AXIN1_RAT
ID AXIN1_RAT Reviewed; 827 AA.
AC O70239;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2002, sequence version 3.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Axin-1;
DE AltName: Full=Axis inhibition protein 1;
DE Short=rAxin;
GN Name=Axin1; Synonyms=Axin;
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], PHOSPHORYLATION, INTERACTION WITH GSK3B AND
RP CNNB1 IN THE BETA-CATENIN DESTRUCTION COMPLEX, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=9482734; DOI=10.1093/emboj/17.5.1371;
RA Ikeda S., Kishida S., Yamamoto H., Murai H., Koyama S., Kikuchi A.;
RT "Axin, a negative regulator of the Wnt signaling pathway, forms a complex
RT with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent
RT phosphorylation of beta-catenin.";
RL EMBO J. 17:1371-1384(1998).
RN [2]
RP SUBCELLULAR LOCATION, INTERACTION WITH MACF1, AND IDENTIFICATION IN A
RP COMPLEX WITH MACF1; APC; GSK3B AND CTNNB1.
RX PubMed=16815997; DOI=10.1101/gad.1411206;
RA Chen H.J., Lin C.M., Lin C.S., Perez-Olle R., Leung C.L., Liem R.K.;
RT "The role of microtubule actin cross-linking factor 1 (MACF1) in the Wnt
RT signaling pathway.";
RL Genes Dev. 20:1933-1945(2006).
CC -!- FUNCTION: Component of the beta-catenin destruction complex required
CC for regulating CTNNB1 levels through phosphorylation and
CC ubiquitination, and modulating Wnt-signaling (By similarity). Controls
CC dorsoventral patterning via two opposing effects; down-regulates beta-
CC catenin to inhibit the Wnt signaling pathway and ventralize embryos,
CC but also dorsalizes embryos by activating a Wnt-independent JNK
CC signaling pathway (By similarity). Also facilitates the phosphorylation
CC of APC by GSK3B (By similarity). Facilitates the phosphorylation of
CC TP53 by HIPK2 upon ultraviolet irradiation (By similarity). Enhances
CC TGF-beta signaling by recruiting the RNF111 E3 ubiquitin ligase and
CC promoting the degradation of inhibitory SMAD7 (By similarity).
CC {ECO:0000250|UniProtKB:O15169}.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with ZBED3; the
CC interaction is direct, enhanced by protein kinase GSK3B and casein
CC kinase CSNK1E activities and decreases GSK3B-induced beta-catenin
CC serine and threonine phosphorylations (By similarity). Component of the
CC AXIN1-HIPK2-TP53 complex (By similarity). Interacts directly in the
CC complex with TP53 and HIPK2 (By similarity). Interacts with DAXX; the
CC interaction stimulates the interaction of DAXX with TP53, stimulates
CC 'Ser-46' phosphorylation of TP53 and induces cell death on UV
CC irradiation (By similarity). Also binds ANKRD6, PIAS1, PIAS2, PIAS4,
CC MAP3K1, MAP3K4, SUMO1, SMAD6, SMAD7 and RNF111 (By similarity).
CC Interacts with DIXDC1; the interaction prevents interaction with MAP3K1
CC (By similarity). Interacts with MDFI; the interaction decreases AXIN1-
CC mediated JUN N-terminal kinase (JNK) activation (By similarity).
CC Interacts with MDFIC; the interaction inhibits beta-cateninin-mediated
CC signaling and AXIN1-mediated JUN N-terminal kinase (JNK) activation (By
CC similarity). Interacts with LRP5 (via its phosphorylated PPPSP motifs);
CC the interaction is stimulated by WNT1 and GSK3B and activates beta-
CC catenin signaling (By similarity). Interacts (via the C-terminal) with
CC PPP1CA; the interaction dephosphorylates AXIN1 and regulates
CC interaction with GSK3B (By similarity). Interacts with PPP2CA; the
CC interaction dephosphorylates AXIN1 (By similarity). Component of the
CC beta-catenin destruction complex, containing at least, CTNNB1, an axin
CC and GSK3B, that regulates CTNNB1 protein levels through phosphorylation
CC and ubiquitination (By similarity). Interacts with CTNNB1 (via the
CC armadillo repeats 2-7) (By similarity). Interacts with GSK3B; the
CC interaction hyperphosphorylates CTNNB1 leading to its ubiquitination
CC and destruction (PubMed:9482734, PubMed:16815997). Interacts with MACF1
CC (PubMed:16815997). Found in a complex composed of MACF1, APC, AXIN1,
CC CTNNB1 and GSK3B (PubMed:16815997). Interacts with TNKS (By
CC similarity). Interacts with DAB2; the interaction is mutually exclusive
CC with the AXIN1:PPP1CA interaction (By similarity). Interacts with WDR26
CC (By similarity). Interacts with GID8 (By similarity). Interacts with
CC SIAH1 and SIAH2; both probably catalyze AXIN1 ubiquitination and
CC subsequent proteasome-mediated ubiquitin-dependent degradation.
CC Interaction with GSK3B and AXIN1 is competitive (By similarity).
CC {ECO:0000250|UniProtKB:O15169, ECO:0000250|UniProtKB:O35625,
CC ECO:0000269|PubMed:16815997, ECO:0000269|PubMed:9482734}.
CC -!- INTERACTION:
CC O70239; O70239: Axin1; NbExp=5; IntAct=EBI-6857773, EBI-6857773;
CC O70239; Q9Y4X0: AMMECR1; Xeno; NbExp=3; IntAct=EBI-6857773, EBI-8583355;
CC O70239; Q03135: CAV1; Xeno; NbExp=5; IntAct=EBI-6857773, EBI-603614;
CC O70239; P49674: CSNK1E; Xeno; NbExp=7; IntAct=EBI-6857773, EBI-749343;
CC O70239; O14640: DVL1; Xeno; NbExp=12; IntAct=EBI-6857773, EBI-723489;
CC O70239; O75581: LRP6; Xeno; NbExp=12; IntAct=EBI-6857773, EBI-910915;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O15169}. Nucleus
CC {ECO:0000250|UniProtKB:O15169}. Cell membrane
CC {ECO:0000269|PubMed:16815997}. Membrane {ECO:0000250|UniProtKB:O35625}.
CC Note=On UV irradiation, translocates to the nucleus and colocalizes
CC with DAAX (By similarity). MACF1 is required for its translocation to
CC cell membrane (By similarity). {ECO:0000250|UniProtKB:O15169,
CC ECO:0000250|UniProtKB:O35625}.
CC -!- TISSUE SPECIFICITY: Highly expressed in testis, thymus and lung. Less
CC expression in cerebrum, cerebellum, heart, kidney, skeletal muscle,
CC spleen and liver. {ECO:0000269|PubMed:9482734}.
CC -!- DOMAIN: The tankyrase-binding motif (also named TBD) is required for
CC interaction with tankyrase TNKS and TNKS2. {ECO:0000250}.
CC -!- PTM: Phosphorylation and dephosphorylation of AXIN1 regulates assembly
CC and function of the beta-catenin complex. Phosphorylated by CK1 and
CC GSK3B. Dephosphorylated by PPP1CA and PPP2CA. Phosphorylation by CK1
CC enhances binding of GSK3B to AXIN1. Also phosphorylated by CDK2 which
CC regulates interaction with CTNBB1 (By similarity). {ECO:0000250}.
CC -!- PTM: ADP-ribosylated by tankyrase TNKS and TNKS2. Poly-ADP-ribosylated
CC protein is recognized by RNF146, followed by ubiquitination and
CC subsequent activation of the Wnt signaling pathway (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Ubiquitinated by RNF146 when poly-ADP-ribosylated, leading to its
CC degradation and subsequent activation of the Wnt signaling pathway.
CC Sumoylation at Lys-858 and Lys-861 prevents ubiquitination and
CC degradation. Sumoylation is required for AXIN1-mediated JNK activation.
CC Deubiquitinated by USP34, deubiquitinated downstream of beta-catenin
CC stabilization step: deubiquitination is important for nuclear
CC accumulation during Wnt signaling to positively regulate beta-catenin
CC (CTNBB1)-mediated transcription (By similarity). Ubiquitination by
CC SIAH1 and SIAH2 induces its proteasomal degradation as part of the
CC activation of the Wnt signaling pathway (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:O15169}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC40066.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={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; AF017756; AAC40066.1; ALT_INIT; mRNA.
DR PIR; T08422; T08422.
DR RefSeq; NP_077381.1; NM_024405.1.
DR PDB; 1WSP; X-ray; 2.90 A; A/B/C=744-827.
DR PDB; 2D5G; X-ray; 3.20 A; A/B/C/D/E/F=743-827.
DR PDBsum; 1WSP; -.
DR PDBsum; 2D5G; -.
DR AlphaFoldDB; O70239; -.
DR SMR; O70239; -.
DR BioGRID; 249455; 9.
DR CORUM; O70239; -.
DR DIP; DIP-29400N; -.
DR ELM; O70239; -.
DR IntAct; O70239; 10.
DR MINT; O70239; -.
DR STRING; 10116.ENSRNOP00000027705; -.
DR iPTMnet; O70239; -.
DR PhosphoSitePlus; O70239; -.
DR PaxDb; O70239; -.
DR PRIDE; O70239; -.
DR GeneID; 79257; -.
DR KEGG; rno:79257; -.
DR UCSC; RGD:620859; rat.
DR CTD; 8312; -.
DR RGD; 620859; Axin1.
DR eggNOG; KOG3589; Eukaryota.
DR InParanoid; O70239; -.
DR Reactome; R-RNO-195253; Degradation of beta-catenin by the destruction complex.
DR Reactome; R-RNO-196299; Beta-catenin phosphorylation cascade.
DR Reactome; R-RNO-201681; TCF dependent signaling in response to WNT.
DR Reactome; R-RNO-4641257; Degradation of AXIN.
DR Reactome; R-RNO-4641262; Disassembly of the destruction complex and recruitment of AXIN to the membrane.
DR Reactome; R-RNO-5689880; Ub-specific processing proteases.
DR EvolutionaryTrace; O70239; -.
DR PRO; PR:O70239; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0030877; C:beta-catenin destruction complex; IDA:BHF-UCL.
DR GO; GO:0005938; C:cell cortex; ISO:RGD.
DR GO; GO:0071944; C:cell periphery; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:BHF-UCL.
DR GO; GO:0016328; C:lateral plasma membrane; ISO:RGD.
DR GO; GO:0015630; C:microtubule cytoskeleton; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IDA:RGD.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:1990909; C:Wnt signalosome; ISO:RGD.
DR GO; GO:0070016; F:armadillo repeat domain binding; IDA:BHF-UCL.
DR GO; GO:0008013; F:beta-catenin binding; IDA:BHF-UCL.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0070411; F:I-SMAD binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0060090; F:molecular adaptor activity; ISO:RGD.
DR GO; GO:0002039; F:p53 binding; ISO:RGD.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:RGD.
DR GO; GO:0019904; F:protein domain specific binding; IPI:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:BHF-UCL.
DR GO; GO:0043621; F:protein self-association; ISO:RGD.
DR GO; GO:0070412; F:R-SMAD binding; ISO:RGD.
DR GO; GO:0005102; F:signaling receptor binding; IPI:BHF-UCL.
DR GO; GO:0030159; F:signaling receptor complex adaptor activity; ISO:RGD.
DR GO; GO:0046332; F:SMAD binding; ISO:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0032147; P:activation of protein kinase activity; ISO:RGD.
DR GO; GO:0007628; P:adult walking behavior; ISO:RGD.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0048318; P:axial mesoderm development; ISO:RGD.
DR GO; GO:0048320; P:axial mesoderm formation; ISO:RGD.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:0048468; P:cell development; IBA:GO_Central.
DR GO; GO:0031122; P:cytoplasmic microtubule organization; ISO:RGD.
DR GO; GO:0009950; P:dorsal/ventral axis specification; ISO:RGD.
DR GO; GO:0009953; P:dorsal/ventral pattern formation; ISO:RGD.
DR GO; GO:0060272; P:embryonic skeletal joint morphogenesis; ISO:RGD.
DR GO; GO:0034101; P:erythrocyte homeostasis; ISO:RGD.
DR GO; GO:0071514; P:genomic imprinting; ISO:RGD.
DR GO; GO:0060322; P:head development; ISO:RGD.
DR GO; GO:0020027; P:hemoglobin metabolic process; ISO:RGD.
DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:RGD.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0051248; P:negative regulation of protein metabolic process; ISO:RGD.
DR GO; GO:0034244; P:negative regulation of transcription elongation from RNA polymerase II promoter; ISO:RGD.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; ISO:RGD.
DR GO; GO:0050877; P:nervous system process; ISO:RGD.
DR GO; GO:0006913; P:nucleocytoplasmic transport; ISO:RGD.
DR GO; GO:0046330; P:positive regulation of JNK cascade; ISS:UniProtKB.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; ISO:RGD.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:RGD.
DR GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; ISO:RGD.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISO:RGD.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; ISO:RGD.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IDA:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; ISO:RGD.
DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; IDA:BHF-UCL.
DR GO; GO:0051443; P:positive regulation of ubiquitin-protein transferase activity; ISO:RGD.
DR GO; GO:0036342; P:post-anal tail morphogenesis; ISO:RGD.
DR GO; GO:0030163; P:protein catabolic process; ISO:RGD.
DR GO; GO:0000209; P:protein polyubiquitination; ISO:RGD.
DR GO; GO:0065003; P:protein-containing complex assembly; ISO:RGD.
DR GO; GO:0060828; P:regulation of canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:0001932; P:regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:1905235; P:response to quercetin; IEP:RGD.
DR GO; GO:0007605; P:sensory perception of sound; ISO:RGD.
DR GO; GO:0016055; P:Wnt signaling pathway; ISO:RGD.
DR CDD; cd11582; Axin_TNKS_binding; 1.
DR Gene3D; 1.10.167.10; -; 1.
DR Gene3D; 1.10.196.10; -; 2.
DR Gene3D; 2.40.240.130; -; 1.
DR IDEAL; IID50195; -.
DR InterPro; IPR043581; Axin-like.
DR InterPro; IPR029797; AXIN1.
DR InterPro; IPR014936; Axin_b-cat-bd.
DR InterPro; IPR032101; Axin_TNKS-bd.
DR InterPro; IPR001158; DIX.
DR InterPro; IPR038207; DIX_dom_sf.
DR InterPro; IPR016137; RGS.
DR InterPro; IPR036305; RGS_sf.
DR InterPro; IPR024066; RGS_subdom1/3.
DR InterPro; IPR044926; RGS_subdomain_2.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR46102; PTHR46102; 1.
DR PANTHER; PTHR46102:SF3; PTHR46102:SF3; 1.
DR Pfam; PF16646; AXIN1_TNKS_BD; 1.
DR Pfam; PF08833; Axin_b-cat_bind; 1.
DR Pfam; PF00778; DIX; 1.
DR Pfam; PF00615; RGS; 1.
DR PRINTS; PR01301; RGSPROTEIN.
DR SMART; SM00021; DAX; 1.
DR SMART; SM00315; RGS; 1.
DR SUPFAM; SSF48097; SSF48097; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR PROSITE; PS50841; DIX; 1.
DR PROSITE; PS50132; RGS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ADP-ribosylation; Apoptosis; Cell membrane; Cytoplasm;
KW Developmental protein; Isopeptide bond; Membrane; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation; Wnt signaling pathway.
FT CHAIN 1..827
FT /note="Axin-1"
FT /id="PRO_0000220890"
FT DOMAIN 88..211
FT /note="RGS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00171"
FT DOMAIN 745..827
FT /note="DIX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00069"
FT REGION 1..81
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 209..338
FT /note="Interaction with TP53"
FT /evidence="ECO:0000250"
FT REGION 215..287
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 315..344
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 348..432
FT /note="Interaction with GSK3B"
FT /evidence="ECO:0000269|PubMed:9482734"
FT REGION 353..411
FT /note="Interaction with SIAH1"
FT /evidence="ECO:0000250|UniProtKB:O15169"
FT REGION 433..501
FT /note="Interaction with CTNNB1"
FT REGION 530..625
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 642..667
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 713..742
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 20..29
FT /note="Tankyrase-binding motif"
FT COMPBIAS 36..63
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 215..235
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 315..339
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 611..625
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 75
FT /note="Phosphoserine; by CK1"
FT /evidence="ECO:0000250|UniProtKB:O15169"
FT MOD_RES 77
FT /note="Phosphoserine; by CK1"
FT /evidence="ECO:0000250|UniProtKB:O15169"
FT MOD_RES 217
FT /note="Phosphoserine; by CK1"
FT /evidence="ECO:0000250|UniProtKB:O15169"
FT MOD_RES 468
FT /note="Phosphoserine; by CK1"
FT /evidence="ECO:0000250|UniProtKB:O15169"
FT MOD_RES 480
FT /note="Phosphothreonine; by GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:O35625"
FT MOD_RES 485
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:O35625"
FT MOD_RES 492
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35625"
FT MOD_RES 509
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15169"
FT MOD_RES 578
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15169"
FT CROSSLNK 822
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 825
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT STRAND 748..754
FT /evidence="ECO:0007829|PDB:1WSP"
FT STRAND 761..768
FT /evidence="ECO:0007829|PDB:1WSP"
FT HELIX 772..778
FT /evidence="ECO:0007829|PDB:1WSP"
FT STRAND 785..792
FT /evidence="ECO:0007829|PDB:1WSP"
FT STRAND 799..805
FT /evidence="ECO:0007829|PDB:1WSP"
FT STRAND 818..825
FT /evidence="ECO:0007829|PDB:1WSP"
SQ SEQUENCE 827 AA; 92285 MW; BB1EE9CCECF6D487 CRC64;
MNVQEQGFPL DLGASFTEDA PRPPVPGEEG ELVSTDSRPV NHSFCSGKGT SIKSETSTAT
PRRSDLDLGY EPEGSASPTP PYLRWAESLH SLLDDQDGIS LFRTFLKQEG CADLLDFWFA
CSGFRKLEPC DSNEEKRLKL ARAIYRKYIL DSNGIVSRQT KPATKSFIKD CVMKQQIDPA
MFDQAQTEIQ STMEENTYPS FLKSDIYLEY TRTGSESPKV CSDQSSGSGT GKGMSGYLPT
LNEDEEWKCD QDADEDDGRD SVPPSRLTQK LLLETAAPRA PSSRRYNEGR ELRYGSWREP
VNPYYVNSGY ALAPATSAND SEQQSLSSDA DTLSLTDSSV DGIPPYRIRK QHRREMQESV
QVNGRVPLPH IPRTYRMPKE IRVEPQKFAE ELIHRLEAVQ RTREAEEKLE ERLKRVRMEE
EGEDGEMPSG PMASHKLPSV PAWHHFPPRY VDMGCSGLRD AHEENPESIL DEHVQRVMRT
PGCQSPGPGH RSPDSGHVAK TAVLGGTASG HGKHAPKLGL KLDSAGLHHH RHVHHHVHHN
SARPKEQMEA EAARRVQSSF SWGPETHGHA KPRSYSESTG TNPSAGDLAF GGKASAPSKR
NTKKAESGKN ASAEVPSTTE DAEKNQKIMQ WIIEGEKEIS RHRKAGHGSS GMRKQQAHES
SRPLSIERPG AVHPWVSAQL RNSVQPSHLF IQDPTMPPNP APNPLTQLEE ARRRLEEEEK
RANKLPSKQR TKSQRKAGGG SAPPCDSIVV AYYFCGEPIP YRTLVRGRAV TLGQFKELLT
KKGSYRYYFK KVSDEFDCGV VFEEVREDEA ILPVFEEKII GKVEKVD
