CCL2_HUMLU
ID CCL2_HUMLU Reviewed; 573 AA.
AC M4IRL4;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 29-MAY-2013, sequence version 1.
DT 03-AUG-2022, entry version 19.
DE RecName: Full=Isovalerate--CoA ligase CCL2 {ECO:0000303|PubMed:23300257};
DE Short=HlCCL2 {ECO:0000303|PubMed:23300257};
DE EC=6.2.1.- {ECO:0000269|PubMed:23300257};
DE AltName: Full=3-methylpentanoate--CoA ligase AAE2 {ECO:0000305|PubMed:23300257};
DE EC=6.2.1.- {ECO:0000269|PubMed:23300257};
DE AltName: Full=4-methylpentanoate--CoA ligase AAE2 {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=Hexanoate--CoA ligase CCL3 {ECO:0000305|PubMed:23300257};
DE EC=6.2.1.- {ECO:0000269|PubMed:23300257};
DE AltName: Full=Pentanoate--CoA ligase CCL3 {ECO:0000305|PubMed:23300257};
DE EC=6.2.1.- {ECO:0000269|PubMed:23300257};
GN Name=CCL2 {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
CC isovalerate to produce 3-methylbutanoyl-CoA (PubMed:23300257). Can also
CC use butanoate, hexanoate, pentanoate, 3-methylpentanoate and 4-
CC methylpentanoate as substrates with a lower efficiency
CC (PubMed:23300257). {ECO:0000269|PubMed:23300257,
CC ECO:0000305|PubMed:30468448}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + CoA + isovalerate = 3-methylbutanoyl-CoA + AMP +
CC diphosphate; Xref=Rhea:RHEA:46184, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:48942, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57345, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:23300257};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46185;
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=ATP + CoA + hexanoate = AMP + diphosphate + hexanoyl-CoA;
CC Xref=Rhea:RHEA:43740, ChEBI:CHEBI:17120, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:62620,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:23300257};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43741;
CC Evidence={ECO:0000269|PubMed:23300257};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + CoA + pentanoate = AMP + diphosphate + pentanoyl-CoA;
CC Xref=Rhea:RHEA:46168, ChEBI:CHEBI:30616, ChEBI:CHEBI:31011,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57389,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:23300257};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46169;
CC Evidence={ECO:0000269|PubMed:23300257};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-methylpentanoate + ATP + CoA = 3-methylpentanoyl-CoA + AMP +
CC diphosphate; Xref=Rhea:RHEA:66992, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:167610,
CC ChEBI:CHEBI:167613, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:23300257};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66993;
CC Evidence={ECO:0000269|PubMed:23300257};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-methylpentanoate + ATP + CoA = 4-methylpentanoyl-CoA + AMP +
CC diphosphate; Xref=Rhea:RHEA:66988, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:74904,
CC ChEBI:CHEBI:131445, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:23300257};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66989;
CC Evidence={ECO:0000269|PubMed:23300257};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=69.7 uM for isovalerate {ECO:0000269|PubMed:23300257};
CC KM=110 uM for CoA {ECO:0000269|PubMed:23300257};
CC Note=kcat is 17.2 min(-1) with isovalerate as substrate
CC (PubMed:23300257). kcat is 23.3 min(-1) with CoA as substrate
CC (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: Restricted to glandular trichomes (lupulin glands).
CC {ECO:0000269|PubMed:23300257}.
CC -!- DEVELOPMENTAL STAGE: Accumulates progressively in glandular trichomes
CC (lupulin glands) after flowering. {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; JQ740204; AGA17919.1; -; mRNA.
DR AlphaFoldDB; M4IRL4; -.
DR SMR; M4IRL4; -.
DR BioCyc; MetaCyc:MON-20124; -.
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 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; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF13193; AMP-binding_C; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cytoplasm; Ligase; Nucleotide-binding.
FT CHAIN 1..573
FT /note="Isovalerate--CoA ligase CCL2"
FT /id="PRO_0000452947"
FT REGION 284..352
FT /note="SBD1"
FT /evidence="ECO:0000250|UniProtKB:Q42524"
FT REGION 353..429
FT /note="SBD2"
FT /evidence="ECO:0000250|UniProtKB:Q42524"
FT BINDING 216..224
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q81G39"
FT BINDING 352..357
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q81G39"
FT BINDING 449
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q81G39"
FT BINDING 461..464
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q81G39"
FT BINDING 556
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q81G39"
SQ SEQUENCE 573 AA; 63196 MW; 6D9B8FC6B888C0E1 CRC64;
MDNYRRLHTP VALCVASPPA PPTTSWKSME GLVQCSANHV PLSPITFLER SSKAYRDNTS
LVYGSVRYTW AQTHHRCLKL ASALTTHLGI SPGDVVATFS YNLPEIYELH FAVPMAGGIL
CTLNARNDSA MVSTLLAHSE AKLIFVEPQL LETARAALDL LAQKDIKPPT LVLLTDSESF
TSSSYDHYNH LLANGSDDFE IRRPKNEWDP ISINYTSGTT ARPKAVVYSH RGAYLNSIAT
VLLHGMGTTS VYLWSVPMFH CNGWCFPWGA AAQGATNICI RKVSPKAIFD NIHLHKVTHF
GAAPTVLNMI VNSPEGNLHT PLPHKVEVMT GGSPPPPKVI ARMEEMGFQV NHIYGLTETC
GPAANCVCKP EWDALQPEER YALKARQGLN HLAMEEMDVR DPVTMESVRA DGATIGEVMF
RGNTVMSGYF KDLKATEEAF EGGWFRSGDL GVKHEDGYIQ LKDRKKDVVI SGGENISTVE
VETVLYSHEA VLEAAVVARP DKLWGETPCA FVTLKEGFDN DVSADQIIKF CRDRLPHYMA
PKTVVFEELP KTSTGKIQKY ILKEKAMAMG SLS
