UniProtKB - Q8TB92 (HMGC2_HUMAN)
Protein
3-hydroxy-3-methylglutaryl-CoA lyase, cytoplasmic
Gene
HMGCLL1
Organism
Homo sapiens (Human)
Status
Functioni
Non-mitochondrial 3-hydroxymethyl-3-methylglutaryl-CoA lyase that catalyzes a cation-dependent cleavage of (S)-3-hydroxy-3-methylglutaryl-CoA into acetyl-CoA and acetoacetate, a key step in ketogenesis, the products of which support energy production in nonhepatic animal tissues.2 Publications
Catalytic activityi
- EC:4.1.3.42 Publications
Cofactori
a divalent metal cation1 Publication
Kineticsi
- KM=40 µM for (S)-3-hydroxy-3-methylglutaryl-CoA (at pH 9)1 Publication
- KM=75 µM for (S)-3-hydroxy-3-methylglutaryl-CoA (at pH 8)1 Publication
- KM=28 µM for (S)-3-hydroxy-3-methylglutaryl-CoA1 Publication
- KM=49 µM for (S)-3-hydroxy-3-methylglutaryl-CoA (in presence of magnesium)1 Publication
- KM=0.18 µM for (S)-3-hydroxy-3-methylglutaryl-CoA (in presence of manganese)1 Publication
- Vmax=12 nmol/min/mg enzyme with (S)-3-hydroxy-3-methylglutaryl-CoA as substrate at pH 91 Publication
- Vmax=25 nmol/min/mg enzyme with (S)-3-hydroxy-3-methylglutaryl-CoA as substrate at pH 81 Publication
: (S)-3-hydroxy-3-methylglutaryl-CoA degradation Pathwayi
This protein is involved in step 1 of the subpathway that synthesizes acetoacetate from (S)-3-hydroxy-3-methylglutaryl-CoA.Proteins known to be involved in this subpathway in this organism are:
- Hydroxymethylglutaryl-CoA lyase, Hydroxymethylglutaryl-CoA lyase, mitochondrial (HMGCL), Hydroxymethylglutaryl-CoA lyase (DKFZp434G1411), 3-hydroxy-3-methylglutarate-CoA lyase (HMGCL), 3-hydroxy-3-methylglutarate-CoA lyase (HMGCL), 3-hydroxy-3-methylglutaryl-CoA lyase, cytoplasmic (HMGCLL1), Hydroxymethylglutaryl-CoA lyase (HMGCLL1), Hydroxymethylglutaryl-CoA lyase (HMGCLL1), Hydroxymethylglutaryl-CoA lyase (HMGCLL1)
View all proteins of this organism that are known to be involved in the subpathway that synthesizes acetoacetate from (S)-3-hydroxy-3-methylglutaryl-CoA, the pathway (S)-3-hydroxy-3-methylglutaryl-CoA degradation and in Metabolic intermediate metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 86 | SubstrateBy similarity | 1 | |
Metal bindingi | 87 | Divalent metal cationBy similarity | 1 | |
Metal bindingi | 278 | Divalent metal cationBy similarity | 1 | |
Metal bindingi | 280 | Divalent metal cationBy similarity | 1 | |
Active sitei | 311 | By similarity | 1 | |
Metal bindingi | 320 | Divalent metal cationBy similarity | 1 |
GO - Molecular functioni
- hydroxymethylglutaryl-CoA lyase activity Source: UniProtKB
- metal ion binding Source: UniProtKB
GO - Biological processi
- ketone body biosynthetic process Source: UniProtKB
- leucine catabolic process Source: GO_Central
- lipid metabolic process Source: GO_Central
Keywordsi
Molecular function | Lyase |
Ligand | Metal-binding |
Enzyme and pathway databases
PathwayCommonsi | Q8TB92 |
Reactomei | R-HSA-77111, Synthesis of Ketone Bodies |
SABIO-RKi | Q8TB92 |
UniPathwayi | UPA00896;UER00863 |
Chemistry databases
SwissLipidsi | SLP:000001291 [Q8TB92-2] |
Names & Taxonomyi
Protein namesi | Recommended name: 3-hydroxy-3-methylglutaryl-CoA lyase, cytoplasmic (EC:4.1.3.42 Publications)Alternative name(s): 3-hydroxy-3-methylglutaryl-CoA lyase-like protein 1 Short name: HMGCL-like 1 Endoplasmic reticulum 3-hydroxy-3-methylglutaryl-CoA lyase1 Publication Short name: er-cHL1 Publication |
Gene namesi | Name:HMGCLL1 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:21359, HMGCLL1 |
MIMi | 619050, gene |
neXtProti | NX_Q8TB92 |
VEuPathDBi | HostDB:ENSG00000146151.12 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum membrane 1 Publication; Peripheral membrane protein
Cytosol
- cytosol 1 Publication
Cytosol
- cytosol Source: UniProtKB
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB
- endoplasmic reticulum membrane Source: UniProtKB-SubCell
Other locations
- membrane Source: UniProtKB
- perinuclear region of cytoplasm Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, Endoplasmic reticulum, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 2 | G → A: Abolishes myristoylation and induces a subcellular location change. 1 Publication | 1 | |
Mutagenesisi | 86 | R → Q: Abolishes catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 237 | L → S: Abolishes catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 278 | H → R: Abolishes catalytic activity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 54511 |
OpenTargetsi | ENSG00000146151 |
PharmGKBi | PA134989971 |
Miscellaneous databases
Pharosi | Q8TB92, Tbio |
Genetic variation databases
BioMutai | HMGCLL1 |
DMDMi | 189028466 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | Removed | |||
ChainiPRO_0000334669 | 2 – 370 | 3-hydroxy-3-methylglutaryl-CoA lyase, cytoplasmicAdd BLAST | 369 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Lipidationi | 2 | N-myristoyl glycine1 Publication | 1 |
Keywords - PTMi
Lipoprotein, MyristateProteomic databases
MassIVEi | Q8TB92 |
MaxQBi | Q8TB92 |
PaxDbi | Q8TB92 |
PeptideAtlasi | Q8TB92 |
PRIDEi | Q8TB92 |
ProteomicsDBi | 29914 73974 [Q8TB92-1] 73975 [Q8TB92-2] 73976 [Q8TB92-4] |
PTM databases
iPTMneti | Q8TB92 |
PhosphoSitePlusi | Q8TB92 |
Expressioni
Gene expression databases
Bgeei | ENSG00000146151, Expressed in cortical plate and 155 other tissues |
ExpressionAtlasi | Q8TB92, baseline and differential |
Genevisiblei | Q8TB92, HS |
Organism-specific databases
HPAi | ENSG00000146151, Tissue enhanced (brain, pituitary gland) |
Interactioni
Protein-protein interaction databases
BioGRIDi | 120006, 8 interactors |
IntActi | Q8TB92, 2 interactors |
STRINGi | 9606.ENSP00000381654 |
Miscellaneous databases
RNActi | Q8TB92, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 78 – 345 | Pyruvate carboxyltransferasePROSITE-ProRule annotationAdd BLAST | 268 |
Sequence similaritiesi
Belongs to the HMG-CoA lyase family.Curated
Phylogenomic databases
eggNOGi | KOG2368, Eukaryota |
GeneTreei | ENSGT00940000159467 |
HOGENOMi | CLU_214024_0_0_1 |
InParanoidi | Q8TB92 |
OMAi | DGHSRAN |
PhylomeDBi | Q8TB92 |
TreeFami | TF105363 |
Family and domain databases
Gene3Di | 3.20.20.70, 1 hit |
InterProi | View protein in InterPro IPR013785, Aldolase_TIM IPR030021, ER-cHL IPR043594, HMGL IPR000891, PYR_CT |
PANTHERi | PTHR42738, PTHR42738, 1 hit PTHR42738:SF5, PTHR42738:SF5, 1 hit |
Pfami | View protein in Pfam PF00682, HMGL-like, 1 hit |
PROSITEi | View protein in PROSITE PS50991, PYR_CT, 1 hit |
s (4+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 4 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q8TB92-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MGNVPSAVKH CLSYQQLLRE HLWIGDSVAG ALDPAQTSLL TNLHCFQPDV
60 70 80 90 100
SGFSVSLAGT VACIHWETSQ LSGLPEFVKI VEVGPRDGLQ NEKVIVPTDI
110 120 130 140 150
KIEFINRLSQ TGLSVIEVTS FVSSRWVPQM ADHTEVMKGI HQYPGVRYPV
160 170 180 190 200
LTPNLQGFHH AVAAGATEIS VFGAASESFS KKNINCSIEE SMGKFEEVVK
210 220 230 240 250
SARHMNIPAR GYVSCALGCP YEGSITPQKV TEVSKRLYGM GCYEISLGDT
260 270 280 290 300
IGVGTPGSMK RMLESVMKEI PPGALAVHCH DTYGQALANI LTALQMGINV
310 320 330 340 350
VDSAVSGLGG CPYAKGASGN VATEDLIYML NGLGLNTGVN LYKVMEAGDF
360 370
ICKAVNKTTN SKVAQASFNA
Isoform 3 (identifier: Q8TB92-4) [UniParc]FASTAAdd to basket
The sequence of this isoform differs from the canonical sequence as follows:
37-53: TSLLTNLHCFQPDVSGF → ELQSVMLMLHHGPLRKP
54-370: Missing.
Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.Curated
Show »Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketB7Z212 | B7Z212_HUMAN | Hydroxymethylglutaryl-CoA lyase | HMGCLL1 | 237 | Annotation score: | ||
G5E9S9 | G5E9S9_HUMAN | Hydroxymethylglutaryl-CoA lyase | HMGCLL1 hCG_2001183 | 151 | Annotation score: | ||
B7Z4D4 | B7Z4D4_HUMAN | Hydroxymethylglutaryl-CoA lyase | HMGCLL1 | 174 | Annotation score: | ||
D6RHJ2 | D6RHJ2_HUMAN | 3-hydroxy-3-methylglutaryl-CoA lyas... | HMGCLL1 | 39 | Annotation score: |
Sequence cautioni
The sequence BAC87045 differs from that shown. Reason: Frameshift.Curated
The sequence BAG51462 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 99 | D → G in BAH11613 (PubMed:14702039).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_033752 | 37 – 66 | Missing in isoform 2 and isoform 4. 2 PublicationsAdd BLAST | 30 | |
Alternative sequenceiVSP_038021 | 37 – 53 | TSLLT…DVSGF → ELQSVMLMLHHGPLRKP in isoform 3. 1 PublicationAdd BLAST | 17 | |
Alternative sequenceiVSP_038022 | 54 – 370 | Missing in isoform 3. 1 PublicationAdd BLAST | 317 | |
Alternative sequenceiVSP_044324 | 130 – 161 | Missing in isoform 4. 1 PublicationAdd BLAST | 32 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK055075 mRNA Translation: BAG51462.1 Sequence problems. AK127587 mRNA Translation: BAC87045.1 Frameshift. AK293856 mRNA Translation: BAH11613.1 AL590290 Genomic DNA No translation available. AL590406 Genomic DNA No translation available. CH471081 Genomic DNA Translation: EAX04442.1 CH471081 Genomic DNA Translation: EAX04444.1 BC024194 mRNA Translation: AAH24194.2 |
CCDSi | CCDS43474.1 [Q8TB92-2] CCDS43475.1 [Q8TB92-1] CCDS75473.1 [Q8TB92-5] |
RefSeqi | NP_001035865.1, NM_001042406.1 [Q8TB92-2] NP_001274670.1, NM_001287741.1 [Q8TB92-5] NP_001274675.1, NM_001287746.1 NP_061909.2, NM_019036.2 [Q8TB92-1] |
Genome annotation databases
Ensembli | ENST00000274901; ENSP00000274901; ENSG00000146151 [Q8TB92-2] ENST00000308161; ENSP00000309737; ENSG00000146151 [Q8TB92-5] ENST00000370852; ENSP00000359889; ENSG00000146151 [Q8TB92-4] ENST00000398661; ENSP00000381654; ENSG00000146151 [Q8TB92-1] |
GeneIDi | 54511 |
KEGGi | hsa:54511 |
UCSCi | uc003pcn.4, human [Q8TB92-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK055075 mRNA Translation: BAG51462.1 Sequence problems. AK127587 mRNA Translation: BAC87045.1 Frameshift. AK293856 mRNA Translation: BAH11613.1 AL590290 Genomic DNA No translation available. AL590406 Genomic DNA No translation available. CH471081 Genomic DNA Translation: EAX04442.1 CH471081 Genomic DNA Translation: EAX04444.1 BC024194 mRNA Translation: AAH24194.2 |
CCDSi | CCDS43474.1 [Q8TB92-2] CCDS43475.1 [Q8TB92-1] CCDS75473.1 [Q8TB92-5] |
RefSeqi | NP_001035865.1, NM_001042406.1 [Q8TB92-2] NP_001274670.1, NM_001287741.1 [Q8TB92-5] NP_001274675.1, NM_001287746.1 NP_061909.2, NM_019036.2 [Q8TB92-1] |
3D structure databases
SMRi | Q8TB92 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 120006, 8 interactors |
IntActi | Q8TB92, 2 interactors |
STRINGi | 9606.ENSP00000381654 |
Chemistry databases
SwissLipidsi | SLP:000001291 [Q8TB92-2] |
PTM databases
iPTMneti | Q8TB92 |
PhosphoSitePlusi | Q8TB92 |
Genetic variation databases
BioMutai | HMGCLL1 |
DMDMi | 189028466 |
Proteomic databases
MassIVEi | Q8TB92 |
MaxQBi | Q8TB92 |
PaxDbi | Q8TB92 |
PeptideAtlasi | Q8TB92 |
PRIDEi | Q8TB92 |
ProteomicsDBi | 29914 73974 [Q8TB92-1] 73975 [Q8TB92-2] 73976 [Q8TB92-4] |
Protocols and materials databases
Antibodypediai | 31030, 55 antibodies |
DNASUi | 54511 |
Genome annotation databases
Ensembli | ENST00000274901; ENSP00000274901; ENSG00000146151 [Q8TB92-2] ENST00000308161; ENSP00000309737; ENSG00000146151 [Q8TB92-5] ENST00000370852; ENSP00000359889; ENSG00000146151 [Q8TB92-4] ENST00000398661; ENSP00000381654; ENSG00000146151 [Q8TB92-1] |
GeneIDi | 54511 |
KEGGi | hsa:54511 |
UCSCi | uc003pcn.4, human [Q8TB92-1] |
Organism-specific databases
CTDi | 54511 |
DisGeNETi | 54511 |
GeneCardsi | HMGCLL1 |
HGNCi | HGNC:21359, HMGCLL1 |
HPAi | ENSG00000146151, Tissue enhanced (brain, pituitary gland) |
MIMi | 619050, gene |
neXtProti | NX_Q8TB92 |
OpenTargetsi | ENSG00000146151 |
PharmGKBi | PA134989971 |
VEuPathDBi | HostDB:ENSG00000146151.12 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2368, Eukaryota |
GeneTreei | ENSGT00940000159467 |
HOGENOMi | CLU_214024_0_0_1 |
InParanoidi | Q8TB92 |
OMAi | DGHSRAN |
PhylomeDBi | Q8TB92 |
TreeFami | TF105363 |
Enzyme and pathway databases
UniPathwayi | UPA00896;UER00863 |
PathwayCommonsi | Q8TB92 |
Reactomei | R-HSA-77111, Synthesis of Ketone Bodies |
SABIO-RKi | Q8TB92 |
Miscellaneous databases
BioGRID-ORCSi | 54511, 31 hits in 868 CRISPR screens |
ChiTaRSi | HMGCLL1, human |
GenomeRNAii | 54511 |
Pharosi | Q8TB92, Tbio |
PROi | PR:Q8TB92 |
RNActi | Q8TB92, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000146151, Expressed in cortical plate and 155 other tissues |
ExpressionAtlasi | Q8TB92, baseline and differential |
Genevisiblei | Q8TB92, HS |
Family and domain databases
Gene3Di | 3.20.20.70, 1 hit |
InterProi | View protein in InterPro IPR013785, Aldolase_TIM IPR030021, ER-cHL IPR043594, HMGL IPR000891, PYR_CT |
PANTHERi | PTHR42738, PTHR42738, 1 hit PTHR42738:SF5, PTHR42738:SF5, 1 hit |
Pfami | View protein in Pfam PF00682, HMGL-like, 1 hit |
PROSITEi | View protein in PROSITE PS50991, PYR_CT, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | HMGC2_HUMAN | |
Accessioni | Q8TB92Primary (citable) accession number: Q8TB92 Secondary accession number(s): B1AQ42 Q6ZSA9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 20, 2008 |
Last sequence update: | May 20, 2008 | |
Last modified: | February 10, 2021 | |
This is version 148 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 6
Human chromosome 6: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families