ID ANAO2_ANAOC Reviewed; 457 AA. AC Q8GZP6; DT 11-DEC-2019, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2003, sequence version 1. DT 26-FEB-2020, entry version 61. DE RecName: Full=11S globulin seed storage protein Ana o 2.0101 {ECO:0000305}; DE AltName: Full=11S globulin Ana o 2 {ECO:0000303|PubMed:20362336, ECO:0000303|PubMed:21861454, ECO:0000303|PubMed:23681851, ECO:0000303|PubMed:26769082}; DE AltName: Full=Allergen Ana o 2 {ECO:0000303|PubMed:14555856, ECO:0000303|PubMed:18795784, ECO:0000303|PubMed:20362336, ECO:0000312|EMBL:AAN76862.1}; DE AltName: Full=Anacardein {ECO:0000303|PubMed:18795784, ECO:0000303|PubMed:20362336, ECO:0000303|PubMed:21138244}; DE AltName: Full=Cashew major protein {ECO:0000303|PubMed:18795784}; DE Short=CMP {ECO:0000303|PubMed:18795784}; DE AltName: Full=Legumin Ana o 2 {ECO:0000303|PubMed:18558706, ECO:0000303|PubMed:20362336, ECO:0000303|PubMed:28959544}; DE AltName: Full=Legumin-like protein Ana o 2 {ECO:0000303|PubMed:14555856}; DE AltName: Allergen=Ana o 2.0101 {ECO:0000305}; DE Contains: DE RecName: Full=11S globulin seed storage protein Ana o 2.0101 acidic chain {ECO:0000305}; DE AltName: Full=11S globulin seed storage protein Ana o 2.0101 large subunit {ECO:0000305}; DE Contains: DE RecName: Full=11S globulin seed storage protein Ana o 2.0101 basic chain {ECO:0000305}; DE AltName: Full=11S globulin seed storage protein Ana o 2.0101 small subunit {ECO:0000305}; DE Flags: Precursor; Fragment; OS Anacardium occidentale (Cashew). OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta; OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae; OC rosids; malvids; Sapindales; Anacardiaceae; Anacardium. OX NCBI_TaxID=171929 {ECO:0000312|EMBL:AAN76862.1}; RN [1] {ECO:0000312|EMBL:AAN76862.1} RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, RP ALLERGEN, AND REGIONS. RC TISSUE=Seed {ECO:0000303|PubMed:14555856}; RX PubMed=14555856; DOI=10.1159/000073262; RA Wang F., Robotham J.M., Teuber S.S., Sathe S.K., Roux K.H.; RT "Ana o 2, a major cashew (Anacardium occidentale L.) nut allergen of the RT legumin family."; RL Int. Arch. Allergy Immunol. 132:27-39(2003). RN [2] RP PROTEIN SEQUENCE OF 16-58; 57-66; 65-113 AND 129-175, IDENTIFICATION BY RP MASS SPECTROMETRY, TISSUE SPECIFICITY, PTM, AND ALLERGEN. RX PubMed=24926808; DOI=10.1021/jf501117p; RA Mattison C.P., Desormeaux W.A., Wasserman R.L., Yoshioka-Tarver M., RA Condon B., Grimm C.C.; RT "Decreased immunoglobulin E (IgE) binding to cashew allergens following RT sodium sulfite treatment and heating."; RL J. Agric. Food Chem. 62:6746-6755(2014). RN [3] RP PROTEIN SEQUENCE OF 30-65; 113-125; 175-217; 184-217; 282-322; 302-314; RP 328-384; 348-360; 368-384; 387-429 AND 410-429, IDENTIFICATION BY MASS RP SPECTROMETRY, TISSUE SPECIFICITY, PTM, AND ALLERGEN. RX PubMed=26769082; DOI=10.1021/acs.jafc.5b04401; RA Reitsma M., Bastiaan-Net S., Sforza S., van der Valk J.P., RA van Gerth van Wijk R., Savelkoul H.F., de Jong N.W., Wichers H.J.; RT "Purification and Characterization of Anacardium occidentale (Cashew) RT Allergens Ana o 1, Ana o 2, and Ana o 3."; RL J. Agric. Food Chem. 64:1191-1201(2016). RN [4] RP PROTEIN SEQUENCE OF 30-57; 39-57; 175-183; 198-217; 282-291; 292-301; RP 369-383 AND 390-396, IDENTIFICATION BY MASS SPECTROMETRY, AND TISSUE RP SPECIFICITY. RX PubMed=28959544; DOI=10.1016/j.toxrep.2015.12.009; RA Mattison C.P., Bren-Mattison Y., Vant-Hull B., Vargas A.M., Wasserman R.L., RA Grimm C.C.; RT "Heat-induced alterations in cashew allergen solubility and IgE binding."; RL Toxicol. Rep. 3:244-251(2016). RN [5] RP PROTEIN SEQUENCE OF 41-55, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, RP ALLERGEN, AND CIRCULAR DICHROISM ANALYSIS. RX PubMed=21138244; DOI=10.1021/jf1030899; RA Kshirsagar H.H., Fajer P., Sharma G.M., Roux K.H., Sathe S.K.; RT "Biochemical and spectroscopic characterization of almond and cashew nut RT seed 11S legumins, amandin and anacardein."; RL J. Agric. Food Chem. 59:386-393(2011). RN [6] RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND ALLERGEN. RX PubMed=18558706; DOI=10.1021/jf8011618; RA Comstock S.S., Robotham J.M., Tawde P., Kshirsagar H., Sathe S.K., RA Roux K.H., Teuber S.S.; RT "Immunoglobulin E-reactive proteins in cashew (Anacardium occidentale) RT apple juice concentrate."; RL J. Agric. Food Chem. 56:5977-5982(2008). RN [7] RP TISSUE SPECIFICITY, ALLERGEN, AND REGION. RX PubMed=18795784; DOI=10.1021/jf801199q; RA Venkatachalam M., Monaghan E.K., Kshirsagar H.H., Robotham J.M., RA O'Donnell S.E., Gerber M.S., Roux K.H., Sathe S.K.; RT "Effects of processing on immunoreactivity of cashew nut (Anacardium RT occidentale L.) seed flour proteins."; RL J. Agric. Food Chem. 56:8998-9005(2008). RN [8] RP SUBUNIT, 3D-STRUCTURE MODELING, REGION, SITE, AND MUTAGENESIS OF GLU-34; RP ASP-36; ARG-38; VAL-39; GLU-40; GLU-42; ASP-50; ASN-52; HIS-53; GLU-54 AND RP ARG-57. RX PubMed=20362338; DOI=10.1016/j.molimm.2010.01.018; RA Xia L., Willison L.N., Porter L., Robotham J.M., Teuber S.S., Sathe S.K., RA Roux K.H.; RT "Mapping of a conformational epitope on the cashew allergen Ana o 2: a RT discontinuous large subunit epitope dependent upon homologous or RT heterologous small subunit association."; RL Mol. Immunol. 47:1808-1816(2010). RN [9] RP TISSUE SPECIFICITY, PTM, AND ALLERGEN. RX PubMed=20362336; DOI=10.1016/j.molimm.2009.12.009; RA Robotham J.M., Xia L., Willison L.N., Teuber S.S., Sathe S.K., Roux K.H.; RT "Characterization of a cashew allergen, 11S globulin (Ana o 2), RT conformational epitope."; RL Mol. Immunol. 47:1830-1838(2010). RN [10] RP SUBUNIT, 3D-STRUCTURE MODELING, AND REGIONS. RX PubMed=21861454; DOI=10.1021/ac201501z; RA Zhang Q., Willison L.N., Tripathi P., Sathe S.K., Roux K.H., Emmett M.R., RA Blakney G.T., Zhang H.M., Marshall A.G.; RT "Epitope mapping of a 95 kDa antigen in complex with antibody by solution- RT phase amide backbone hydrogen/deuterium exchange monitored by Fourier RT transform ion cyclotron resonance mass spectrometry."; RL Anal. Chem. 83:7129-7136(2011). RN [11] RP 3D-STRUCTURE MODELING, AND REGIONS. RX PubMed=23681851; DOI=10.1007/s13361-013-0644-7; RA Zhang Q., Noble K.A., Mao Y., Young N.L., Sathe S.K., Roux K.H., RA Marshall A.G.; RT "Rapid screening for potential epitopes reactive with a polycolonal RT antibody by solution-phase H/D exchange monitored by FT-ICR mass RT spectrometry."; RL J. Am. Soc. Mass Spectrom. 24:1016-1025(2013). RN [12] RP TISSUE SPECIFICITY, AND ALLERGEN. RX PubMed=25766831; DOI=10.1016/j.foodchem.2015.02.056; RA Chung S.Y., Mattison C.P., Reed S., Wasserman R.L., Desormeaux W.A.; RT "Treatment with oleic acid reduces IgE binding to peanut and cashew RT allergens."; RL Food Chem. 180:295-300(2015). RN [13] RP ALLERGEN, AND REGIONS. RX PubMed=27129138; DOI=10.1111/cea.12746; RA Archila L.D., Chow I.T., McGinty J.W., Renand A., Jeong D., Robinson D., RA Farrington M.L., Kwok W.W.; RT "Ana o 1 and Ana o 2 cashew allergens share cross-reactive CD4(+) T cell RT epitopes with other tree nuts."; RL Clin. Exp. Allergy 46:871-883(2016). RN [14] RP TISSUE SPECIFICITY, ALLERGEN, AND BIOTECHNOLOGY. RX PubMed=27513566; DOI=10.1111/cea.12794; RA van der Valk J.P., Gerth van Wijk R., Vergouwe Y., Steyerberg E.W., RA Reitsma M., Wichers H.J., Savelkoul H.F., Vlieg-Boerstra B., de Groot H., RA Dubois A.E., de Jong N.W.; RT "sIgE Ana o 1, 2 and 3 accurately distinguish tolerant from allergic RT children sensitized to cashew nuts."; RL Clin. Exp. Allergy 47:113-120(2017). CC -!- FUNCTION: Seed storage protein. {ECO:0000255|RuleBase:RU003681, CC ECO:0000305|PubMed:14555856, ECO:0000305|PubMed:18558706, CC ECO:0000305|PubMed:18795784, ECO:0000305|PubMed:20362336, CC ECO:0000305|PubMed:21138244, ECO:0000305|PubMed:24926808, CC ECO:0000305|PubMed:25766831, ECO:0000305|PubMed:26769082, CC ECO:0000305|PubMed:27513566, ECO:0000305|PubMed:28959544}. CC -!- SUBUNIT: Homotrimer (PubMed:21861454). Hexamer (PubMed:20362338). Each CC subunit is composed of an acidic and a basic chain derived from a CC single precursor and linked by a disulfide bond (By similarity). CC {ECO:0000250|UniProtKB:P04776, ECO:0000269|PubMed:20362338, CC ECO:0000269|PubMed:21861454}. CC -!- TISSUE SPECIFICITY: Expressed in seed (at protein level) CC (PubMed:14555856, PubMed:18558706, PubMed:18795784, PubMed:20362336, CC PubMed:21138244, PubMed:25766831, PubMed:26769082, PubMed:24926808, CC PubMed:28959544, PubMed:27513566). Expressed in the juice of the cashew CC apple (at protein level) (PubMed:18558706). CC {ECO:0000269|PubMed:14555856, ECO:0000269|PubMed:18558706, CC ECO:0000269|PubMed:18795784, ECO:0000269|PubMed:20362336, CC ECO:0000269|PubMed:21138244, ECO:0000269|PubMed:24926808, CC ECO:0000269|PubMed:25766831, ECO:0000269|PubMed:26769082, CC ECO:0000269|PubMed:27513566, ECO:0000269|PubMed:28959544}. CC -!- DEVELOPMENTAL STAGE: Expressed during seed maturation CC (PubMed:14555856). Expressed in mature raw cashew nut (PubMed:18558706, CC PubMed:21138244). {ECO:0000269|PubMed:14555856, CC ECO:0000269|PubMed:18558706, ECO:0000269|PubMed:21138244}. CC -!- PTM: Proteolytically processed from a single precursor to produce an CC acidic and a basic chain that are linked by a disulfide bond CC (PubMed:14555856, PubMed:20362336, PubMed:24926808, PubMed:26769082). CC Not glycosylated (PubMed:26769082). {ECO:0000269|PubMed:20362336, CC ECO:0000269|PubMed:24926808, ECO:0000269|PubMed:26769082, CC ECO:0000305|PubMed:14555856}. CC -!- ALLERGEN: Causes an allergic reaction in human (PubMed:14555856, CC PubMed:18558706, PubMed:20362336, PubMed:24926808, PubMed:25766831, CC PubMed:27129138, PubMed:26769082, PubMed:27513566). Binds to IgE of CC patients allergic to cashew nuts (PubMed:14555856, PubMed:18558706, CC PubMed:20362336, PubMed:24926808, PubMed:25766831, PubMed:26769082, CC PubMed:27513566). Recombinant protein binds to IgE in 62% of the 21 CC patients tested (PubMed:14555856). Reduced IgE-binding following 50 mM CC sodium sulfite treatment at 100 degrees Celsius or by 5 mM CC dithiothreitol (DTT) (PubMed:24926808). IgE-binding is reduced by 35% CC with 5 mM sodium oleate treatment at 70 degrees Celsius for 60 min only CC if followed by an additional overnight incubation at 37 degrees Celsius CC (PubMed:25766831). Allergenicity is removed from the cashew apple juice CC concentrate by 5 kDa filtration (PubMed:18558706). Retains CC immunoreactivity for mouse monoclonal antibodies (mAbs) 4C3 and 4H9 CC after a variety of processing treatments including autoclaving, CC blanching, microwave heating, dry roasting, gamma-irradiation and pH CC (PubMed:18795784). Significantly reduced immunoreactivity for mouse mAb CC 4C3 by 2.5 mM sodium dodecyl sulfate (SDS) or 2% v/v reducing agent CC beta-mercaptoethanol (beta-ME) with heat (100 degrees Celsius for 10 CC min) treatments (PubMed:21138244). Exposure to extreme pH (1 or 13) and CC extreme heat treatments (autoclaving for 30 min or roasting at 200 CC degrees Celsius for 15 min) results in almost complete loss of binding CC to mouse mAb 4C3 (PubMed:18795784). Mouse mAb 2B5 recognizes a CC conformational epitope on the acidic chain of this protein, the CC recognition of which requires the association of the basic chain, but CC is independent of their post-translational cleavage. The antibody CC competes with patient IgE for binding to the epitope. The epitope is CC destroyed by physical (boiling) and chemical (0.5 M beta-ME, 10% SDS CC and 6 M urea) denturation (PubMed:20362336). Cashew allergic patients CC elicit responses to this protein by CD4(+) T cells with T-helper 2 CC (Th2) and Th2/T-helper 17 (Th17) phenotypes (PubMed:27129138). CC {ECO:0000269|PubMed:14555856, ECO:0000269|PubMed:18558706, CC ECO:0000269|PubMed:18795784, ECO:0000269|PubMed:20362336, CC ECO:0000269|PubMed:21138244, ECO:0000269|PubMed:24926808, CC ECO:0000269|PubMed:25766831, ECO:0000269|PubMed:26769082, CC ECO:0000269|PubMed:27129138, ECO:0000269|PubMed:27513566}. CC -!- BIOTECHNOLOGY: Can be used as part of the diagnostics for predicting CC the risk for positive double-blind, placebo-controlled food challenge CC test (DBPCFC) in cashew-allergic children. The risk increases with CC higher specific IgE levels to this protein. CC {ECO:0000269|PubMed:27513566}. CC -!- SIMILARITY: Belongs to the 11S seed storage protein (globulins) family. CC {ECO:0000255|RuleBase:RU003681, 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; AF453947; AAN76862.1; -; mRNA. DR SMR; Q8GZP6; -. DR Allergome; 3077; Ana o 2.0101. DR Allergome; 976; Ana o 2. DR PRIDE; Q8GZP6; -. DR GO; GO:0019863; F:IgE binding; IEA:UniProtKB-KW. DR GO; GO:0019864; F:IgG binding; IEA:UniProtKB-KW. DR GO; GO:0045735; F:nutrient reservoir activity; IC:UniProtKB. DR GO; GO:0070207; P:protein homotrimerization; IDA:UniProtKB. DR GO; GO:0010431; P:seed maturation; IEP:UniProtKB. DR Gene3D; 2.60.120.10; -; 2. DR InterPro; IPR022379; 11S_seedstore_CS. DR InterPro; IPR006044; 11S_seedstore_pln. DR InterPro; IPR006045; Cupin_1. DR InterPro; IPR014710; RmlC-like_jellyroll. DR InterPro; IPR011051; RmlC_Cupin_sf. DR Pfam; PF00190; Cupin_1; 2. DR PRINTS; PR00439; 11SGLOBULIN. DR SMART; SM00835; Cupin_1; 2. DR SUPFAM; SSF51182; SSF51182; 1. DR PROSITE; PS00305; 11S_SEED_STORAGE; 1. PE 1: Evidence at protein level; KW Allergen; Direct protein sequencing; Disulfide bond; IgE-binding protein; KW IgG-binding protein; Seed storage protein; Signal; Storage protein. FT SIGNAL <1..14 FT /evidence="ECO:0000255" FT CHAIN 15..271 FT /note="11S globulin seed storage protein Ana o 2.0101 FT acidic chain" FT /evidence="ECO:0000255, ECO:0000305|PubMed:14555856, FT ECO:0000305|PubMed:20362336" FT /id="PRO_0000448659" FT CHAIN 272..457 FT /note="11S globulin seed storage protein Ana o 2.0101 basic FT chain" FT /evidence="ECO:0000305|PubMed:14555856, FT ECO:0000305|PubMed:20362336" FT /id="PRO_0000448660" FT DOMAIN 30..220 FT /note="Cupin type-1 1" FT /evidence="ECO:0000255" FT DOMAIN 284..433 FT /note="Cupin type-1 2" FT /evidence="ECO:0000255" FT REGION 15..29 FT /note="IgE-binding" FT /evidence="ECO:0000269|PubMed:14555856" FT REGION 29..37 FT /note="Conformational epitope; mouse monoclonal antibody FT (mAb) 2B5-binding" FT /evidence="ECO:0000269|PubMed:21861454" FT REGION 31..48 FT /note="Conformational epitope; mouse monoclonal antibody FT (mAb) 2B5-binding" FT /evidence="ECO:0000269|PubMed:21861454" FT REGION 32..45 FT /note="Binds goat polyclonal antibodies (pAbs)" FT /evidence="ECO:0000269|PubMed:23681851" FT REGION 34..57 FT /note="Mouse monoclonal antibody (mAb) 2B5-binding" FT /evidence="ECO:0000269|PubMed:20362338" FT REGION 41..55 FT /note="Mouse monoclonal antibody (mAb) 4H9-binding" FT /evidence="ECO:0000269|PubMed:18795784" FT REGION 55..86 FT /note="Binds goat polyclonal antibodies (pAbs)" FT /evidence="ECO:0000269|PubMed:23681851" FT REGION 105..119 FT /note="IgE-binding" FT /evidence="ECO:0000269|PubMed:14555856" FT REGION 215..239 FT /note="Binds goat polyclonal antibodies (pAbs)" FT /evidence="ECO:0000269|PubMed:23681851" FT REGION 233..252 FT /note="CD4(+) T cell-reactive epitope" FT /evidence="ECO:0000269|PubMed:27129138" FT REGION 265..289 FT /note="Linear epitope; mouse monoclonal antibody (mAb) 1F5- FT binding" FT /evidence="ECO:0000269|PubMed:21861454" FT REGION 289..308 FT /note="CD4(+) T cell-reactive epitope" FT /evidence="ECO:0000269|PubMed:27129138" FT REGION 297..316 FT /note="CD4(+) T cell-reactive epitope" FT /evidence="ECO:0000269|PubMed:27129138" FT REGION 321..340 FT /note="CD4(+) T cell-reactive epitope" FT /evidence="ECO:0000269|PubMed:27129138" FT REGION 329..348 FT /note="CD4(+) T cell-reactive epitope" FT /evidence="ECO:0000269|PubMed:27129138" FT REGION 377..396 FT /note="CD4(+) T cell-reactive epitope" FT /evidence="ECO:0000269|PubMed:27129138" FT REGION 395..416 FT /note="Binds goat polyclonal antibodies (pAbs), but buried FT in the 3D-structure model" FT /evidence="ECO:0000269|PubMed:23681851" FT MOTIF 271..276 FT /note="NGXEET; peptidase recognition motif" FT /evidence="ECO:0000250|UniProtKB:Q2TPW5" FT SITE 34 FT /note="Critical for epitope recognition by the mouse FT monoclonal antibody (mAb) 2B5" FT /evidence="ECO:0000269|PubMed:20362338" FT DISULFID 25..58 FT /evidence="ECO:0000250|UniProtKB:P04776" FT DISULFID 101..278 FT /note="Interchain (between acidic and basic chains)" FT /evidence="ECO:0000250|UniProtKB:P04776" FT MUTAGEN 34 FT /note="E->A: Significantly reduced binding to mouse FT monoclonal antibody (mAb) 2B5." FT /evidence="ECO:0000269|PubMed:20362338" FT MUTAGEN 36 FT /note="D->A: Loss of binding to mouse monoclonal antibody FT (mAb) 2B5." FT /evidence="ECO:0000269|PubMed:20362338" FT MUTAGEN 38 FT /note="R->A: Loss of binding to mouse monoclonal antibody FT (mAb) 2B5." FT /evidence="ECO:0000269|PubMed:20362338" FT MUTAGEN 39 FT /note="V->A: Significantly reduced binding to mouse FT monoclonal antibody (mAb) 2B5." FT /evidence="ECO:0000269|PubMed:20362338" FT MUTAGEN 40 FT /note="E->A: Significantly reduced binding to mouse FT monoclonal antibody (mAb) 2B5." FT /evidence="ECO:0000269|PubMed:20362338" FT MUTAGEN 42 FT /note="E->A: Significantly reduced binding to mouse FT monoclonal antibody (mAb) 2B5." FT /evidence="ECO:0000269|PubMed:20362338" FT MUTAGEN 50 FT /note="D->A: Loss of binding to mouse monoclonal antibody FT (mAb) 2B5." FT /evidence="ECO:0000269|PubMed:20362338" FT MUTAGEN 52 FT /note="N->A: No effect in binding to mouse monoclonal FT antibody (mAb) 2B5." FT /evidence="ECO:0000269|PubMed:20362338" FT MUTAGEN 53 FT /note="H->A: Significantly reduced binding to mouse FT monoclonal antibody (mAb) 2B5." FT /evidence="ECO:0000269|PubMed:20362338" FT MUTAGEN 54 FT /note="E->A: No effect in binding to mouse monoclonal FT antibody (mAb) 2B5." FT /evidence="ECO:0000269|PubMed:20362338" FT MUTAGEN 57 FT /note="R->A: Significantly reduced binding to mouse FT monoclonal antibody (mAb) 2B5." FT /evidence="ECO:0000269|PubMed:20362338" FT NON_TER 1 FT /evidence="ECO:0000312|EMBL:AAN76862.1" SQ SEQUENCE 457 AA; 51996 MW; 91413A7A10E6419C CRC64; LSVCFLILFH GCLASRQEWQ QQDECQIDRL DALEPDNRVE YEAGTVEAWD PNHEQFRCAG VALVRHTIQP NGLLLPQYSN APQLIYVVQG EGMTGISYPG CPETYQAPQQ GRQQGQSGRF QDRHQKIRRF RRGDIIAIPA GVAHWCYNEG NSPVVTVTLL DVSNSQNQLD RTPRKFHLAG NPKDVFQQQQ QHQSRGRNLF SGFDTELLAE AFQVDERLIK QLKSEDNRGG IVKVKDDELR VIRPSRSQSE RGSESEEESE DEKRRWGQRD NGIEETICTM RLKENINDPA RADIYTPEVG RLTTLNSLNL PILKWLQLSV EKGVLYKNAL VLPHWNLNSH SIIYGCKGKG QVQVVDNFGN RVFDGEVREG QMLVVPQNFA VVKRAREERF EWISFKTNDR AMTSPLAGRT SVLGGMPEEV LANAFQISRE DARKIKFNNQ QTTLTSGESS HHMRDDA //