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D3Z7P3 (GLSK_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 41. 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:
Glutaminase kidney isoform, mitochondrial

Short name=GLS
EC=3.5.1.2
Gene names
Name:Gls
Synonyms:Gls1, Kiaa0838
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length674 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the first reaction in the primary pathway for the renal catabolism of glutamine. Plays a role in maintaining acid-base homeostasis. Regulates the levels of the neurotransmitter glutamate in the brain. Ref.4 Ref.5 Ref.7

Catalytic activity

L-glutamine + H2O = L-glutamate + NH3. Ref.7

Enzyme regulation

Isoform 1 and isoform 2 are activated by phosphate, due to increased affinity for glutamine. At phosphate concentrations above 10 mM, isoform 2 is more efficient than isoform 1. Ref.7

Subunit structure

Homotetramer. Interacts with ATCAY; the interaction is direct and may control GLS localization, negatively regulating its activity. Ref.3 Ref.7

Subcellular location

Isoform 1: Cytoplasmcytosol By similarity Ref.4.

Isoform 2: Mitochondrion Ref.4.

Disruption phenotype

Death during the first days after birth. Pups appear normal and display normal levels of activity, but their activity is disorganized. Pups do not orient to the dam, do not succeed in grasping a nipple and do not feed properly. In addition, they display altered respiration. Ref.4

Sequence similarities

Belongs to the glutaminase family.

Contains 2 ANK repeats.

Sequence caution

The sequence BAD32317.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: D3Z7P3-1)

Also known as: KGA;

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: D3Z7P3-2)

Also known as: Glutaminase C; GAC;

The sequence of this isoform differs from the canonical sequence as follows:
     556-674: VKSVINLLFA...TVHKNLDGLL → HSFGPLDYES...YRMESLGERS

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 1616Mitochondrion By similarity
Chain17 – 674658Glutaminase kidney isoform, mitochondrial HAMAP-Rule MF_00313
PRO_0000417583

Regions

Repeat590 – 61930ANK 1 HAMAP-Rule MF_00313
Repeat624 – 65330ANK 2 HAMAP-Rule MF_00313
Compositional bias59 – 624Poly-Gly HAMAP-Rule MF_00313
Compositional bias91 – 999Poly-Gln HAMAP-Rule MF_00313

Sites

Binding site2911Substrate
Binding site3401Substrate
Binding site3861Substrate
Binding site3931Substrate
Binding site4191Substrate
Binding site4711Substrate
Binding site4891Substrate; via amide nitrogen

Amino acid modifications

Modified residue1351N6-succinyllysine Ref.6
Modified residue1691N6-succinyllysine Ref.6
Modified residue3161N6-acetyllysine By similarity

Natural variations

Alternative sequence556 – 674119VKSVI…LDGLL → HSFGPLDYESLQQELALKDT VWKKVSPESSDDTSTTVVYR MESLGERS in isoform 2.
VSP_043804

Experimental info

Mutagenesis3941F → S: Impairs tetramerization and promotes formation of homodimers. Ref.7

Secondary structure

..................................................................... 674
Helix Strand Turn

Details...

Sequences

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

Last modified April 20, 2010. Version 1.
Checksum: C46824C83E1D9639

FASTA67473,964
        10         20         30         40         50         60 
MMRLRGSAML RELLLRPPAA VGAVLRRAQP LGTLCRRPRG GSRPTAGLVA AARLHPWWGG 

        70         80         90        100        110        120 
GGRAKGPGAG GLSSSPSEIL QELGKGGTPP QQQQQQQQQP GASPPAAPGP KDSPGETDAF 

       130        140        150        160        170        180 
GNSEGKEMVA AGDNKIKQGL LPSLEDLLFY TIAEGQEKIP VHKFITALKS TGLRTSDPRL 

       190        200        210        220        230        240 
KECMDMLRLT LQTTSDGVML DKDLFKKCVQ SNIVLLTQAF RRKFVIPDFM SFTSHIDELY 

       250        260        270        280        290        300 
ESAKKQSGGK VADYIPQLAK FSPDLWGVSV CTVDGQRHSI GDTKVPFCLQ SCVKPLKYAI 

       310        320        330        340        350        360 
AVNDLGTEYV HRYVGKEPSG LRFNKLFLNE DDKPHNPMVN AGAIVVTSLI KQGVNNAEKF 

       370        380        390        400        410        420 
DYVMQFLNKM AGNEYVGFSN ATFQSERESG DRNFAIGYYL KEKKCFPEGT DMVGILDFYF 

       430        440        450        460        470        480 
QLCSIEVTCE SASVMAATLA NGGFCPITGE RVLSPEAVRN TLSLMHSCGM YDFSGQFAFH 

       490        500        510        520        530        540 
VGLPAKSGVA GGILLVVPNV MGMMCWSPPL DKMGNSVKGI HFCHDLVSLC NFHNYDNLRH 

       550        560        570        580        590        600 
FAKKLDPRRE GGDQRVKSVI NLLFAAYTGD VSALRRFALS AMDMEQRDYD SRTALHVAAA 

       610        620        630        640        650        660 
EGHVEVVKFL LEACKVNPFP KDRWNNTPMD EALHFGHHDV FKILQEYQVQ YTPQGDSDDG 

       670 
KGNQTVHKNL DGLL 

« Hide

Isoform 2 (Glutaminase C) (GAC) [UniParc].

Checksum: E896A4EDA7287755
Show »

FASTA60365,995

References

« Hide 'large scale' references
[1]"Prediction of the coding sequences of mouse homologues of KIAA gene: IV. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H., Nagase T., Ohara O., Koga H.
DNA Res. 11:205-218(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Embryonic tail.
[2]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], ALTERNATIVE SPLICING.
Strain: C57BL/6J.
[3]"Brain-specific BNIP-2-homology protein Caytaxin relocalises glutaminase to neurite terminals and reduces glutamate levels."
Buschdorf J.P., Li Chew L., Zhang B., Cao Q., Liang F.Y., Liou Y.C., Zhou Y.T., Low B.C.
J. Cell Sci. 119:3337-3350(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ATCAY.
[4]"Mice lacking brain/kidney phosphate-activated glutaminase have impaired glutamatergic synaptic transmission, altered breathing, disorganized goal-directed behavior and die shortly after birth."
Masson J., Darmon M., Conjard A., Chuhma N., Ropert N., Thoby-Brisson M., Foutz A.S., Parrot S., Miller G.M., Jorisch R., Polan J., Hamon M., Hen R., Rayport S.
J. Neurosci. 26:4660-4671(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION.
[5]"Brain slices from glutaminase-deficient mice metabolize less glutamine: a cellular metabolomic study with carbon 13 NMR."
El Hage M., Masson J., Conjard-Duplany A., Ferrier B., Baverel G., Martin G.
J. Cereb. Blood Flow Metab. 32:816-824(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-135 AND LYS-169, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
[7]"Mitochondrial localization and structure-based phosphate activation mechanism of glutaminase C with implications for cancer metabolism."
Cassago A., Ferreira A.P., Ferreira I.M., Fornezari C., Gomes E.R., Greene K.S., Pereira H.M., Garratt R.C., Dias S.M., Ambrosio A.L.
Proc. Natl. Acad. Sci. U.S.A. 109:1092-1097(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.42 ANGSTROMS) OF 128-555 (ISOFORM 2) IN COMPLEX WITH GLUTAMATE AND PHOSPHATE, FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, ALTERNATIVE SPLICING, MUTAGENESIS OF PHE-394, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK173039 mRNA. Translation: BAD32317.1. Different initiation.
AC123752 Genomic DNA. No translation available.
RefSeqNP_001074550.1. NM_001081081.2.
NP_001106854.1. NM_001113383.1.
UniGeneMm.398608.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3SS3X-ray2.42A/B/C/D128-555[»]
3SS4X-ray2.85A/B/C/D128-555[»]
3SS5X-ray2.80A/B/C/D128-555[»]
4JKTX-ray2.77A/B/C/D128-555[»]
ProteinModelPortalD3Z7P3.
SMRD3Z7P3. Positions 142-646.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-60006N.
STRING10090.ENSMUSP00000110158.

Proteomic databases

PRIDED3Z7P3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000114510; ENSMUSP00000110155; ENSMUSG00000026103. [D3Z7P3-2]
ENSMUST00000114513; ENSMUSP00000110158; ENSMUSG00000026103. [D3Z7P3-1]
GeneID14660.
KEGGmmu:14660.
UCSCuc007aye.2. mouse. [D3Z7P3-1]

Organism-specific databases

CTD2744.
MGIMGI:95752. Gls.
RougeSearch...

Phylogenomic databases

GeneTreeENSGT00390000010463.
HOGENOMHOG000216891.
KOK01425.
OMACMEMLKV.
OrthoDBEOG7S4X5F.
TreeFamTF313359.

Gene expression databases

BgeeD3Z7P3.

Family and domain databases

Gene3D1.25.40.20. 2 hits.
3.40.710.10. 1 hit.
HAMAPMF_00313. Glutaminase.
InterProIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR012338. Beta-lactam/transpept-like.
IPR015868. Glutaminase.
[Graphical view]
PANTHERPTHR12544. PTHR12544. 1 hit.
PfamPF12796. Ank_2. 1 hit.
PF04960. Glutaminase. 1 hit.
[Graphical view]
SMARTSM00248. ANK. 2 hits.
[Graphical view]
SUPFAMSSF48403. SSF48403. 1 hit.
SSF56601. SSF56601. 1 hit.
TIGRFAMsTIGR03814. Gln_ase. 1 hit.
PROSITEPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSGLS. mouse.
NextBio286530.
PROD3Z7P3.
SOURCESearch...

Entry information

Entry nameGLSK_MOUSE
AccessionPrimary (citable) accession number: D3Z7P3
Secondary accession number(s): E9PUF0, Q69ZX9
Entry history
Integrated into UniProtKB/Swiss-Prot: June 13, 2012
Last sequence update: April 20, 2010
Last modified: April 16, 2014
This is version 41 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot