Human Gene HMGCLL1 (uc003pcn.3)
  Description: Homo sapiens 3-hydroxymethyl-3-methylglutaryl-CoA lyase-like 1 (HMGCLL1), transcript variant 1, mRNA.
Transcript (Including UTRs)
   Position: hg19 chr6:55,299,171-55,444,012 Size: 144,842 Total Exon Count: 10 Strand: -
Coding Region
   Position: hg19 chr6:55,300,460-55,443,853 Size: 143,394 Coding Exon Count: 10 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr6:55,299,171-55,444,012)mRNA (may differ from genome)Protein (370 aa)
Gene SorterGenome BrowserOther Species FASTATable SchemaAlphaFoldBioGPS
EnsemblEntrez GeneExonPrimerGeneCardsGeneNetworkH-INV
HGNCHPRDLynxMGIneXtProtPubMed
ReactomeTreefamUniProtKBBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: HMGC2_HUMAN
DESCRIPTION: RecName: Full=3-hydroxymethyl-3-methylglutaryl-CoA lyase, cytoplasmic; EC=4.1.3.4; AltName: Full=3-hydroxymethyl-3-methylglutaryl-CoA lyase-like protein 1; AltName: Full=Endoplasmic reticulum 3-hydroxymethyl-3-methylglutaryl-CoA lyase; Short=er-cHL;
FUNCTION: 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.
CATALYTIC ACTIVITY: (S)-3-hydroxy-3-methylglutaryl-CoA = acetyl- CoA + acetoacetate.
COFACTOR: Divalent metal cations (Probable).
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=40 uM for (S)-3-hydroxy-3-methylglutaryl-CoA (at pH 9) (PubMed:22847177); KM=75 uM for (S)-3-hydroxy-3-methylglutaryl-CoA (at pH 8) (PubMed:22847177); KM=28 uM for (S)-3-hydroxy-3-methylglutaryl-CoA (PubMed:22865860); KM=49 uM for (S)-3-hydroxy-3-methylglutaryl-CoA (in presence of magnesium) (PubMed:22865860); KM=0.18 uM for (S)-3-hydroxy-3-methylglutaryl-CoA (in presence of manganese) (PubMed:22865860); Vmax=12 nmol/min/mg enzyme with (S)-3-hydroxy-3-methylglutaryl- CoA as substrate at pH 9 (PubMed:22847177); Vmax=25 nmol/min/mg enzyme with (S)-3-hydroxy-3-methylglutaryl- CoA as substrate at pH 8 (PubMed:22847177);
PATHWAY: Metabolic intermediate metabolism; (S)-3-hydroxy-3- methylglutaryl-CoA degradation; acetoacetate from (S)-3-hydroxy-3- methylglutaryl-CoA: step 1/1.
SUBCELLULAR LOCATION: Cytoplasm, cytosol. Endoplasmic reticulum membrane; Peripheral membrane protein.
SIMILARITY: Belongs to the HMG-CoA lyase family.
SEQUENCE CAUTION: Sequence=BAC87045.1; Type=Frameshift; Positions=253; Sequence=BAG51462.1; Type=Erroneous translation; Note=Wrong choice of CDS;

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): HMGCLL1
CDC HuGE Published Literature: HMGCLL1

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • C472791 3-(4'-hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid
  • D007649 Ketamine

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 3.54 RPKM in Brain - Hypothalamus
Total median expression: 40.51 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -66.40159-0.418 Picture PostScript Text
3' UTR -295.161289-0.229 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR013785 - Aldolase_TIM
IPR000891 - PYR_CT

Pfam Domains:
PF00682 - HMGL-like

SCOP Domains:
51569 - Aldolase

ModBase Predicted Comparative 3D Structure on Q8TB92
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
      
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003824 catalytic activity
GO:0004419 hydroxymethylglutaryl-CoA lyase activity
GO:0016829 lyase activity
GO:0046872 metal ion binding

Biological Process:
GO:0046951 ketone body biosynthetic process

Cellular Component:
GO:0005737 cytoplasm
GO:0005783 endoplasmic reticulum
GO:0005789 endoplasmic reticulum membrane
GO:0005829 cytosol
GO:0016020 membrane
GO:0048471 perinuclear region of cytoplasm


-  Descriptions from all associated GenBank mRNAs
  AF131827 - Homo sapiens clone 24959 mRNA sequence, partial cds.
AK127587 - Homo sapiens cDNA FLJ45682 fis, clone FCBBF3001018, moderately similar to Hydroxymethylglutaryl-CoA lyase (EC 4.1.3.4).
AK055075 - Homo sapiens cDNA FLJ30513 fis, clone BRAWH2000651, moderately similar to HYDROXYMETHYLGLUTARYL-COA LYASE (EC 4.1.3.4).
AK294210 - Homo sapiens cDNA FLJ57919 complete cds.
AK297191 - Homo sapiens cDNA FLJ57397 complete cds.
AK293856 - Homo sapiens cDNA FLJ57911 complete cds.
BC024194 - Homo sapiens 3-hydroxymethyl-3-methylglutaryl-Coenzyme A lyase-like 1, mRNA (cDNA clone MGC:33395 IMAGE:4818781), complete cds.
HQ447228 - Synthetic construct Homo sapiens clone IMAGE:100070531; CCSB001733_01 3-hydroxymethyl-3-methylglutaryl-Coenzyme A lyase-like 1 (HMGCLL1) gene, encodes complete protein.
KJ894033 - Synthetic construct Homo sapiens clone ccsbBroadEn_03427 HMGCLL1 gene, encodes complete protein.
CU692876 - Synthetic construct Homo sapiens gateway clone IMAGE:100018145 5' read HMGCLL1 mRNA.
AL137605 - Homo sapiens mRNA; cDNA DKFZp434G1411 (from clone DKFZp434G1411); partial cds.
JD511053 - Sequence 492077 from Patent EP1572962.
JD301123 - Sequence 282147 from Patent EP1572962.
JD567080 - Sequence 548104 from Patent EP1572962.
JD355390 - Sequence 336414 from Patent EP1572962.
JD279568 - Sequence 260592 from Patent EP1572962.
JD499489 - Sequence 480513 from Patent EP1572962.
JD492821 - Sequence 473845 from Patent EP1572962.
JD047088 - Sequence 28112 from Patent EP1572962.
JD449740 - Sequence 430764 from Patent EP1572962.
JD325038 - Sequence 306062 from Patent EP1572962.
JD215851 - Sequence 196875 from Patent EP1572962.
JD520436 - Sequence 501460 from Patent EP1572962.
JD086245 - Sequence 67269 from Patent EP1572962.
JD119206 - Sequence 100230 from Patent EP1572962.
JD228463 - Sequence 209487 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  BioCyc Knowledge Library
LEU-DEG2-PWY - leucine degradation I
PWY3DJ-6 - Leucine Catabolism
PWY3FA-941 - ketogenesis
PWY66-367 - ketogenesis

Reactome (by CSHL, EBI, and GO)

Protein Q8TB92 (Reactome details) participates in the following event(s):

R-HSA-6788597 HMGCLL1:Mg2+ cleaves bHMG-CoA to Ac-CoA and ACA
R-HSA-77111 Synthesis of Ketone Bodies
R-HSA-74182 Ketone body metabolism
R-HSA-556833 Metabolism of lipids
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: B1AQ42, B3KNV0, B7Z1S7, F8W793, HMGC2_HUMAN, NM_019036, NP_061909, Q6ZSA9, Q8TB92
UCSC ID: uc003pcn.3
RefSeq Accession: NM_019036
Protein: Q8TB92 (aka HMGC2_HUMAN)
CCDS: CCDS43475.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_019036.2
exon count: 10CDS single in 3' UTR: no RNA size: 2571
ORF size: 1113CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2426.00frame shift in genome: no % Coverage: 99.61
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.