CARD9_RAT
ID CARD9_RAT Reviewed; 536 AA.
AC Q9EPY0; F1LQK8;
DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Caspase recruitment domain-containing protein 9 {ECO:0000303|PubMed:11053425};
DE Short=rCARD9 {ECO:0000303|PubMed:11053425};
GN Name=Card9 {ECO:0000303|PubMed:11053425, ECO:0000312|RGD:708370};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RX PubMed=11053425; DOI=10.1074/jbc.c000726200;
RA Bertin J., Guo Y., Wang L., Srinivasula S.M., Jacobson M.D., Poyet J.-L.,
RA Merriam S., Du M.-Q., Dyer M.J.S., Robison K.E., DiStefano P.S.,
RA Alnemri E.S.;
RT "CARD9 is a novel caspase recruitment domain-containing protein that
RT interacts with Bcl10/CLAP and activates NF-kappa B.";
RL J. Biol. Chem. 275:41082-41086(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [3]
RP PHOSPHORYLATION AT THR-531 AND THR-533, MUTAGENESIS OF THR-526; SER-528;
RP THR-531 AND THR-533, FUNCTION, AND INTERACTION WITH VHL.
RX PubMed=17936701; DOI=10.1016/j.molcel.2007.09.010;
RA Yang H., Minamishima Y.A., Yan Q., Schlisio S., Ebert B.L., Zhang X.,
RA Zhang L., Kim W.Y., Olumi A.F., Kaelin W.G. Jr.;
RT "pVHL acts as an adaptor to promote the inhibitory phosphorylation of the
RT NF-kappaB agonist Card9 by CK2.";
RL Mol. Cell 28:15-27(2007).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; SER-424; SER-425; SER-451
RP AND SER-461, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Adapter protein that plays a key role in innate immune
CC response against fungi by forming signaling complexes downstream of C-
CC type lectin receptors (By similarity). CARD9-mediated signals are
CC essential for antifungal immunity against a subset of fungi from the
CC phylum Ascomycota (By similarity). Transduces signals in myeloid cells
CC downstream of C-type lectin receptors CLEC7A (dectin-1), CLEC6A
CC (dectin-2) and CLEC4E (Mincle), which detect pathogen-associated
CC molecular pattern metabolites (PAMPs), such as fungal carbohydrates,
CC and trigger CARD9 activation (PubMed:17936701). Upon activation, CARD9
CC homooligomerizes to form a nucleating helical template that recruits
CC BCL10 via CARD-CARD interaction, thereby promoting polymerization of
CC BCL10 and subsequent recruitment of MALT1: this leads to activation of
CC NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14)
CC pathways which stimulate expression of genes encoding pro-inflammatory
CC cytokines and chemokines (PubMed:17936701). CARD9 signaling in antigen-
CC presenting cells links innate sensing of fungi to the activation of
CC adaptive immunity and provides a cytokine milieu that induces the
CC development and subsequent of interleukin 17-producing T helper (Th17)
CC cells (By similarity). Also involved in activation of myeloid cells via
CC classical ITAM-associated receptors and TLR: required for TLR-mediated
CC activation of MAPK, while it is not required for TLR-induced activation
CC of NF-kappa-B (By similarity). CARD9 can also be engaged independently
CC of BCL10: forms a complex with RASGRF1 downstream of C-type lectin
CC receptors, which recruits and activates HRAS, leading to ERK activation
CC and the production of cytokines (By similarity). Acts as an important
CC regulator of the intestinal commensal fungi (mycobiota) component of
CC the gut microbiota (By similarity). Plays an essential role in
CC antifungal immunity against dissemination of gut fungi: acts by
CC promoting induction of antifungal IgG antibodies response in CX3CR1(+)
CC macrophages to confer protection against disseminated C.albicans or
CC C.auris infection (By similarity). Also mediates immunity against other
CC pathogens, such as certain bacteria, viruses and parasites; CARD9
CC signaling is however redundant with other innate immune responses (By
CC similarity). In response to L.monocytogenes infection, required for the
CC production of inflammatory cytokines activated by intracellular
CC peptidoglycan: acts by connecting NOD2 recognition of peptidoglycan to
CC downstream activation of MAP kinases (MAPK) without activating NF-
CC kappa-B (By similarity). {ECO:0000250|UniProtKB:A2AIV8,
CC ECO:0000269|PubMed:17936701}.
CC -!- ACTIVITY REGULATION: Maintained in an autoinhibited state via
CC homodimerization in which the CARD domain forms an extensive
CC interaction with the adjacent linker and coiled-coil regions (By
CC similarity). Activation downstream of C-type lectin receptors, by
CC phosphorylation by PRKCD and/or ubiquitination by TRIM62, triggers
CC disruption of the CARD domain-coiled coil interface, CARD9
CC homooligomerization and BCL10 recruitment, followed by activation of
CC NF-kappa-B and MAP kinase p38 pathways (By similarity). Zinc-binding
CC inhibits activation by stabilizing the CARD ground-state conformation
CC and restricting its capacity to form BCL10-nucleating filaments (By
CC similarity). {ECO:0000250|UniProtKB:A2AIV8,
CC ECO:0000250|UniProtKB:Q9H257}.
CC -!- SUBUNIT: Monomer. Homodimer; homodimerization is mediated by the CARD
CC domain which forms an extensive interaction with the adjacent linker
CC and coiled-coil regions; leads to an autoinhibited state. Homomultimer;
CC polymerizes following activation, forming a nucleating helical template
CC that seeds BCL10-filament formation via a CARD-CARD interaction (By
CC similarity). Interacts (via CARD domain) with BCL10 (via CARD domain);
CC interaction takes place following CARD9 activation and polymerization,
CC leading to the formation of a filamentous CBM complex assembly.
CC Component of a CBM complex (CARD9-BCL10, MALT1), composed of CARD9,
CC BCL10 and MALT1. Interacts with RASGRF1. Interacts with NOD2 (via NACHT
CC domain); interaction is direct. Interacts with RIPK2 (By similarity).
CC Interacts with VHL; without leading to protein degradation
CC (PubMed:17936701). {ECO:0000250|UniProtKB:A2AIV8,
CC ECO:0000250|UniProtKB:Q9H257, ECO:0000269|PubMed:17936701}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9H257}.
CC -!- DOMAIN: The linker region, also named autoinhibitory interface, is
CC required to prevent constitutive activation and maintain CARD9 in an
CC autoinhibitory state. Disruption of this region triggers polymerization
CC and activation, leading to formation of BCL10-nucleating filaments.
CC {ECO:0000250|UniProtKB:Q9H257}.
CC -!- PTM: Phosphorylated at Thr-231 by PRKCD downstream of C-type lectin
CC receptors activation: phosphorylation promotes interaction with BCL10,
CC followed by activation of NF-kappa-B and MAP kinase p38 pathways (By
CC similarity). Phosphorylated at Thr-531 and Thr-533 by CK2 following
CC interaction with VHL, leading to inhibit the ability to activate NF-
CC kappa-B (PubMed:17936701). {ECO:0000250|UniProtKB:A2AIV8,
CC ECO:0000269|PubMed:17936701}.
CC -!- PTM: Ubiquitinated at Lys-125 via 'Lys-27'-linked ubiquitin by TRIM62
CC downstream of C-type lectin receptors activation; leading to CARD9
CC activation, followed by activation of NF-kappa-B and MAP kinase p38
CC pathways. Deubiquitinated at Lys-125 by USP15, inhibiting CARD9.
CC {ECO:0000250|UniProtKB:Q9H257}.
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DR EMBL; AF311288; AAG28791.1; -; mRNA.
DR EMBL; AABR06021907; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_071639.1; NM_022303.1.
DR AlphaFoldDB; Q9EPY0; -.
DR SMR; Q9EPY0; -.
DR STRING; 10116.ENSRNOP00000025456; -.
DR iPTMnet; Q9EPY0; -.
DR PhosphoSitePlus; Q9EPY0; -.
DR jPOST; Q9EPY0; -.
DR PaxDb; Q9EPY0; -.
DR PRIDE; Q9EPY0; -.
DR Ensembl; ENSRNOT00000091484; ENSRNOP00000074450; ENSRNOG00000051470.
DR GeneID; 64171; -.
DR KEGG; rno:64171; -.
DR UCSC; RGD:708370; rat.
DR CTD; 64170; -.
DR RGD; 708370; Card9.
DR eggNOG; ENOG502R00K; Eukaryota.
DR GeneTree; ENSGT00940000160570; -.
DR HOGENOM; CLU_038057_1_0_1; -.
DR InParanoid; Q9EPY0; -.
DR OMA; EDEECWI; -.
DR OrthoDB; 115953at2759; -.
DR Reactome; R-RNO-5607764; CLEC7A (Dectin-1) signaling.
DR PRO; PR:Q9EPY0; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000051470; Expressed in esophagus and 19 other tissues.
DR Genevisible; Q9EPY0; RN.
DR GO; GO:0032449; C:CBM complex; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0050700; F:CARD domain binding; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019904; F:protein domain specific binding; IMP:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0043621; F:protein self-association; ISO:RGD.
DR GO; GO:0061760; P:antifungal innate immune response; ISS:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; ISO:RGD.
DR GO; GO:0051607; P:defense response to virus; ISO:RGD.
DR GO; GO:0048874; P:host-mediated regulation of intestinal microbiota composition; ISS:UniProtKB.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IMP:RGD.
DR GO; GO:0016064; P:immunoglobulin mediated immune response; ISS:UniProtKB.
DR GO; GO:0007254; P:JNK cascade; IEA:Ensembl.
DR GO; GO:0002446; P:neutrophil mediated immunity; ISS:UniProtKB.
DR GO; GO:0032722; P:positive regulation of chemokine production; ISO:RGD.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
DR GO; GO:0001819; P:positive regulation of cytokine production; ISS:UniProtKB.
DR GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; ISS:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; ISS:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISO:RGD.
DR GO; GO:0045089; P:positive regulation of innate immune response; ISO:RGD.
DR GO; GO:0032740; P:positive regulation of interleukin-17 production; ISS:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:UniProtKB.
DR GO; GO:0046330; P:positive regulation of JNK cascade; ISO:RGD.
DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; IEA:Ensembl.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0032874; P:positive regulation of stress-activated MAPK cascade; ISS:UniProtKB.
DR GO; GO:2000318; P:positive regulation of T-helper 17 type immune response; ISO:RGD.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:RGD.
DR GO; GO:0051260; P:protein homooligomerization; ISS:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro.
DR GO; GO:0032663; P:regulation of interleukin-2 production; ISO:RGD.
DR GO; GO:0032675; P:regulation of interleukin-6 production; ISO:RGD.
DR GO; GO:0032680; P:regulation of tumor necrosis factor production; ISO:RGD.
DR GO; GO:0043330; P:response to exogenous dsRNA; ISO:RGD.
DR GO; GO:0009620; P:response to fungus; ISO:RGD.
DR GO; GO:0032495; P:response to muramyl dipeptide; ISO:RGD.
DR GO; GO:0032494; P:response to peptidoglycan; ISO:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:RGD.
DR CDD; cd08809; CARD_CARD9; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR001315; CARD.
DR InterPro; IPR042142; CARD_CARD9.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR Pfam; PF00619; CARD; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR PROSITE; PS50209; CARD; 1.
PE 1: Evidence at protein level;
KW Adaptive immunity; Coiled coil; Cytoplasm; Immunity; Innate immunity;
KW Isopeptide bond; Metal-binding; Phosphoprotein; Reference proteome;
KW Ubl conjugation; Zinc.
FT CHAIN 1..536
FT /note="Caspase recruitment domain-containing protein 9"
FT /id="PRO_0000144083"
FT DOMAIN 6..98
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT REGION 99..116
FT /note="Linker"
FT /evidence="ECO:0000250|UniProtKB:Q9H257"
FT REGION 425..451
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 472..536
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 117..277
FT /evidence="ECO:0000255"
FT COILED 303..420
FT /evidence="ECO:0000255"
FT COMPBIAS 425..442
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 484..507
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 517..536
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 3
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9H257"
FT BINDING 10
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9H257"
FT BINDING 73
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9H257"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 231
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:A2AIV8"
FT MOD_RES 277
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H257"
FT MOD_RES 424
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 425
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 431
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A2AIV8"
FT MOD_RES 451
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 461
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 483
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H257"
FT MOD_RES 498
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H257"
FT MOD_RES 531
FT /note="Phosphothreonine; by CK2"
FT /evidence="ECO:0000269|PubMed:17936701"
FT MOD_RES 533
FT /note="Phosphothreonine; by CK2"
FT /evidence="ECO:0000269|PubMed:17936701"
FT CROSSLNK 125
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9H257"
FT MUTAGEN 526
FT /note="T->A: Abolished phosphorylation by CK2 and increased
FT activation of NF-kappa-B; when associated with A-528; A-531
FT and A-533."
FT /evidence="ECO:0000269|PubMed:17936701"
FT MUTAGEN 528
FT /note="S->A: Abolished phosphorylation by CK2 and increased
FT activation of NF-kappa-B; when associated with A-526; A-531
FT and A-533."
FT /evidence="ECO:0000269|PubMed:17936701"
FT MUTAGEN 531
FT /note="T->A: Abolished phosphorylation by CK2 and increased
FT activation of NF-kappa-B; when associated with A-526; A-528
FT and A-533."
FT /evidence="ECO:0000269|PubMed:17936701"
FT MUTAGEN 533
FT /note="T->A: Abolished phosphorylation by CK2 and increased
FT activation of NF-kappa-B; when associated with A-526; A-528
FT and A-531."
FT /evidence="ECO:0000269|PubMed:17936701"
SQ SEQUENCE 536 AA; 62632 MW; 6F33089CB7E6BAC9 CRC64;
MSDYENDDEC WSALESFRVK LISVIDPSRI TPYLRQCKVL NPDDEEQVLS DPNLVIRKRK
VGVLLDILQR TGHKGYVAFL ESLELYYPQL YRKVTGKEPA RVFSMIIDAS GESGLTQLLM
TEVMKLQKKV QDLTALLSSK DDFIKELRVK DSLLRKHQER VQRLKEECEL SSAELKRCKD
ENYDLAMRLA HLSEEKGAAL MRNRDLQLEV DQLRHSLMKA EDDCKVERKH TLKLRHAMEQ
RPSQELLWDL QQERDLLQAR VQELEVSVQE GKLHRNSPYI QVLEEDWRQA LQEHQEQAST
IFSLRKDLRQ AEALRTRCME EKEMFELQCL ALRKDAKMYK DRIEAILQQM EEVSIERDQA
MTSREELHAQ CAQSFQDKDK LRKQVRELDE KADELQLQLF QTESRLLAAE GRLKQQQLDM
LILSSDLEDS SPRNSQELSL PQDLEEDAQL SDKGVLADRE SPEQPFVVLN KKHLSQTHDT
VPSSSEPPEK ERRRLKESFE NYRRKRALRK MQNSWRQGEG DHGNTTGSDN TDTEGS
