ID CYND4_CYNDA Reviewed; 522 AA. AC Q5QJ60; DT 11-DEC-2019, integrated into UniProtKB/Swiss-Prot. DT 04-JAN-2005, sequence version 1. DT 22-FEB-2023, entry version 74. DE RecName: Full=Berberine bridge enzyme-like Cyn d 4 {ECO:0000305}; DE AltName: Full=60 kDa pollen antigen {ECO:0000303|PubMed:8828524, ECO:0000303|PubMed:8900140}; DE Short=BG60 {ECO:0000303|PubMed:20080962, ECO:0000303|PubMed:8828524, ECO:0000303|PubMed:8900140}; DE AltName: Full=Cyn d BG60 {ECO:0000303|PubMed:20080962}; DE AltName: Full=FAD-linked oxidoreductase BG60 {ECO:0000312|EMBL:AAS02108.1}; DE EC=1.-.-.- {ECO:0000305}; DE AltName: Full=Pollen isoallergen BG60 {ECO:0000303|PubMed:10479622, ECO:0000303|PubMed:11162583, ECO:0000303|PubMed:22993084}; DE AltName: Allergen=Cyn d 4 {ECO:0000303|PubMed:22993084}; DE Flags: Precursor; OS Cynodon dactylon (Bermuda grass) (Panicum dactylon). OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta; OC Spermatophyta; Magnoliopsida; Liliopsida; Poales; Poaceae; PACMAD clade; OC Chloridoideae; Cynodonteae; Eleusininae; Cynodon. OX NCBI_TaxID=28909 {ECO:0000312|EMBL:AAS02108.1}; RN [1] {ECO:0000312|EMBL:AAS02108.1} RP NUCLEOTIDE SEQUENCE [MRNA]. RA Chuang J.-G., Chow L.-P., Su S.-N.; RT "Molecular cloning and expression of an allergen BG60 from Bermuda grass RT (Cynodon dactylon)."; RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases. RN [2] RP PROTEIN SEQUENCE OF 76-86; 195-218; 347-365 AND 464-476, COFACTOR, TISSUE RP SPECIFICITY, PTM, AND CIRCULAR DICHROISM ANALYSIS. RX PubMed=11162583; DOI=10.1006/bbrc.2000.4203; RA Liaw S., Lee D.Y., Chow L.P., Lau G.X., Su S.N., Chow L.; RT "Structural characterization of the 60-kDa bermuda grass pollen RT isoallergens, a covalent flavoprotein."; RL Biochem. Biophys. Res. Commun. 280:738-743(2001). RN [3] RP TISSUE SPECIFICITY, PTM, GLYCOSYLATION, AND ALLERGEN. RX PubMed=8828524; DOI=10.1016/s0091-6749(96)70080-5; RA Su S.N., Shu P., Lau G.X., Yang S.Y., Huang S.W., Lee Y.C.; RT "Immunologic and physicochemical studies of Bermuda grass pollen antigen RT BG60."; RL J. Allergy Clin. Immunol. 98:486-494(1996). RN [4] RP TISSUE SPECIFICITY, AND GLYCOSYLATION. RX PubMed=8900140; DOI=10.1074/jbc.271.43.26653; RA Ohsuga H., Su S.N., Takahashi N., Yang S.Y., Nakagawa H., Shimada I., RA Arata Y., Lee Y.C.; RT "The carbohydrate moiety of the bermuda grass antigen BG60. New RT oligosaccharides of plant origin."; RL J. Biol. Chem. 271:26653-26658(1996). RN [5] RP CRYSTALLIZATION, SUBUNIT, TISSUE SPECIFICITY, AND PTM. RX PubMed=10479622; DOI=10.1006/jsbi.1999.4133; RA Liaw S.H., Lee D.Y., Yang S.Y., Su S.N.; RT "Crystallization and preliminary diffraction data of 60-kDa glycosylated RT pollen isoallergens from Bermuda grass."; RL J. Struct. Biol. 127:83-87(1999). RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY, TISSUE SPECIFICITY, PTM, RP GLYCOSYLATION, AND ALLERGEN. RX PubMed=16121337; DOI=10.1002/pmic.200401229; RA Kao S.H., Su S.N., Huang S.W., Tsai J.J., Chow L.P.; RT "Sub-proteome analysis of novel IgE-binding proteins from Bermuda grass RT pollen."; RL Proteomics 5:3805-3813(2005). RN [7] RP ALLERGEN. RX PubMed=20080962; DOI=10.1074/jbc.m109.058370; RA Hsu S.C., Chen C.H., Tsai S.H., Kawasaki H., Hung C.H., Chu Y.T., RA Chang H.W., Zhou Y., Fu J., Plunkett B., Su S.N., Vieths S., Lee R.T., RA Lee Y.C., Huang S.K.; RT "Functional interaction of common allergens and a C-type lectin receptor, RT dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN), on human RT dendritic cells."; RL J. Biol. Chem. 285:7903-7910(2010). RN [8] {ECO:0007744|PDB:4DNS} RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 26-522 IN COMPLEX WITH FAD, RP COFACTOR, SUBUNIT, TISSUE SPECIFICITY, DISULFIDE BONDS, AND GLYCOSYLATION RP AT ASN-88 AND ASN-325. RX PubMed=22993084; DOI=10.1107/s0907444912027552; RA Huang T.H., Peng H.J., Su S.N., Liaw S.H.; RT "Various cross-reactivity of the grass pollen group 4 allergens: RT crystallographic study of the Bermuda grass isoallergen Cyn d 4."; RL Acta Crystallogr. D 68:1303-1310(2012). CC -!- COFACTOR: CC Name=FAD; Xref=ChEBI:CHEBI:57692; CC Evidence={ECO:0000269|PubMed:11162583, ECO:0000269|PubMed:22993084}; CC Note=Binds 1 FAD per subunit in a bicovalent manner. CC {ECO:0000269|PubMed:22993084}; CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:10479622, CC ECO:0000269|PubMed:22993084}. CC -!- TISSUE SPECIFICITY: Expressed in pollen (at protein level). CC {ECO:0000269|PubMed:10479622, ECO:0000269|PubMed:11162583, CC ECO:0000269|PubMed:16121337, ECO:0000269|PubMed:22993084, CC ECO:0000269|PubMed:8828524, ECO:0000269|PubMed:8900140}. CC -!- PTM: The FAD cofactor is bound via a bicovalent 6-S-cysteinyl, 8alpha- CC N1-histidyl FAD linkage. {ECO:0000269|PubMed:22993084}. CC -!- PTM: The N-terminus is blocked. {ECO:0000269|PubMed:10479622, CC ECO:0000269|PubMed:11162583, ECO:0000269|PubMed:16121337, CC ECO:0000269|PubMed:8828524}. CC -!- PTM: Glycosylated (PubMed:16121337). N-glycosylated (PubMed:8828524, CC PubMed:8900140). Contains fucose, N-acetylglucosamine, and mannose as CC main carbohydrates (in a ratio of approximately 3:2:1), and a minute CC amount of xylose (PubMed:8828524). The two most abundant CC oligosaccharides are Fuc(1)GlcNAc(2)Man(3) and Fuc(1)GlcNAc(2)Man(2), CC together comprising about 80% of the total carbohydrate content. They CC are structurally unusual in having a L-Fuc alpha-(1,3)-linked to Asn- CC linked GlcNAc without a Xyl beta-(1,2)-linked to the branching Man. The CC other oligosaccharides make up only 9% of the total carbohydrate CC content and are characterized by the presence of Xyl beta-(1,2)-linked CC to the branching Man (PubMed:8900140). {ECO:0000269|PubMed:16121337, CC ECO:0000269|PubMed:8828524, ECO:0000269|PubMed:8900140}. CC -!- ALLERGEN: Causes an allergic reaction in human. Binds to IgE of CC patients allergic to Bermuda grass pollen (BGP) (PubMed:8828524, CC PubMed:16121337). Binds to IgE in all 18 patients tested CC (PubMed:8828524). Binds to IgE in 50% of the 10 patients tested CC (PubMed:16121337). Periodate oxidation decreases the binding activity CC to IgE from 20% to 65% as the concentration of periodate increases from CC 1 mmol/L to 10 mmol/L, indicating the involvement of the carbohydrate CC moiety of this protein in immune responses (PubMed:8828524). The CC fucosylated glycan structures of this protein can bind the human C-type CC lectin receptors CD209 (DC-SIGN) and its related receptor CLEC4M (L- CC SIGN). The interaction provokes an immune response leading to the CC activation of RAF1 and ERK kinases and to the induction of tumor CC necrosis factor (TNF)-alpha expression in human THP-1 cells and CC monocyte-derived dendritic cells (MDDCs) (PubMed:20080962). CC {ECO:0000269|PubMed:16121337, ECO:0000269|PubMed:20080962, CC ECO:0000269|PubMed:8828524}. CC -!- SIMILARITY: Belongs to the oxygen-dependent FAD-linked oxidoreductase CC 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; AY451241; AAS02108.1; -; mRNA. DR PDB; 4DNS; X-ray; 2.15 A; A/B=26-522. DR PDBsum; 4DNS; -. DR AlphaFoldDB; Q5QJ60; -. DR SMR; Q5QJ60; -. DR Allergome; 819; Cyn d 4. DR iPTMnet; Q5QJ60; -. DR GO; GO:0071949; F:FAD binding; IDA:UniProtKB. DR GO; GO:0016491; F:oxidoreductase activity; IC:UniProtKB. DR Gene3D; 3.30.465.10; -; 1. DR Gene3D; 3.40.462.20; -; 1. DR Gene3D; 3.30.43.10; Uridine Diphospho-n-acetylenolpyruvylglucosamine Reductase, domain 2; 1. DR InterPro; IPR012951; BBE. DR InterPro; IPR016166; FAD-bd_PCMH. DR InterPro; IPR036318; FAD-bd_PCMH-like_sf. DR InterPro; IPR016167; FAD-bd_PCMH_sub1. DR InterPro; IPR016169; FAD-bd_PCMH_sub2. DR InterPro; IPR006094; Oxid_FAD_bind_N. DR PANTHER; PTHR32448:SF119; OS06G0548800 PROTEIN; 1. DR PANTHER; PTHR32448; OS08G0158400 PROTEIN; 1. DR Pfam; PF08031; BBE; 1. DR Pfam; PF01565; FAD_binding_4; 1. DR SUPFAM; SSF56176; FAD-binding/transporter-associated domain-like; 1. DR PROSITE; PS51387; FAD_PCMH; 1. PE 1: Evidence at protein level; KW 3D-structure; Allergen; Direct protein sequencing; Disulfide bond; FAD; KW Flavoprotein; Glycoprotein; Nucleotide-binding; Oxidoreductase; Signal. FT SIGNAL 1..25 FT /evidence="ECO:0000255" FT CHAIN 26..522 FT /note="Berberine bridge enzyme-like Cyn d 4" FT /evidence="ECO:0000255" FT /id="PRO_5004261372" FT DOMAIN 76..252 FT /note="FAD-binding PCMH-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718" FT BINDING 108..114 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:22993084, FT ECO:0007744|PDB:4DNS" FT BINDING 119 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:22993084, FT ECO:0007744|PDB:4DNS" FT BINDING 152 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:22993084, FT ECO:0007744|PDB:4DNS" FT BINDING 176..177 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:22993084, FT ECO:0007744|PDB:4DNS" FT BINDING 181..185 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:22993084, FT ECO:0007744|PDB:4DNS" FT BINDING 191 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:22993084, FT ECO:0007744|PDB:4DNS" FT BINDING 237 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:22993084, FT ECO:0007744|PDB:4DNS" FT BINDING 242 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:22993084, FT ECO:0007744|PDB:4DNS" FT BINDING 461..465 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:22993084, FT ECO:0007744|PDB:4DNS" FT CARBOHYD 88 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498, FT ECO:0000269|PubMed:22993084, ECO:0007744|PDB:4DNS" FT CARBOHYD 325 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498, FT ECO:0000269|PubMed:22993084, ECO:0007744|PDB:4DNS" FT CARBOHYD 354 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 477 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT DISULFID 41..98 FT /evidence="ECO:0000269|PubMed:22993084, FT ECO:0007744|PDB:4DNS" FT DISULFID 308..329 FT /evidence="ECO:0000269|PubMed:22993084, FT ECO:0007744|PDB:4DNS" FT CROSSLNK 113..177 FT /note="6-(S-cysteinyl)-8alpha-(pros-histidyl)-FAD (His- FT Cys)" FT /evidence="ECO:0000269|PubMed:22993084, FT ECO:0007744|PDB:4DNS" FT HELIX 38..43 FT /evidence="ECO:0007829|PDB:4DNS" FT HELIX 48..50 FT /evidence="ECO:0007829|PDB:4DNS" FT STRAND 51..53 FT /evidence="ECO:0007829|PDB:4DNS" FT HELIX 59..64 FT /evidence="ECO:0007829|PDB:4DNS" FT HELIX 70..72 FT /evidence="ECO:0007829|PDB:4DNS" FT STRAND 74..78 FT /evidence="ECO:0007829|PDB:4DNS" FT STRAND 81..84 FT /evidence="ECO:0007829|PDB:4DNS" FT HELIX 89..101 FT /evidence="ECO:0007829|PDB:4DNS" FT STRAND 105..111 FT /evidence="ECO:0007829|PDB:4DNS" FT TURN 118..120 FT /evidence="ECO:0007829|PDB:4DNS" FT STRAND 122..124 FT /evidence="ECO:0007829|PDB:4DNS" FT STRAND 128..132 FT /evidence="ECO:0007829|PDB:4DNS" FT HELIX 133..135 FT /evidence="ECO:0007829|PDB:4DNS" FT STRAND 139..141 FT /evidence="ECO:0007829|PDB:4DNS" FT TURN 143..145 FT /evidence="ECO:0007829|PDB:4DNS" FT STRAND 147..151 FT /evidence="ECO:0007829|PDB:4DNS" FT HELIX 156..166 FT /evidence="ECO:0007829|PDB:4DNS" FT HELIX 182..187 FT /evidence="ECO:0007829|PDB:4DNS" FT HELIX 195..198 FT /evidence="ECO:0007829|PDB:4DNS" FT HELIX 202..204 FT /evidence="ECO:0007829|PDB:4DNS" FT STRAND 205..211 FT /evidence="ECO:0007829|PDB:4DNS" FT HELIX 220..223 FT /evidence="ECO:0007829|PDB:4DNS" FT HELIX 225..230 FT /evidence="ECO:0007829|PDB:4DNS" FT TURN 231..233 FT /evidence="ECO:0007829|PDB:4DNS" FT STRAND 241..248 FT /evidence="ECO:0007829|PDB:4DNS" FT STRAND 256..264 FT /evidence="ECO:0007829|PDB:4DNS" FT HELIX 265..267 FT /evidence="ECO:0007829|PDB:4DNS" FT HELIX 269..279 FT /evidence="ECO:0007829|PDB:4DNS" FT TURN 280..282 FT /evidence="ECO:0007829|PDB:4DNS" FT STRAND 287..294 FT /evidence="ECO:0007829|PDB:4DNS" FT STRAND 297..306 FT /evidence="ECO:0007829|PDB:4DNS" FT HELIX 308..318 FT /evidence="ECO:0007829|PDB:4DNS" FT HELIX 320..322 FT /evidence="ECO:0007829|PDB:4DNS" FT STRAND 330..332 FT /evidence="ECO:0007829|PDB:4DNS" FT HELIX 334..343 FT /evidence="ECO:0007829|PDB:4DNS" FT HELIX 349..353 FT /evidence="ECO:0007829|PDB:4DNS" FT STRAND 361..370 FT /evidence="ECO:0007829|PDB:4DNS" FT HELIX 376..384 FT /evidence="ECO:0007829|PDB:4DNS" FT HELIX 385..387 FT /evidence="ECO:0007829|PDB:4DNS" FT STRAND 393..398 FT /evidence="ECO:0007829|PDB:4DNS" FT HELIX 401..405 FT /evidence="ECO:0007829|PDB:4DNS" FT STRAND 410..412 FT /evidence="ECO:0007829|PDB:4DNS" FT STRAND 421..430 FT /evidence="ECO:0007829|PDB:4DNS" FT HELIX 432..434 FT /evidence="ECO:0007829|PDB:4DNS" FT HELIX 436..449 FT /evidence="ECO:0007829|PDB:4DNS" FT TURN 450..452 FT /evidence="ECO:0007829|PDB:4DNS" FT HELIX 467..469 FT /evidence="ECO:0007829|PDB:4DNS" FT HELIX 481..492 FT /evidence="ECO:0007829|PDB:4DNS" FT HELIX 493..495 FT /evidence="ECO:0007829|PDB:4DNS" FT HELIX 496..506 FT /evidence="ECO:0007829|PDB:4DNS" SQ SEQUENCE 522 AA; 57413 MW; 3C781F7FC155B33F CRC64; MARSRAFAFA LLICAVAASC HVALSAPPPY AKQVERDFLT CLTKDIPPRQ LYAKSSPAYA SVWSSTVRNI KFLSDKTVKP LYIITPTNAS HIQAAVVCGR RHGMRIRVRS GGHDYEGLSY RSEKPEPFAV VDMNKMRAVS IDGKAATAWV DSGAQLGDLY YGIAKASPKL GFPAGVCTTI GVGGHFSGGG FGMLLRKYGT AADNVIDAKV VDAQGRLLDR KAMGEDHFWA IRGGGGESFG IVASWQVKLL PVPPKVTVFQ VHKGIKEGAI DLVTKWQTVA PALPDDLMIR IMAMGQGAMF EALYLGTCKD LVLLMTARFP ELGMNATHCK EMTWIESVPY IPMGPKGTVR DLLNRTSNIK AFGKYKSDYV LEPIPKSDWE KIFTWLVKPG AGVMIMDPYG GGIASVPESA TPFPRRSGVL FNIQYVVYWF GEGAAALPTQ WTRDIYDFMT PYVSKNPRQA YVNYRDLDLG VNQVVGNVST YASGKVWGEK YFKGNFERLA RTKGKIDPED YFRNEQSIPP LL //