CASPB_DANRE
ID CASPB_DANRE Reviewed; 404 AA.
AC Q504J1; A0A0R4ILD1; Q4U0E2; Q9DDJ2;
DT 11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2005, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Caspase b {ECO:0000312|ZFIN:ZDB-GENE-020812-1};
DE EC=3.4.22.58 {ECO:0000269|PubMed:12464617, ECO:0000269|PubMed:30076291};
DE AltName: Full=Caspase 19a {ECO:0000312|EMBL:AWP39899.1};
DE Contains:
DE RecName: Full=Caspase b subunit p20 {ECO:0000305|PubMed:30076291, ECO:0000305|PubMed:30150286};
DE Contains:
DE RecName: Full=Caspase b subunit p10 {ECO:0000305|PubMed:30076291, ECO:0000305|PubMed:30150286};
DE Flags: Precursor;
GN Name=caspb {ECO:0000312|ZFIN:ZDB-GENE-020812-1};
GN Synonyms=casp19a {ECO:0000312|ZFIN:ZDB-GENE-020812-1},
GN caspy2 {ECO:0000312|ZFIN:ZDB-GENE-020812-1};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955 {ECO:0000312|EMBL:AAH95000.1};
RN [1] {ECO:0000312|EMBL:AWP39899.1}
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RX PubMed=29791492; DOI=10.1371/journal.pone.0197966;
RA Spead O., Verreet T., Donelson C.J., Poulain F.E.;
RT "Characterization of the caspase family in zebrafish.";
RL PLoS ONE 13:E0197966-E0197966(2018).
RN [2] {ECO:0000312|EMBL:AAG45230.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10917738; DOI=10.1038/sj.cdd.4400679;
RA Inohara N., Nunez G.;
RT "Genes with homology to mammalian apoptosis regulators identified in
RT zebrafish.";
RL Cell Death Differ. 7:509-510(2000).
RN [3] {ECO:0000312|EMBL:AAY44398.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Tuebingen {ECO:0000312|EMBL:AAY44398.1};
RA Deng H.-X., Liu L., Wei Y.-Q., Zhao X.;
RT "Caspyb, a zebrafish caspase can induce cell apoptosis.";
RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000312|Proteomes:UP000000437}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen {ECO:0000312|Proteomes:UP000000437};
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [5] {ECO:0000312|EMBL:AAH95000.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Larva {ECO:0000312|EMBL:AAH95000.1};
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
RN [6] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, AND DEVELOPMENTAL STAGE.
RX PubMed=12464617; DOI=10.1074/jbc.m203944200;
RA Masumoto J., Zhou W., Chen F.F., Su F., Kuwada J.Y., Hidaka E.,
RA Katsuyama T., Sagara J., Taniguchi S., Ngo-Hazelett P., Postlethwait J.H.,
RA Nunez G., Inohara N.;
RT "Caspy, a zebrafish caspase, activated by ASC oligomerization is required
RT for pharyngeal arch development.";
RL J. Biol. Chem. 278:4268-4276(2003).
RN [7] {ECO:0000305}
RP DEVELOPMENTAL STAGE, AND INDUCTION BY PENTACHLOROPHENOL.
RX PubMed=28402832; DOI=10.1016/j.chemosphere.2017.03.100;
RA Zhao J., Huang G., Xu T., Yin D., Bai J., Gu W.;
RT "Early developmental exposure to pentachlorophenol causes alterations on
RT mRNA expressions of caspase protease family in zebrafish embryos.";
RL Chemosphere 180:141-148(2017).
RN [8] {ECO:0000305}
RP INTERACTION WITH CASPA.
RX PubMed=29791979; DOI=10.1111/febs.14514;
RA Li Y., Huang Y., Cao X., Yin X., Jin X., Liu S., Jiang J., Jiang W.,
RA Xiao T.S., Zhou R., Cai G., Hu B., Jin T.;
RT "Functional and structural characterization of zebrafish ASC.";
RL FEBS J. 285:2691-2707(2018).
RN [9] {ECO:0000305}
RP FUNCTION, PROTEOLYTIC CLEAVAGE, IDENTIFICATION IN NLRP1 INFLAMMASOME,
RP INTERACTION WITH PYCARD, SUBCELLULAR LOCATION, AND INDUCTION BY E.TARDA.
RX PubMed=30150286; DOI=10.4049/jimmunol.1800498;
RA Li J.Y., Gao K., Shao T., Fan D.D., Hu C.B., Sun C.C., Dong W.R., Lin A.F.,
RA Xiang L.X., Shao J.Z.;
RT "Characterization of an NLRP1 Inflammasome from Zebrafish Reveals a Unique
RT Sequential Activation Mechanism Underlying Inflammatory Caspases in Ancient
RT Vertebrates.";
RL J. Immunol. 201:1946-1966(2018).
RN [10] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, ACTIVITY REGULATION, SUBUNIT,
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION BY LPS AND E.PISCICIDA,
RP DOMAIN, PROTEOLYTIC CLEAVAGE, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP CYS-296.
RX PubMed=30076291; DOI=10.1038/s41467-018-04984-1;
RA Yang D., Zheng X., Chen S., Wang Z., Xu W., Tan J., Hu T., Hou M., Wang W.,
RA Gu Z., Wang Q., Zhang R., Zhang Y., Liu Q.;
RT "Sensing of cytosolic LPS through caspy2 pyrin domain mediates noncanonical
RT inflammasome activation in zebrafish.";
RL Nat. Commun. 9:3052-3052(2018).
CC -!- FUNCTION: Thiol protease which cleaves IL-1 beta (il1b), releasing the
CC mature cytokine which is involved in a variety of inflammatory
CC processes, and mediates apoptosis (PubMed:12464617, PubMed:30150286).
CC Component of the NLRP1 inflammasome, which plays a crucial role in
CC innate immunity and inflammation (PubMed:30150286). In response to
CC pathogens and other damage-associated signals, recruited to the NLRP1
CC inflammasome in its precursor form following the recruitment of caspase
CC caspa (PubMed:30150286). Its subsequent activation causes the cleavage
CC of the midformed pro-il1b and results in il1b maturation and secretion
CC in the extracellular milieu (PubMed:30150286). Activated by direct
CC binding to bacterial lipopolysaccharides (LPS), which causes non-
CC canonical inflammasome activation and results in the pyroptosis of
CC infected cells and their extrusion into the gut lumen, as well as in
CC cytokine secretion (PubMed:30076291). Plays a crucial role in the
CC restriction of bacterial infection to intestinal sites
CC (PubMed:30076291). Pyroptosis limits bacterial replication, while
CC cytokine secretion promotes the recruitment and activation of immune
CC cells and triggers mucosal inflammation (By similarity). Promotes
CC pyroptosis by bacterial infection by E.piscicida (PubMed:30076291).
CC {ECO:0000250|UniProtKB:P49662, ECO:0000269|PubMed:12464617,
CC ECO:0000269|PubMed:30076291, ECO:0000269|PubMed:30150286}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Strict requirement for Asp at the P1 position. It has a
CC preferred cleavage sequence of Tyr-Val-Ala-Asp-|- but also cleaves at
CC Asp-Glu-Val-Asp-|-.; EC=3.4.22.58;
CC Evidence={ECO:0000269|PubMed:12464617, ECO:0000269|PubMed:30076291};
CC -!- ACTIVITY REGULATION: Activated by homooligomerization induced by direct
CC binding to cytosolic LPS. {ECO:0000269|PubMed:30076291}.
CC -!- SUBUNIT: Upon direct LPS-binding, forms large homooligomers, resulting
CC in its activation (PubMed:30076291). These oligomers are often referred
CC to as 'non-canonical inflammasomes' (PubMed:30076291). Heterotetramer
CC that consists of two anti-parallel arranged heterodimers, each one
CC formed by a 20 kDa (p20) and a 10 kDa (p10) subunit (Probable).
CC Interacts with caspa (PubMed:29791979). Interacts with pycard; the
CC interaction only occurs in the presence of nlrp1 (PubMed:30150286).
CC Component of NLRP1 inflammasomes (PubMed:30150286). Inflammasomes are
CC supramolecular complexes that assemble in the cytosol in response to
CC pathogens and other damage-associated signals and play critical roles
CC in innate immunity and inflammation (PubMed:30150286). The NLRP1
CC inflammasome is composed of the signal sensor nlrp1, and the adapter
CC pycard (asc), which recruit effector pro-inflammatory caspases caspa
CC and/or caspb (PubMed:30150286). The interaction between nlrp1 and
CC pycard is required for the sequential recruitment of caspa and then
CC caspb (PubMed:30150286). Caspa is preferentially recruited first and
CC this causes the cleavage of pro-il1b into the midformed il1b
CC (PubMed:30150286). This is followed by the recruitment of caspb, which
CC is activated and cleaves the midformed il1b resulting in il1b
CC maturation (PubMed:30150286). {ECO:0000269|PubMed:29791979,
CC ECO:0000269|PubMed:30076291, ECO:0000269|PubMed:30150286,
CC ECO:0000305|PubMed:30076291, ECO:0000305|PubMed:30150286}.
CC -!- SUBCELLULAR LOCATION: Inflammasome {ECO:0000269|PubMed:30150286}.
CC Cytoplasm {ECO:0000269|PubMed:30150286}. Note=Co-localizes with pycard,
CC caspa and nlrp1 in the cytoplasm (PubMed:30150286). Co-localizes with
CC pycard at large cytoplasmic aggregates, known as specks
CC (PubMed:30150286). {ECO:0000269|PubMed:30150286}.
CC -!- TISSUE SPECIFICITY: Expressed in the spleen, kidney and liver, and
CC highly expressed in the gills and gut. {ECO:0000269|PubMed:30076291}.
CC -!- DEVELOPMENTAL STAGE: During embryonic development, highly expressed at
CC 8 hours post-fertilization (hpf) (PubMed:28402832). Expressed at the
CC pharyngula stage at 24 hpf and expression is maintained for 7 days
CC post-fertilization (PubMed:29791492, PubMed:28402832, PubMed:30076291).
CC During this time, expressed in the pharyngeal arches, and in the
CC epidermis and proctoderm at 48 hpf, and in the epidermis at 72 hpf
CC (PubMed:29791492, PubMed:12464617, PubMed:30076291). Also expressed in
CC the mouth at 48 and 72 hpf (PubMed:12464617, PubMed:30076291).
CC {ECO:0000269|PubMed:12464617, ECO:0000269|PubMed:28402832,
CC ECO:0000269|PubMed:29791492, ECO:0000269|PubMed:30076291}.
CC -!- INDUCTION: Up-regulated in response to pentachlorophenol (PCP), a toxic
CC pollutant (PubMed:28402832). Up-regulated in response to bacterial
CC lipopolysaccharides (LPS) and bacterial infection with E.piscicida
CC (PubMed:30076291). Up-regulated in response to bacterial infection with
CC E.tarda (PubMed:30150286). {ECO:0000269|PubMed:28402832,
CC ECO:0000269|PubMed:30076291, ECO:0000269|PubMed:30150286}.
CC -!- DOMAIN: The Pyrin domain mediates LPS recognition and
CC homooligomerization. {ECO:0000269|PubMed:30076291}.
CC -!- PTM: The two subunits are derived from the precursor sequence by an
CC autocatalytic mechanism. {ECO:0000305|PubMed:30076291,
CC ECO:0000305|PubMed:30150286}.
CC -!- DISRUPTION PHENOTYPE: Impaired pyroptosis in response to bacterial
CC infection with E.piscicida (PubMed:30076291). Morpholino knockdown
CC results in no observed phenotype (PubMed:30076291). Morpholino
CC knockdown results in impaired gut bacterial clearance following
CC bacterial infection with E.piscicida (PubMed:30076291). Morpholino
CC knockdown results in pericardial edema, erosion of the tail fin and
CC body axis, and impaired up-regulation of il1b, tnfa, il6, il8, il10 and
CC ifng1 cytokines in response to bacterial lipopolysaccharides (LPS)
CC (PubMed:30076291). {ECO:0000269|PubMed:30076291}.
CC -!- SIMILARITY: Belongs to the peptidase C14A family. {ECO:0000255,
CC ECO:0000255|RuleBase:RU003971}.
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DR EMBL; MG958005; AWP39899.1; -; mRNA.
DR EMBL; AF327410; AAG45230.1; -; mRNA.
DR EMBL; DQ022755; AAY44398.1; -; mRNA.
DR EMBL; BX469930; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC095000; AAH95000.1; -; mRNA.
DR EMBL; BC164498; AAI64498.1; -; mRNA.
DR RefSeq; NP_690840.2; NM_152884.2.
DR AlphaFoldDB; Q504J1; -.
DR SMR; Q504J1; -.
DR ComplexPortal; CPX-4948; NLRP1 inflammasome, variant 2.
DR STRING; 7955.ENSDARP00000068268; -.
DR MEROPS; C14.031; -.
DR PaxDb; Q504J1; -.
DR Ensembl; ENSDART00000073778; ENSDARP00000068268; ENSDARG00000052039.
DR Ensembl; ENSDART00000160970; ENSDARP00000134896; ENSDARG00000052039.
DR GeneID; 259303; -.
DR KEGG; dre:259303; -.
DR CTD; 259303; -.
DR ZFIN; ZDB-GENE-020812-1; caspb.
DR eggNOG; KOG3573; Eukaryota.
DR GeneTree; ENSGT00940000162428; -.
DR HOGENOM; CLU_036904_0_1_1; -.
DR OMA; WRVDILG; -.
DR OrthoDB; 1327703at2759; -.
DR TreeFam; TF102023; -.
DR Reactome; R-DRE-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-DRE-448706; Interleukin-1 processing.
DR Reactome; R-DRE-9008059; Interleukin-37 signaling.
DR PRO; PR:Q504J1; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 1.
DR Bgee; ENSDARG00000052039; Expressed in pharyngeal gill and 18 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0072558; C:NLRP1 inflammasome complex; IPI:ComplexPortal.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:ZFIN.
DR GO; GO:0097199; F:cysteine-type endopeptidase activity involved in apoptotic signaling pathway; IBA:GO_Central.
DR GO; GO:0008047; F:enzyme activator activity; IDA:ZFIN.
DR GO; GO:0001530; F:lipopolysaccharide binding; IDA:ZFIN.
DR GO; GO:0042742; P:defense response to bacterium; IDA:ZFIN.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0002221; P:pattern recognition receptor signaling pathway; IC:ComplexPortal.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:ZFIN.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IC:ComplexPortal.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IC:ComplexPortal.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0070269; P:pyroptosis; IDA:ZFIN.
DR CDD; cd00032; CASc; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR029030; Caspase-like_dom_sf.
DR InterPro; IPR033139; Caspase_cys_AS.
DR InterPro; IPR016129; Caspase_his_AS.
DR InterPro; IPR004020; DAPIN.
DR InterPro; IPR011029; DEATH-like_dom_sf.
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 Pfam; PF02758; PYRIN; 1.
DR PRINTS; PR00376; IL1BCENZYME.
DR SMART; SM00115; CASc; 1.
DR SMART; SM01289; PYRIN; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF52129; SSF52129; 1.
DR PROSITE; PS01122; CASPASE_CYS; 1.
DR PROSITE; PS01121; CASPASE_HIS; 1.
DR PROSITE; PS50207; CASPASE_P10; 1.
DR PROSITE; PS50208; CASPASE_P20; 1.
DR PROSITE; PS50824; DAPIN; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Cytoplasm; Hydrolase; Immunity; Inflammasome;
KW Inflammatory response; Innate immunity; Necrosis; Protease;
KW Reference proteome; Thiol protease; Zymogen.
FT PROPEP 1..171
FT /evidence="ECO:0000305|PubMed:30076291"
FT /id="PRO_0000448784"
FT CHAIN 172..300
FT /note="Caspase b subunit p20"
FT /evidence="ECO:0000305|PubMed:30076291,
FT ECO:0000305|PubMed:30150286"
FT /id="PRO_0000448785"
FT PROPEP 301..316
FT /evidence="ECO:0000305"
FT /id="PRO_0000448786"
FT CHAIN 317..404
FT /note="Caspase b subunit p10"
FT /evidence="ECO:0000305|PubMed:30076291,
FT ECO:0000305|PubMed:30150286"
FT /id="PRO_0000448787"
FT DOMAIN 8..80
FT /note="Pyrin"
FT /evidence="ECO:0000255"
FT ACT_SITE 249
FT /evidence="ECO:0000250|UniProtKB:P29466"
FT ACT_SITE 296
FT /evidence="ECO:0000269|PubMed:30076291"
FT MUTAGEN 296
FT /note="C->A: Abolishes catalytic activity. Abolishes
FT pyroptosis induced by bacterial lipopolysaccharides (LPS)."
FT /evidence="ECO:0000269|PubMed:30076291"
FT CONFLICT 18
FT /note="S -> A (in Ref. 3; AAY44398 and 2; AAG45230)"
FT /evidence="ECO:0000305"
FT CONFLICT 192
FT /note="N -> D (in Ref. 2; AAG45230)"
FT /evidence="ECO:0000305"
FT CONFLICT 213
FT /note="I -> M (in Ref. 2; AAG45230)"
FT /evidence="ECO:0000305"
FT CONFLICT 274
FT /note="S -> A (in Ref. 2; AAG45230)"
FT /evidence="ECO:0000305"
FT CONFLICT 380
FT /note="Q -> K (in Ref. 3; AAY44398 and 2; AAG45230)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 404 AA; 46090 MW; 02A7528805D8DD3F CRC64;
MEDITQLLSD VLEDLVESEL KQFTRQLWIG VKPGVEPIPR GKLENKDRQD VVDSMVQQYS
EDAGTITVQT LRKIKQNERA KRLESNLLKV QSQGQENKQN SEEPQPIPQI ISQPIQQIIS
QPINNAGSED LQPIQADWQR PRQIIPCSQE TKNTLLKAHG DDIYTPRSGT QRKGLALLIT
NIQFANTQHN RNGADRDEEN AEWLLRSLGF AVIKYRNLSG KDIRRAVENF SKRREHEDAD
STFIVIMSHG TRIDNKDAIV GVSDDVYFIE ETFSHLNSVN CPALIDKPKV ILIQACRGGQ
SSGVLAQDSV FASDSWVHME KDFVCFMSTM PNTFAYRNPI EGSFFISYIV DVFCSSAHRD
DIMELFRKVT LRMEKDQRFQ GQAKLLPCIE RTSISKRFYL FPGL
