CCL4_HUMLU
ID CCL4_HUMLU Reviewed; 556 AA.
AC M4IQQ5;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 29-MAY-2013, sequence version 1.
DT 03-AUG-2022, entry version 22.
DE RecName: Full=2-methylpropanoate--CoA ligase CCL4 {ECO:0000305|PubMed:23300257};
DE Short=HlCCL4 {ECO:0000303|PubMed:23300257};
DE EC=6.2.1.- {ECO:0000269|PubMed:23300257};
DE AltName: Full=2-methylbutanoate--CoA ligase CCL4 {ECO:0000305|PubMed:23300257};
DE EC=6.2.1.- {ECO:0000269|PubMed:23300257};
DE AltName: Full=Butanoate--CoA ligase CCL3 {ECO:0000305|PubMed:23300257};
DE EC=6.2.1.- {ECO:0000269|PubMed:23300257};
DE AltName: Full=Propionate--CoA ligase CCL3 {ECO:0000305|PubMed:23300257};
DE EC=6.2.1.17 {ECO:0000269|PubMed:23300257};
GN Name=CCL4 {ECO:0000303|PubMed:23300257};
OS Humulus lupulus (European hop).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC rosids; fabids; Rosales; Cannabaceae; Humulus.
OX NCBI_TaxID=3486;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, CATALYTIC
RP ACTIVITY, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, BIOPHYSICOCHEMICAL
RP PROPERTIES, GENE FAMILY, AND NOMENCLATURE.
RC STRAIN=cv. Nugget;
RX PubMed=23300257; DOI=10.1093/mp/sst004;
RA Xu H., Zhang F., Liu B., Huhman D.V., Sumner L.W., Dixon R.A., Wang G.;
RT "Characterization of the formation of branched short-chain fatty acid:CoAs
RT for bitter acid biosynthesis in hop glandular trichomes.";
RL Mol. Plant 6:1301-1317(2013).
RN [2]
RP PATHWAY, AND REVIEW.
RX PubMed=30468448; DOI=10.1039/c8np00077h;
RA Liu Y., Jing S.-X., Luo S.-H., Li S.-H.;
RT "Non-volatile natural products in plant glandular trichomes: chemistry,
RT biological activities and biosynthesis.";
RL Nat. Prod. Rep. 36:626-665(2019).
CC -!- FUNCTION: Involved in the biosynthesis of prenylated phenolics natural
CC products which contribute to the bitter taste of beer and display broad
CC biological activities (Probable). Catalyzes the ligation of CoA on 2-
CC methylpropanoate (isobutyric acid) and 2-methylbutanoate to produce 2-
CC methylpropanoyl-CoA and 2-methylbutanoyl-CoA, respectively
CC (PubMed:23300257). Can also use propanoate and butanoate as substrates
CC with a lower efficiency (PubMed:23300257).
CC {ECO:0000269|PubMed:23300257, ECO:0000305|PubMed:30468448}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-methylpropanoate + ATP + CoA = 2-methylpropanoyl-CoA + AMP +
CC diphosphate; Xref=Rhea:RHEA:46176, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:48944, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57338, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:23300257};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46177;
CC Evidence={ECO:0000269|PubMed:23300257};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + CoA + propanoate = AMP + diphosphate + propanoyl-CoA;
CC Xref=Rhea:RHEA:20373, ChEBI:CHEBI:17272, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57392,
CC ChEBI:CHEBI:456215; EC=6.2.1.17;
CC Evidence={ECO:0000269|PubMed:23300257};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20374;
CC Evidence={ECO:0000269|PubMed:23300257};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + butanoate + CoA = AMP + butanoyl-CoA + diphosphate;
CC Xref=Rhea:RHEA:46172, ChEBI:CHEBI:17968, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57371,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:23300257};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46173;
CC Evidence={ECO:0000269|PubMed:23300257};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-methylbutanoate + ATP + CoA = 2-methylbutanoyl-CoA + AMP +
CC diphosphate; Xref=Rhea:RHEA:46180, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:48946, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57336, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:23300257};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46181;
CC Evidence={ECO:0000269|PubMed:23300257};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=164 uM for 2-methylpropanoate {ECO:0000269|PubMed:23300257};
CC KM=25.2 uM for 2-methylbutanoate {ECO:0000269|PubMed:23300257};
CC KM=356 uM for CoA {ECO:0000269|PubMed:23300257};
CC Note=kcat is 18.3 min(-1) with 2-methylpropanoate as substrate
CC (PubMed:23300257). kcat is 10.5 min(-1) with 2-methylbutanoate as
CC substrate (PubMed:23300257). kcat is 167 min(-1) with CoA as
CC substrate (PubMed:23300257). {ECO:0000269|PubMed:23300257};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000305|PubMed:30468448}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:23300257}.
CC -!- TISSUE SPECIFICITY: Mostly expressed in old leaves and in cones and
CC glandular trichomes (lupulin glands) after flowering, and, to a lower
CC extent, in stems, young leaves and flowers.
CC {ECO:0000269|PubMed:23300257}.
CC -!- DEVELOPMENTAL STAGE: Accumulates progressively in cones and glandular
CC trichomes (lupulin glands) after flowering.
CC {ECO:0000269|PubMed:23300257}.
CC -!- DOMAIN: Both substrate-binding domains (SBD1 and SBD2) are involved in
CC the substrate recognition, and are sufficient to confer the substrate
CC specificity. {ECO:0000250|UniProtKB:Q42524}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; JQ740206; AGA17921.1; -; mRNA.
DR AlphaFoldDB; M4IQQ5; -.
DR SMR; M4IQQ5; -.
DR BioCyc; MetaCyc:MON-20125; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0047760; F:butyrate-CoA ligase activity; IDA:UniProtKB.
DR GO; GO:0016405; F:CoA-ligase activity; IDA:UniProtKB.
DR GO; GO:0043759; F:methylbutanoate-CoA ligase activity; IDA:UniProtKB.
DR GO; GO:0050218; F:propionate-CoA ligase activity; IDA:UniProtKB.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR InterPro; IPR025110; AMP-bd_C.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF13193; AMP-binding_C; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cytoplasm; Ligase; Nucleotide-binding.
FT CHAIN 1..556
FT /note="2-methylpropanoate--CoA ligase CCL4"
FT /id="PRO_0000452949"
FT REGION 260..325
FT /note="SBD1"
FT /evidence="ECO:0000250|UniProtKB:Q42524"
FT REGION 326..402
FT /note="SBD2"
FT /evidence="ECO:0000250|UniProtKB:Q42524"
FT BINDING 192..200
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q81G39"
FT BINDING 325..330
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q81G39"
FT BINDING 423
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q81G39"
FT BINDING 435..438
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q81G39"
FT BINDING 531
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q81G39"
SQ SEQUENCE 556 AA; 60893 MW; E4B13084E0B65FEE CRC64;
MEDLKPRPAS SSPLTPLGFL ERAATVYGDC TSVVYDAVSY TWSQTHRRCL CLASSIASLG
IENGHVVSVL APNVPQMYEL HFAVPMAGAI LNAVNLRLDA RTISILLHHS ESKLIFVDHL
SRDLILEAIA LFPKQAPVPR LVFMADESES GNSSELGKEF FCSYKDLIDR GDPDFKWVMP
KSEWDPMILN YTSGTTSSPK GVVHCHRGIF IMTVDSLIDW GVPKQPVYLW TLPMFHANGW
SYPWGMAAVG GTNICLRKFD SEIIYDMIKR HGVTHMCGAP VVLNMLSNAP GSEPLKTTVQ
IMTAGAPPPS AVLFRTESLG FAVSHGYGLT ETAGLVVSCA WKKEWNHLPA TERARLKSRQ
GVGTVMQTKI DVVDPVTGAA VKRDGSTLGE VVLRGGSVML GYLKDPEGTA KSMTADGWFY
TGDVGVMHPD GYLEIKDRSK DVIISGGENL SSVEVESILY SHPDILEAAV VARPDEFWGE
TPCAFVSLKK GLTKKPTEKE IVEYCRSKLP RYMVPKTVVF KEELPKTSTG KVQKFILRDM
ARGMGSATAG ASRSRM
