTAEFLPRRNIMFGCSTL (in isoform 10)"
FT /evidence="ECO:0000303|PubMed:9228018"
FT /id="VSP_000834"
FT VAR_SEQ 267..305
FT /note="LRDTFTSLGYEVQKFLHLSMHGISQILGQFACMPEHRDY -> CGVRGPAGG
FT QQPLGGGWASDEECGIQGSEARAVHSSPRS (in isoform 9)"
FT /evidence="ECO:0000303|PubMed:9228018"
FT /id="VSP_000836"
FT VAR_SEQ 293..480
FT /note="Missing (in isoform 12)"
FT /evidence="ECO:0000303|PubMed:10200473"
FT /id="VSP_000833"
FT VAR_SEQ 301..480
FT /note="Missing (in isoform 10)"
FT /evidence="ECO:0000303|PubMed:9228018"
FT /id="VSP_000835"
FT VAR_SEQ 306..480
FT /note="Missing (in isoform 9)"
FT /evidence="ECO:0000303|PubMed:9228018"
FT /id="VSP_000837"
FT VAR_SEQ 436..480
FT /note="KRPLLDLHIELNGYMYDWNSRVSAKEKYYVWLQHTLRKKLILSYT -> GTI
FT PGSGITESKDMHFSSLGCILLDVL (in isoform 11, isoform 7 and
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:10200473,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:9326610,
FT ECO:0000303|Ref.6"
FT /id="VSP_000838"
FT VAR_SEQ 436..480
FT /note="Missing (in isoform 14)"
FT /evidence="ECO:0000303|PubMed:9208847"
FT /id="VSP_000839"
FT VAR_SEQ 449..480
FT /note="YMYDWNSRVSAKEKYYVWLQHTLRKKLILSYT -> L (in isoform
FT 5)"
FT /evidence="ECO:0000303|Ref.6"
FT /id="VSP_000840"
FT VAR_SEQ 453..480
FT /note="WNSRVSAKEKYYVWLQHTLRKKLILSYT -> SLEHTGGRY (in
FT isoform 6)"
FT /evidence="ECO:0000303|Ref.6"
FT /id="VSP_000841"
FT VARIANT 203
FT /note="L -> I (in dbSNP:rs13424615)"
FT /id="VAR_048619"
FT MUTAGEN 360
FT /note="Y->F: Decreases apoptosis-inducing activity. Reduces
FT interaction with caspase-3 and proteolytic processing."
FT /evidence="ECO:0000269|PubMed:9208847"
FT MUTAGEN 376
FT /note="D->N,A: Abolishes proteolytic processing."
FT /evidence="ECO:0000269|PubMed:9228018"
FT CONFLICT 130..132
FT /note="SFL -> ISW (in Ref. 8; AAC15825/AAC15826)"
FT /evidence="ECO:0000305"
FT CONFLICT 343
FT /note="D -> E (in Ref. 8; AAC15825)"
FT /evidence="ECO:0000305"
FT CONFLICT 364
FT /note="E -> D (in Ref. 6; AAB99794)"
FT /evidence="ECO:0000305"
FT CONFLICT 366..368
FT /note="QLE -> PAG (in Ref. 8; AAC15825)"
FT /evidence="ECO:0000305"
FT CONFLICT 369
FT /note="D -> N (in Ref. 7; CAA74366)"
FT /evidence="ECO:0000305"
FT CONFLICT 372
FT /note="L -> F (in Ref. 6; AAB99793)"
FT /evidence="ECO:0000305"
FT CONFLICT 373..374
FT /note="LE -> WR (in Ref. 8; AAC15825)"
FT /evidence="ECO:0000305"
FT HELIX 2..12
FT /evidence="ECO:0007829|PDB:6M6O"
FT TURN 15..17
FT /evidence="ECO:0007829|PDB:6M6O"
FT HELIX 18..24
FT /evidence="ECO:0007829|PDB:6M6O"
FT TURN 25..28
FT /evidence="ECO:0007829|PDB:6M6O"
FT HELIX 38..47
FT /evidence="ECO:0007829|PDB:6M6O"
FT HELIX 52..61
FT /evidence="ECO:0007829|PDB:6M6O"
FT HELIX 67..71
FT /evidence="ECO:0007829|PDB:2N5R"
FT HELIX 76..84
FT /evidence="ECO:0007829|PDB:6M6O"
FT HELIX 92..103
FT /evidence="ECO:0007829|PDB:6M6O"
FT HELIX 106..120
FT /evidence="ECO:0007829|PDB:6M6O"
FT HELIX 131..141
FT /evidence="ECO:0007829|PDB:6M6O"
FT HELIX 151..158
FT /evidence="ECO:0007829|PDB:6M6O"
FT HELIX 162..173
FT /evidence="ECO:0007829|PDB:6M6O"
FT STRAND 239..241
FT /evidence="ECO:0007829|PDB:3H11"
FT STRAND 249..260
FT /evidence="ECO:0007829|PDB:3H11"
FT HELIX 266..274
FT /evidence="ECO:0007829|PDB:3H11"
FT STRAND 276..283
FT /evidence="ECO:0007829|PDB:3H11"
FT HELIX 286..297
FT /evidence="ECO:0007829|PDB:3H11"
FT HELIX 300..304
FT /evidence="ECO:0007829|PDB:3H11"
FT STRAND 306..317
FT /evidence="ECO:0007829|PDB:3H11"
FT HELIX 333..340
FT /evidence="ECO:0007829|PDB:3H11"
FT TURN 342..344
FT /evidence="ECO:0007829|PDB:3H11"
FT HELIX 346..348
FT /evidence="ECO:0007829|PDB:3H11"
FT STRAND 353..361
FT /evidence="ECO:0007829|PDB:3H11"
FT STRAND 400..409
FT /evidence="ECO:0007829|PDB:3H11"
FT HELIX 410..412
FT /evidence="ECO:0007829|PDB:3H11"
FT HELIX 422..433
FT /evidence="ECO:0007829|PDB:3H11"
FT HELIX 439..454
FT /evidence="ECO:0007829|PDB:3H11"
FT HELIX 459..461
FT /evidence="ECO:0007829|PDB:3H11"
FT STRAND 463..469
FT /evidence="ECO:0007829|PDB:3H11"
SQ SEQUENCE 480 AA; 55344 MW; 8C6D7E92AE1EB672 CRC64;
MSAEVIHQVE EALDTDEKEM LLFLCRDVAI DVVPPNVRDL LDILRERGKL SVGDLAELLY
RVRRFDLLKR ILKMDRKAVE THLLRNPHLV SDYRVLMAEI GEDLDKSDVS SLIFLMKDYM
GRGKISKEKS FLDLVVELEK LNLVAPDQLD LLEKCLKNIH RIDLKTKIQK YKQSVQGAGT
SYRNVLQAAI QKSLKDPSNN FRLHNGRSKE QRLKEQLGAQ QEPVKKSIQE SEAFLPQSIP
EERYKMKSKP LGICLIIDCI GNETELLRDT FTSLGYEVQK FLHLSMHGIS QILGQFACMP
EHRDYDSFVC VLVSRGGSQS VYGVDQTHSG LPLHHIRRMF MGDSCPYLAG KPKMFFIQNY
VVSEGQLEDS SLLEVDGPAM KNVEFKAQKR GLCTVHREAD FFWSLCTADM SLLEQSHSSP
SLYLQCLSQK LRQERKRPLL DLHIELNGYM YDWNSRVSAK EKYYVWLQHT LRKKLILSYT
