ID VCL_CORAV Reviewed; 448 AA. AC Q8S4P9; DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2002, sequence version 1. DT 07-APR-2021, entry version 52. DE RecName: Full=Vicilin Cor a 11.0101 {ECO:0000305}; DE AltName: Full=7S globulin {ECO:0000303|PubMed:19006093, ECO:0000303|PubMed:21563837, ECO:0000303|PubMed:21735061, ECO:0000303|PubMed:31753489}; DE AltName: Full=7S seed storage protein {ECO:0000303|PubMed:19006093}; DE AltName: Full=7S vicilin-like protein Cor a 11 {ECO:0000303|PubMed:22812192, ECO:0000303|Ref.12}; DE AltName: Full=Allergen Cor a 11 {ECO:0000303|PubMed:21563837, ECO:0000303|PubMed:22966848, ECO:0000303|PubMed:23411333, ECO:0000303|Ref.12}; DE AltName: Full=Vicilin Cor a 11 {ECO:0000303|PubMed:15233621, ECO:0000303|PubMed:21563837, ECO:0000303|PubMed:21735061, ECO:0000303|PubMed:22616776}; DE AltName: Full=Vicilin HZ.1 {ECO:0000303|PubMed:31753489}; DE AltName: Allergen=Cor a 11.0101 {ECO:0000305}; OS Corylus avellana (European hazel) (Corylus maxima). OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta; OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae; OC rosids; fabids; Fagales; Betulaceae; Corylus. OX NCBI_TaxID=13451 {ECO:0000312|EMBL:AAL86739.1}; RN [1] {ECO:0000312|EMBL:AAL86739.1} RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 48-59; 56-72; 73-79; 80-89; RP 92-100; 101-127; 130-136; 140-152; 153-174; 175-201; 202-213; 241-251; RP 252-268; 269-278; 279-304; 305-315; 319-349; 353-388; 389-394; 395-403; RP 407-415; 416-419; 420-442 AND 423-445, TISSUE SPECIFICITY, DEVELOPMENTAL RP STAGE, PTM, IDENTIFICATION BY MASS SPECTROMETRY, ALLERGEN, SITE, RP GLYCOSYLATION AT ASN-301, AND CIRCULAR DICHROISM ANALYSIS. RC STRAIN=cv. Piemonte {ECO:0000312|EMBL:AAL86739.1}; RC TISSUE=Seed {ECO:0000303|PubMed:15233621}; RX PubMed=15233621; DOI=10.1042/bj20041062; RA Lauer I., Foetisch K., Kolarich D., Ballmer-Weber B.K., Conti A., RA Altmann F., Vieths S., Scheurer S.; RT "Hazelnut (Corylus avellana) vicilin Cor a 11: molecular characterization RT of a glycoprotein and its allergenic activity."; RL Biochem. J. 383:327-334(2004). RN [2] RP PROTEIN SEQUENCE OF 1-11; 5-13; 73-89; 141-152; 175-201; 216-228; 305-315 RP AND 395-403, TISSUE SPECIFICITY, IDENTIFICATION BY MASS SPECTROMETRY, AND RP BIOTECHNOLOGY. RX PubMed=25209075; DOI=10.1021/jf504007d; RA De Ceglie C., Calvano C.D., Zambonin C.G.; RT "Determination of hidden hazelnut oil proteins in extra virgin olive oil by RT cold acetone precipitation followed by in-solution tryptic digestion and RT MALDI-TOF-MS analysis."; RL J. Agric. Food Chem. 62:9401-9409(2014). RN [3] RP PROTEIN SEQUENCE OF 48-62; 73-89; 92-127; 130-136; 140-169; 175-213; RP 241-278; 305-315; 319-345; 353-388; 395-403; 407-415 AND 423-442, SUBUNIT, RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, PTM, IDENTIFICATION BY MASS RP SPECTROMETRY, ALLERGEN, AND CIRCULAR DICHROISM ANALYSIS. RC TISSUE=Seed {ECO:0000303|PubMed:19006093}; RX PubMed=19006093; DOI=10.1002/mnfr.200800083; RA Rigby N.M., Marsh J., Sancho A.I., Wellner K., Akkerdaas J., van Ree R., RA Knulst A., Fernandez-Rivas M., Brettlova V., Schilte P.P., Summer C., RA Pumphrey R., Shewry P.R., Mills E.N.; RT "The purification and characterisation of allergenic hazelnut seed RT proteins."; RL Mol. Nutr. Food Res. 52:S251-S261(2008). RN [4] {ECO:0007744|PDB:6L4C} RP PROTEIN SEQUENCE OF 48-67, X-RAY CRYSTALLOGRAPHY (3.19 ANGSTROMS) OF 25-448 RP IN COMPLEX WITH COPPER, FUNCTION, SUBUNIT, TISSUE SPECIFICITY, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=31753489; DOI=10.1016/j.bbrc.2019.11.072; RA Shikhi M., Jain A., Salunke D.M.; RT "Comparative study of 7S globulin from Corylus avellana and Solanum RT lycopersicum revealed importance of salicylic acid and Cu-binding loop in RT modulating their function."; RL Biochem. Biophys. Res. Commun. 522:127-132(2020). RN [5] RP PROTEIN SEQUENCE OF 56-72; 80-89; 92-100; 101-127; 141-152; 153-169; RP 175-201; 202-213; 241-251; 252-268; 269-278; 279-288; 305-315; 395-403; RP 407-415 AND 423-435, TISSUE SPECIFICITY, IDENTIFICATION BY MASS RP SPECTROMETRY, AND BIOTECHNOLOGY. RX PubMed=22966848; DOI=10.1080/19440049.2012.719639; RA Cucu T., De Meulenaer B., Devreese B.; RT "MALDI-based identification of stable hazelnut protein derived tryptic RT marker peptides."; RL Food Addit. Contam. Part A Chem. Anal. Control Expo. Risk Assess. RL 29:1821-1831(2012). RN [6] RP PROTEIN SEQUENCE OF 92-100; 202-213 AND 407-415, TISSUE SPECIFICITY, RP IDENTIFICATION BY MASS SPECTROMETRY, AND BIOTECHNOLOGY. RX PubMed=21735061; DOI=10.1007/s00216-011-5218-6; RA Ansari P., Stoppacher N., Baumgartner S.; RT "Marker peptide selection for the determination of hazelnut by LC-MS/MS and RT occurrence in other nuts."; RL Anal. Bioanal. Chem. 402:2607-2615(2012). RN [7] RP PROTEIN SEQUENCE OF 92-100; 202-213 AND 407-415, TISSUE SPECIFICITY, RP IDENTIFICATION BY MASS SPECTROMETRY, AND BIOTECHNOLOGY. RX PubMed=24577577; DOI=10.1007/s00216-014-7679-x; RA Costa J., Ansari P., Mafra I., Oliveira M.B., Baumgartner S.; RT "Assessing hazelnut allergens by protein- and DNA-based approaches: LC- RT MS/MS, ELISA and real-time PCR."; RL Anal. Bioanal. Chem. 406:2581-2590(2014). RN [8] RP TISSUE SPECIFICITY, AND ALLERGEN. RX PubMed=21563837; DOI=10.1021/jf2007375; RA Iwan M., Vissers Y.M., Fiedorowicz E., Kostyra H., Kostyra E., RA Savelkoul H.F., Wichers H.J.; RT "Impact of Maillard reaction on immunoreactivity and allergenicity of the RT hazelnut allergen Cor a 11."; RL J. Agric. Food Chem. 59:7163-7171(2011). RN [9] RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, ALLERGEN, AND 3D-STRUCTURE RP MODELING. RX PubMed=22616776; DOI=10.1186/2043-9113-2-12; RA Lopez E., Cuadrado C., Burbano C., Jimenez M.A., Rodriguez J., Crespo J.F.; RT "Effects of autoclaving and high pressure on allergenicity of hazelnut RT proteins."; RL J. Clin. Bioinforma. 2:12-12(2012). RN [10] RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND ALLERGEN. RX PubMed=22812192; RA Verweij M.M., Hagendorens M.M., Trashin S., Cucu T., De Meulenaer B., RA Devreese B., Bridts C.H., De Clerck L.S., Ebo D.G.; RT "Age-dependent sensitization to the 7S-vicilin-like protein Cor a 11 from RT hazelnut (Corylus avellana) in a birch-endemic region."; RL J. Investig. Allergol. Clin. Immunol. 22:245-251(2012). RN [11] RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND BIOTECHNOLOGY. RX PubMed=23411333; DOI=10.1016/j.foodchem.2012.11.036; RA Iniesto E., Jimenez A., Prieto N., Cabanillas B., Burbano C., Pedrosa M.M., RA Rodriguez J., Muzquiz M., Crespo J.F., Cuadrado C., Linacero R.; RT "Real Time PCR to detect hazelnut allergen coding sequences in processed RT foods."; RL Food Chem. 138:1976-1981(2013). RN [12] RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND BIOTECHNOLOGY. RX DOI=10.1111/ijfs.12079; RA Garino C., Locatelli M., Coisson J.D., D'Andrea M., Cereti E., RA Travaglia F., Arlorio M.; RT "Gene transcription analysis of hazelnut (C orylus avellana L.) allergens RT Cor a 1, Cor a 8 and Cor a 11: a comparative study."; RL Int. J. Food Sci. Technol. 48:1208-1217(2013). CC -!- FUNCTION: Seed storage protein (PubMed:15233621, PubMed:19006093, CC PubMed:21563837, PubMed:21735061, PubMed:22966848, PubMed:22616776, CC PubMed:22812192, PubMed:23411333, Ref.12, PubMed:24577577, CC PubMed:25209075). Does not have superoxide dismutase (SOD) activity CC (PubMed:31753489). {ECO:0000269|PubMed:31753489, CC ECO:0000305|PubMed:15233621, ECO:0000305|PubMed:19006093, CC ECO:0000305|PubMed:21563837, ECO:0000305|PubMed:21735061, CC ECO:0000305|PubMed:22616776, ECO:0000305|PubMed:22812192, CC ECO:0000305|PubMed:22966848, ECO:0000305|PubMed:23411333, CC ECO:0000305|PubMed:24577577, ECO:0000305|PubMed:25209075, CC ECO:0000305|Ref.12}. CC -!- SUBUNIT: Homotrimer (PubMed:19006093, PubMed:31753489). Homohexamer CC (PubMed:19006093). {ECO:0000269|PubMed:19006093, CC ECO:0000269|PubMed:31753489}. CC -!- TISSUE SPECIFICITY: Expressed in seed (at protein level) CC (PubMed:15233621, PubMed:19006093, PubMed:21563837, PubMed:21735061, CC PubMed:22966848, PubMed:22616776, PubMed:22812192, PubMed:23411333, CC PubMed:24577577, PubMed:25209075, PubMed:31753489). Expressed in seed CC (Ref.12). {ECO:0000269|PubMed:15233621, ECO:0000269|PubMed:19006093, CC ECO:0000269|PubMed:21563837, ECO:0000269|PubMed:21735061, CC ECO:0000269|PubMed:22616776, ECO:0000269|PubMed:22812192, CC ECO:0000269|PubMed:22966848, ECO:0000269|PubMed:23411333, CC ECO:0000269|PubMed:24577577, ECO:0000269|PubMed:25209075, CC ECO:0000269|PubMed:31753489, ECO:0000269|Ref.12}. CC -!- DEVELOPMENTAL STAGE: Expressed during seed maturation. Expressed at CC three fruit developmental stages, at early stage (approximately 45 days CC before harvest), at middle stage (approximately 30 days before harvest) CC and at final harvest stage. Expressed more in ripe than in unripe seeds CC (Ref.12). Expressed in raw seeds (PubMed:15233621, PubMed:19006093, CC PubMed:22616776, PubMed:22812192, PubMed:23411333). CC {ECO:0000269|PubMed:15233621, ECO:0000269|PubMed:19006093, CC ECO:0000269|PubMed:22616776, ECO:0000269|PubMed:22812192, CC ECO:0000269|PubMed:23411333, ECO:0000269|Ref.12}. CC -!- PTM: N-glycosylated at Asn-301 mostly with xylosylated paucimannosidic- CC type N-glycan MMX (an N-linked glycan with beta-1,2-xylose residue in CC the structure) and also with MMXF (a complex N-linked glycan with CC alpha-1,3-fucose and beta-1,2-xylose residues in the structure). CC {ECO:0000269|PubMed:15233621}. CC -!- PTM: A mixture of proteolytically processed and unprocessed subunits CC exist. {ECO:0000269|PubMed:19006093}. CC -!- ALLERGEN: Causes an allergic reaction in human. Binds to IgE of CC patients allergic to hazelnuts (PubMed:15233621, PubMed:19006093, CC PubMed:21563837, PubMed:22616776, PubMed:22812192). Natural CC glycosylated protein binds to IgE in 47% and recombinant (non- CC glycosylated) protein in 43-40% of the 65 tested adult patients from CC Switzerland and Germany (PubMed:15233621). Natural protein binds to IgE CC in 50% of the tested patients from Netherlands (PubMed:19006093). The CC IgE-binding of the natural protein can be decreased by glycation CC (Maillard reaction) of the protein at 60 and 145 (routine hazelnut CC roasting condition), but not at 37 degrees Celsius (PubMed:21563837). CC IgE-binding of the natural protein is also strongly reduced by CC autoclaving at 138 degrees Celsius for 15 or 30 minutes, but not by CC high pressure treatment alone (300 Mba, 400 Mba, 500 Mba and 600 Mba) CC (PubMed:22616776). Allerginicity to this protein in a birch-endemic CC region (Belgium) seems to be predominantly found in children with CC severe hazelnut allergy compared to adults or children with milder CC forms of hazelnut-allergy. Natural protein binds to IgE in 36%, 40% and CC 12.5% of the 22 preschool children, 10 schoolchildren and 8 adults CC tested, respectively, with systemic allergic reactions toward hazelnut. CC In a set of 40 patients (6 preschool children, 10 schoolchildren and 24 CC adults) having oral allergy symptoms, only 2 patients (of preschool CC age) show IgE-binding to this protein. Also, only 8% of the 24 CC hazelnut-allergic infants with atopic dermatitis tested show IgE CC reactivity to this protein (PubMed:22812192). Induces histamine release CC from human basophils (PubMed:15233621, PubMed:22812192). Both natural CC and recombinant proteins induce histamine release from human basophils CC in a similar manner indicating that the carbohydrate structures are not CC involved in IgE-binding (PubMed:15233621). Induces beta-hexosaminidase CC release from humanized rat basophilic leukemia (RBL) cells. Heating, CC with or without glucose, at 145 degrees Celsius increases the basophil CC degranulation capacity (PubMed:21563837). {ECO:0000269|PubMed:15233621, CC ECO:0000269|PubMed:19006093, ECO:0000269|PubMed:21563837, CC ECO:0000269|PubMed:22616776, ECO:0000269|PubMed:22812192}. CC -!- BIOTECHNOLOGY: In order to protect patients that are allergic to CC hazelnuts, it is extremely important to find ways to detect traces CC amounts of hazelnut in foods that should not contain it for the food CC labeling and safety purposes. This protein is used in the development CC of these methods (PubMed:21735061, PubMed:22966848, PubMed:23411333, CC PubMed:24577577, PubMed:25209075). For the detection of hazelnut, a CC liquid chromatography tandem mass spectrometry (LC-MS/MS) method in CC selected reaction monitoring (SRM) mode is developed by using selected CC marker peptides from this protein as standards (PubMed:21735061). It is CC found that LC-MS/MS performs well in detecting these peptides in CC prepared model chocolates spiked with hazelnut. The sensitivity level CC is approximately 1 mg/kg (PubMed:24577577). A stable peptide (residues CC 395-403) from this protein is identified by MALDI-MS and it can be used CC as an analytical target for the development of robust quantitative CC analytical methods. This peptide is identifiable even when the protein CC goes through a number of changes at the molecular level, such as CC denaturation, the Maillard reaction and oxidation, reactions that CC typically occur during food processing (PubMed:22966848). A CC quantitative method is developed, where the coding DNA of this protein CC is first extracted based on hexadecyltrimethylammonium bromide (CTAB)- CC phenol-chloroform method and then detected by Real-Time PCR (RT-PCR) in CC commercial foods such as chocolates, biscuits, cereal snacks, cookies CC and nougat with 100% specificity and with 1 ppm sensitivity limit of CC detection of raw hazelnut. The reliability of the method is even more CC improved if two other hazelnut target genes (allergens Cor a 9 and Cor CC a 13) are amplified in addition to this one. The detection is proven to CC be accurate even when the quality and quantity of the DNA is greatly CC diminished by roasting and autoclaving. High-hydrostatic pressure CC treatment has no effect on DNA (PubMed:23411333). The transcription CC level of the gene encoding this protein is investigated by a relative CC quantitative RT-PCR technique in order to compare the transcript CC amounts between different cultivars, and in one of the cultivars also CC in relation to different years of harvest and ripening stages. Each CC hazelnut sample is classified by the Principal Components Analysis CC (PCA) to better interpret the results. The method may help in choosing CC hypoallergenic genotypes of hazelnut for both growers and consumers CC (Ref.12). Cold acetone extraction of proteins followed by in-solution CC tryptic digestion and MALDI-TOF-MS (in alpha-cyano-4-chlorocinnamic CC acid matrix) is found as a rapid and sensitive method to detect CC residual amounts of hazelnut proteins in extra virgin olive oil CC samples, which have been adulterated with cold-pressed hazelnut oil. CC Peptides from this protein can be used as stable markers in this CC technique serving as a direct proof of illegal hazelnut existence in CC olive oil (PubMed:25209075). {ECO:0000269|PubMed:21735061, CC ECO:0000269|PubMed:22966848, ECO:0000269|PubMed:23411333, CC ECO:0000269|PubMed:24577577, ECO:0000269|PubMed:25209075, CC ECO:0000269|Ref.12}. CC -!- SIMILARITY: Belongs to the 7S seed storage protein family. CC {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; AF441864; AAL86739.1; -; mRNA. DR PDB; 6L4C; X-ray; 3.19 A; A/B/C=25-448. DR PDBsum; 6L4C; -. DR SMR; Q8S4P9; -. DR Allergome; 3216; Cor a 11.0101. DR Allergome; 690; Cor a 11. DR PRIDE; Q8S4P9; -. DR GO; GO:0043245; C:extraorganismal space; IDA:UniProtKB. DR GO; GO:0005507; F:copper ion binding; IDA:UniProtKB. DR GO; GO:0045735; F:nutrient reservoir activity; IDA:UniProtKB. DR GO; GO:0034214; P:protein hexamerization; IDA:UniProtKB. DR GO; GO:0070207; P:protein homotrimerization; IDA:UniProtKB. DR GO; GO:0019430; P:removal of superoxide radicals; IEA:GOC. DR Gene3D; 2.60.120.10; -; 2. DR InterPro; IPR006045; Cupin_1. DR InterPro; IPR014710; RmlC-like_jellyroll. DR InterPro; IPR011051; RmlC_Cupin_sf. DR Pfam; PF00190; Cupin_1; 2. DR SMART; SM00835; Cupin_1; 2. DR SUPFAM; SSF51182; SSF51182; 2. PE 1: Evidence at protein level; KW 3D-structure; Allergen; Copper; Direct protein sequencing; Glycoprotein; KW Metal-binding; Repeat; Seed storage protein; Storage protein. FT CHAIN 1..448 FT /note="Vicilin Cor a 11.0101" FT /id="PRO_0000451919" FT DOMAIN 84..220 FT /note="Cupin type-1 1" FT /evidence="ECO:0000255" FT DOMAIN 263..418 FT /note="Cupin type-1 2" FT /evidence="ECO:0000255" FT METAL 333 FT /note="Copper" FT /evidence="ECO:0000269|PubMed:31753489, FT ECO:0007744|PDB:6L4C" FT METAL 335 FT /note="Copper; via pros nitrogen" FT /evidence="ECO:0000269|PubMed:31753489, FT ECO:0007744|PDB:6L4C" FT METAL 362 FT /note="Copper; via tele nitrogen" FT /evidence="ECO:0000269|PubMed:31753489, FT ECO:0007744|PDB:6L4C" FT SITE 47..48 FT /note="Cleavage" FT /evidence="ECO:0000305|PubMed:19006093, FT ECO:0000305|PubMed:31753489" FT SITE 85 FT /note="Not glycosylated" FT /evidence="ECO:0000269|PubMed:15233621" FT CARBOHYD 47 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 301 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498, FT ECO:0000269|PubMed:15233621" FT CONFLICT 49 FT /note="S -> E (in Ref. 4; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 55 FT /note="K -> E (in Ref. 1; AA sequence and 4; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 58 FT /note="E -> D (in Ref. 1; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 59 FT /note="E -> N (in Ref. 1; AA sequence and 4; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 64 FT /note="F -> L (in Ref. 4; AA sequence)" FT /evidence="ECO:0000305" SQ SEQUENCE 448 AA; 50856 MW; D748661592AA55F0 CRC64; MLPKEDPELK KCKHKCRDER QFDEQQRRDG KQICEEKARE RQQEEGNSSE ESYGKEQEEN PYVFQDEHFE SRVKTEEGRV QVLENFTKRS RLLSGIENFR LAILEANPHT FISPAHFDAE LVLFVAKGRA TITMVREEKR ESFNVEHGDI IRIPAGTPVY MINRDENEKL FIVKILQPVS APGHFEAFYG AGGEDPESFY RAFSWEVLEA ALKVRREQLE KVFGEQSKGS IVKASREKIR ALSQHEEGPP RIWPFGGESS GPINLLHKHP SQSNQFGRLY EAHPDDHKQL QDLDLMVSFA NITKGSMAGP YYNSRATKIS VVVEGEGFFE MACPHLSSSS GSYQKISARL RRGVVFVAPA GHPVAVIASQ NNNLQVLCFE VNAHGNSRFP LAGKGNIVNE FERDAKELAF NLPSREVERI FKNQDQAFFF PGPNKQQEEG GRGGRAFE //