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Protein

Glutaminase liver isoform, mitochondrial

Gene

GLS2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays an important role in the regulation of glutamine catabolism. Promotes mitochondrial respiration and increases ATP generation in cells by catalyzing the synthesis of glutamate and alpha-ketoglutarate. Increases cellular anti-oxidant function via NADH and glutathione production. May play a role in preventing tumor proliferation.1 Publication

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei219SubstrateBy similarity1
Binding sitei268SubstrateBy similarity1
Binding sitei314SubstrateBy similarity1
Binding sitei321SubstrateBy similarity1
Binding sitei347SubstrateBy similarity1
Binding sitei399SubstrateBy similarity1
Binding sitei417Substrate; via amide nitrogenBy similarity1

GO - Molecular functioni

GO - Biological processi

  • cellular amino acid biosynthetic process Source: Reactome
  • cellular amino acid metabolic process Source: ProtInc
  • glutamate biosynthetic process Source: GO_Central
  • glutamate secretion Source: Reactome
  • glutamine catabolic process Source: GO_Central
  • positive regulation of protein targeting to mitochondrion Source: ParkinsonsUK-UCL
  • reactive oxygen species metabolic process Source: MGI
  • regulation of apoptotic process Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Enzyme and pathway databases

BioCyciZFISH:HS06001-MONOMER.
ReactomeiR-HSA-210500. Glutamate Neurotransmitter Release Cycle.
R-HSA-5628897. TP53 Regulates Metabolic Genes.
R-HSA-70614. Amino acid synthesis and interconversion (transamination).
SABIO-RKQ9UI32.

Names & Taxonomyi

Protein namesi
Recommended name:
Glutaminase liver isoform, mitochondrial (EC:3.5.1.2)
Short name:
GLS
Alternative name(s):
L-glutaminase
L-glutamine amidohydrolase
Gene namesi
Name:GLS2
Synonyms:GA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:29570. GLS2.

Subcellular locationi

GO - Cellular componenti

  • mitochondrial matrix Source: GO_Central
  • mitochondrion Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Organism-specific databases

DisGeNETi27165.
OpenTargetsiENSG00000135423.
PharmGKBiPA134933506.

Chemistry databases

DrugBankiDB00130. L-Glutamine.

Polymorphism and mutation databases

BioMutaiGLS2.
DMDMi145559477.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 14MitochondrionSequence analysisAdd BLAST14
ChainiPRO_000001162515 – 602Glutaminase liver isoform, mitochondrialAdd BLAST588

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei253N6-succinyllysineBy similarity1
Modified residuei279N6-acetyllysineBy similarity1
Modified residuei284N6-acetyllysineBy similarity1
Modified residuei329N6-acetyllysineBy similarity1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ9UI32.
PaxDbiQ9UI32.
PeptideAtlasiQ9UI32.
PRIDEiQ9UI32.

PTM databases

iPTMnetiQ9UI32.
PhosphoSitePlusiQ9UI32.

Expressioni

Tissue specificityi

Highly expressed in liver. Expressed in brain and pancreas. Not observed in heart, placenta, lung, skeletal muscle and kidney. Expression is significantly reduced in hepatocellular carcinomas.2 Publications

Inductioni

Up-regulated by P53 (at protein and mRNA level) under both stressed and non-stressed conditions.1 Publication

Gene expression databases

BgeeiENSG00000135423.
CleanExiHS_GLS2.
ExpressionAtlasiQ9UI32. baseline and differential.
GenevisibleiQ9UI32. HS.

Organism-specific databases

HPAiHPA038608.

Interactioni

Subunit structurei

Interacts with the PDZ domain of the syntrophin SNTA1. Interacts with the PDZ domain of TAX1BP3.1 Publication

Protein-protein interaction databases

BioGridi118044. 3 interactors.
IntActiQ9UI32. 2 interactors.
MINTiMINT-157952.
STRINGi9606.ENSP00000310447.

Structurei

Secondary structure

1602
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi157 – 171Combined sources15
Beta strandi177 – 179Combined sources3
Helixi187 – 189Combined sources3
Beta strandi195 – 200Combined sources6
Beta strandi205 – 210Combined sources6
Helixi218 – 221Combined sources4
Helixi222 – 233Combined sources12
Helixi235 – 238Combined sources4
Turni239 – 241Combined sources3
Helixi268 – 277Combined sources10
Turni278 – 281Combined sources4
Helixi284 – 298Combined sources15
Turni299 – 301Combined sources3
Helixi308 – 317Combined sources10
Helixi319 – 330Combined sources12
Helixi340 – 351Combined sources12
Beta strandi353 – 355Combined sources3
Helixi357 – 368Combined sources12
Turni369 – 371Combined sources3
Turni374 – 376Combined sources3
Helixi383 – 396Combined sources14
Helixi399 – 401Combined sources3
Helixi402 – 408Combined sources7
Beta strandi413 – 415Combined sources3
Beta strandi419 – 425Combined sources7
Turni426 – 428Combined sources3
Beta strandi429 – 434Combined sources6
Beta strandi442 – 444Combined sources3
Helixi445 – 458Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4BQMX-ray2.18A/B154-479[»]
ProteinModelPortaliQ9UI32.
SMRiQ9UI32.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati518 – 551ANK 1Add BLAST34
Repeati552 – 585ANK 2Add BLAST34

Sequence similaritiesi

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

Keywords - Domaini

ANK repeat, Repeat, Transit peptide

Phylogenomic databases

eggNOGiKOG0506. Eukaryota.
COG2066. LUCA.
GeneTreeiENSGT00390000010463.
HOGENOMiHOG000012985.
HOVERGENiHBG005856.
InParanoidiQ9UI32.
KOiK01425.
OMAiCVKPLTY.
OrthoDBiEOG091G03YU.
PhylomeDBiQ9UI32.
TreeFamiTF313359.

Family and domain databases

Gene3Di1.25.40.20. 1 hit.
3.40.710.10. 1 hit.
HAMAPiMF_00313. Glutaminase. 1 hit.
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. AlignAdd to basket

Isoform 1 (identifier: Q9UI32-1) [UniParc]FASTAAdd to basket

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
MRSMKALQKA LSRAGSHCGR GGWGHPSRSP LLGGGVRHHL SEAAAQGRET
60 70 80 90 100
PHSHQPQHQD HDSSESGMLS RLGDLLFYTI AEGQERIPIH KFTTALKATG
110 120 130 140 150
LQTSDPRLRD CMSEMHRVVQ ESSSGGLLDR DLFRKCVSSN IVLLTQAFRK
160 170 180 190 200
KFVIPDFEEF TGHVDRIFED VKELTGGKVA AYIPQLAKSN PDLWGVSLCT
210 220 230 240 250
VDGQRHSVGH TKIPFCLQSC VKPLTYAISI STLGTDYVHK FVGKEPSGLR
260 270 280 290 300
YNKLSLNEEG IPHNPMVNAG AIVVSSLIKM DCNKAEKFDF VLQYLNKMAG
310 320 330 340 350
NEYMGFSNAT FQSEKETGDR NYAIGYYLKE KKCFPKGVDM MAALDLYFQL
360 370 380 390 400
CSVEVTCESG SVMAATLANG GICPITGESV LSAEAVRNTL SLMHSCGMYD
410 420 430 440 450
FSGQFAFHVG LPAKSAVSGA ILLVVPNVMG MMCLSPPLDK LGNSHRGTSF
460 470 480 490 500
CQKLVSLFNF HNYDNLRHCA RKLDPRREGA EIRNKTVVNL LFAAYSGDVS
510 520 530 540 550
ALRRFALSAM DMEQKDYDSR TALHVAAAEG HIEVVKFLIE ACKVNPFAKD
560 570 580 590 600
RWGNIPLDDA VQFNHLEVVK LLQDYQDSYT LSETQAEAAA EALSKENLES

MV
Length:602
Mass (Da):66,323
Last modified:April 17, 2007 - v2
Checksum:i6D0E1EFF01BC3843
GO
Isoform 2 (identifier: Q9UI32-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     136-209: CVSSNIVLLT...TVDGQRHSVG → HSERSLSFLI...QRSPSACSPV
     210-602: Missing.

Note: No experimental confirmation available.
Show »
Length:209
Mass (Da):23,055
Checksum:iC3D6450C81DD26AD
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti87I → T in AAF21933 (PubMed:10620514).Curated1
Sequence conflicti140N → S in AAF21933 (PubMed:10620514).Curated1
Sequence conflicti257N → D in AAF21933 (PubMed:10620514).Curated1
Sequence conflicti328 – 329LK → HE in AAF21933 (PubMed:10620514).Curated2
Sequence conflicti560A → V in AAF33826 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_031615581L → P.1 PublicationCorresponds to variant rs2657879dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_057009136 – 209CVSSN…RHSVG → HSERSLSFLILRSSRAMWIA SLRMSKSSLEAKWQPTSLSW PSQTQTCGVSPCALWMVNGT LWATQRSPSACSPV in isoform 2. 1 PublicationAdd BLAST74
Alternative sequenceiVSP_057010210 – 602Missing in isoform 2. 1 PublicationAdd BLAST393

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF110330 mRNA. Translation: AAF21933.1.
AF110331 mRNA. Translation: AAF21934.1.
AF348119 Genomic DNA. Translation: AAO13298.2.
AF223944 mRNA. Translation: AAF33826.1.
AK303772 mRNA. Translation: BAH14045.1.
AC097104 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW96943.1.
CCDSiCCDS8921.1. [Q9UI32-1]
RefSeqiNP_001267727.1. NM_001280798.1.
NP_037399.2. NM_013267.3. [Q9UI32-1]
UniGeneiHs.212606.

Genome annotation databases

EnsembliENST00000311966; ENSP00000310447; ENSG00000135423. [Q9UI32-1]
ENST00000486896; ENSP00000419661; ENSG00000135423. [Q9UI32-2]
GeneIDi27165.
KEGGihsa:27165.
UCSCiuc001slj.5. human. [Q9UI32-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF110330 mRNA. Translation: AAF21933.1.
AF110331 mRNA. Translation: AAF21934.1.
AF348119 Genomic DNA. Translation: AAO13298.2.
AF223944 mRNA. Translation: AAF33826.1.
AK303772 mRNA. Translation: BAH14045.1.
AC097104 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW96943.1.
CCDSiCCDS8921.1. [Q9UI32-1]
RefSeqiNP_001267727.1. NM_001280798.1.
NP_037399.2. NM_013267.3. [Q9UI32-1]
UniGeneiHs.212606.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4BQMX-ray2.18A/B154-479[»]
ProteinModelPortaliQ9UI32.
SMRiQ9UI32.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118044. 3 interactors.
IntActiQ9UI32. 2 interactors.
MINTiMINT-157952.
STRINGi9606.ENSP00000310447.

Chemistry databases

DrugBankiDB00130. L-Glutamine.

PTM databases

iPTMnetiQ9UI32.
PhosphoSitePlusiQ9UI32.

Polymorphism and mutation databases

BioMutaiGLS2.
DMDMi145559477.

Proteomic databases

EPDiQ9UI32.
PaxDbiQ9UI32.
PeptideAtlasiQ9UI32.
PRIDEiQ9UI32.

Protocols and materials databases

DNASUi27165.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000311966; ENSP00000310447; ENSG00000135423. [Q9UI32-1]
ENST00000486896; ENSP00000419661; ENSG00000135423. [Q9UI32-2]
GeneIDi27165.
KEGGihsa:27165.
UCSCiuc001slj.5. human. [Q9UI32-1]

Organism-specific databases

CTDi27165.
DisGeNETi27165.
GeneCardsiGLS2.
HGNCiHGNC:29570. GLS2.
HPAiHPA038608.
MIMi606365. gene.
neXtProtiNX_Q9UI32.
OpenTargetsiENSG00000135423.
PharmGKBiPA134933506.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0506. Eukaryota.
COG2066. LUCA.
GeneTreeiENSGT00390000010463.
HOGENOMiHOG000012985.
HOVERGENiHBG005856.
InParanoidiQ9UI32.
KOiK01425.
OMAiCVKPLTY.
OrthoDBiEOG091G03YU.
PhylomeDBiQ9UI32.
TreeFamiTF313359.

Enzyme and pathway databases

BioCyciZFISH:HS06001-MONOMER.
ReactomeiR-HSA-210500. Glutamate Neurotransmitter Release Cycle.
R-HSA-5628897. TP53 Regulates Metabolic Genes.
R-HSA-70614. Amino acid synthesis and interconversion (transamination).
SABIO-RKQ9UI32.

Miscellaneous databases

ChiTaRSiGLS2. human.
GenomeRNAii27165.
PROiQ9UI32.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000135423.
CleanExiHS_GLS2.
ExpressionAtlasiQ9UI32. baseline and differential.
GenevisibleiQ9UI32. HS.

Family and domain databases

Gene3Di1.25.40.20. 1 hit.
3.40.710.10. 1 hit.
HAMAPiMF_00313. Glutaminase. 1 hit.
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]
ProtoNetiSearch...

Entry informationi

Entry nameiGLSL_HUMAN
AccessioniPrimary (citable) accession number: Q9UI32
Secondary accession number(s): B7Z8Q9
, Q8IX91, Q9NYY2, Q9UI31
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: April 17, 2007
Last modified: November 30, 2016
This is version 155 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.