ID   MTDH_ALTAL              Reviewed;         266 AA.
AC   P0C0Y4; Q2TV80; Q8J231;
DT   24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT   31-OCT-2006, sequence version 2.
DT   03-AUG-2022, entry version 59.
DE   RecName: Full=NADP-dependent mannitol dehydrogenase {ECO:0000303|PubMed:17177674};
DE            Short=MtDH;
DE            EC=1.1.1.138 {ECO:0000269|PubMed:17177674};
DE   AltName: Full=Mannitol 2-dehydrogenase [NADP(+)];
DE   AltName: Allergen=Alt a 8;
OS   Alternaria alternata (Alternaria rot fungus) (Torula alternata).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC   Pleosporomycetidae; Pleosporales; Pleosporineae; Pleosporaceae; Alternaria;
OC   Alternaria sect. Alternaria; Alternaria alternata complex.
OX   NCBI_TaxID=5599;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP   PROPERTIES, MASS SPECTROMETRY, AND ALLERGEN.
RC   STRAIN=08-0203-Berlin;
RX   PubMed=17177674; DOI=10.1111/j.1365-2222.2006.02582.x;
RA   Schneider P.B., Denk U., Breitenbach M., Richter K.,
RA   Schmid-Grendelmeier P., Nobbe S., Himly M., Mari A., Ebner C.,
RA   Simon-Nobbe B.;
RT   "Alternaria alternata NADP-dependent mannitol dehydrogenase is an important
RT   fungal allergen.";
RL   Clin. Exp. Allergy 36:1513-1524(2006).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=A5;
RA   Velez H., Ehrenshaft M., Daub M.E.;
RT   "Alternaria alternata mannitol metabolism in plant-pathogen interactions.";
RL   Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   SUBCELLULAR LOCATION.
RX   PubMed=22078468; DOI=10.1016/j.jaci.2011.10.008;
RA   Twaroch T.E., Arcalis E., Sterflinger K., Stoeger E., Swoboda I.,
RA   Valenta R.;
RT   "Predominant localization of the major Alternaria allergen Alt a 1 in the
RT   cell wall of airborne spores.";
RL   J. Allergy Clin. Immunol. 129:1148-1149(2012).
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=D-mannitol + NADP(+) = D-fructose + H(+) + NADPH;
CC         Xref=Rhea:RHEA:16765, ChEBI:CHEBI:15378, ChEBI:CHEBI:16899,
CC         ChEBI:CHEBI:37721, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC         EC=1.1.1.138; Evidence={ECO:0000269|PubMed:17177674};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=474 mM for D-fructose {ECO:0000269|PubMed:17177674};
CC         KM=18.7 uM for NADPH {ECO:0000269|PubMed:17177674};
CC   -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:O93868}.
CC   -!- SUBCELLULAR LOCATION: Vacuole {ECO:0000269|PubMed:22078468}.
CC   -!- MASS SPECTROMETRY: Mass=28618; Method=Electrospray;
CC       Evidence={ECO:0000269|PubMed:17177674};
CC   -!- ALLERGEN: Causes an allergic reaction in human. Binds to IgE.
CC       {ECO:0000269|PubMed:17177674}.
CC   -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC       family. {ECO:0000305}.
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DR   EMBL; AY191815; AAO91800.1; -; mRNA.
DR   EMBL; AF541874; AAN28666.1; -; Genomic_DNA.
DR   RefSeq; XP_018388094.1; XM_018534204.1.
DR   AlphaFoldDB; P0C0Y4; -.
DR   SMR; P0C0Y4; -.
DR   Allergome; 22; Alt a 8.
DR   Allergome; 3065; Alt a 8.0101.
DR   GeneID; 29119798; -.
DR   KEGG; aalt:CC77DRAFT_931278; -.
DR   BRENDA; 1.1.1.138; 267.
DR   SABIO-RK; P0C0Y4; -.
DR   GO; GO:0005773; C:vacuole; IDA:UniProtKB.
DR   GO; GO:0050085; F:mannitol 2-dehydrogenase (NADP+) activity; IDA:UniProtKB.
DR   GO; GO:0050661; F:NADP binding; ISS:UniProtKB.
DR   GO; GO:0019594; P:mannitol metabolic process; IDA:UniProtKB.
DR   GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR002347; SDR_fam.
DR   PRINTS; PR00081; GDHRDH.
DR   PRINTS; PR00080; SDRFAMILY.
DR   SUPFAM; SSF51735; SSF51735; 1.
PE   1: Evidence at protein level;
KW   Allergen; NADP; Oxidoreductase; Vacuole.
FT   CHAIN           1..266
FT                   /note="NADP-dependent mannitol dehydrogenase"
FT                   /id="PRO_0000054727"
FT   ACT_SITE        159
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:O93868"
FT   ACT_SITE        174
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:O93868"
FT   ACT_SITE        178
FT                   /note="Lowers pKa of active site Tyr"
FT                   /evidence="ECO:0000250|UniProtKB:O93868"
FT   BINDING         107
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:O93868"
FT   BINDING         174
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:O93868"
FT   BINDING         178
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:O93868"
FT   BINDING         206
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:O93868"
FT   CONFLICT        4
FT                   /note="S -> T (in Ref. 1; AAO91800)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   266 AA;  28735 MW;  96CC180295A38901 CRC64;
     MPISVPQATE LKDLFSLKGK VVIVTGASGP TGIGTEAARG CAEYGADLAI TYNSRAEGAE
     KNAKEMSEKY GVKVKAYKCQ VNEYAQCEKL VQDVIKDFGK VDVFIANAGK TADNGILDAT
     VEQWNEVIQT DLTGTFNCAR AVGLHFRERK TGSLVITSSM SGHIANFPQE QASYNVAKAG
     CIHLAKSLAN EWRDFARVNS ISPGYIDTGL SDFVPQDIQK LWHSMIPMGR DAKATELKGA
     YVYFASDASS YCTGSDLLID GGYCVR