This gene encodes a member of the glutaredoxin family. Glutaredoxins are oxidoreductase enzymes that reduce a variety of substrates using glutathione as a cofactor. The encoded protein binds to and modulates the function of protein kinase C theta. The encoded protein may also inhibit apoptosis and play a role in cellular growth, and the expression of this gene may be a marker f... See more...

Aliases for GLRX3 Gene

Aliases for GLRX3 Gene

  • Glutaredoxin 3 2 3 5
  • PKC-Interacting Cousin Of Thioredoxin 3 4
  • PKC-Theta-Interacting Protein 3 4
  • Thioredoxin-Like Protein 2 3 4
  • PKCq-Interacting Protein 3 4
  • Glutaredoxin-3 3 4
  • Glutaredoxin 4 2 3
  • TXNL2 3 4
  • PICOT 3 4
  • Testicular Tissue Protein Li 75 3
  • Thioredoxin-Like 2 2
  • GLRX4 3
  • TXNL3 3
  • GRX3 3
  • GRX4 3

External Ids for GLRX3 Gene

Previous HGNC Symbols for GLRX3 Gene

  • TXNL2

Previous GeneCards Identifiers for GLRX3 Gene

  • GC10P131826
  • GC10P131934
  • GC10P125514

Summaries for GLRX3 Gene

Entrez Gene Summary for GLRX3 Gene

  • This gene encodes a member of the glutaredoxin family. Glutaredoxins are oxidoreductase enzymes that reduce a variety of substrates using glutathione as a cofactor. The encoded protein binds to and modulates the function of protein kinase C theta. The encoded protein may also inhibit apoptosis and play a role in cellular growth, and the expression of this gene may be a marker for cancer. Pseudogenes of this gene are located on the short arm of chromosomes 6 and 9. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2010]

GeneCards Summary for GLRX3 Gene

GLRX3 (Glutaredoxin 3) is a Protein Coding gene. Diseases associated with GLRX3 include Multiple Mitochondrial Dysfunctions Syndrome 2 With Hyperglycinemia and Aceruloplasminemia. Gene Ontology (GO) annotations related to this gene include protein kinase C binding. An important paralog of this gene is GLRX5.

UniProtKB/Swiss-Prot Summary for GLRX3 Gene

  • Together with BOLA2, acts as a cytosolic iron-sulfur (Fe-S) cluster assembly factor that facilitates [2Fe-2S] cluster insertion into a subset of cytosolic proteins (PubMed:26613676, PubMed:27519415). Acts as a critical negative regulator of cardiac hypertrophy and a positive inotropic regulator (By similarity). Required for hemoglobin maturation (PubMed:23615448). Does not possess any thyoredoxin activity since it lacks the conserved motif that is essential for catalytic activity.

Gene Wiki entry for GLRX3 Gene

Additional gene information for GLRX3 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GLRX3 Gene

Genomics for GLRX3 Gene

GeneHancer (GH) Regulatory Elements for GLRX3 Gene

Promoters and enhancers for GLRX3 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH10J130108 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas 510.8 -25.6 -25629 3.7 FOXK2 ZBTB40 ZNF217 EP300 CTCF ZSCAN5C SIN3A TCF12 NRF1 POLR2G C10orf143 GLRX3 LOC102724883 CTAGE7P lnc-GLRX3-2
GH10J130135 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas 506.9 +0.8 810 4.4 HNRNPK ZNF217 EP300 SIN3A TCF12 NRF1 USF1 POLR2G SP1 PHF8 GLRX3 lnc-C10orf143-11 PPIAP32 lnc-GLRX3-2 lnc-GLRX3-1
GH10J130171 Enhancer 1 Ensembl ENCODE 17.3 +34.0 34026 2.8 EP300 ZNF639 ZIC2 TRIM28 ATF2 OSR2 ZBTB17 TCF7L2 ZNF76 ZBTB1 GLRX3 PPIAP32 lnc-GLRX3-1
GH10J130158 Enhancer 0.8 UCNEbase Ensembl 18.1 +21.9 21926 3.4 ZSCAN5C BATF PKNOX1 VEZF1 JUNB GLRX3 PPIAP32 lnc-GLRX3-1
GH10J130105 Promoter/Enhancer 0.9 Ensembl ENCODE CraniofacialAtlas 13 -30.5 -30506 0.7 CHD1 JUND EP300 TBP PRDM10 CTAGE7P ENSG00000277218 PPIAP32 GLRX3 C10orf143 lnc-GLRX3-2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GLRX3 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for GLRX3

Top Transcription factor binding sites by QIAGEN in the GLRX3 gene promoter:
  • AhR
  • Arnt
  • Nkx2-5
  • NRSF form 1
  • NRSF form 2
  • POU6F1 (c2)
  • SRF
  • SRF (504 AA)
  • ZIC2

Genomic Locations for GLRX3 Gene

Genomic Locations for GLRX3 Gene
chr10:130,136,375-130,184,521
(GRCh38/hg38)
Size:
48,147 bases
Orientation:
Plus strand
chr10:131,934,639-131,982,785
(GRCh37/hg19)
Size:
48,147 bases
Orientation:
Plus strand

Genomic View for GLRX3 Gene

Genes around GLRX3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GLRX3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GLRX3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GLRX3 Gene

Proteins for GLRX3 Gene

  • Protein details for GLRX3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O76003-GLRX3_HUMAN
    Recommended name:
    Glutaredoxin-3
    Protein Accession:
    O76003
    Secondary Accessions:
    • B3KMP7
    • B3KMQ5
    • D3DRG2
    • Q5JV01
    • Q96CE0
    • Q9P1B0
    • Q9P1B1

    Protein attributes for GLRX3 Gene

    Size:
    335 amino acids
    Molecular mass:
    37432 Da
    Quaternary structure:
    • Homodimer; the homodimer is independent of 2Fe-2S clusters (PubMed:27519415). Heterotrimer; forms a heterotrimeric complex composed by two BOLA2 molecules and one GLRX3 molecule; linked by [2Fe-2S] clusters (PubMed:22309771, PubMed:26613676, PubMed:27519415). Interacts (via N-terminus) with PRKCQ/PKC-theta (PubMed:10636891). Interacts (via C-terminus) with CSRP3 (By similarity). Interacts with CSRP2 (By similarity).
    Miscellaneous:
    • Silencing of Grx3 in HeLa cells decreases the activities of several cytosolic Fe/S proteins, such as ACO1, a major component of post-transcriptional iron regulation. As a consequence, Grx3-depleted cells show decreased levels of ferritin and increased levels of transferrin receptor, features characteristic of cellular iron starvation (PubMed:23615448).

    Three dimensional structures from OCA and Proteopedia for GLRX3 Gene

neXtProt entry for GLRX3 Gene

Post-translational modifications for GLRX3 Gene

  • Ubiquitination at Lys240
  • Modification sites at PhosphoSitePlus

Other Protein References for GLRX3 Gene

No data available for DME Specific Peptides for GLRX3 Gene

Domains & Families for GLRX3 Gene

Gene Families for GLRX3 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for GLRX3 Gene

Blocks:
  • Thioredoxin type domain
  • Glutaredoxin
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for GLRX3 Gene

GenScript: Design optimal peptide antigens:
  • Thioredoxin-like protein 2 (GLRX3_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O76003

UniProtKB/Swiss-Prot:

GLRX3_HUMAN :
  • The thioredoxin domain lacks the two redox-active cysteines. This strongly suggests that it lacks thioredoxin activity.
Domain:
  • The thioredoxin domain lacks the two redox-active cysteines. This strongly suggests that it lacks thioredoxin activity.
genes like me logo Genes that share domains with GLRX3: view

Function for GLRX3 Gene

Molecular function for GLRX3 Gene

UniProtKB/Swiss-Prot Function:
Together with BOLA2, acts as a cytosolic iron-sulfur (Fe-S) cluster assembly factor that facilitates [2Fe-2S] cluster insertion into a subset of cytosolic proteins (PubMed:26613676, PubMed:27519415). Acts as a critical negative regulator of cardiac hypertrophy and a positive inotropic regulator (By similarity). Required for hemoglobin maturation (PubMed:23615448). Does not possess any thyoredoxin activity since it lacks the conserved motif that is essential for catalytic activity.

Phenotypes From GWAS Catalog for GLRX3 Gene

Gene Ontology (GO) - Molecular Function for GLRX3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003723 RNA binding HDA 22658674
GO:0005080 protein kinase C binding IEA --
GO:0005515 protein binding IPI 10636891
GO:0009055 electron transfer activity IEA --
GO:0015035 protein disulfide oxidoreductase activity IEA --
genes like me logo Genes that share ontologies with GLRX3: view
genes like me logo Genes that share phenotypes with GLRX3: view

Animal Models for GLRX3 Gene

MGI Knock Outs for GLRX3:
  • Glrx3 Glrx3<tm1.1(KOMP)Vlcg>

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GLRX3

Clone Products

  • Addgene plasmids for GLRX3

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for GLRX3 Gene

Localization for GLRX3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for GLRX3 Gene

Cytoplasm, cytosol. Cytoplasm, cell cortex. Cytoplasm, myofibril, sarcomere, Z line. Note=Under the plasma membrane (By similarity). After PMA stimulation, GLRX3 and PRKCQ/PKC-theta translocate to a more extended submembrane area (By similarity). In the Z line, found associated with CSRP3 (By similarity). {ECO:0000250 UniProtKB:Q9CQM9}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for GLRX3 gene
Compartment Confidence
cytosol 5
nucleus 4
mitochondrion 3
plasma membrane 2
endoplasmic reticulum 2
extracellular 1
cytoskeleton 1
peroxisome 1
endosome 1
lysosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for GLRX3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005623 cell IEA --
GO:0005634 nucleus IBA 21873635
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol IBA 21873635
GO:0005938 cell cortex IEA --
genes like me logo Genes that share ontologies with GLRX3: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for GLRX3 Gene

Pathways & Interactions for GLRX3 Gene

PathCards logo

SuperPathways for GLRX3 Gene

No Data Available

Gene Ontology (GO) - Biological Process for GLRX3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002026 regulation of the force of heart contraction ISS 18258855
GO:0006879 cellular iron ion homeostasis IBA 21873635
GO:0010614 negative regulation of cardiac muscle hypertrophy ISS --
GO:0022900 electron transport chain IEA --
GO:0044571 [2Fe-2S] cluster assembly IDA 27519415
genes like me logo Genes that share ontologies with GLRX3: view

No data available for Pathways by source and SIGNOR curated interactions for GLRX3 Gene

Drugs & Compounds for GLRX3 Gene

(1) Drugs for GLRX3 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(2) Additional Compounds for GLRX3 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with GLRX3: view

Transcripts for GLRX3 Gene

mRNA/cDNA for GLRX3 Gene

3 REFSEQ mRNAs :
11 NCBI additional mRNA sequence :
6 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GLRX3

Clone Products

  • Addgene plasmids for GLRX3

Alternative Splicing Database (ASD) splice patterns (SP) for GLRX3 Gene

ExUns: 1a · 1b ^ 2 ^ 3a · 3b · 3c ^ 4 ^ 5a · 5b ^ 6a · 6b ^ 7 ^ 8a · 8b ^ 9 ^ 10 ^ 11 ^ 12 ^ 13
SP1: - -
SP2:
SP3: - - -
SP4: -
SP5:

Relevant External Links for GLRX3 Gene

GeneLoc Exon Structure for
GLRX3

Expression for GLRX3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for GLRX3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for GLRX3 Gene



Protein tissue co-expression partners for GLRX3 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for GLRX3

SOURCE GeneReport for Unigene cluster for GLRX3 Gene:

Hs.42644

mRNA Expression by UniProt/SwissProt for GLRX3 Gene:

O76003-GLRX3_HUMAN
Tissue specificity: Expressed in heart, spleen, testis and, to a lower extent, in thymus and peripheral blood leukocytes. Weakly expressed in lung, placenta, colon and small intestine.

Evidence on tissue expression from TISSUES for GLRX3 Gene

  • Liver(4.3)
  • Skin(4.3)
  • Spleen(4.3)
  • Bone marrow(4.2)
  • Nervous system(4)
  • Heart(2.2)
genes like me logo Genes that share expression patterns with GLRX3: view

No data available for mRNA differential expression in normal tissues , Protein differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for GLRX3 Gene

Orthologs for GLRX3 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for GLRX3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia GLRX3 31 30
  • 99.5 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Glrx3 30
  • 90.99 (n)
dog
(Canis familiaris)
Mammalia GLRX3 31 30
  • 90.78 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Glrx3 17 31 30
  • 90.46 (n)
cow
(Bos Taurus)
Mammalia GLRX3 31 30
  • 90.15 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia GLRX3 31
  • 78 (a)
OneToOne
chicken
(Gallus gallus)
Aves GLRX3 31 30
  • 79.04 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia GLRX3 31
  • 77 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia glrx3 30
  • 72.87 (n)
Str.7370 30
African clawed frog
(Xenopus laevis)
Amphibia Xl.9203 30
zebrafish
(Danio rerio)
Actinopterygii glrx3 31 30
  • 68.99 (n)
OneToOne
wufb38e09 30
fruit fly
(Drosophila melanogaster)
Insecta CG6523 31
  • 45 (a)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea glrx-3 31 30
  • 57.27 (n)
OneToOne
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes GRX4 33 31 30
  • 52.33 (n)
GRX3 31
  • 33 (a)
OneToMany
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0C17842g 30
  • 52.24 (n)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_AGR111W 30
  • 51.74 (n)
thale cress
(Arabidopsis thaliana)
eudicotyledons AT4G04950 30
  • 58.5 (n)
Alicante grape
(Vitis vinifera)
eudicotyledons Vvi.6485 30
rice
(Oryza sativa)
Liliopsida Os10g0500700 30
  • 54.55 (n)
Os.11576 30
wheat
(Triticum aestivum)
Liliopsida Ta.20390 30
corn
(Zea mays)
Liliopsida Zm.7955 30
barley
(Hordeum vulgare)
Liliopsida Hv.4967 30
sea squirt
(Ciona savignyi)
Ascidiacea CSA.9660 31
  • 56 (a)
OneToOne
Cin.13908 30
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes grx4 30
  • 52.45 (n)
bread mold
(Neurospora crassa)
Ascomycetes NCU09803 30
  • 51.83 (n)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.13908 30
Species where no ortholog for GLRX3 was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)

Evolution for GLRX3 Gene

ENSEMBL:
Gene Tree for GLRX3 (if available)
TreeFam:
Gene Tree for GLRX3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GLRX3: view image

Paralogs for GLRX3 Gene

Paralogs for GLRX3 Gene

Pseudogenes.org Pseudogenes for GLRX3 Gene

genes like me logo Genes that share paralogs with GLRX3: view

Variants for GLRX3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for GLRX3 Gene

SNP ID Clinical significance and condition Chr 10 pos Variation AA Info Type
771743 Benign: not provided 130,166,520(+) G/A SYNONYMOUS_VARIANT
rs13991 - p.Gln21His
rs2274217 - p.Pro123Ser

Additional dbSNP identifiers (rs#s) for GLRX3 Gene

Structural Variations from Database of Genomic Variants (DGV) for GLRX3 Gene

Variant ID Type Subtype PubMed ID
nsv1048253 CNV gain 25217958
nsv825630 CNV gain 20364138
nsv832024 CNV loss 17160897

Variation tolerance for GLRX3 Gene

Residual Variation Intolerance Score: 36.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 9.33; 88.34% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GLRX3 Gene

Human Gene Mutation Database (HGMD)
GLRX3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
GLRX3

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GLRX3 Gene

Disorders for GLRX3 Gene

MalaCards: The human disease database

(2) MalaCards diseases for GLRX3 Gene - From: DISEASES

Disorder Aliases PubMed IDs
multiple mitochondrial dysfunctions syndrome 2 with hyperglycinemia
  • mmds2
aceruloplasminemia
  • hypoceruloplasminemia, hereditary
- elite association - COSMIC cancer census association via MalaCards
Search GLRX3 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for GLRX3

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with GLRX3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for GLRX3 Gene

Publications for GLRX3 Gene

  1. Characterization of 16 novel human genes showing high similarity to yeast sequences. (PMID: 11124703) Stanchi F … Valle G (Yeast (Chichester, England) 2001) 2 3 4 54
  2. Inhibition of the c-Jun N-terminal kinase/AP-1 and NF-kappaB pathways by PICOT, a novel protein kinase C-interacting protein with a thioredoxin homology domain. (PMID: 10636891) Witte S … Altman A (The Journal of biological chemistry 2000) 2 3 4 54
  3. A Glutaredoxin·BolA Complex Serves as an Iron-Sulfur Cluster Chaperone for the Cytosolic Cluster Assembly Machinery. (PMID: 27519415) Frey AG … Philpott CC (The Journal of biological chemistry 2016) 3 4 54
  4. Elucidating the Molecular Function of Human BOLA2 in GRX3-Dependent Anamorsin Maturation Pathway. (PMID: 26613676) Banci L … Muzzioli R (Journal of the American Chemical Society 2015) 3 4 54
  5. Crucial function of vertebrate glutaredoxin 3 (PICOT) in iron homeostasis and hemoglobin maturation. (PMID: 23615448) Haunhorst P … Lillig CH (Molecular biology of the cell 2013) 3 4 54

Products for GLRX3 Gene

Sources for GLRX3 Gene