NL1B5_MOUSE
ID NL1B5_MOUSE Reviewed; 1196 AA.
AC Q0GKD5; Q2LKV0;
DT 09-DEC-2015, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 85.
DE RecName: Full=NACHT, LRR and PYD domains-containing protein 1b allele 5 {ECO:0000303|PubMed:16429160};
DE EC=3.4.-.- {ECO:0000250|UniProtKB:Q2LKW6};
DE Contains:
DE RecName: Full=NACHT, LRR and PYD domains-containing protein 1b, C-terminus {ECO:0000305};
DE Short=Nlrp1b1-CT {ECO:0000305};
DE Contains:
DE RecName: Full=NACHT, LRR and PYD domains-containing protein 1b, N-terminus {ECO:0000305};
DE Short=Nlrp1b1-NT {ECO:0000305};
GN Name=Nlrp1b; Synonyms=Nalp1b;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090 {ECO:0000312|EMBL:ABI18116.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, ACTIVITY
RP REGULATION, AND TISSUE SPECIFICITY.
RC STRAIN=129S1/SvImJ;
RX PubMed=16429160; DOI=10.1038/ng1724;
RA Boyden E.D., Dietrich W.F.;
RT "Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin.";
RL Nat. Genet. 38:240-244(2006).
RN [2]
RP TISSUE SPECIFICITY.
RX PubMed=23506131; DOI=10.1186/1471-2164-14-188;
RA Sastalla I., Crown D., Masters S.L., McKenzie A., Leppla S.H., Moayeri M.;
RT "Transcriptional analysis of the three Nlrp1 paralogs in mice.";
RL BMC Genomics 14:188-188(2013).
RN [3]
RP ACTIVITY REGULATION, FUNCTION, AND ACTIVATION BY ANTHRAX LETHAL TOXIN AND
RP METABOLIC INHIBITORS.
RX PubMed=24935976; DOI=10.1128/iai.02167-14;
RA Neiman-Zenevich J., Liao K.C., Mogridge J.;
RT "Distinct regions of NLRP1B are required to respond to anthrax lethal toxin
RT and metabolic inhibition.";
RL Infect. Immun. 82:3697-3703(2014).
RN [4]
RP FUNCTION, ACTIVITY REGULATION, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=31383852; DOI=10.1038/s41419-019-1817-5;
RA Gai K., Okondo M.C., Rao S.D., Chui A.J., Ball D.P., Johnson D.C.,
RA Bachovchin D.A.;
RT "DPP8/9 inhibitors are universal activators of functional NLRP1 alleles.";
RL Cell Death Dis. 10:587-587(2019).
RN [5]
RP REVIEW.
RX PubMed=32558991; DOI=10.1111/imr.12884;
RA Taabazuing C.Y., Griswold A.R., Bachovchin D.A.;
RT "The NLRP1 and CARD8 inflammasomes.";
RL Immunol. Rev. 297:13-25(2020).
CC -!- FUNCTION: Acts as the sensor component of the Nlrp1b inflammasome,
CC which mediates inflammasome activation in response to various pathogen-
CC associated signals, leading to subsequent pyroptosis (By similarity).
CC Inflammasomes are supramolecular complexes that assemble in the cytosol
CC in response to pathogens and other damage-associated signals and play
CC critical roles in innate immunity and inflammation (By similarity).
CC Acts as a recognition receptor (PRR): recognizes specific pathogens and
CC other damage-associated signals, such as B.anthracis lethal toxin (LT)
CC or Val-boroPro inhibitor, and mediates the formation of the
CC inflammasome polymeric complex (PubMed:16429160, PubMed:31383852). In
CC response to pathogen-associated signals, the N-terminal part of Nlrp1b
CC is degraded by the proteasome, releasing the cleaved C-terminal part of
CC the protein (NACHT, LRR and PYD domains-containing protein 1b, C-
CC terminus), which polymerizes to initiate the formation of the
CC inflammasome complex: the inflammasome directly recruits pro-caspase-1
CC (proCASP1) independently of PYCARD/ASC and promotes caspase-1 (CASP1)
CC activation, which subsequently cleaves and activates inflammatory
CC cytokines IL1B and IL18 and gasdermin-D (GSDMD), leading to pyroptosis
CC (By similarity). Activation of Nlrp1b inflammasome is also required for
CC HMGB1 secretion; the active cytokines and HMGB1 stimulate inflammatory
CC responses (By similarity). Primary mediator of macrophage
CC susceptibility to B.anthracis LT: in response to B.anthracis infection,
CC macrophages and dendritic cells release IL1B and undergo pyroptosis
CC (PubMed:16429160, PubMed:24935976). This early inflammatory response to
CC the toxin increases resistance to infection by B.anthracis spores
CC (PubMed:16429160, PubMed:24935976). {ECO:0000250|UniProtKB:Q2LKW6,
CC ECO:0000269|PubMed:16429160, ECO:0000269|PubMed:24935976,
CC ECO:0000269|PubMed:31383852}.
CC -!- FUNCTION: [NACHT, LRR and PYD domains-containing protein 1b allele 5]:
CC Constitutes the precursor of the Nlrp1b inflammasome, which mediates
CC autoproteolytic processing within the FIIND domain to generate the N-
CC terminal and C-terminal parts, which are associated non-covalently in
CC absence of pathogens and other damage-associated signals.
CC {ECO:0000250|UniProtKB:Q2LKW6}.
CC -!- FUNCTION: [NACHT, LRR and PYD domains-containing protein 1b, N-
CC terminus]: Regulatory part that prevents formation of the Nlrp1b
CC inflammasome: in absence of pathogens and other damage-associated
CC signals, interacts with the C-terminal part of Nlrp1b (NACHT, LRR and
CC PYD domains-containing protein 1b, C-terminus), preventing activation
CC of the Nlrp1b inflammasome. In response to pathogen-associated signals,
CC this part is ubiquitinated by the N-end rule pathway and degraded by
CC the proteasome, releasing the cleaved C-terminal part of the protein,
CC which polymerizes and forms the Nlrp1b inflammasome.
CC {ECO:0000250|UniProtKB:Q2LKW6}.
CC -!- FUNCTION: [NACHT, LRR and PYD domains-containing protein 1b, C-
CC terminus]: Constitutes the active part of the Nlrp1b inflammasome. In
CC absence of pathogens and other damage-associated signals, interacts
CC with the N-terminal part of Nlrp1b (NACHT, LRR and PYD domains-
CC containing protein 1b, N-terminus), preventing activation of the Nlrp1b
CC inflammasome. In response to pathogen-associated signals, the N-
CC terminal part of Nlrp1b is degraded by the proteasome, releasing this
CC form, which polymerizes to form the Nlrp1b inflammasome complex: the
CC Nlrp1b inflammasome complex then directly recruits pro-caspase-1
CC (proCASP1) and promotes caspase-1 (CASP1) activation, leading to
CC gasdermin-D (GSDMD) cleavage and subsequent pyroptosis.
CC {ECO:0000250|UniProtKB:Q2LKW6}.
CC -!- ACTIVITY REGULATION: Activated by cleavage by B.anthracis lethal toxin
CC (LT) endopeptidase (PubMed:16429160, PubMed:24935976). Cleavage by LT
CC promotes ubiquitination and degradation of the N-terminal part,
CC releasing the cleaved C-terminal part of the protein (NACHT, LRR and
CC PYD domains-containing protein 1b, C-terminus), which polymerizes and
CC forms the Nlrp1b inflammasome (By similarity). Nlrp1b inflammasome is
CC inhibited by DPP8 and DPP9, which sequester the C-terminal fragment of
CC Nlrp1b (NACHT, LRR and PYD domains-containing protein 1b, C-terminus)
CC in a ternary complex, thereby preventing Nlrp1b oligomerization and
CC activation (By similarity). Nlrp1b inflammasome is activated by Val-
CC boroPro (Talabostat, PT-100), an inhibitor of dipeptidyl peptidases
CC DPP8 and DPP9 (PubMed:31383852). Val-boroPro relieves inhibition of
CC DPP8 and/or DPP9 by promoting disruption of the ternary complex,
CC releasing its C-terminal part from autoinhibition (By similarity).
CC Activated by metabolic inhibitors, such as 2-deoxy-D-glucose and sodium
CC azide (PubMed:24935976). Not activated by muramyl dipeptide, nor by
CC full-length bacterial peptidoglycan (PubMed:24935976).
CC {ECO:0000250|UniProtKB:Q2LKW6, ECO:0000250|UniProtKB:Q9C000,
CC ECO:0000269|PubMed:16429160, ECO:0000269|PubMed:24935976,
CC ECO:0000269|PubMed:31383852}.
CC -!- SUBUNIT: Interacts with DPP9; leading to inhibit activation of the
CC inflammasome (By similarity). DPP9 acts via formation of a ternary
CC complex, composed of a DPP9 homodimer, one full-length Nlrp1b protein,
CC and one cleaved C-terminus of Nlrp1b (NACHT, LRR and PYD domains-
CC containing protein 1b, C-terminus) (By similarity). Interacts with
CC DPP8; leading to inhibit activation of the inflammasome, probably via
CC formation of a ternary complex with DPP8 (By similarity). Interacts
CC (via LRR repeats) with BCL2 and BCL2L1 (via the loop between motifs BH4
CC and BH3). Interacts with NOD2; this interaction may increase IL1B
CC release (By similarity). Interacts with EIF2AK2/PKR; this interaction
CC requires EIF2AK2 activity, is accompanied by EIF2AK2
CC autophosphorylation and promotes inflammasome assembly in response to
CC B.anthracis lethal toxin (By similarity). Interacts with MEFV; this
CC interaction targets Nlrp1b to degradation by autophagy, hence
CC preventing excessive IL1B- and IL18-mediated inflammation (By
CC similarity). {ECO:0000250|UniProtKB:Q2LKW6,
CC ECO:0000250|UniProtKB:Q9C000}.
CC -!- SUBUNIT: [NACHT, LRR and PYD domains-containing protein 1b, N-
CC terminus]: Interacts with the C-terminal part of Nlrp1b (NACHT, LRR and
CC PYD domains-containing protein 1b, C-terminus) in absence of pathogens
CC and other damage-associated signals. {ECO:0000250|UniProtKB:Q2LKW6}.
CC -!- SUBUNIT: [NACHT, LRR and PYD domains-containing protein 1b, C-
CC terminus]: Interacts with the N-terminal part of Nlrp1b (NACHT, LRR and
CC PYD domains-containing protein 1b, N-terminus) in absence of pathogens
CC and other damage-associated signals (By similarity). Homomultimer;
CC forms the Nlrp1b inflammasome polymeric complex, a filament composed of
CC homopolymers of this form in response to pathogens and other damage-
CC associated signals. The Nlrp1b inflammasome polymeric complex directly
CC recruits pro-caspase-1 (proCASP1) independently of PYCARD/ASC.
CC Interacts (via CARD domain) with CASP1 (via CARD domain); leading to
CC CASP1 activation (By similarity). {ECO:0000250|UniProtKB:Q2LKW6}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q2LKW6}.
CC -!- SUBCELLULAR LOCATION: [NACHT, LRR and PYD domains-containing protein
CC 1b, C-terminus]: Inflammasome {ECO:0000250|UniProtKB:Q2LKW6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q0GKD5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q0GKD5-2; Sequence=VSP_058010;
CC -!- TISSUE SPECIFICITY: Expressed in macrophages.
CC {ECO:0000269|PubMed:16429160, ECO:0000269|PubMed:23506131}.
CC -!- DOMAIN: The CARD domain is involved in the interaction with CASP1 and
CC CASP4/CASP11. {ECO:0000250|UniProtKB:Q9C000}.
CC -!- DOMAIN: The leucine-rich repeat (LRR) domain may be involved in
CC autoinhibition in the absence of activating signal, possibly through
CC intramolecular interaction with the NACHT domain.
CC {ECO:0000250|UniProtKB:Q2LKW6}.
CC -!- DOMAIN: The FIIND (domain with function to find) region is involved in
CC homomerization, but not in CASP1-binding. Autocatalytic cleavage in
CC this region occurs constitutively, prior to activation signals, and is
CC required for inflammasome activity (IL1B release), possibly by
CC facilitating CASP1 binding. Both N- and C-terminal fragments remain
CC associated. {ECO:0000250|UniProtKB:Q2LKW6}.
CC -!- DOMAIN: [NACHT, LRR and PYD domains-containing protein 1b, C-terminus]:
CC The C-terminal part of Nlrp1b oligomerizes to form the core of the
CC Nlrp1b inflammasome filament: in the filament, the CARD domains form a
CC central helical filaments that are promoted by oligomerized, but
CC flexibly linked, UPA regions surrounding the filaments. The UPA region
CC reduces the threshold needed for filament formation and signaling.
CC {ECO:0000250|UniProtKB:Q9C000}.
CC -!- PTM: [NACHT, LRR and PYD domains-containing protein 1b allele 5]:
CC Autocatalytically cleaved. Autocatalytic cleavage in FIIND region
CC occurs constitutively, prior to activation signals, and is required for
CC inflammasome activity (IL1B release), possibly by facilitating CASP1
CC binding. Both N- and C-terminal parts remain associated non-covalently.
CC {ECO:0000305|PubMed:31383852}.
CC -!- PTM: [NACHT, LRR and PYD domains-containing protein 1b, N-terminus]:
CC Ubiquitinated by the N-end rule pathway in response to pathogens and
CC other damage-associated signals, leading to its degradation by the
CC proteasome and subsequent release of the cleaved C-terminal part of the
CC protein (NACHT, LRR and PYD domains-containing protein 1b, C-terminus),
CC which polymerizes and forms the Nlrp1b inflammasome.
CC {ECO:0000250|UniProtKB:Q2LKW6}.
CC -!- PTM: [NACHT, LRR and PYD domains-containing protein 1b, N-terminus]:
CC (Microbial infection) Cleavage by B.anthracis lethal toxin (LT)
CC endopeptidase promotes ubiquitination and degradation of the N-terminal
CC part, releasing the cleaved C-terminal part of the protein (NACHT, LRR
CC and PYD domains-containing protein 1b, C-terminus), which polymerizes
CC and forms the Nlrp1b inflammasome. {ECO:0000305|PubMed:16429160,
CC ECO:0000305|PubMed:24935976}.
CC -!- POLYMORPHISM: Nlrp1b gene is extremely polymorphic. 5 alleles have been
CC described in 18 inbred strains: 1 (AC Q2LKW6), 2 (AC A1Z198), 3 (AC
CC Q2LKV5), 4 (AC Q2LKV2) and 5 (this entry). These alleles define
CC susceptibility to B.anthracis lethal toxin (LT). Alleles 1 (carried by
CC strains 129S1/SvImJ, BALB/cJ, C3H/HeJ, CBA/J, FVB/NJ, NON/ShiLtJ, NZO
CC (NZO/HlLtJ) and SWR/J) and 5 (CAST/EiJ) confer macrophage
CC susceptibility to LT. Strains with macrophages resistant to anthrax LT
CC carry alleles 2 (A/J, C57BL/6J and I/LnJ), 3 (AKR/J, NOD/LtJ and SJL/J)
CC or 4 (DBA/2J, P/J and SM/J). Sensitivity to LT leads to IL1B release,
CC macrophage pyroptosis and neutrophil recruitment. This early
CC inflammatory response confers increased resistance to infection by B.
CC anthracis spores (PubMed:16429160). The sequence shown in this entry is
CC that of allele 5 (PubMed:16429160). {ECO:0000269|PubMed:16429160,
CC ECO:0000303|PubMed:16429160}.
CC -!- MISCELLANEOUS: Three tandem Nrlp1 paralogs, Nrlp1a, Nrlp1b and Nrlp1c,
CC have been identified. Nlrp1c is predicted to be a pseudogene. Neither
CC Nlrp1a, nor Nrlp1c are expressed in anthrax lethal toxin susceptible
CC strains, hence neither of them is thought to play an important role in
CC this phenotype. {ECO:0000269|PubMed:23506131,
CC ECO:0000305|PubMed:16429160}.
CC -!- MISCELLANEOUS: In macrophages and dendritic cells, NLRP1 inflammasome
CC activation of CASP1 and IL1B maturation can be dampened by direct
CC contact with activated effector and memory T-cells. This effect may be
CC mediated by hexameric TNF ligands, such as CD40LG.
CC {ECO:0000250|UniProtKB:Q2LKW6}.
CC -!- SIMILARITY: Belongs to the NLRP family. {ECO:0000305}.
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DR EMBL; DQ117600; AAZ40526.1; -; mRNA.
DR EMBL; DQ860103; ABI18116.1; -; mRNA.
DR EMBL; DQ860104; ABI18117.1; -; mRNA.
DR AlphaFoldDB; Q0GKD5; -.
DR SMR; Q0GKD5; -.
DR ComplexPortal; CPX-4270; NLRP1b inflammasome, allele-5 variant.
DR MEROPS; S79.002; -.
DR PRIDE; Q0GKD5; -.
DR MGI; MGI:3582959; Nlrp1b.
DR GO; GO:0005737; C:cytoplasm; IC:ComplexPortal.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0061702; C:inflammasome complex; ISO:MGI.
DR GO; GO:0072558; C:NLRP1 inflammasome complex; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0016887; F:ATP hydrolysis activity; ISO:MGI.
DR GO; GO:0140608; F:cysteine-type endopeptidase activator activity; ISO:MGI.
DR GO; GO:0003690; F:double-stranded DNA binding; ISO:MGI.
DR GO; GO:0003725; F:double-stranded RNA binding; ISO:MGI.
DR GO; GO:0004175; F:endopeptidase activity; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0043621; F:protein self-association; ISO:MGI.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
DR GO; GO:0140374; P:antiviral innate immune response; ISO:MGI.
DR GO; GO:0051607; P:defense response to virus; ISO:MGI.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0051402; P:neuron apoptotic process; ISO:MGI.
DR GO; GO:1904784; P:NLRP1 inflammasome complex assembly; ISO:MGI.
DR GO; GO:0002221; P:pattern recognition receptor signaling pathway; IC:ComplexPortal.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISO:MGI.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISO:MGI.
DR GO; GO:0030163; P:protein catabolic process; IMP:MGI.
DR GO; GO:0051260; P:protein homooligomerization; ISO:MGI.
DR GO; GO:0070269; P:pyroptosis; IMP:MGI.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro.
DR GO; GO:0097264; P:self proteolysis; ISO:MGI.
DR CDD; cd08330; CARD_ASC_NALP1; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR001315; CARD.
DR InterPro; IPR033516; CARD8/ASC/NALP1_CARD.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR025307; FIIND_dom.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR007111; NACHT_NTPase.
DR InterPro; IPR041267; NLRP_HD2.
DR InterPro; IPR041075; NOD2_WH.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF00619; CARD; 1.
DR Pfam; PF13553; FIIND; 1.
DR Pfam; PF05729; NACHT; 1.
DR Pfam; PF17776; NLRC4_HD2; 1.
DR Pfam; PF17779; NOD2_WH; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50209; CARD; 1.
DR PROSITE; PS51830; FIIND; 1.
DR PROSITE; PS50837; NACHT; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cytoplasm; Hydrolase; Immunity;
KW Inflammasome; Inflammatory response; Innate immunity; Leucine-rich repeat;
KW Necrosis; Nucleotide-binding; Protease; Repeat; Ubl conjugation.
FT CHAIN 1..1196
FT /note="NACHT, LRR and PYD domains-containing protein 1b
FT allele 5"
FT /id="PRO_0000435107"
FT CHAIN 1..922
FT /note="NACHT, LRR and PYD domains-containing protein 1b, N-
FT terminus"
FT /evidence="ECO:0000250|UniProtKB:Q2LKW6"
FT /id="PRO_0000452859"
FT CHAIN 923..1196
FT /note="NACHT, LRR and PYD domains-containing protein 1b, C-
FT terminus"
FT /evidence="ECO:0000250|UniProtKB:Q2LKW6"
FT /id="PRO_0000452860"
FT DOMAIN 126..435
FT /note="NACHT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT REPEAT 627..647
FT /note="LRR 1"
FT REPEAT 684..704
FT /note="LRR 2"
FT DOMAIN 789..1072
FT /note="FIIND"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01174"
FT DOMAIN 1106..1189
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 789..922
FT /note="ZU5"
FT /evidence="ECO:0000250|UniProtKB:Q9C000"
FT REGION 923..1072
FT /note="UPA"
FT /evidence="ECO:0000250|UniProtKB:Q9C000"
FT COMPBIAS 8..22
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 132..139
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT SITE 44..45
FT /note="Probable cleavage; by anthrax lethal toxin
FT endopeptidase component"
FT /evidence="ECO:0000250|UniProtKB:Q2LKW6"
FT SITE 896
FT /note="Trigger for autolytic processing"
FT /evidence="ECO:0000250|UniProtKB:Q9C000"
FT SITE 922..923
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:Q9C000,
FT ECO:0000255|PROSITE-ProRule:PRU01174"
FT VAR_SEQ 1061..1084
FT /note="Missing (in isoform 2)"
FT /id="VSP_058010"
SQ SEQUENCE 1196 AA; 136518 MW; E7AE9B4DA716D0A0 CRC64;
MEESPPKQKS NTKVTQHEGQ QDLNTTRHMN VELKHRPKLE RHLKLGMIPV VYMKQGEEIL
YPAQSLREEN LIQNFTSLLL LQKLCPKDPE NMVRKSWASC VPEEGGHMIN IQDLFGPNIG
TQKEPQLVII EGAAGIGKST LARLVKRAWK EGQLYRDHFQ HVFFFSCREL AQCKKLSLAE
LIAQGQEVPT APINQILSHP EKLLFILDGI DEPAWVLADQ NPELCLHWSQ RQPVHTLLGS
LLGKSIFPEA FFLLTTRTTA LQKFIPSLPM PCQVEVLGFS GIERENYFYK YFANQRHAIT
AFMMVESNPV LLTLCEVPWV CWLVCTCLKK QMEQGRVLSL KSQTTTALCL KYLSLTIPDK
HRRTQVKALC SLAAEGIWKR RTLFSESDLC KQGLDEDAVA TFLKTGVLQK QASSLSYSFA
HLCLQEFFAA ISCILEDSEE RHGNMEMDRI VETLVERYGR QNLFEAPTVR FLFGLLGKEG
VKGMEKLFSC SLHGKTNLKL LWHILVKSQP HQPPCLGLLH CLYENQDMEL LTHVMHDLQG
TIVPGPNDIA HTVLQTNVKH LVVQTDMELM VATFCIQFYC HVRTLQLNME KQQGYALISP
RMVLYRWTPI TNASWEILFY NLKFTRNLEG LDLSGNSLRY SVVQSLCNTL RYPGCQLKTL
WLVKCGLTSR HCSLLASVLS AHSSLTELYL QLNDLGDDGV RMLCEGLRNP VCNLSILWLD
LYSLSAQVIT ELRTLEEKNP KLYIRSIWMP HMMVPTENMD EEAILTTFKQ QRQEPGDKPM
EILGTEEDFW GPTGPVATEL VDRVRNLYRV QLPMAGSYHC PSTGLHFVVT RAVTIEIEFC
AWSQFLDKTP LQQSHMVVGP LFDIKAEQGA VTAVYLPHFV SLKDTEASTF DFKVAHFQEH
GMVLETPDRV KPGYTVLKNP SFSPMGVVLR IIPAARHFIP ITSITLIYYR LNLEEVTLHL
YLVPNDCTIQ KAIDDEEMKF QFVRINKPPP VDNLFIGSRY IVSGSENLEI TPKELELCYR
SSKEFQLFSE IYVGNMGSEI KLQIKNKKHM KLIWEALLKP EFKFDHLCDQ EFCTILKNIM
ISPAGDLRPA LPRIAQALKD APSLLHFMDQ HREQLVARVT SVDPLLDKLH GLVLNEESYE
AVRAENTNQD KMRKLFNLSR SWSRACKDLF YQALKETHPH LVMDLFEKSG GVSLGS
