CEP01_AMBAR
ID CEP01_AMBAR Reviewed; 386 AA.
AC V5LU01;
DT 31-JUL-2019, integrated into UniProtKB/Swiss-Prot.
DT 19-FEB-2014, sequence version 1.
DT 03-AUG-2022, entry version 35.
DE RecName: Full=Cysteine protease Amb a 11.0101 {ECO:0000305};
DE EC=3.4.22.- {ECO:0000269|PubMed:25865353, ECO:0000269|PubMed:27129273};
DE AltName: Full=Amino acid thiol protease {ECO:0000303|PubMed:25865353};
DE AltName: Full=Pollen allergen Amb a 11 {ECO:0000303|PubMed:25865353, ECO:0000303|PubMed:27129273};
DE AltName: Allergen=Amb a 11.0101 {ECO:0000303|PubMed:25865353};
DE Flags: Precursor;
OS Ambrosia artemisiifolia (Common ragweed).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC asterids; campanulids; Asterales; Asteraceae; Asteroideae;
OC Heliantheae alliance; Heliantheae; Ambrosia.
OX NCBI_TaxID=4212 {ECO:0000312|EMBL:AHA56102.1};
RN [1] {ECO:0000312|EMBL:AHA56102.1}
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 109-301 AND 310-370,
RP 3D-STRUCTURE MODELING, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP TISSUE SPECIFICITY, IDENTIFICATION BY MASS SPECTROMETRY, ALLERGEN,
RP GLYCOSYLATION AT ASN-127, AND CIRCULAR DICHROISM ANALYSIS.
RC TISSUE=Pollen {ECO:0000303|PubMed:25865353};
RX PubMed=25865353; DOI=10.1016/j.jaci.2015.03.001;
RA Bouley J., Groeme R., Le Mignon M., Jain K., Chabre H., Bordas-Le Floch V.,
RA Couret M.N., Bussieres L., Lautrette A., Naveau M., Baron-Bodo V.,
RA Lombardi V., Mascarell L., Batard T., Nony E., Moingeon P.;
RT "Identification of the cysteine protease Amb a 11 as a novel major allergen
RT from short ragweed.";
RL J. Allergy Clin. Immunol. 136:1055-1064(2015).
RN [2] {ECO:0007744|PDB:5EF4, ECO:0007744|PDB:5EGW}
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 23-386, FUNCTION, CATALYTIC
RP ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT,
RP CLEAVAGE, ALLERGEN, ACTIVE SITE, DISULFIDE BONDS, AND MUTAGENESIS OF
RP CYS-155 AND 371-LYS--LEU-386.
RX PubMed=27129273; DOI=10.1074/jbc.m115.702001;
RA Groeme R., Airouche S., Kopecny D., Jaekel J., Savko M., Berjont N.,
RA Bussieres L., Le Mignon M., Jagic F., Zieglmayer P., Baron-Bodo V.,
RA Bordas-Le Floch V., Mascarell L., Briozzo P., Moingeon P.;
RT "Structural and Functional Characterization of the Major Allergen Amb a 11
RT from Short Ragweed Pollen.";
RL J. Biol. Chem. 291:13076-13087(2016).
CC -!- FUNCTION: Cysteine protease. Hydrolyzes casein and synthetic peptide
CC Boc-Val-Leu-Lys-7-amino-4-methylcoumarin (Boc-VLK-AMC) in vitro.
CC {ECO:0000269|PubMed:25865353, ECO:0000269|PubMed:27129273}.
CC -!- ACTIVITY REGULATION: Activated by L-cysteine (PubMed:27129273).
CC Inhibited by cysteine protease inhibitor E64 (PubMed:25865353,
CC PubMed:27129273). Inhibited by cysteine/serine protease inhibitor
CC leupeptin. Not inhibited by serine protease inhibitors 4-(2-
CC aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) and
CC phenylmethanesulfonyl fluoride (PMSF), metallo protease inhibitor
CC bestatin or aspartic protease inhibitor pepstatin A (PubMed:27129273).
CC {ECO:0000269|PubMed:25865353, ECO:0000269|PubMed:27129273}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is between 8 and 9. {ECO:0000269|PubMed:27129273};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:27129273}.
CC -!- TISSUE SPECIFICITY: Expressed in pollen (at protein and mRNA level).
CC {ECO:0000269|PubMed:25865353}.
CC -!- PTM: Autocatalytic proteolytic cleavage of N-terminal activation
CC peptide. {ECO:0000269|PubMed:27129273}.
CC -!- PTM: N-glycosylated. Glycosylation is not required for binding to IgE.
CC {ECO:0000269|PubMed:25865353}.
CC -!- ALLERGEN: Causes an allergic reaction in human. Binds to IgE in 54% of
CC the 92 patients, including both Europeans and Americans, tested
CC allergic to ragweed pollen. Purified native protein under non-
CC denaturing conditions binds to IgE in 66% of the same 92 patients
CC tested (PubMed:25865353). Binds to IgE of mice. In mice, the
CC allergicity especially to the proteolytically active form of this
CC protein leads to airway hyperresponsiveness, lung inflammation
CC characterized by eosinophil and type 2 innate lymphoid cell (ILC2)
CC infiltrates in bronchoalveolar lavages (BALs), and responses of the T-
CC helper 2 (Th2) cells (PubMed:27129273). Causes activation of human
CC basophils (PubMed:25865353). {ECO:0000269|PubMed:25865353,
CC ECO:0000269|PubMed:27129273}.
CC -!- SIMILARITY: Belongs to the peptidase C1 family. {ECO:0000305}.
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DR EMBL; KF528831; AHA56102.1; -; mRNA.
DR PDB; 5EF4; X-ray; 2.05 A; A/B=23-386.
DR PDB; 5EGW; X-ray; 2.70 A; A/B=23-386.
DR PDBsum; 5EF4; -.
DR PDBsum; 5EGW; -.
DR AlphaFoldDB; V5LU01; -.
DR SMR; V5LU01; -.
DR Allergome; 11405; Amb a 11.
DR Allergome; 11406; Amb a 11.0101.
DR iPTMnet; V5LU01; -.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd02248; Peptidase_C1A; 1.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR025661; Pept_asp_AS.
DR InterPro; IPR000169; Pept_cys_AS.
DR InterPro; IPR000668; Peptidase_C1A_C.
DR InterPro; IPR039417; Peptidase_C1A_papain-like.
DR InterPro; IPR013201; Prot_inhib_I29.
DR Pfam; PF08246; Inhibitor_I29; 1.
DR Pfam; PF00112; Peptidase_C1; 1.
DR PRINTS; PR00705; PAPAIN.
DR SMART; SM00848; Inhibitor_I29; 1.
DR SMART; SM00645; Pept_C1; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS00640; THIOL_PROTEASE_ASN; 1.
DR PROSITE; PS00139; THIOL_PROTEASE_CYS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Allergen; Autocatalytic cleavage; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Hydrolase; Protease; Signal; Thiol protease;
KW Zymogen.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT PROPEP 23..108
FT /note="Activation peptide"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25865353"
FT /id="PRO_0000447673"
FT CHAIN 109..370
FT /note="Cysteine protease Amb a 11.0101"
FT /evidence="ECO:0000305|PubMed:25865353"
FT /id="PRO_5018702241"
FT PROPEP 371..386
FT /note="Removed in mature form"
FT /evidence="ECO:0000305|PubMed:25865353"
FT /id="PRO_0000447674"
FT REGION 340..377
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 353..370
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 155
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10088,
FT ECO:0000269|PubMed:27129273"
FT ACT_SITE 289
FT /evidence="ECO:0000305|PubMed:27129273"
FT ACT_SITE 310
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10090,
FT ECO:0000305|PubMed:27129273"
FT CARBOHYD 127
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:25865353"
FT DISULFID 152..193
FT /evidence="ECO:0000269|PubMed:27129273,
FT ECO:0007744|PDB:5EF4, ECO:0007744|PDB:5EGW"
FT DISULFID 186..226
FT /evidence="ECO:0000269|PubMed:27129273,
FT ECO:0007744|PDB:5EF4, ECO:0007744|PDB:5EGW"
FT DISULFID 283..334
FT /evidence="ECO:0000269|PubMed:27129273,
FT ECO:0007744|PDB:5EF4, ECO:0007744|PDB:5EGW"
FT MUTAGEN 155
FT /note="C->S: Loss of catalytic activity. Loss of protein
FT maturation in vitro."
FT /evidence="ECO:0000269|PubMed:27129273"
FT MUTAGEN 371..386
FT /note="Missing: No effect in protein maturation in vitro."
FT /evidence="ECO:0000269|PubMed:27129273"
FT HELIX 27..31
FT /evidence="ECO:0007829|PDB:5EF4"
FT HELIX 33..46
FT /evidence="ECO:0007829|PDB:5EF4"
FT HELIX 54..70
FT /evidence="ECO:0007829|PDB:5EF4"
FT STRAND 76..79
FT /evidence="ECO:0007829|PDB:5EF4"
FT TURN 83..86
FT /evidence="ECO:0007829|PDB:5EF4"
FT HELIX 89..96
FT /evidence="ECO:0007829|PDB:5EF4"
FT HELIX 101..108
FT /evidence="ECO:0007829|PDB:5EF4"
FT STRAND 117..121
FT /evidence="ECO:0007829|PDB:5EGW"
FT TURN 124..127
FT /evidence="ECO:0007829|PDB:5EF4"
FT STRAND 133..136
FT /evidence="ECO:0007829|PDB:5EGW"
FT HELIX 137..140
FT /evidence="ECO:0007829|PDB:5EF4"
FT HELIX 155..172
FT /evidence="ECO:0007829|PDB:5EF4"
FT HELIX 180..186
FT /evidence="ECO:0007829|PDB:5EF4"
FT TURN 188..191
FT /evidence="ECO:0007829|PDB:5EGW"
FT HELIX 192..194
FT /evidence="ECO:0007829|PDB:5EF4"
FT HELIX 198..207
FT /evidence="ECO:0007829|PDB:5EF4"
FT TURN 214..216
FT /evidence="ECO:0007829|PDB:5EF4"
FT HELIX 228..230
FT /evidence="ECO:0007829|PDB:5EF4"
FT STRAND 239..242
FT /evidence="ECO:0007829|PDB:5EF4"
FT HELIX 248..255
FT /evidence="ECO:0007829|PDB:5EF4"
FT STRAND 260..264
FT /evidence="ECO:0007829|PDB:5EF4"
FT HELIX 269..272
FT /evidence="ECO:0007829|PDB:5EF4"
FT STRAND 273..279
FT /evidence="ECO:0007829|PDB:5EF4"
FT STRAND 289..298
FT /evidence="ECO:0007829|PDB:5EF4"
FT STRAND 304..309
FT /evidence="ECO:0007829|PDB:5EF4"
FT STRAND 321..329
FT /evidence="ECO:0007829|PDB:5EF4"
FT HELIX 333..335
FT /evidence="ECO:0007829|PDB:5EF4"
FT STRAND 338..344
FT /evidence="ECO:0007829|PDB:5EF4"
FT STRAND 365..367
FT /evidence="ECO:0007829|PDB:5EGW"
FT STRAND 370..372
FT /evidence="ECO:0007829|PDB:5EGW"
FT STRAND 376..378
FT /evidence="ECO:0007829|PDB:5EGW"
SQ SEQUENCE 386 AA; 43157 MW; 43D36BD6B9E92B13 CRC64;
MEINKLVCFS FSLVLILGLV ESFHYHEREL ESEEGFMGMY DRWREQHNIE MRSPERFNVF
KYNVRRIHES NKMDKPYKLK VNEFADMTNL EFVNTYANSK ISHFQALRGS APGSIDTDPN
KDFIYANVTK IPDKVDWREK NAVTDVKGQG GCGSCWAFAA VVALEGINAI RTGKLVKFSE
QQLVDCDMTN AGCDGGLMEP AFTYVIKHGG IAPEASYPYV GKRETCDKAK IKDVLKIDGR
QNVPGLDEEA LRKAVAHQPV ATGIQLSGHG LQFYSEGVYT GDCGTEPNHG VGIVGYGENE
KGIKFWTVKN SWGPTWGEKG YIHLQRGARK EGLCGVAMHS SFPIMNDPNP PKDDPNGPKD
DPDAPKDPKF KTTQRLQGIR TKLLEL
