Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q8TB92 (HMGC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
3-hydroxymethyl-3-methylglutaryl-CoA lyase, cytoplasmic

EC=4.1.3.4
Alternative name(s):
3-hydroxymethyl-3-methylglutaryl-CoA lyase-like protein 1
Endoplasmic reticulum 3-hydroxymethyl-3-methylglutaryl-CoA lyase
Short name=er-cHL
Gene names
Name:HMGCLL1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length370 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.5 Ref.6

Catalytic activity

(S)-3-hydroxy-3-methylglutaryl-CoA = acetyl-CoA + acetoacetate. Ref.5 Ref.6

Cofactor

Divalent metal cations Probable. Ref.5

Pathway

Metabolic intermediate metabolism; (S)-3-hydroxy-3-methylglutaryl-CoA degradation; acetoacetate from (S)-3-hydroxy-3-methylglutaryl-CoA: step 1/1.

Subcellular location

Cytoplasmcytosol. Endoplasmic reticulum membrane; Peripheral membrane protein Ref.5 Ref.6.

Sequence similarities

Belongs to the HMG-CoA lyase family.

Biophysicochemical properties

Kinetic parameters:

KM=40 µM for (S)-3-hydroxy-3-methylglutaryl-CoA (at pH 9) (Ref.6) Ref.5 Ref.6

KM=75 µM for (S)-3-hydroxy-3-methylglutaryl-CoA (at pH 8) (Ref.6)

KM=28 µM for (S)-3-hydroxy-3-methylglutaryl-CoA (Ref.5)

KM=49 µM for (S)-3-hydroxy-3-methylglutaryl-CoA (in presence of magnesium) (Ref.5)

KM=0.18 µM for (S)-3-hydroxy-3-methylglutaryl-CoA (in presence of manganese) (Ref.5)

Vmax=12 nmol/min/mg enzyme with (S)-3-hydroxy-3-methylglutaryl-CoA as substrate at pH 9 (Ref.6)

Vmax=25 nmol/min/mg enzyme with (S)-3-hydroxy-3-methylglutaryl-CoA as substrate at pH 8 (Ref.6)

Sequence caution

The sequence BAC87045.1 differs from that shown. Reason: Frameshift at position 253.

The sequence BAG51462.1 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8TB92-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q8TB92-2)

The sequence of this isoform differs from the canonical sequence as follows:
     37-66: Missing.
Isoform 3 (identifier: Q8TB92-4)

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. No experimental confirmation available.
Isoform 4 (identifier: Q8TB92-5)

The sequence of this isoform differs from the canonical sequence as follows:
     37-66: Missing.
     130-161: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed
Chain2 – 3703693-hydroxymethyl-3-methylglutaryl-CoA lyase, cytoplasmic
PRO_0000334669

Sites

Active site3111 By similarity
Metal binding871Divalent metal cation By similarity
Metal binding2781Divalent metal cation By similarity
Metal binding2801Divalent metal cation By similarity
Metal binding3201Divalent metal cation By similarity
Binding site861Substrate By similarity

Amino acid modifications

Lipidation21N-myristoyl glycine Ref.5

Natural variations

Alternative sequence37 – 6630Missing in isoform 2 and isoform 4.
VSP_033752
Alternative sequence37 – 5317TSLLT…DVSGF → ELQSVMLMLHHGPLRKP in isoform 3.
VSP_038021
Alternative sequence54 – 370317Missing in isoform 3.
VSP_038022
Alternative sequence130 – 16132Missing in isoform 4.
VSP_044324

Experimental info

Mutagenesis21G → A: Abolishes myristoylation and induces a subcellular location change. Ref.5
Mutagenesis861R → Q: Abolishes catalytic activity. Ref.6
Mutagenesis2371L → S: Abolishes catalytic activity. Ref.6
Mutagenesis2781H → R: Abolishes catalytic activity. Ref.6
Sequence conflict991D → G in BAH11613. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 20, 2008. Version 3.
Checksum: 7DDEE81555E092A1

FASTA37039,514
        10         20         30         40         50         60 
MGNVPSAVKH CLSYQQLLRE HLWIGDSVAG ALDPAQTSLL TNLHCFQPDV SGFSVSLAGT 

        70         80         90        100        110        120 
VACIHWETSQ LSGLPEFVKI VEVGPRDGLQ NEKVIVPTDI KIEFINRLSQ TGLSVIEVTS 

       130        140        150        160        170        180 
FVSSRWVPQM ADHTEVMKGI HQYPGVRYPV LTPNLQGFHH AVAAGATEIS VFGAASESFS 

       190        200        210        220        230        240 
KKNINCSIEE SMGKFEEVVK SARHMNIPAR GYVSCALGCP YEGSITPQKV TEVSKRLYGM 

       250        260        270        280        290        300 
GCYEISLGDT IGVGTPGSMK RMLESVMKEI PPGALAVHCH DTYGQALANI LTALQMGINV 

       310        320        330        340        350        360 
VDSAVSGLGG CPYAKGASGN VATEDLIYML NGLGLNTGVN LYKVMEAGDF ICKAVNKTTN 

       370 
SKVAQASFNA 

« Hide

Isoform 2 [UniParc].

Checksum: 6F175387821614CC
Show »

FASTA34036,328
Isoform 3 [UniParc].

Checksum: 16F3265215AF8A2A
Show »

FASTA535,874
Isoform 4 [UniParc].

Checksum: 49ED9FE7EC8038BB
Show »

FASTA30832,701

References

« Hide 'large scale' references
[1]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4).
Tissue: Brain and Cerebellum.
[2]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Brain.
[5]"Identification and characterization of an extramitochondrial human 3-Hydroxy-3-methylglutaryl-CoA lyase."
Montgomery C., Pei Z., Watkins P.A., Miziorko H.M.
J. Biol. Chem. 287:33227-33236(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, SUBCELLULAR LOCATION, MYRISTOYLATION AT GLY-2, MUTAGENESIS OF GLY-2.
[6]"Characterization of a novel HMG-CoA Lyase enzyme with a dual location in endoplasmic reticulum and cytosol."
Arnedo M., Menao S., Puisac B., Teresa-Rodrigo M.E., Gil-Rodriguez M.C., Lopez-Vinas E., Gomez-Puertas P., Casals N., Casale C.H., Hegardt F.G., Pie J.
J. Lipid Res. 53:2046-2056(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ARG-86; LEU-237 AND HIS-278.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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. Translation: CAI40662.1.
CH471081 Genomic DNA. Translation: EAX04442.1.
CH471081 Genomic DNA. Translation: EAX04444.1.
BC024194 mRNA. Translation: AAH24194.2.
RefSeqNP_001035865.1. NM_001042406.1.
NP_001274670.1. NM_001287741.1.
NP_001274675.1. NM_001287746.1.
NP_061909.2. NM_019036.2.
UniGeneHs.147054.

3D structure databases

ProteinModelPortalQ8TB92.
SMRQ8TB92. Positions 74-367.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000381654.

PTM databases

PhosphoSiteQ8TB92.

Polymorphism databases

DMDM189028466.

Proteomic databases

PaxDbQ8TB92.
PRIDEQ8TB92.

Protocols and materials databases

DNASU54511.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000274901; ENSP00000274901; ENSG00000146151. [Q8TB92-2]
ENST00000308161; ENSP00000309737; ENSG00000146151. [Q8TB92-5]
ENST00000358072; ENSP00000350779; ENSG00000146151. [Q8TB92-4]
ENST00000370852; ENSP00000359889; ENSG00000146151. [Q8TB92-4]
ENST00000398661; ENSP00000381654; ENSG00000146151. [Q8TB92-1]
GeneID54511.
KEGGhsa:54511.
UCSCuc003pcn.3. human. [Q8TB92-1]
uc003pco.3. human. [Q8TB92-2]
uc011dxc.2. human. [Q8TB92-5]

Organism-specific databases

CTD54511.
GeneCardsGC06M055299.
HGNCHGNC:21359. HMGCLL1.
HPAHPA030223.
neXtProtNX_Q8TB92.
PharmGKBPA134989971.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0119.
HOGENOMHOG000219757.
HOVERGENHBG064656.
InParanoidQ8TB92.
OMARYICTEL.
PhylomeDBQ8TB92.
TreeFamTF105363.

Enzyme and pathway databases

UniPathwayUPA00896; UER00863.

Gene expression databases

ArrayExpressQ8TB92.
BgeeQ8TB92.
CleanExHS_HMGCLL1.
GenevestigatorQ8TB92.

Family and domain databases

Gene3D3.20.20.70. 1 hit.
InterProIPR013785. Aldolase_TIM.
IPR027167. HMG-CoA_lyase.
IPR000891. PYR_CT.
[Graphical view]
PANTHERPTHR10277:SF20. PTHR10277:SF20. 1 hit.
PfamPF00682. HMGL-like. 1 hit.
[Graphical view]
PROSITEPS50991. PYR_CT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi54511.
NextBio56890.
PROQ8TB92.

Entry information

Entry nameHMGC2_HUMAN
AccessionPrimary (citable) accession number: Q8TB92
Secondary accession number(s): B1AQ42 expand/collapse secondary AC list , B3KNV0, B7Z1S7, F8W793, Q6ZSA9
Entry history
Integrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: May 20, 2008
Last modified: April 16, 2014
This is version 100 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM