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D3Z7P3

- GLSK_MOUSE

UniProt

D3Z7P3 - GLSK_MOUSE

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Protein

Glutaminase kidney isoform, mitochondrial

Gene

Gls

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.3 Publications

Catalytic activityi

L-glutamine + H2O = L-glutamate + NH3.1 Publication

Enzyme regulationi

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 1.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei291 – 2911Substrate
Binding sitei340 – 3401Substrate
Binding sitei386 – 3861Substrate
Binding sitei393 – 3931Substrate
Binding sitei419 – 4191Substrate
Binding sitei471 – 4711Substrate
Binding sitei489 – 4891Substrate; via amide nitrogen

GO - Molecular functioni

  1. glutaminase activity Source: UniProtKB

GO - Biological processi

  1. glutamate biosynthetic process Source: UniProtKB
  2. glutamine catabolic process Source: UniProtKB
  3. protein homotetramerization Source: UniProtKB
  4. regulation of respiratory gaseous exchange by neurological system process Source: MGI
  5. suckling behavior Source: MGI
  6. synaptic transmission Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Enzyme and pathway databases

ReactomeiREACT_229514. Glutamate Neurotransmitter Release Cycle.
REACT_239550. Amino acid synthesis and interconversion (transamination).

Names & Taxonomyi

Protein namesi
Recommended name:
Glutaminase kidney isoform, mitochondrial (EC:3.5.1.2)
Short name:
GLS
Gene namesi
Name:Gls
Synonyms:Gls1, Kiaa0838
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 1

Organism-specific databases

MGIiMGI:95752. Gls.

Subcellular locationi

Isoform 1 : Cytoplasmcytosol By similarity

GO - Cellular componenti

  1. mitochondrion Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion

Pathology & Biotechi

Disruption phenotypei

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.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi394 – 3941F → S: Impairs tetramerization and promotes formation of homodimers. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 1616MitochondrionBy similarityAdd
BLAST
Chaini17 – 674658Glutaminase kidney isoform, mitochondrialPRO_0000417583Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei135 – 1351N6-succinyllysine1 Publication
Modified residuei169 – 1691N6-succinyllysine1 Publication
Modified residuei316 – 3161N6-acetyllysineBy similarity

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiD3Z7P3.
PRIDEiD3Z7P3.

Expressioni

Gene expression databases

BgeeiD3Z7P3.
ExpressionAtlasiD3Z7P3. baseline and differential.

Interactioni

Subunit structurei

Homotetramer. Interacts with ATCAY; the interaction is direct and may control GLS localization, negatively regulating its activity.2 Publications

Protein-protein interaction databases

DIPiDIP-60006N.
STRINGi10090.ENSMUSP00000110158.

Structurei

Secondary structure

1
674
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi145 – 1517Combined sources
Beta strandi157 – 1604Combined sources
Helixi161 – 17010Combined sources
Helixi178 – 1803Combined sources
Helixi181 – 19313Combined sources
Helixi202 – 2098Combined sources
Helixi210 – 2123Combined sources
Helixi213 – 2208Combined sources
Beta strandi224 – 2274Combined sources
Helixi229 – 24315Combined sources
Beta strandi249 – 2513Combined sources
Helixi256 – 2594Combined sources
Beta strandi267 – 2726Combined sources
Beta strandi277 – 2826Combined sources
Helixi290 – 2934Combined sources
Helixi294 – 31320Combined sources
Beta strandi321 – 3288Combined sources
Beta strandi332 – 3354Combined sources
Helixi340 – 34910Combined sources
Turni350 – 3534Combined sources
Helixi356 – 37015Combined sources
Turni371 – 3733Combined sources
Beta strandi376 – 3783Combined sources
Helixi380 – 3889Combined sources
Helixi391 – 40212Combined sources
Helixi412 – 42312Combined sources
Beta strandi425 – 4273Combined sources
Helixi429 – 44012Combined sources
Turni441 – 4433Combined sources
Turni446 – 4483Combined sources
Helixi455 – 46814Combined sources
Helixi471 – 4733Combined sources
Helixi474 – 4807Combined sources
Beta strandi485 – 4873Combined sources
Beta strandi491 – 4977Combined sources
Turni498 – 5003Combined sources
Beta strandi501 – 5066Combined sources
Beta strandi508 – 5103Combined sources
Beta strandi514 – 5163Combined sources
Helixi517 – 52913Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3SS3X-ray2.42A/B/C/D128-602[»]
3SS4X-ray2.85A/B/C/D128-602[»]
3SS5X-ray2.80A/B/C/D128-602[»]
4JKTX-ray2.77A/B/C/D128-555[»]
ProteinModelPortaliD3Z7P3.
SMRiD3Z7P3. Positions 142-646.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati590 – 61930ANK 1Add
BLAST
Repeati624 – 65330ANK 2Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi59 – 624Poly-Gly
Compositional biasi91 – 999Poly-Gln

Sequence similaritiesi

Belongs to the glutaminase family.Curated
Contains 2 ANK repeats.Curated

Keywords - Domaini

ANK repeat, Repeat, Transit peptide

Phylogenomic databases

GeneTreeiENSGT00390000010463.
HOGENOMiHOG000216891.
InParanoidiD3Z7P3.
KOiK01425.
OMAiGMDMEQR.
OrthoDBiEOG7S4X5F.
TreeFamiTF313359.

Family and domain databases

Gene3Di1.25.40.20. 2 hits.
3.40.710.10. 1 hit.
HAMAPiMF_00313. Glutaminase.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR012338. Beta-lactam/transpept-like.
IPR015868. Glutaminase.
[Graphical view]
PANTHERiPTHR12544. PTHR12544. 1 hit.
PfamiPF12796. Ank_2. 1 hit.
PF04960. Glutaminase. 1 hit.
[Graphical view]
SMARTiSM00248. ANK. 2 hits.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
SSF56601. SSF56601. 1 hit.
TIGRFAMsiTIGR03814. Gln_ase. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: D3Z7P3-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MMRLRGSAML RELLLRPPAA VGAVLRRAQP LGTLCRRPRG GSRPTAGLVA
60 70 80 90 100
AARLHPWWGG GGRAKGPGAG GLSSSPSEIL QELGKGGTPP QQQQQQQQQP
110 120 130 140 150
GASPPAAPGP KDSPGETDAF GNSEGKEMVA AGDNKIKQGL LPSLEDLLFY
160 170 180 190 200
TIAEGQEKIP VHKFITALKS TGLRTSDPRL KECMDMLRLT LQTTSDGVML
210 220 230 240 250
DKDLFKKCVQ SNIVLLTQAF RRKFVIPDFM SFTSHIDELY ESAKKQSGGK
260 270 280 290 300
VADYIPQLAK FSPDLWGVSV CTVDGQRHSI GDTKVPFCLQ SCVKPLKYAI
310 320 330 340 350
AVNDLGTEYV HRYVGKEPSG LRFNKLFLNE DDKPHNPMVN AGAIVVTSLI
360 370 380 390 400
KQGVNNAEKF DYVMQFLNKM AGNEYVGFSN ATFQSERESG DRNFAIGYYL
410 420 430 440 450
KEKKCFPEGT DMVGILDFYF QLCSIEVTCE SASVMAATLA NGGFCPITGE
460 470 480 490 500
RVLSPEAVRN TLSLMHSCGM YDFSGQFAFH VGLPAKSGVA GGILLVVPNV
510 520 530 540 550
MGMMCWSPPL DKMGNSVKGI HFCHDLVSLC NFHNYDNLRH FAKKLDPRRE
560 570 580 590 600
GGDQRVKSVI NLLFAAYTGD VSALRRFALS AMDMEQRDYD SRTALHVAAA
610 620 630 640 650
EGHVEVVKFL LEACKVNPFP KDRWNNTPMD EALHFGHHDV FKILQEYQVQ
660 670
YTPQGDSDDG KGNQTVHKNL DGLL
Length:674
Mass (Da):73,964
Last modified:April 20, 2010 - v1
Checksum:iC46824C83E1D9639
GO
Isoform 2 (identifier: D3Z7P3-2) [UniParc]FASTAAdd to Basket

Also known as: Glutaminase C, GAC

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

Show »
Length:603
Mass (Da):65,995
Checksum:iE896A4EDA7287755
GO

Sequence cautioni

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

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei556 – 674119VKSVI…LDGLL → HSFGPLDYESLQQELALKDT VWKKVSPESSDDTSTTVVYR MESLGERS in isoform 2. 1 PublicationVSP_043804Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK173039 mRNA. Translation: BAD32317.1. Different initiation.
AC123752 Genomic DNA. No translation available.
CCDSiCCDS35561.1. [D3Z7P3-1]
CCDS48256.1. [D3Z7P3-2]
RefSeqiNP_001074550.1. NM_001081081.2. [D3Z7P3-1]
NP_001106854.1. NM_001113383.1. [D3Z7P3-2]
UniGeneiMm.398608.

Genome annotation databases

EnsembliENSMUST00000114510; ENSMUSP00000110155; ENSMUSG00000026103. [D3Z7P3-2]
ENSMUST00000114513; ENSMUSP00000110158; ENSMUSG00000026103. [D3Z7P3-1]
GeneIDi14660.
KEGGimmu:14660.
UCSCiuc007aye.2. mouse. [D3Z7P3-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK173039 mRNA. Translation: BAD32317.1 . Different initiation.
AC123752 Genomic DNA. No translation available.
CCDSi CCDS35561.1. [D3Z7P3-1 ]
CCDS48256.1. [D3Z7P3-2 ]
RefSeqi NP_001074550.1. NM_001081081.2. [D3Z7P3-1 ]
NP_001106854.1. NM_001113383.1. [D3Z7P3-2 ]
UniGenei Mm.398608.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
3SS3 X-ray 2.42 A/B/C/D 128-602 [» ]
3SS4 X-ray 2.85 A/B/C/D 128-602 [» ]
3SS5 X-ray 2.80 A/B/C/D 128-602 [» ]
4JKT X-ray 2.77 A/B/C/D 128-555 [» ]
ProteinModelPortali D3Z7P3.
SMRi D3Z7P3. Positions 142-646.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

DIPi DIP-60006N.
STRINGi 10090.ENSMUSP00000110158.

Proteomic databases

MaxQBi D3Z7P3.
PRIDEi D3Z7P3.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000114510 ; ENSMUSP00000110155 ; ENSMUSG00000026103 . [D3Z7P3-2 ]
ENSMUST00000114513 ; ENSMUSP00000110158 ; ENSMUSG00000026103 . [D3Z7P3-1 ]
GeneIDi 14660.
KEGGi mmu:14660.
UCSCi uc007aye.2. mouse. [D3Z7P3-1 ]

Organism-specific databases

CTDi 2744.
MGIi MGI:95752. Gls.
Rougei Search...

Phylogenomic databases

GeneTreei ENSGT00390000010463.
HOGENOMi HOG000216891.
InParanoidi D3Z7P3.
KOi K01425.
OMAi GMDMEQR.
OrthoDBi EOG7S4X5F.
TreeFami TF313359.

Enzyme and pathway databases

Reactomei REACT_229514. Glutamate Neurotransmitter Release Cycle.
REACT_239550. Amino acid synthesis and interconversion (transamination).

Miscellaneous databases

ChiTaRSi Gls. mouse.
NextBioi 286530.
PROi D3Z7P3.
SOURCEi Search...

Gene expression databases

Bgeei D3Z7P3.
ExpressionAtlasi D3Z7P3. baseline and differential.

Family and domain databases

Gene3Di 1.25.40.20. 2 hits.
3.40.710.10. 1 hit.
HAMAPi MF_00313. Glutaminase.
InterProi IPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR012338. Beta-lactam/transpept-like.
IPR015868. Glutaminase.
[Graphical view ]
PANTHERi PTHR12544. PTHR12544. 1 hit.
Pfami PF12796. Ank_2. 1 hit.
PF04960. Glutaminase. 1 hit.
[Graphical view ]
SMARTi SM00248. ANK. 2 hits.
[Graphical view ]
SUPFAMi SSF48403. SSF48403. 1 hit.
SSF56601. SSF56601. 1 hit.
TIGRFAMsi TIGR03814. Gln_ase. 1 hit.
PROSITEi PS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.

Entry informationi

Entry nameiGLSK_MOUSE
AccessioniPrimary (citable) accession number: D3Z7P3
Secondary accession number(s): E9PUF0, Q69ZX9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 13, 2012
Last sequence update: April 20, 2010
Last modified: November 26, 2014
This is version 47 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3