Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Glutaredoxin-related protein 5, mitochondrial

Gene

GLRX5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
Complete GO annotation...

Keywords - Ligandi

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

Enzyme and pathway databases

BioCyciZFISH:G66-31781-MONOMER.

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

HGNCiHGNC:20134. GLRX5.

Subcellular locationi

GO - Cellular componenti

  • dendrite Source: Ensembl
  • mitochondrial matrix Source: UniProtKB
  • mitochondrion Source: UniProtKB
  • neuronal cell body Source: Ensembl
  • nucleus Source: Ensembl
Complete GO annotation...

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 Publications1
Natural variantiVAR_074551148L → S in SIDBA3; deficiency in Fe-S cluster synthesis; does not impair ISCU binding. 2 PublicationsCorresponds to variant rs765487627dbSNPEnsembl.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. Spasticity-ataxia-gait anomalies syndrome.
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.
TopDownProteomicsiQ86SX6.

PTM databases

iPTMnetiQ86SX6.
PhosphoSitePlusiQ86SX6.

Expressioni

Gene expression databases

BgeeiENSG00000182512.
CleanExiHS_GLRX5.
ExpressionAtlasiQ86SX6. baseline and differential.
GenevisibleiQ86SX6. HS.

Organism-specific databases

HPAiHPA042465.
HPA063716.

Interactioni

Subunit structurei

Homodimer (PubMed:21029046). Interacts with ISCU (PubMed:26100117).1 Publication1 Publication

Protein-protein interaction databases

BioGridi119386. 22 interactors.
IntActiQ86SX6. 2 interactors.
STRINGi9606.ENSP00000328570.

Structurei

Secondary structure

1157
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi42 – 51Combined sources10
Beta strandi52 – 60Combined sources9
Beta strandi62 – 67Combined sources6
Helixi68 – 79Combined sources12
Beta strandi86 – 89Combined sources4
Helixi94 – 104Combined sources11
Beta strandi111 – 114Combined sources4
Beta strandi117 – 120Combined sources4
Helixi122 – 131Combined sources10
Helixi133 – 140Combined sources8
Turni146 – 148Combined sources3

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...

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 binding5
Regioni122 – 123Glutathione binding2

Compositional bias

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

Sequence similaritiesi

Contains 1 glutaredoxin domain.PROSITE-ProRule annotation

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.
Gene3Di3.40.30.10. 1 hit.
InterProiIPR002109. Glutaredoxin.
IPR033658. GRX_PICOT-like.
IPR004480. Monothiol_GRX-rel.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PANTHERiPTHR10293. PTHR10293. 1 hit.
PfamiPF00462. Glutaredoxin. 1 hit.
[Graphical view]
SUPFAMiSSF52833. SSF52833. 1 hit.
TIGRFAMsiTIGR00365. TIGR00365. 1 hit.
PROSITEiPS51354. GLUTAREDOXIN_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

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

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 Publications1
Natural variantiVAR_026125146A → T.2 PublicationsCorresponds to variant rs11628901dbSNPEnsembl.1
Natural variantiVAR_074551148L → S in SIDBA3; deficiency in Fe-S cluster synthesis; does not impair ISCU binding. 2 PublicationsCorresponds to variant rs765487627dbSNPEnsembl.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

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.
IntActiQ86SX6. 2 interactors.
STRINGi9606.ENSP00000328570.

PTM databases

iPTMnetiQ86SX6.
PhosphoSitePlusiQ86SX6.

Polymorphism and mutation databases

BioMutaiGLRX5.
DMDMi83288163.

Proteomic databases

EPDiQ86SX6.
MaxQBiQ86SX6.
PaxDbiQ86SX6.
PeptideAtlasiQ86SX6.
PRIDEiQ86SX6.
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.
GeneCardsiGLRX5.
HGNCiHGNC:20134. GLRX5.
HPAiHPA042465.
HPA063716.
MalaCardsiGLRX5.
MIMi609588. gene.
616859. phenotype.
616860. phenotype.
neXtProtiNX_Q86SX6.
OpenTargetsiENSG00000182512.
Orphaneti255132. Adult-onset autosomal recessive sideroblastic anemia.
401866. Spasticity-ataxia-gait anomalies syndrome.
PharmGKBiPA134992547.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:G66-31781-MONOMER.

Miscellaneous databases

EvolutionaryTraceiQ86SX6.
GeneWikiiGLRX5.
GenomeRNAii51218.
PROiQ86SX6.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000182512.
CleanExiHS_GLRX5.
ExpressionAtlasiQ86SX6. baseline and differential.
GenevisibleiQ86SX6. HS.

Family and domain databases

CDDicd03028. GRX_PICOT_like. 1 hit.
Gene3Di3.40.30.10. 1 hit.
InterProiIPR002109. Glutaredoxin.
IPR033658. GRX_PICOT-like.
IPR004480. Monothiol_GRX-rel.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PANTHERiPTHR10293. PTHR10293. 1 hit.
PfamiPF00462. Glutaredoxin. 1 hit.
[Graphical view]
SUPFAMiSSF52833. SSF52833. 1 hit.
TIGRFAMsiTIGR00365. TIGR00365. 1 hit.
PROSITEiPS51354. GLUTAREDOXIN_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGLRX5_HUMAN
AccessioniPrimary (citable) accession number: Q86SX6
Secondary accession number(s): Q0X088
, Q3YML0, Q86WY3, Q8IZ54
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 2005
Last sequence update: February 1, 2005
Last modified: November 30, 2016
This is version 123 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 14
    Human chromosome 14: 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.