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Protein

Glutaredoxin-related protein 5, mitochondrial

Gene

GLRX5

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

Functioni

Monothiol glutaredoxin involved in the biogenesis of iron-sulfur clusters (PubMed:20364084). Involved in protein lipoylation, acting in the pathway that provides an iron-sulfur cluster to lipoate synthase (PubMed:24334290). Required for normal iron homeostasis. Required for normal regulation of hemoglobin synthesis by the iron-sulfur protein ACO1 (PubMed:20364084). May protect cells against apoptosis due to reactive oxygen species and oxidative stress (By similarity).By similarity2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei59Glutathione1 Publication1
Metal bindingi67Iron-sulfur (2Fe-2S); shared with dimeric partner1
Binding sitei109Glutathione; via amide nitrogen and carbonyl oxygen1 Publication1

GO - Molecular functioni

GO - Biological processi

  • cell redox homeostasis Source: InterPro
  • hemopoiesis Source: UniProtKB
  • protein lipoylation Source: UniProtKB
  • small molecule metabolic process Source: Reactome

Keywordsi

Ligand2Fe-2S, Iron, Iron-sulfur, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-1362409 Mitochondrial iron-sulfur cluster biogenesis

Names & Taxonomyi

Protein namesi
Recommended name:
Glutaredoxin-related protein 5, mitochondrial
Alternative name(s):
Monothiol glutaredoxin-5
Gene namesi
Name:GLRX5
Synonyms:C14orf87
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000182512.4
HGNCiHGNC:20134 GLRX5
MIMi609588 gene
neXtProtiNX_Q86SX6

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

Involvement in diseasei

Anemia, sideroblastic, 3, pyridoxine-refractory (SIDBA3)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of sideroblastic anemia, a bone marrow disorder defined by the presence of pathologic iron deposits in erythroblast mitochondria. Sideroblastic anemia is characterized by anemia of varying severity, hypochromic peripheral erythrocytes, systemic iron overload secondary to chronic ineffective erythropoiesis, and the presence of bone marrow ringed sideroblasts. Sideroblasts are characterized by iron-loaded mitochondria clustered around the nucleus. SIDBA3 is refractory to treatment with vitamin B6, while iron chelation therapy may result in clinical improvement. SIDBA3 inheritance is autosomal recessive.
See also OMIM:616860
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_074550101K → Q in SIDBA3; deficiency in Fe-S cluster synthesis; does not impair ISCU binding. 2 PublicationsCorresponds to variant dbSNP:rs869312752EnsemblClinVar.1
Natural variantiVAR_074551148L → S in SIDBA3; deficiency in Fe-S cluster synthesis; does not impair ISCU binding. 2 PublicationsCorresponds to variant dbSNP:rs765487627EnsemblClinVar.1
Spasticity, childhood-onset, with hyperglycinemia (SPAHGC)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive disorder characterized by childhood-onset of spasticity, spinal lesions, leukodystrophy, optic atrophy in some patients, non-ketotic hyperglycinemia, and defective enzymatic glycine cleavage. Glycine levels in the cerebrospinal fluid are mildly increased in some but not all patients. The increase is less pronounced than in patients with classic non-ketotic hyperglycinemia.
See also OMIM:616859
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07667251Missing in SPAHGC; no effect on protein abundance in patient cells; probably reduced activity in iron-sulfur cluster assembly that results in reduced production of the lipoate cofactor and protein lipoylation. Curated1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi51218
MalaCardsiGLRX5
MIMi616859 phenotype
616860 phenotype
OpenTargetsiENSG00000182512
Orphaneti255132 Adult-onset autosomal recessive sideroblastic anemia
401866 Childhood-onset spasticity with hyperglycinemia
PharmGKBiPA134992547

Polymorphism and mutation databases

BioMutaiGLRX5
DMDMi83288163

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 31MitochondrionSequence analysisCombined sourcesAdd BLAST31
ChainiPRO_000014165032 – 157Glutaredoxin-related protein 5, mitochondrialAdd BLAST126

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei59N6-succinyllysineBy similarity1
Modified residuei156PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ86SX6
MaxQBiQ86SX6
PaxDbiQ86SX6
PeptideAtlasiQ86SX6
PRIDEiQ86SX6
ProteomicsDBi69646
TopDownProteomicsiQ86SX6

PTM databases

iPTMnetiQ86SX6
PhosphoSitePlusiQ86SX6

Expressioni

Gene expression databases

BgeeiENSG00000182512 Expressed in 228 organ(s), highest expression level in trabecular bone tissue
CleanExiHS_GLRX5
ExpressionAtlasiQ86SX6 baseline and differential
GenevisibleiQ86SX6 HS

Organism-specific databases

HPAiHPA042465
HPA063716

Interactioni

Subunit structurei

Homodimer (PubMed:21029046). Interacts with ISCU (PubMed:26100117). Interacts with BOLA1 (PubMed:27532773, PubMed:27532772).1 Publication3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
HSCBQ8IWL33EBI-1049910,EBI-1805738

Protein-protein interaction databases

BioGridi119386, 22 interactors
DIPiDIP-50654N
IntActiQ86SX6, 13 interactors
STRINGi9606.ENSP00000328570

Structurei

Secondary structure

1157
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ86SX6
SMRiQ86SX6
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ86SX6

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini42 – 145GlutaredoxinPROSITE-ProRule annotationAdd BLAST104

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni97 – 101Glutathione binding1 Publication5
Regioni122 – 123Glutathione binding1 Publication2

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi8 – 11Poly-Ala4
Compositional biasi16 – 23Poly-Gly8
Compositional biasi33 – 40Poly-Gly8

Sequence similaritiesi

Keywords - Domaini

Redox-active center, Transit peptide

Phylogenomic databases

eggNOGiKOG0911 Eukaryota
COG0278 LUCA
GeneTreeiENSGT00550000075082
HOGENOMiHOG000095211
HOVERGENiHBG051012
InParanoidiQ86SX6
KOiK07390
OMAiVDKATMD
OrthoDBiEOG091G0YN0
PhylomeDBiQ86SX6
TreeFamiTF318988

Family and domain databases

CDDicd03028 GRX_PICOT_like, 1 hit
InterProiView protein in InterPro
IPR002109 Glutaredoxin
IPR033658 GRX_PICOT-like
IPR014434 Monothiol_GRX
IPR004480 Monothiol_GRX-rel
IPR036249 Thioredoxin-like_sf
PANTHERiPTHR10293 PTHR10293, 1 hit
PfamiView protein in Pfam
PF00462 Glutaredoxin, 1 hit
PIRSFiPIRSF005894 Monothiol_GRX, 1 hit
SUPFAMiSSF52833 SSF52833, 1 hit
TIGRFAMsiTIGR00365 TIGR00365, 1 hit
PROSITEiView protein in PROSITE
PS51354 GLUTAREDOXIN_2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

Q86SX6-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSGSLGRAAA ALLRWGRGAG GGGLWGPGVR AAGSGAGGGG SAEQLDALVK
60 70 80 90 100
KDKVVVFLKG TPEQPQCGFS NAVVQILRLH GVRDYAAYNV LDDPELRQGI
110 120 130 140 150
KDYSNWPTIP QVYLNGEFVG GCDILLQMHQ NGDLVEELKK LGIHSALLDE

KKDQDSK
Length:157
Mass (Da):16,628
Last modified:February 1, 2005 - v2
Checksum:i5E6873BD5DE91F86
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YJM6H0YJM6_HUMAN
Glutaredoxin-related protein 5, mit...
GLRX5
137Annotation score:

Sequence cautioni

The sequence CAD62364 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07667251Missing in SPAHGC; no effect on protein abundance in patient cells; probably reduced activity in iron-sulfur cluster assembly that results in reduced production of the lipoate cofactor and protein lipoylation. Curated1 Publication1
Natural variantiVAR_074550101K → Q in SIDBA3; deficiency in Fe-S cluster synthesis; does not impair ISCU binding. 2 PublicationsCorresponds to variant dbSNP:rs869312752EnsemblClinVar.1
Natural variantiVAR_026125146A → T2 PublicationsCorresponds to variant dbSNP:rs11628901EnsemblClinVar.1
Natural variantiVAR_074551148L → S in SIDBA3; deficiency in Fe-S cluster synthesis; does not impair ISCU binding. 2 PublicationsCorresponds to variant dbSNP:rs765487627EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ083331 mRNA Translation: AAZ30731.1
BX248075 mRNA Translation: CAD62364.1 Different initiation.
AB223038 mRNA Translation: BAF02301.1
CH471061 Genomic DNA Translation: EAW81607.1
BC023528 mRNA Translation: AAH23528.2
BC047680 mRNA Translation: AAH47680.1
CCDSiCCDS9936.1
RefSeqiNP_057501.2, NM_016417.2
UniGeneiHs.744943

Genome annotation databases

EnsembliENST00000331334; ENSP00000328570; ENSG00000182512
GeneIDi51218
KEGGihsa:51218
UCSCiuc001yem.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ083331 mRNA Translation: AAZ30731.1
BX248075 mRNA Translation: CAD62364.1 Different initiation.
AB223038 mRNA Translation: BAF02301.1
CH471061 Genomic DNA Translation: EAW81607.1
BC023528 mRNA Translation: AAH23528.2
BC047680 mRNA Translation: AAH47680.1
CCDSiCCDS9936.1
RefSeqiNP_057501.2, NM_016417.2
UniGeneiHs.744943

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2MMZNMR-A35-150[»]
2WULX-ray2.40A/B/C/D35-150[»]
ProteinModelPortaliQ86SX6
SMRiQ86SX6
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119386, 22 interactors
DIPiDIP-50654N
IntActiQ86SX6, 13 interactors
STRINGi9606.ENSP00000328570

PTM databases

iPTMnetiQ86SX6
PhosphoSitePlusiQ86SX6

Polymorphism and mutation databases

BioMutaiGLRX5
DMDMi83288163

Proteomic databases

EPDiQ86SX6
MaxQBiQ86SX6
PaxDbiQ86SX6
PeptideAtlasiQ86SX6
PRIDEiQ86SX6
ProteomicsDBi69646
TopDownProteomicsiQ86SX6

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000331334; ENSP00000328570; ENSG00000182512
GeneIDi51218
KEGGihsa:51218
UCSCiuc001yem.2 human

Organism-specific databases

CTDi51218
DisGeNETi51218
EuPathDBiHostDB:ENSG00000182512.4
GeneCardsiGLRX5
HGNCiHGNC:20134 GLRX5
HPAiHPA042465
HPA063716
MalaCardsiGLRX5
MIMi609588 gene
616859 phenotype
616860 phenotype
neXtProtiNX_Q86SX6
OpenTargetsiENSG00000182512
Orphaneti255132 Adult-onset autosomal recessive sideroblastic anemia
401866 Childhood-onset spasticity with hyperglycinemia
PharmGKBiPA134992547
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0911 Eukaryota
COG0278 LUCA
GeneTreeiENSGT00550000075082
HOGENOMiHOG000095211
HOVERGENiHBG051012
InParanoidiQ86SX6
KOiK07390
OMAiVDKATMD
OrthoDBiEOG091G0YN0
PhylomeDBiQ86SX6
TreeFamiTF318988

Enzyme and pathway databases

ReactomeiR-HSA-1362409 Mitochondrial iron-sulfur cluster biogenesis

Miscellaneous databases

EvolutionaryTraceiQ86SX6
GeneWikiiGLRX5
GenomeRNAii51218
PROiPR:Q86SX6
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000182512 Expressed in 228 organ(s), highest expression level in trabecular bone tissue
CleanExiHS_GLRX5
ExpressionAtlasiQ86SX6 baseline and differential
GenevisibleiQ86SX6 HS

Family and domain databases

CDDicd03028 GRX_PICOT_like, 1 hit
InterProiView protein in InterPro
IPR002109 Glutaredoxin
IPR033658 GRX_PICOT-like
IPR014434 Monothiol_GRX
IPR004480 Monothiol_GRX-rel
IPR036249 Thioredoxin-like_sf
PANTHERiPTHR10293 PTHR10293, 1 hit
PfamiView protein in Pfam
PF00462 Glutaredoxin, 1 hit
PIRSFiPIRSF005894 Monothiol_GRX, 1 hit
SUPFAMiSSF52833 SSF52833, 1 hit
TIGRFAMsiTIGR00365 TIGR00365, 1 hit
PROSITEiView protein in PROSITE
PS51354 GLUTAREDOXIN_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiGLRX5_HUMAN
AccessioniPrimary (citable) accession number: Q86SX6
Secondary accession number(s): Q0X088
, Q3YML0, Q86WY3, Q8IZ54
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 2005
Last sequence update: February 1, 2005
Last modified: November 7, 2018
This is version 138 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 14
    Human chromosome 14: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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