CHLA_DICDI
ID CHLA_DICDI Reviewed; 603 AA.
AC Q54FI4;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 80.
DE RecName: Full=Flavin-dependent halogenase chlA {ECO:0000303|PubMed:20231486};
DE EC=1.14.14.- {ECO:0000269|PubMed:20231486};
DE AltName: Full=Chlorination protein A {ECO:0000303|PubMed:20231486};
GN Name=ChlA {ECO:0000303|PubMed:20231486};
GN ORFNames=DDB0189108 {ECO:0000312|EMBL:EAL62046.1};
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [2]
RP FUNCTION.
RX PubMed=9446571; DOI=10.1074/jbc.273.5.2669;
RA Kay R.R.;
RT "The biosynthesis of differentiation-inducing factor, a chlorinated signal
RT molecule regulating Dictyostelium development.";
RL J. Biol. Chem. 273:2669-2675(1998).
RN [3]
RP FUNCTION.
RX PubMed=16906151; DOI=10.1038/nchembio811;
RA Austin M.B., Saito T., Bowman M.E., Haydock S., Kato A., Moore B.S.,
RA Kay R.R., Noel J.P.;
RT "Biosynthesis of Dictyostelium discoideum differentiation-inducing factor
RT by a hybrid type I fatty acid-type III polyketide synthase.";
RL Nat. Chem. Biol. 2:494-502(2006).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, AND MUTAGENESIS OF
RP LYS-86.
RX PubMed=20231486; DOI=10.1073/pnas.1001681107;
RA Neumann C.S., Walsh C.T., Kay R.R.;
RT "A flavin-dependent halogenase catalyzes the chlorination step in the
RT biosynthesis of Dictyostelium differentiation-inducing factor 1.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:5798-5803(2010).
CC -!- FUNCTION: Flavin-dependent halogenase; part of the gene cluster that
CC mediates the biosynthesis of DIF-1 (Differentiation Inducing Factor-1),
CC a signal molecule involved in the differentiation of pstO (prestalk-O)
CC cells (PubMed:20231486). The three-step process begins with the
CC formation of (2,4,6-trihydroxyphenyl)-1-hexan-1-one (THPH) by the
CC polyketide synthase StlB (PubMed:16906151). THPH is then dichlorinated
CC by the flavin-dependent halogenase ChlA (PubMed:20231486). The last
CC step of DIF-1 biosynthesis is the O-methylation of dichloro-THPH (or
CC des-methyl-DIF-1) by the methyltransferase DmtA to yield DIF-1
CC (PubMed:9446571). {ECO:0000269|PubMed:16906151,
CC ECO:0000269|PubMed:20231486, ECO:0000269|PubMed:9446571}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2,4,6-trihydroxyphenylhexan-1-one + chloride + FADH2 + O2 =
CC (3-chloro-2,4,6-trihydroxyphenyl)hexan-1-one + FAD + H(+) + 2 H2O;
CC Xref=Rhea:RHEA:64356, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17996, ChEBI:CHEBI:57692,
CC ChEBI:CHEBI:58307, ChEBI:CHEBI:150865, ChEBI:CHEBI:152555;
CC Evidence={ECO:0000269|PubMed:20231486};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64357;
CC Evidence={ECO:0000269|PubMed:20231486};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3-chloro-2,4,6-trihydroxyphenyl)hexan-1-one + chloride +
CC FADH2 + O2 = (3,5-dichloro-2,4,6-trihydroxyphenyl)hexan-1-one + FAD +
CC 2 H2O; Xref=Rhea:RHEA:64360, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17996, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307,
CC ChEBI:CHEBI:90398, ChEBI:CHEBI:152555;
CC Evidence={ECO:0000269|PubMed:20231486};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64361;
CC Evidence={ECO:0000269|PubMed:20231486};
CC -!- DISRUPTION PHENOTYPE: Impairs the production of DIF-1 and leads to
CC deficiencies in slug structure and fruiting body formation.
CC {ECO:0000269|PubMed:20231486}.
CC -!- SIMILARITY: Belongs to the flavin-dependent halogenase family.
CC {ECO:0000305}.
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DR EMBL; AAFI01000244; EAL62046.1; -; Genomic_DNA.
DR RefSeq; XP_635556.1; XM_630464.1.
DR AlphaFoldDB; Q54FI4; -.
DR SMR; Q54FI4; -.
DR STRING; 44689.DDB0189108; -.
DR PaxDb; Q54FI4; -.
DR GeneID; 8627854; -.
DR KEGG; ddi:DDB_G0290825; -.
DR dictyBase; DDB_G0290825; chlA.
DR eggNOG; ENOG502SW7V; Eukaryota.
DR HOGENOM; CLU_449585_0_0_1; -.
DR InParanoid; Q54FI4; -.
DR OMA; ANAVWWR; -.
DR GO; GO:0003824; F:catalytic activity; IDA:dictyBase.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0031154; P:culmination involved in sorocarp development; IMP:dictyBase.
DR GO; GO:0031148; P:DIF-1 biosynthetic process; IMP:dictyBase.
DR GO; GO:0031153; P:slug development involved in sorocarp development; IMP:dictyBase.
DR GO; GO:0030587; P:sorocarp development; HMP:dictyBase.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR006905; Flavin_halogenase.
DR Pfam; PF04820; Trp_halogenase; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Monooxygenase; Oxidoreductase.
FT CHAIN 1..603
FT /note="Flavin-dependent halogenase chlA"
FT /id="PRO_0000450882"
FT BINDING 16..19
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P95480"
FT BINDING 42..60
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P95480"
FT BINDING 352..353
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:P95480"
FT BINDING 453..454
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P95480"
FT MUTAGEN 86
FT /note="K->A: Abolishes chlorination activity."
FT /evidence="ECO:0000269|PubMed:20231486"
SQ SEQUENCE 603 AA; 70153 MW; 35EAB460968DEAD1 CRC64;
MDTNIINHYD IIIIGGGIAG LSATRHLLLK MPELSGRIAV IEPRSERRDN LDEDYKVGES
TVEVSAMFFA KELELQDYLI ENHPPKFSLQ FHWPRELSKT DTIEDYYSTW AVKNPDIQAF
QLNRCKIERD LLKMVIAQGA VYYHGRVRNV DNLDNDDMKS IDVEILSEVE SGADFKLQQS
IERITLTTDY IVDASGRNFT VGSRTDNILK DPKHLFGLDN ASTWVRVKNT ERSLFDFKSQ
DVTCSWTYDT NHFFGPGYWI WMIPLERGSR DYSIGVSYHR DKIQPSQLNS LDKFMSFLEK
NQKLLYNLIK SGEIVDFHRW PKLAHTSKTF FSKNNWCVIG DAAAIFDPFY STGMVMIAME
IECLTEMLKF KLSNAANDYH RRVEAFDKLI RCVTQINNHL IKDHSNHLGN ASIMSWRIYF
ESSTYFSILL PAYIGKYHLC PIFSDHFTTD HENGLALRNQ LLATLDYANE NSINIGFMDN
HRGGQLLGDW SPTSSWDYDH ALSLAKYGHK RLNLPKCLSW SNFYLSLIIC KLYYRVYGIG
ALWNSSFFKS LSNTTYRFSK FYFLSKLHSF NMIGTPNNDY YDKIQKDFKS YNYNQNNIVD
WKY
