ID PKP3_MOUSE Reviewed; 797 AA. AC Q9QY23; A4QPD8; Q0VGP3; Q3KQL7; DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot. DT 12-JUN-2007, sequence version 2. DT 02-OCT-2024, entry version 154. DE RecName: Full=Plakophilin-3; GN Name=Pkp3; 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; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=10381383; DOI=10.1242/jcs.112.14.2265; RA Bonne S., van Hengel J., Nollet F., Kools P., van Roy F.; RT "Plakophilin-3, a novel armadillo-like protein present in nuclei and RT desmosomes of epithelial cells."; RL J. Cell Sci. 112:2265-2276(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Colon, and Eye; 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 [3] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=17242355; DOI=10.1073/pnas.0609836104; RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; RT "Large-scale phosphorylation analysis of mouse liver."; RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). RN [4] RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION RP PHENOTYPE. RX PubMed=18079750; DOI=10.1038/sj.jid.5701189; RA Sklyarova T., Bonne S., D'Hooge P., Denecker G., Goossens S., De Rycke R., RA Borgonie G., Boesl M., van Roy F., van Hengel J.; RT "Plakophilin-3-deficient mice develop hair coat abnormalities and are prone RT to cutaneous inflammation."; RL J. Invest. Dermatol. 128:1375-1385(2008). RN [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-123; SER-180 AND SER-331, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brown adipose tissue, Kidney, Lung, and Pancreas; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [6] RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-261, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryo; RX PubMed=24129315; DOI=10.1074/mcp.o113.027870; RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M., RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V., RA Bedford M.T., Comb M.J.; RT "Immunoaffinity enrichment and mass spectrometry analysis of protein RT methylation."; RL Mol. Cell. Proteomics 13:372-387(2014). RN [7] RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION, AND RP DISRUPTION PHENOTYPE. RX PubMed=26173741; DOI=10.1002/eji.201445440; RA Sklyarova T., van Hengel J., Van Wonterghem E., Libert C., van Roy F., RA Vandenbroucke R.E.; RT "Hematopoietic plakophilin-3 regulates acute tissue-specific and systemic RT inflammation in mice."; RL Eur. J. Immunol. 45:2898-2910(2015). RN [8] RP FUNCTION, INTERACTION WITH RB1 AND CDKN1A, TISSUE SPECIFICITY, AND RP DISRUPTION PHENOTYPE. RX PubMed=36689330; DOI=10.1016/j.celrep.2023.112031; RA Mueller L., Keil R., Hatzfeld M.; RT "Plakophilin 3 facilitates G1/S phase transition and enhances proliferation RT by capturing RB protein in the cytoplasm and promoting EGFR signaling."; RL Cell Rep. 42:112031-112031(2023). CC -!- FUNCTION: A component of desmosome cell-cell junctions that positively CC regulate cellular adhesion (By similarity). Required for the CC localization of DSG2, DSP and PKP2 to mature desmosome junctions (By CC similarity). Required for the formation of DSP-containing desmosome CC precursors in the cytoplasm during desmosome assembly (By similarity). CC Also regulates the accumulation of CDH1 to mature desmosome junctions, CC via cAMP-dependent signaling and its interaction with activated RAP1A CC (By similarity). Positively regulates the stabilization of PKP2 mRNA CC and therefore protein abundance, via its interaction with FXR1, may CC also regulate the protein abundance of DSP via the same mechanism CC (PubMed:18079750). May also regulate the protein abundance of the CC desmosome component PKP1 (PubMed:18079750). Required for the CC organization of desmosome junctions at intercellular borders between CC basal keratinocytes of the epidermis, as a result plays a role in CC maintenance of the dermal barrier and regulation of the dermal CC inflammatory response (PubMed:18079750). Acts as a negative regulator CC of the inflammatory response in hematopoietic cells of the skin and CC intestine, via modulation of proinflammatory cytokine production CC (PubMed:26173741). Important for epithelial barrier maintenance in the CC intestine to reduce intestinal permeability, thereby plays a role in CC protection from intestinal-derived endotoxemia (PubMed:26173741). CC Required for the development of hair follicles, via a role in the CC regulation of inner root sheaf length, correct alignment and anterior- CC posterior polarity of hair follicles (PubMed:18079750). Promotes CC proliferation and cell-cycle G1/S phase transition of keratinocytes CC (PubMed:36689330). Promotes E2F1-driven transcription of G1/S phase CC promoting genes by acting to release E2F1 from its inhibitory CC interaction with RB1, via sequestering RB1 and CDKN1A to the cytoplasm CC and thereby increasing CDK4- and CDK6-driven phosphorylation of RB1 CC (PubMed:36689330). May act as a scaffold protein to facilitate MAPK CC phosphorylation of RPS6KA protein family members and subsequently CC promote downstream EGFR signaling (PubMed:36689330). May play a role in CC the positive regulation of transcription of Wnt-mediated TCF-responsive CC target genes (By similarity). {ECO:0000250|UniProtKB:Q9Y446, CC ECO:0000269|PubMed:18079750, ECO:0000269|PubMed:26173741, CC ECO:0000269|PubMed:36689330}. CC -!- SUBUNIT: Found in a complex composed of CDH1, RAP1A and PKP3; PKP3 acts CC as a scaffold protein within the complex, the complex is required for CC CDH1 localization to mature desmosome cell junctions (By similarity). CC Interacts with FXR1; the interaction facilitates the binding of PKP3 to CC PKP2 mRNA (By similarity). Interacts (via ARM repeats) with GSK3B; the CC interaction may be involved in PKP3 protein degradation (By CC similarity). Interacts with hyperphosphorylated and hypophosphorylated CC RB1; the interaction inhibits RB1 interaction with and repression of CC the transcription factor E2F1, potentially via sequestering RB1 to the CC cytoplasm (PubMed:36689330). Interacts with CDKN1A; the interaction CC sequesters CDKN1A to the cytoplasm thereby repressing its role as an CC inhibitor of CDK4- and CDK6-driven RB1 phosphorylation CC (PubMed:36689330). Interacts (via N-terminus) with SFN; the interaction CC maintains the cytoplasmic pool of PKP3 and restricts PKP3 localization CC to existing desmosome cell junctions (By similarity). Interacts (via N- CC terminus) with JUP; the interaction is required for PKP3 localization CC to desmosome cell-cell junctions (By similarity). CC {ECO:0000250|UniProtKB:Q9Y446, ECO:0000269|PubMed:36689330}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9Y446}. Cell CC junction, desmosome {ECO:0000269|PubMed:18079750, CC ECO:0000269|PubMed:26173741}. Cytoplasm {ECO:0000250|UniProtKB:Q9Y446}. CC Cell membrane {ECO:0000250|UniProtKB:Q9Y446}; Peripheral membrane CC protein {ECO:0000305}. Note=Translocates to the nucleus following CC canonical WNT signaling activation by WNT3A (By similarity). Maintains CC a cytoplasmic pool which can then be translocated to the desmosome, the CC cytoplasmic pool is maintained through PKP3 interaction with SFN (By CC similarity). Aberrant increases in translocation to the desmosome CC result in cell junction instability and therefore decreased cell CC adhesion (By similarity). {ECO:0000250|UniProtKB:Q9Y446}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9QY23-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9QY23-2; Sequence=VSP_026139; CC -!- TISSUE SPECIFICITY: Expressed in all layers of the epidermis, but is CC most abundant in the basal layer (at protein level) (PubMed:18079750). CC Expressed in the anagen non-keratinized inner root sheath cuticle and CC hair cuticle (at protein level) (PubMed:18079750). Also expressed in CC the matrix, precursors of the inner root sheath and hair shaft lineages CC (at protein level) (PubMed:18079750). Expressed at apical membranes in CC the outer hair root sheath and basal layer keratinocytes (at protein CC level) (PubMed:18079750). Expressed in intestinal epithelial cells and CC lamina propria of the ileum (at protein level) (PubMed:26173741). CC Expressed in keratinocytes (at protein level) (PubMed:36689330). CC {ECO:0000269|PubMed:18079750, ECO:0000269|PubMed:26173741, CC ECO:0000269|PubMed:36689330}. CC -!- INDUCTION: Induced by bacterial lipopolysaccharide and phorbol CC myristate acetate in neutrophils. {ECO:0000269|PubMed:26173741}. CC -!- PTM: Phosphorylated at Ser-285 when localized to the cytoplasm, PKP3 at CC desmosome cell junctions is not phosphorylated (By similarity). CC Phosphorylation at Try-195 by SRC is induced by reactive oxygen species CC and potentially acts as a release mechanism from desmosome cell-cell CC junctions (By similarity). {ECO:0000250|UniProtKB:Q9Y446}. CC -!- DISRUPTION PHENOTYPE: Knockout mice are viable, produced at the CC expected Mendelian ratio and appeared normal at birth CC (PubMed:18079750). Increase in protein abundance of Pkp1, Pkp2, Cdh1, CC Ctnna1 and Ctnnb1, and decrease in Jup protein abundance in the CC epidermis of newborn mice (PubMed:18079750). Delayed hair growth at P7, CC as a result of misaligned anterior-posterior polarity in hair follicles CC that show shortened inner root sheath and hair shafts with densely CC packed medullas lacking normal airspaces at P8 (PubMed:18079750). CC Disorganization or complete loss of desmosome cell-cell junctions in CC the epidermis and loss of Dsp expression in the basal layer of the CC outer root sheath and in the matrix cells surrounding the dermal CC papillae of the whisker follicles at P8 (PubMed:18079750). Acute CC dermatitis and 70% of mice develop sparse coats by three weeks of age, CC by two months of age 90% were almost bald on their ventral side CC (PubMed:18079750). Loss of the seal between intercellular borders CC between the basal cells of the epidermis, potentially as a result of CC loss of at least half of the lateral desmosomes at two months of age CC (PubMed:18079750). Increases lethality in response to CC lipopolysaccharide-induced systemic inflammatory response syndrome CC (PubMed:26173741). Increase in mRNA expression of proinflammatory CC cytokines and chemokines Il6, Il1b, Tnf, Ifny, Il17a and Isyna1/iNos in CC the skin following PMA challenge and significant decreases in CC inflammatory gene expression such as Tnf and Il6 in CC lipopolysaccharide- or PMA-challenged neutrophils (PubMed:26173741). CC Conditional knockout in intestinal epithelial cells shows no changes in CC survival, intestinal ulceration or cytokine production following CC dextran sulfate sodium (DSS)-induced colitis, however does show an CC increase in lethality following lipopolysaccharide-induced systemic CC inflammatory response syndrome (PubMed:26173741). Conditional knockout CC in hematopoietic cells show earlier development of more pronounced CC edema, extensive hemorrhage and intraepithelial edema are evident in CC skin sections of the ear (PubMed:26173741). Increase in mast cell CC numbers two hours post PMA challenge, followed by an increase in CC granulocyte numbers in the dermis and the epidermis (PubMed:26173741). CC Mice show a heightened proinflammatory state in response to CC lipopolysaccharide-induced systemic inflammatory response syndrome CC (PubMed:26173741). Following DSS-induced colitis these is an increase CC in weight loss, colon shortening, mucosal ulceration and macrophage CC infiltration (PubMed:26173741). Colonic supernatants show higher levels CC of Tnf, Il1b, Il6 and Il10 mRNA during colitis (PubMed:26173741). CC Increases keratinocyte proliferation in conditions that would usually CC result in density-dependent inhibition of growth, as a result of G1/S CC phase transition delay (PubMed:36689330). Decrease in total Egfr CC protein abundance and its phosphorylation, as a result an increase in CC downstream phosphorylation of Rps6ka family members (PubMed:36689330). CC Reduction in the proportion of hyperphosphorylated Rb1, an increase in CC the interaction between Rb1 and E2f1, resulting in an increase in CC nuclear Rb1 (PubMed:36689330). Increase in protein abundance and CC nuclear localization of Cdkn1a and an increase in Runx3 gene CC transcription (PubMed:36689330). {ECO:0000269|PubMed:18079750, CC ECO:0000269|PubMed:26173741, ECO:0000269|PubMed:36689330}. CC -!- SIMILARITY: Belongs to the beta-catenin family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF136719; AAD55892.1; -; mRNA. DR EMBL; BC090668; AAH90668.1; -; mRNA. DR EMBL; BC106141; AAI06142.1; -; mRNA. DR EMBL; BC139775; AAI39776.1; -; mRNA. DR CCDS; CCDS21999.1; -. [Q9QY23-1] DR CCDS; CCDS52437.1; -. [Q9QY23-2] DR RefSeq; NP_001156396.1; NM_001162924.1. [Q9QY23-2] DR RefSeq; NP_062736.2; NM_019762.2. [Q9QY23-1] DR AlphaFoldDB; Q9QY23; -. DR SMR; Q9QY23; -. DR BioGRID; 207999; 6. DR IntAct; Q9QY23; 2. DR STRING; 10090.ENSMUSP00000101654; -. DR iPTMnet; Q9QY23; -. DR PhosphoSitePlus; Q9QY23; -. DR PaxDb; 10090-ENSMUSP00000101654; -. DR PeptideAtlas; Q9QY23; -. DR ProteomicsDB; 289754; -. [Q9QY23-1] DR ProteomicsDB; 289755; -. [Q9QY23-2] DR Antibodypedia; 4571; 297 antibodies from 34 providers. DR DNASU; 56460; -. DR Ensembl; ENSMUST00000066873.5; ENSMUSP00000069961.5; ENSMUSG00000054065.13. [Q9QY23-1] DR Ensembl; ENSMUST00000106039.9; ENSMUSP00000101654.3; ENSMUSG00000054065.13. [Q9QY23-2] DR GeneID; 56460; -. DR KEGG; mmu:56460; -. DR UCSC; uc009kjh.2; mouse. [Q9QY23-2] DR UCSC; uc009kji.2; mouse. [Q9QY23-1] DR AGR; MGI:1891830; -. DR CTD; 11187; -. DR MGI; MGI:1891830; Pkp3. DR VEuPathDB; HostDB:ENSMUSG00000054065; -. DR eggNOG; KOG1048; Eukaryota. DR GeneTree; ENSGT00940000159515; -. DR HOGENOM; CLU_009111_2_0_1; -. DR InParanoid; Q9QY23; -. DR OMA; DSYCGHR; -. DR OrthoDB; 5473239at2759; -. DR PhylomeDB; Q9QY23; -. DR TreeFam; TF321877; -. DR Reactome; R-MMU-6805567; Keratinization. DR Reactome; R-MMU-6809371; Formation of the cornified envelope. DR BioGRID-ORCS; 56460; 0 hits in 78 CRISPR screens. DR ChiTaRS; Pkp3; mouse. DR PRO; PR:Q9QY23; -. DR Proteomes; UP000000589; Chromosome 7. DR RNAct; Q9QY23; protein. DR Bgee; ENSMUSG00000054065; Expressed in lip and 176 other cell types or tissues. DR ExpressionAtlas; Q9QY23; baseline and differential. DR GO; GO:0005912; C:adherens junction; IBA:GO_Central. DR GO; GO:0005911; C:cell-cell junction; IDA:UniProtKB. DR GO; GO:0001533; C:cornified envelope; IDA:MGI. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0030057; C:desmosome; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0005914; C:spot adherens junction; ISS:MGI. DR GO; GO:0045294; F:alpha-catenin binding; IEA:Ensembl. DR GO; GO:0045296; F:cadherin binding; IBA:GO_Central. DR GO; GO:0019899; F:enzyme binding; IEA:Ensembl. DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW. DR GO; GO:0098609; P:cell-cell adhesion; IBA:GO_Central. DR GO; GO:0002159; P:desmosome assembly; IEA:Ensembl. DR GO; GO:0002934; P:desmosome organization; IMP:UniProtKB. DR GO; GO:0090136; P:epithelial cell-cell adhesion; IMP:UniProtKB. DR GO; GO:0010669; P:epithelial structure maintenance; IMP:UniProtKB. DR GO; GO:1902373; P:negative regulation of mRNA catabolic process; IEA:Ensembl. DR GO; GO:0045785; P:positive regulation of cell adhesion; ISS:UniProtKB. DR GO; GO:1902808; P:positive regulation of cell cycle G1/S phase transition; IMP:UniProtKB. DR GO; GO:0022409; P:positive regulation of cell-cell adhesion; ISS:UniProtKB. DR GO; GO:1903829; P:positive regulation of protein localization; IMP:UniProtKB. DR GO; GO:0072659; P:protein localization to plasma membrane; IEA:Ensembl. DR GO; GO:0002718; P:regulation of cytokine production involved in immune response; IMP:UniProtKB. DR GO; GO:0051797; P:regulation of hair follicle development; IMP:UniProtKB. DR Gene3D; 1.25.10.10; Leucine-rich Repeat Variant; 1. DR InterPro; IPR011989; ARM-like. DR InterPro; IPR016024; ARM-type_fold. DR InterPro; IPR000225; Armadillo. DR InterPro; IPR028435; Plakophilin/d_Catenin. DR PANTHER; PTHR10372:SF1; PLAKOPHILIN-3; 1. DR PANTHER; PTHR10372; PLAKOPHILLIN-RELATED; 1. DR Pfam; PF00514; Arm; 2. DR SMART; SM00185; ARM; 4. DR SUPFAM; SSF48371; ARM repeat; 1. DR PROSITE; PS50176; ARM_REPEAT; 1. PE 1: Evidence at protein level; KW Alternative splicing; Cell adhesion; Cell junction; Cell membrane; KW Cytoplasm; Membrane; Methylation; Nucleus; Phosphoprotein; KW Reference proteome; Repeat; RNA-binding. FT CHAIN 1..797 FT /note="Plakophilin-3" FT /id="PRO_0000064288" FT REPEAT 305..348 FT /note="ARM 1" FT REPEAT 351..390 FT /note="ARM 2" FT REPEAT 393..432 FT /note="ARM 3" FT REPEAT 449..487 FT /note="ARM 4" FT REPEAT 491..536 FT /note="ARM 5" FT REPEAT 596..637 FT /note="ARM 6" FT REPEAT 645..684 FT /note="ARM 7" FT REPEAT 689..730 FT /note="ARM 8" FT REGION 58..81 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 219..241 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 253..274 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 283..288 FT /note="Required for interaction with SFN" FT /evidence="ECO:0000250|UniProtKB:Q9Y446" FT REGION 294..724 FT /note="Required for interaction with GSK3B" FT /evidence="ECO:0000250|UniProtKB:Q9Y446" FT REGION 516..797 FT /note="Required for binding to PKP2 mRNA" FT /evidence="ECO:0000250|UniProtKB:Q9Y446" FT MOD_RES 81 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q9Y446" FT MOD_RES 123 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 180 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 183 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9Y446" FT MOD_RES 195 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q9Y446" FT MOD_RES 240 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9Y446" FT MOD_RES 250 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q9Y446" FT MOD_RES 261 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 285 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9Y446" FT MOD_RES 313 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9Y446" FT MOD_RES 314 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9Y446" FT MOD_RES 331 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT VAR_SEQ 1..12 FT /note="MQEGNFLLSALQ -> MEPTAGSRTRMEPRRNCPTAGTSRMSQGASGGQTSG FT K (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_026139" FT CONFLICT 182 FT /note="R -> P (in Ref. 1; AAD55892)" FT /evidence="ECO:0000305" FT CONFLICT 216 FT /note="E -> K (in Ref. 1; AAD55892)" FT /evidence="ECO:0000305" FT CONFLICT 459 FT /note="A -> P (in Ref. 1; AAD55892)" FT /evidence="ECO:0000305" SQ SEQUENCE 797 AA; 87333 MW; C2ECF73BDE7323B1 CRC64; MQEGNFLLSA LQPETGVCSL ALPSDLQLDR RGAEGPEADR LRAARVQEQV RARLLQLGQQ SRHNGSAELD GSAESARGMP RGQYHTMQTG FSSRSQGMSG DKTSTFRPIA KPAYSPASWS SRSAVDLTCS RRLSSAHNGG SAFGAVGYGG TQPTPPMPTR PVSFHERGGA ASRADYDTLS LRSLRLGPGG LDDRYSVVSE QLEPAAASTY RAYAYERQAS SGSSRAGGLD WPEATEGPPS RTIRAPAMRT LQRFQSSHRS RGGTGSVSGA GLEPVARAPS VRSLSLSLAD SGHLPDVRGL DSYTGHRTLQ RLSSGFDDID LPSAVKYLMA SDPNLQVLGA AYIQHRCYSD AAAKKQARSL QAVPRLVKLF NHANQEVQRH ATGAMRNLIY DNVDNKLALV EENGIFELLR TLREQDDELR KNVTGILWNL SSSDHLKDRL ARDTLEQLTD LVLSPLSGAG GPPLIQQNAS EAEIFYNATG FLRNLSSASQ ATRQKMRECH GLVDALVTYI NHALDVGKCE DKSVENAVCV LRNLSYRLYD EMPPSALQRL EGRGRRDMAG APPGEMVGCF TPQSRRLREL PLTADALTFA EVSKDPKGLE WLWSPQIVGL YNRLLQRCEL NRHTTEAAAG ALQNITAGDR RWAGVLSRLA LEQERILNPL LDRVRTADHN QLRSLTGLIR NLSRNARNKD EMSTKVVSHL IEKLPGSVGE KCPPAEVLVN IIAVLNNLVV ASPIAARDLL YFDGLRKLVF IKKKRDSPDS EKSSRAASSL LANLWQYSKL HRDFRAKGYR KEDFLGP //