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Protein

Glutaminase liver isoform, mitochondrial

Gene

GLS2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

  • glutaminase activity Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionHydrolase

Enzyme and pathway databases

ReactomeiR-HSA-210500 Glutamate Neurotransmitter Release Cycle
R-HSA-5628897 TP53 Regulates Metabolic Genes
R-HSA-70614 Amino acid synthesis and interconversion (transamination)
SABIO-RKiQ9UI32

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

EuPathDBiHostDB:ENSG00000135423.12
HGNCiHGNC:29570 GLS2
MIMi606365 gene
neXtProtiNX_Q9UI32

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Organism-specific databases

DisGeNETi27165
OpenTargetsiENSG00000135423
PharmGKBiPA134933506

Chemistry databases

DrugBankiDB00142 L-Glutamic Acid
DB00130 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
ProteomicsDBi84460

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 Expressed in 166 organ(s), highest expression level in liver
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, 3 interactors
STRINGi9606.ENSP00000310447

Structurei

Secondary structure

1602
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Keywords - Domaini

ANK repeat, Repeat, Transit peptide

Phylogenomic databases

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

Family and domain databases

CDDicd00204 ANK, 1 hit
Gene3Di1.25.40.20, 1 hit
HAMAPiMF_00313 Glutaminase, 1 hit
InterProiView protein in InterPro
IPR002110 Ankyrin_rpt
IPR020683 Ankyrin_rpt-contain_dom
IPR036770 Ankyrin_rpt-contain_sf
IPR012338 Beta-lactam/transpept-like
IPR015868 Glutaminase
PANTHERiPTHR12544 PTHR12544, 1 hit
PfamiView protein in Pfam
PF12796 Ank_2, 1 hit
PF04960 Glutaminase, 1 hit
SMARTiView protein in SMART
SM00248 ANK, 2 hits
SUPFAMiSSF48403 SSF48403, 1 hit
SSF56601 SSF56601, 1 hit
TIGRFAMsiTIGR03814 Gln_ase, 1 hit
PROSITEiView protein in PROSITE
PS50297 ANK_REP_REGION, 1 hit
PS50088 ANK_REPEAT, 1 hit

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

This entry has 2 described isoforms and 8 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A087X004A0A087X004_HUMAN
Glutaminase 2 (Liver, mitochondrial...
GLS2 hCG_24976
337Annotation score:
E5G745E5G745_HUMAN
Glutaminase liver isoform, mitochon...
GLS2
280Annotation score:
G5E9X4G5E9X4_HUMAN
Glutaminase 2 (Liver, mitochondrial...
GLS2 hCG_24976
327Annotation score:
C9J3Q2C9J3Q2_HUMAN
Glutaminase liver isoform, mitochon...
GLS2
184Annotation score:
A8K0A6A8K0A6_HUMAN
Glutaminase liver isoform, mitochon...
GLS2
177Annotation score:
F8WBC9F8WBC9_HUMAN
Glutaminase liver isoform, mitochon...
GLS2
62Annotation score:
F8WBL8F8WBL8_HUMAN
Glutaminase liver isoform, mitochon...
GLS2
157Annotation score:
F8WEU7F8WEU7_HUMAN
Glutaminase liver isoform, mitochon...
GLS2
103Annotation score:

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 → P1 PublicationCorresponds to variant dbSNP:rs2657879Ensembl.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

Similar proteinsi

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[»]
5U0KX-ray2.55A/B/C/D/E/F/G/H/I/J485-602[»]
ProteinModelPortaliQ9UI32
SMRiQ9UI32
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118044, 3 interactors
IntActiQ9UI32, 3 interactors
STRINGi9606.ENSP00000310447

Chemistry databases

DrugBankiDB00142 L-Glutamic Acid
DB00130 L-Glutamine

PTM databases

iPTMnetiQ9UI32
PhosphoSitePlusiQ9UI32

Polymorphism and mutation databases

BioMutaiGLS2
DMDMi145559477

Proteomic databases

EPDiQ9UI32
PaxDbiQ9UI32
PeptideAtlasiQ9UI32
PRIDEiQ9UI32
ProteomicsDBi84460

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
EuPathDBiHostDB:ENSG00000135423.12
GeneCardsiGLS2
HGNCiHGNC:29570 GLS2
HPAiHPA038608
MIMi606365 gene
neXtProtiNX_Q9UI32
OpenTargetsiENSG00000135423
PharmGKBiPA134933506
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiR-HSA-210500 Glutamate Neurotransmitter Release Cycle
R-HSA-5628897 TP53 Regulates Metabolic Genes
R-HSA-70614 Amino acid synthesis and interconversion (transamination)
SABIO-RKiQ9UI32

Miscellaneous databases

ChiTaRSiGLS2 human
GenomeRNAii27165
PROiPR:Q9UI32
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000135423 Expressed in 166 organ(s), highest expression level in liver
CleanExiHS_GLS2
ExpressionAtlasiQ9UI32 baseline and differential
GenevisibleiQ9UI32 HS

Family and domain databases

CDDicd00204 ANK, 1 hit
Gene3Di1.25.40.20, 1 hit
HAMAPiMF_00313 Glutaminase, 1 hit
InterProiView protein in InterPro
IPR002110 Ankyrin_rpt
IPR020683 Ankyrin_rpt-contain_dom
IPR036770 Ankyrin_rpt-contain_sf
IPR012338 Beta-lactam/transpept-like
IPR015868 Glutaminase
PANTHERiPTHR12544 PTHR12544, 1 hit
PfamiView protein in Pfam
PF12796 Ank_2, 1 hit
PF04960 Glutaminase, 1 hit
SMARTiView protein in SMART
SM00248 ANK, 2 hits
SUPFAMiSSF48403 SSF48403, 1 hit
SSF56601 SSF56601, 1 hit
TIGRFAMsiTIGR03814 Gln_ase, 1 hit
PROSITEiView protein in PROSITE
PS50297 ANK_REP_REGION, 1 hit
PS50088 ANK_REPEAT, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiGLSL_HUMAN
AccessioniPrimary (citable) accession number: Q9UI32
Secondary accession number(s): B7Z8Q9
, Q8IX91, Q9NYY2, Q9UI31
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: April 17, 2007
Last modified: November 7, 2018
This is version 170 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
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