O76003 · GLRX3_HUMAN

  • Protein
    Glutaredoxin-3
  • Gene
    GLRX3
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

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

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).

Features

Showing features for binding site.

133550100150200250300
TypeIDPosition(s)Description
Binding site159[2Fe-2S] cluster (UniProtKB | ChEBI); ligand shared between dimeric partners
Binding site261[2Fe-2S] cluster (UniProtKB | ChEBI); ligand shared between dimeric partners

GO annotations

AspectTerm
Cellular Componentcell cortex
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular Componentdendrite
Cellular Componentiron-sulfur cluster assembly complex
Cellular Componentnucleus
Cellular ComponentZ disc
Molecular Functionidentical protein binding
Molecular Functioniron-sulfur cluster binding
Molecular Functionmetal ion binding
Molecular Functionprotein kinase C binding
Molecular FunctionRNA binding
Biological Process[2Fe-2S] cluster assembly
Biological Processcell redox homeostasis
Biological Processintracellular iron ion homeostasis
Biological Processiron-sulfur cluster assembly
Biological Processnegative regulation of cardiac muscle hypertrophy
Biological Processprotein maturation by iron-sulfur cluster transfer
Biological Processregulation of the force of heart contraction

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Glutaredoxin-3
  • Alternative names
    • PKC-interacting cousin of thioredoxin
      (PICOT
      )
    • PKC-theta-interacting protein (PKCq-interacting protein)
    • Thioredoxin-like protein 2

Gene names

    • Name
      GLRX3
    • Synonyms
      PICOT
      , TXNL2
    • ORF names
      HUSSY-22

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    O76003
  • Secondary accessions
    • B3KMP7
    • B3KMQ5
    • D3DRG2
    • Q5JV01
    • Q96CE0

Proteomes

Organism-specific databases

Subcellular Location

Cytoplasm, cytosol
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).

Keywords

Disease & Variants

Features

Showing features for natural variant, mutagenesis.

TypeIDPosition(s)Description
Natural variantVAR_01687521in dbSNP:rs13991
Natural variantVAR_016876123in dbSNP:rs2274217
Mutagenesis159Loss of 2Fe-2S-binding; when associated with S-261. Loss of 2Fe-2S-binding and interaction with BOLA2; when associated with 197-D-A-198.
Mutagenesis197-198Loss of 2Fe-2S-binding and interaction with BOLA2; when associated with S-159.
Mutagenesis261Loss of 2Fe-2S-binding; when associated with S-159. Loss of 2Fe-2S-binding and interaction with BOLA2; when associated with 299-D-A-300.
Mutagenesis299-300Loss of 2Fe-2S-binding and interaction with BOLA2; when associated with S-261.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 418 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Organism-specific databases

Miscellaneous

Genetic variation databases

PTM/Processing

Features

Showing features for initiator methionine, modified residue, chain, modified residue (large scale data).

TypeIDPosition(s)SourceDescription
Initiator methionine1UniProtRemoved
Modified residue2UniProtN-acetylalanine
ChainPRO_00001200192-335UniProtGlutaredoxin-3
Modified residue117UniProtPhosphoserine
Modified residue (large scale data)117PRIDEPhosphoserine
Modified residue120UniProtPhosphoserine
Modified residue (large scale data)120PRIDEPhosphoserine

Keywords

Proteomic databases

2D gel databases

PTM databases

Expression

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.

Gene expression databases

Organism-specific databases

Interaction

Subunit

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).

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
BINARY O76003ADAMTSL3 P829873EBI-374781, EBI-10221726
BINARY O76003ALKBH3 Q96Q833EBI-374781, EBI-6658697
BINARY O76003BOLA1 Q9Y3E216EBI-374781, EBI-1049556
BINARY O76003BOLA2-SMG1P6 A0A087WZT33EBI-374781, EBI-12006120
BINARY O76003BOLA2B Q9H3K64EBI-374781, EBI-1642537
BINARY O76003BOLA3 Q53S335EBI-374781, EBI-12086950
BINARY O76003CA9 Q167909EBI-374781, EBI-12259996
BINARY O76003CBLB Q131913EBI-374781, EBI-744027
BINARY O76003CDC20B Q86Y33-53EBI-374781, EBI-11983537
BINARY O76003CERCAM Q5T4B23EBI-374781, EBI-12261896
BINARY O76003CGGBP1 Q9UFW83EBI-374781, EBI-723153
BINARY O76003CIAPIN1 Q6FI8124EBI-374781, EBI-750511
BINARY O76003CIAPIN1 Q6FI81-12EBI-374781, EBI-16172762
BINARY O76003COL8A1 P276583EBI-374781, EBI-747133
BINARY O76003FAM118A Q9NWS63EBI-374781, EBI-8638992
BINARY O76003FLJ13057 Q53SE73EBI-374781, EBI-10172181
BINARY O76003GLRX3 O760033EBI-374781, EBI-374781
BINARY O76003GNG13 Q9P2W33EBI-374781, EBI-11427343
BINARY O76003GRN P287999EBI-374781, EBI-747754
BINARY O76003HEPH Q9BQS7-33EBI-374781, EBI-22734368
BINARY O76003HSD3B7 Q9H2F33EBI-374781, EBI-3918847
BINARY O76003IKZF1 Q134223EBI-374781, EBI-745305
BINARY O76003IL10 P223013EBI-374781, EBI-1031632
BINARY O76003IRX6 P784125EBI-374781, EBI-12100506
BINARY O76003KLHDC9 Q8NEP75EBI-374781, EBI-12214879
BINARY O76003KPRP Q5T7493EBI-374781, EBI-10981970
BINARY O76003KRT31 Q153233EBI-374781, EBI-948001
BINARY O76003KRT38 O760153EBI-374781, EBI-1047263
BINARY O76003KRTAP10-11 P604124EBI-374781, EBI-10217483
BINARY O76003KRTAP10-5 P603706EBI-374781, EBI-10172150
BINARY O76003KRTAP10-8 P604108EBI-374781, EBI-10171774
BINARY O76003KRTAP10-9 P604118EBI-374781, EBI-10172052
BINARY O76003KRTAP12-3 P603283EBI-374781, EBI-11953334
BINARY O76003KRTAP4-11 Q9BYQ68EBI-374781, EBI-10302392
BINARY O76003KRTAP4-12 Q9BQ667EBI-374781, EBI-739863
BINARY O76003KRTAP4-2 Q9BYR53EBI-374781, EBI-10172511
BINARY O76003KRTAP4-4 Q9BYR33EBI-374781, EBI-11958132
BINARY O76003KRTAP4-5 Q9BYR25EBI-374781, EBI-11993254
BINARY O76003KRTAP4-7 Q9BYR03EBI-374781, EBI-10302547
BINARY O76003KRTAP5-11 Q6L8G43EBI-374781, EBI-11993296
BINARY O76003KRTAP5-3 Q6L8H27EBI-374781, EBI-11974251
BINARY O76003KRTAP5-4 Q6L8H13EBI-374781, EBI-11963072
BINARY O76003KRTAP5-6 Q6L8G97EBI-374781, EBI-10250562
BINARY O76003KRTAP5-9 P263718EBI-374781, EBI-3958099
BINARY O76003KRTAP9-2 Q9BYQ48EBI-374781, EBI-1044640
BINARY O76003KRTAP9-3 Q9BYQ33EBI-374781, EBI-1043191
BINARY O76003KRTAP9-8 Q9BYQ03EBI-374781, EBI-11958364
BINARY O76003LCE2D Q5TA826EBI-374781, EBI-10246750
BINARY O76003LNX1 Q8TBB13EBI-374781, EBI-739832
BINARY O76003MAPKBP1 O603366EBI-374781, EBI-947402
BINARY O76003METAP1 P535823EBI-374781, EBI-1051435
BINARY O76003MOXD1 Q6UVY67EBI-374781, EBI-7134667
BINARY O76003NDOR1 Q9UHB42EBI-374781, EBI-10249760
BINARY O76003NOTCH2NLA Q7Z3S93EBI-374781, EBI-945833
BINARY O76003NTF4 P341303EBI-374781, EBI-3907456
BINARY O76003OLFM3 Q96PB73EBI-374781, EBI-10292253
BINARY O76003PCSK5 Q928243EBI-374781, EBI-751290
BINARY O76003PFDN5 Q994713EBI-374781, EBI-357275
BINARY O76003PLSCR1 O151624EBI-374781, EBI-740019
BINARY O76003PRKCQ Q047595EBI-374781, EBI-374762
BINARY O76003RCOR3 Q9P2K3-23EBI-374781, EBI-1504830
BINARY O76003RECK Q6P9E23EBI-374781, EBI-10253121
BINARY O76003RGS20 O760816EBI-374781, EBI-1052678
BINARY O76003RGS20 O76081-63EBI-374781, EBI-10178530
BINARY O76003SMARCC1 Q929223EBI-374781, EBI-355653
BINARY O76003SOX7 Q9BT813EBI-374781, EBI-7239117
BINARY O76003STAU1 O957933EBI-374781, EBI-358174
BINARY O76003STRA6 Q9BX79-63EBI-374781, EBI-12140683
BINARY O76003TCF4 P158843EBI-374781, EBI-533224
BINARY O76003TCL1B O959885EBI-374781, EBI-727338
BINARY O76003TMEM25 Q86YD34EBI-374781, EBI-10260688
BINARY O76003TRAF1 Q130775EBI-374781, EBI-359224
BINARY O76003TRIM36 Q9NQ866EBI-374781, EBI-2341518
BINARY O76003TRIM42 Q8IWZ56EBI-374781, EBI-5235829
BINARY O76003UGP2 Q168513EBI-374781, EBI-743729
BINARY O76003ZBTB44 Q8NCP53EBI-374781, EBI-5658292
BINARY O76003ZNF124 Q159733EBI-374781, EBI-2555767
BINARY O76003ZNF148 Q9UQR13EBI-374781, EBI-2688184
BINARY O76003ZNF410 Q86VK4-33EBI-374781, EBI-11741890
BINARY O76003ZNF426 Q9BUY53EBI-374781, EBI-743265
BINARY O76003ZNF490 Q9ULM23EBI-374781, EBI-1105370
BINARY O76003ZNF544 Q6NX493EBI-374781, EBI-2841978
BINARY O76003ZNF774 Q6NX453EBI-374781, EBI-10251462
View interactors in UniProtKB
View CPX-6861 in Complex Portal

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for domain.

TypeIDPosition(s)Description
Domain2-117Thioredoxin
Domain144-236Glutaredoxin 1
Domain237-335Glutaredoxin 2

Domain

The thioredoxin domain lacks the two redox-active cysteines. This strongly suggests that it lacks thioredoxin activity.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    335
  • Mass (Da)
    37,432
  • Last updated
    2003-09-26 v2
  • Checksum
    46D644413D9EDFDA
MAAGAAEAAVAAVEEVGSAGQFEELLRLKAKSLLVVHFWAPWAPQCAQMNEVMAELAKELPQVSFVKLEAEGVPEVSEKYEISSVPTFLFFKNSQKIDRLDGAHAPELTKKVQRHASSGSFLPSANEHLKEDLNLRLKKLTHAAPCMLFMKGTPQEPRCGFSKQMVEILHKHNIQFSSFDIFSDEEVRQGLKAYSSWPTYPQLYVSGELIGGLDIIKELEASEELDTICPKAPKLEERLKVLTNKASVMLFMKGNKQEAKCGFSKQILEILNSTGVEYETFDILEDEEVRQGLKAYSNWPTYPQLYVKGELVGGLDIVKELKENGELLPILRGEN

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict2in Ref. 2; CAA09375
Sequence conflict67in Ref. 3; BAG51067
Sequence conflict210in Ref. 3; BAG51059

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF118649
EMBL· GenBank· DDBJ
AAF28841.1
EMBL· GenBank· DDBJ
mRNA
AF118652
EMBL· GenBank· DDBJ
AAF28844.1
EMBL· GenBank· DDBJ
mRNA
AJ010841
EMBL· GenBank· DDBJ
CAA09375.1
EMBL· GenBank· DDBJ
mRNA
AK022131
EMBL· GenBank· DDBJ
BAG51067.1
EMBL· GenBank· DDBJ
mRNA
AK021926
EMBL· GenBank· DDBJ
BAG51059.1
EMBL· GenBank· DDBJ
mRNA
AL139123
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
CH471066
EMBL· GenBank· DDBJ
EAW49152.1
EMBL· GenBank· DDBJ
Genomic DNA
CH471066
EMBL· GenBank· DDBJ
EAW49154.1
EMBL· GenBank· DDBJ
Genomic DNA
CH471066
EMBL· GenBank· DDBJ
EAW49155.1
EMBL· GenBank· DDBJ
Genomic DNA
BC005289
EMBL· GenBank· DDBJ
AAH05289.1
EMBL· GenBank· DDBJ
mRNA
BC014372
EMBL· GenBank· DDBJ
AAH14372.2
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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