UniProtKB - Q2KIE6 (HMCS2_BOVIN)
Protein
Hydroxymethylglutaryl-CoA synthase, mitochondrial
Gene
HMGCS2
Organism
Bos taurus (Bovine)
Status
Functioni
Catalyzes the first irreversible step in ketogenesis, condensing acetyl-CoA to acetoacetyl-CoA to form HMG-CoA, which is converted by HMG-CoA reductase (HMGCR) into mevalonate.By similarity
Catalytic activityi
: (R)-mevalonate biosynthesis Pathwayi
This protein is involved in step 2 of the subpathway that synthesizes (R)-mevalonate from acetyl-CoA.Proteins known to be involved in the 3 steps of the subpathway in this organism are:
- no protein annotated in this organism
- 3-hydroxy-3-methylglutaryl coenzyme A synthase (HMGCS1), 3-hydroxy-3-methylglutaryl coenzyme A synthase (HMGCS1), Hydroxymethylglutaryl-CoA synthase, mitochondrial (HMGCS2), 3-hydroxy-3-methylglutaryl coenzyme A synthase (HMGCS1)
- 3-hydroxy-3-methylglutaryl coenzyme A reductase (hmgcr), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)
View all proteins of this organism that are known to be involved in the subpathway that synthesizes (R)-mevalonate from acetyl-CoA, the pathway (R)-mevalonate biosynthesis and in Metabolic intermediate biosynthesis.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 80 | SubstrateBy similarity | 1 | |
Active sitei | 132 | Proton donor/acceptorPROSITE-ProRule annotation | 1 | |
Active sitei | 166 | Acyl-thioester intermediatePROSITE-ProRule annotation | 1 | |
Binding sitei | 204 | SubstrateBy similarity | 1 | |
Binding sitei | 258 | SubstrateBy similarity | 1 | |
Active sitei | 301 | Proton donor/acceptorPROSITE-ProRule annotation | 1 | |
Binding sitei | 380 | SubstrateBy similarity | 1 |
GO - Molecular functioni
- hydroxymethylglutaryl-CoA synthase activity Source: UniProtKB
- identical protein binding Source: UniProtKB
GO - Biological processi
- acetyl-CoA metabolic process Source: GO_Central
- cholesterol biosynthetic process Source: UniProtKB-KW
- farnesyl diphosphate biosynthetic process, mevalonate pathway Source: GO_Central
- ketone body biosynthetic process Source: Ensembl
Keywordsi
Molecular function | Transferase |
Biological process | Cholesterol biosynthesis, Cholesterol metabolism, Lipid biosynthesis, Lipid metabolism, Steroid biosynthesis, Steroid metabolism, Sterol biosynthesis, Sterol metabolism |
Enzyme and pathway databases
Reactomei | R-BTA-77111, Synthesis of Ketone Bodies |
UniPathwayi | UPA00058;UER00102 |
Names & Taxonomyi
Protein namesi | Recommended name: Hydroxymethylglutaryl-CoA synthase, mitochondrial (EC:2.3.3.10By similarity)Short name: HMG-CoA synthase Alternative name(s): 3-hydroxy-3-methylglutaryl coenzyme A synthase |
Gene namesi | Name:HMGCS2 |
Organismi | Bos taurus (Bovine) |
Taxonomic identifieri | 9913 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Artiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos |
Proteomesi |
|
Organism-specific databases
VGNCi | VGNC:29881, HMGCS2 |
Subcellular locationi
Mitochondrion
- Mitochondrion By similarity
Mitochondrion
- mitochondrion Source: GO_Central
Keywords - Cellular componenti
MitochondrionPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transit peptidei | 1 – 37 | MitochondrionCuratedAdd BLAST | 37 | |
ChainiPRO_0000236276 | 38 – 508 | Hydroxymethylglutaryl-CoA synthase, mitochondrialAdd BLAST | 471 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 52 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 243 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 256 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 256 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 306 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 310 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 310 | N6-succinyllysine; alternate1 Publication | 1 | |
Modified residuei | 333 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 342 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 342 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 350 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 350 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 354 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 354 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 358 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 358 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 433 | PhosphoserineBy similarity | 1 | |
Modified residuei | 437 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 440 | PhosphoserineBy similarity | 1 | |
Modified residuei | 447 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 447 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 456 | PhosphoserineBy similarity | 1 | |
Modified residuei | 473 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 473 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 477 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Succinylated. Desuccinylated by SIRT5. Succinylation, at least at Lys-310, inhibits the enzymatic activity.By similarity
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
PaxDbi | Q2KIE6 |
PeptideAtlasi | Q2KIE6 |
PRIDEi | Q2KIE6 |
Expressioni
Gene expression databases
Bgeei | ENSBTAG00000003898, Expressed in liver and 6 other tissues |
Interactioni
Subunit structurei
Homodimer.
By similarityGO - Molecular functioni
- identical protein binding Source: UniProtKB
Protein-protein interaction databases
STRINGi | 9913.ENSBTAP00000005088 |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
Transit peptidePhylogenomic databases
eggNOGi | KOG1393, Eukaryota |
GeneTreei | ENSGT00390000006096 |
HOGENOMi | CLU_008065_0_1_1 |
InParanoidi | Q2KIE6 |
OMAi | EVKHACY |
OrthoDBi | 495111at2759 |
TreeFami | TF105361 |
Family and domain databases
Gene3Di | 3.40.47.10, 1 hit |
InterProi | View protein in InterPro IPR000590, HMG_CoA_synt_AS IPR013746, HMG_CoA_synt_C_dom IPR013528, HMG_CoA_synth_N IPR010122, HMG_CoA_synthase_euk IPR016039, Thiolase-like |
Pfami | View protein in Pfam PF08540, HMG_CoA_synt_C, 1 hit PF01154, HMG_CoA_synt_N, 1 hit |
SUPFAMi | SSF53901, SSF53901, 2 hits |
TIGRFAMsi | TIGR01833, HMG-CoA-S_euk, 1 hit |
PROSITEi | View protein in PROSITE PS01226, HMG_COA_SYNTHASE, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
Q2KIE6-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MQRLLTPVRQ VLQVKRVMQE ASLLPARLLP AAHPSFSTVP AVPLAKTDTW
60 70 80 90 100
PKDVGILAME VYFPAQYVDQ TELEKFNKVE AGRYTVGLGQ TQMGFCSVQE
110 120 130 140 150
DVNSLCLTVV QQLMERTQLP WDSVGRLEVG TETIIDKSKA VKTVLMELFQ
160 170 180 190 200
DSGNTDIEGI DTTNACYGGT ASLFNAANWM ESSSWDGRYA LVVCGDIAVY
210 220 230 240 250
PSGNARPTGG AGAVAMLVGP EAPLVLERGL RGTHMENVYD FYKPDVTSEY
260 270 280 290 300
PLVDGKLSIQ CYLRALDKCY AFYRQKIEKQ WKQAGIDRPF TLDDVQYMIF
310 320 330 340 350
HTPFCKLVQK SLARLMFNDF LLASGDTQTG IYKGLEAFRG LKLEDTYTNK
360 370 380 390 400
DVDKAFLKAS LNMFNKKTKN SLYLSTYNGN MYTSSLYGCL ASLLAHHSAQ
410 420 430 440 450
DLAGSRIGAF SYGSGLAASF FSFRVSQDAS PGSPLEKLVS STSDLQKRLA
460 470 480 490 500
SRKRVSPEEF TEIMNQREQY YHKMNFSPPG DKNSLFPGTW YLERVDELYR
RKYARRPV
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | BC112666 mRNA Translation: AAI12667.1 |
RefSeqi | NP_001039348.1, NM_001045883.1 XP_010801406.1, XM_010803104.2 |
Genome annotation databases
Ensembli | ENSBTAT00000005088; ENSBTAP00000005088; ENSBTAG00000003898 |
GeneIDi | 503684 |
KEGGi | bta:503684 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | BC112666 mRNA Translation: AAI12667.1 |
RefSeqi | NP_001039348.1, NM_001045883.1 XP_010801406.1, XM_010803104.2 |
3D structure databases
SMRi | Q2KIE6 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 9913.ENSBTAP00000005088 |
Proteomic databases
PaxDbi | Q2KIE6 |
PeptideAtlasi | Q2KIE6 |
PRIDEi | Q2KIE6 |
Genome annotation databases
Ensembli | ENSBTAT00000005088; ENSBTAP00000005088; ENSBTAG00000003898 |
GeneIDi | 503684 |
KEGGi | bta:503684 |
Organism-specific databases
CTDi | 3158 |
VGNCi | VGNC:29881, HMGCS2 |
Phylogenomic databases
eggNOGi | KOG1393, Eukaryota |
GeneTreei | ENSGT00390000006096 |
HOGENOMi | CLU_008065_0_1_1 |
InParanoidi | Q2KIE6 |
OMAi | EVKHACY |
OrthoDBi | 495111at2759 |
TreeFami | TF105361 |
Enzyme and pathway databases
UniPathwayi | UPA00058;UER00102 |
Reactomei | R-BTA-77111, Synthesis of Ketone Bodies |
Gene expression databases
Bgeei | ENSBTAG00000003898, Expressed in liver and 6 other tissues |
Family and domain databases
Gene3Di | 3.40.47.10, 1 hit |
InterProi | View protein in InterPro IPR000590, HMG_CoA_synt_AS IPR013746, HMG_CoA_synt_C_dom IPR013528, HMG_CoA_synth_N IPR010122, HMG_CoA_synthase_euk IPR016039, Thiolase-like |
Pfami | View protein in Pfam PF08540, HMG_CoA_synt_C, 1 hit PF01154, HMG_CoA_synt_N, 1 hit |
SUPFAMi | SSF53901, SSF53901, 2 hits |
TIGRFAMsi | TIGR01833, HMG-CoA-S_euk, 1 hit |
PROSITEi | View protein in PROSITE PS01226, HMG_COA_SYNTHASE, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | HMCS2_BOVIN | |
Accessioni | Q2KIE6Primary (citable) accession number: Q2KIE6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 30, 2006 |
Last sequence update: | March 7, 2006 | |
Last modified: | December 2, 2020 | |
This is version 100 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families