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Protein

Glutaredoxin-3

Gene

GLRX3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.By similarity3 Publications

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).1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi159Iron-sulfur (2Fe-2S); shared with dimeric partner2 Publications1
Metal bindingi261Iron-sulfur (2Fe-2S); shared with dimeric partner2 Publications1

GO - Molecular functioni

GO - Biological processi

  • [2Fe-2S] cluster assembly Source: UniProtKB
  • cell redox homeostasis Source: InterPro
  • negative regulation of cardiac muscle hypertrophy Source: UniProtKB
  • protein maturation by iron-sulfur cluster transfer Source: UniProtKB
  • regulation of the force of heart contraction Source: UniProtKB

Keywordsi

LigandIron, Iron-sulfur, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-917937. Iron uptake and transport.

Names & Taxonomyi

Protein namesi
Recommended name:
Glutaredoxin-3
Alternative name(s):
PKC-interacting cousin of thioredoxin1 Publication
Short name:
PICOT1 Publication
PKC-theta-interacting protein
Short name:
PKCq-interacting protein
Thioredoxin-like protein 2
Gene namesi
Name:GLRX3
Synonyms:PICOT1 Publication, TXNL2
ORF Names:HUSSY-22
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000108010.11.
HGNCiHGNC:15987. GLRX3.

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

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi159C → S: Loss 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. 2 Publications1
Mutagenesisi197 – 198WP → DA: Loss of 2Fe-2S-binding and interaction with BOLA2; when associated with S-159. 1 Publication2
Mutagenesisi261C → S: Loss 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. 2 Publications1
Mutagenesisi299 – 300WP → DA: Loss of 2Fe-2S-binding and interaction with BOLA2; when associated with S-261. 1 Publication2

Organism-specific databases

DisGeNETi10539.
OpenTargetsiENSG00000108010.
PharmGKBiPA162389829.

Polymorphism and mutation databases

BioMutaiGLRX3.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001200192 – 335Glutaredoxin-3Add BLAST334

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei117PhosphoserineCombined sources1
Modified residuei120PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO76003.
MaxQBiO76003.
PaxDbiO76003.
PeptideAtlasiO76003.
PRIDEiO76003.

2D gel databases

REPRODUCTION-2DPAGEiIPI00008552.

PTM databases

iPTMnetiO76003.
PhosphoSitePlusiO76003.

Miscellaneous databases

PMAP-CutDBiO76003.

Expressioni

Tissue specificityi

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

BgeeiENSG00000108010.
CleanExiHS_GLRX3.
ExpressionAtlasiO76003. baseline and differential.
GenevisibleiO76003. HS.

Organism-specific databases

HPAiHPA028941.

Interactioni

Subunit structurei

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).By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself2EBI-374781,EBI-374781
ALKBH3Q96Q833EBI-374781,EBI-6658697
BOLA1Q9Y3E29EBI-374781,EBI-1049556
CBLBQ131913EBI-374781,EBI-744027
CGGBP1Q9UFW83EBI-374781,EBI-723153
CIAPIN1Q6FI8113EBI-374781,EBI-750511
CIAPIN1Q6FI81-12EBI-374781,EBI-16172762
FAM118AQ9NWS63EBI-374781,EBI-8638992
FLJ13057Q53SE73EBI-374781,EBI-10172181
GRNP287997EBI-374781,EBI-747754
IKZF1Q134223EBI-374781,EBI-745305
KRT31Q153233EBI-374781,EBI-948001
KRT38O760153EBI-374781,EBI-1047263
KRTAP10-11P604124EBI-374781,EBI-10217483
KRTAP10-5P603705EBI-374781,EBI-10172150
KRTAP10-8P604107EBI-374781,EBI-10171774
KRTAP10-9P604115EBI-374781,EBI-10172052
KRTAP4-11Q9BYQ65EBI-374781,EBI-10302392
KRTAP4-12Q9BQ666EBI-374781,EBI-739863
KRTAP4-2Q9BYR53EBI-374781,EBI-10172511
KRTAP4-7Q9BYR03EBI-374781,EBI-10302547
KRTAP5-3Q6L8H24EBI-374781,EBI-11974251
KRTAP5-6Q6L8G93EBI-374781,EBI-10250562
KRTAP5-9P263717EBI-374781,EBI-3958099
KRTAP9-2Q9BYQ45EBI-374781,EBI-1044640
LCE2DQ5TA823EBI-374781,EBI-10246750
MAPKBP1O603365EBI-374781,EBI-947402
MOXD1Q6UVY65EBI-374781,EBI-7134667
NOTCH2NLQ7Z3S93EBI-374781,EBI-945833
OLFM3Q96PB73EBI-374781,EBI-10292253
PCSK5Q928243EBI-374781,EBI-751290
PFDN5Q994713EBI-374781,EBI-357275
PLSCR1O151624EBI-374781,EBI-740019
PRKCQQ047595EBI-374781,EBI-374762
RCOR3Q9P2K3-24EBI-374781,EBI-1504830
RGS20O760813EBI-374781,EBI-1052678
RGS20O76081-63EBI-374781,EBI-10178530
SOX7Q9BT813EBI-374781,EBI-7239117
STAU1O957933EBI-374781,EBI-358174
STRA6Q9BX79-64EBI-374781,EBI-12140683
TCF4P158843EBI-374781,EBI-533224
TMEM25Q86YD33EBI-374781,EBI-10260688
TRAF1Q130775EBI-374781,EBI-359224
TRIM36Q9NQ865EBI-374781,EBI-2341518
TRIM42Q8IWZ56EBI-374781,EBI-5235829
UGP2Q168513EBI-374781,EBI-743729
ZBTB44Q8NCP53EBI-374781,EBI-5658292
ZNF148Q9UQR13EBI-374781,EBI-2688184
ZNF23P170273EBI-374781,EBI-5657766
ZNF426Q9BUY53EBI-374781,EBI-743265
ZNF544Q6NX493EBI-374781,EBI-2841978

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • protein kinase C binding Source: Ensembl

Protein-protein interaction databases

BioGridi115793. 96 interactors.
DIPiDIP-31306N.
IntActiO76003. 95 interactors.
MINTiMINT-5002296.
STRINGi9606.ENSP00000330836.

Structurei

Secondary structure

1335
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi13 – 16Combined sources4
Helixi19 – 28Combined sources10
Turni29 – 31Combined sources3
Beta strandi34 – 39Combined sources6
Helixi44 – 59Combined sources16
Beta strandi63 – 69Combined sources7
Turni70 – 72Combined sources3
Helixi74 – 79Combined sources6
Beta strandi84 – 92Combined sources9
Beta strandi95 – 103Combined sources9
Helixi105 – 115Combined sources11
Helixi133 – 141Combined sources9
Beta strandi143 – 152Combined sources10
Beta strandi154 – 159Combined sources6
Helixi160 – 171Combined sources12
Beta strandi177 – 180Combined sources4
Helixi181 – 183Combined sources3
Helixi185 – 195Combined sources11
Beta strandi202 – 205Combined sources4
Beta strandi208 – 211Combined sources4
Helixi213 – 221Combined sources9
Helixi225 – 228Combined sources4
Helixi233 – 243Combined sources11
Beta strandi245 – 254Combined sources10
Beta strandi256 – 259Combined sources4
Helixi263 – 273Combined sources11
Beta strandi279 – 282Combined sources4
Helixi283 – 285Combined sources3
Helixi287 – 297Combined sources11
Beta strandi304 – 307Combined sources4
Beta strandi310 – 313Combined sources4
Helixi315 – 323Combined sources9
Helixi327 – 331Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DIYNMR-A1-117[»]
2WZ9X-ray1.55A1-125[»]
2YANX-ray1.90A/B232-334[»]
3ZYWX-ray1.84A/B130-232[»]
ProteinModelPortaliO76003.
SMRiO76003.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO76003.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 117ThioredoxinPROSITE-ProRule annotationAdd BLAST116
Domaini144 – 236Glutaredoxin 1PROSITE-ProRule annotationAdd BLAST93
Domaini237 – 335Glutaredoxin 2PROSITE-ProRule annotationAdd BLAST99

Domaini

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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0911. Eukaryota.
COG0278. LUCA.
GeneTreeiENSGT00550000075030.
HOVERGENiHBG054719.
InParanoidiO76003.
OMAiNNWPTFP.
OrthoDBiEOG091G0YN0.
PhylomeDBiO76003.
TreeFamiTF314151.

Family and domain databases

CDDicd03028. GRX_PICOT_like. 2 hits.
InterProiView protein in InterPro
IPR002109. Glutaredoxin.
IPR033658. GRX_PICOT-like.
IPR004480. Monothiol_GRX-rel.
IPR036249. Thioredoxin-like_sf.
IPR013766. Thioredoxin_domain.
PANTHERiPTHR10293. PTHR10293. 1 hit.
PfamiView protein in Pfam
PF00462. Glutaredoxin. 2 hits.
PF00085. Thioredoxin. 1 hit.
SUPFAMiSSF52833. SSF52833. 3 hits.
TIGRFAMsiTIGR00365. TIGR00365. 1 hit.
PROSITEiView protein in PROSITE
PS51354. GLUTAREDOXIN_2. 2 hits.
PS51352. THIOREDOXIN_2. 1 hit.

Sequencei

Sequence statusi: Complete.

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

O76003-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAGAAEAAV AAVEEVGSAG QFEELLRLKA KSLLVVHFWA PWAPQCAQMN
60 70 80 90 100
EVMAELAKEL PQVSFVKLEA EGVPEVSEKY EISSVPTFLF FKNSQKIDRL
110 120 130 140 150
DGAHAPELTK KVQRHASSGS FLPSANEHLK EDLNLRLKKL THAAPCMLFM
160 170 180 190 200
KGTPQEPRCG FSKQMVEILH KHNIQFSSFD IFSDEEVRQG LKAYSSWPTY
210 220 230 240 250
PQLYVSGELI GGLDIIKELE ASEELDTICP KAPKLEERLK VLTNKASVML
260 270 280 290 300
FMKGNKQEAK CGFSKQILEI LNSTGVEYET FDILEDEEVR QGLKAYSNWP
310 320 330
TYPQLYVKGE LVGGLDIVKE LKENGELLPI LRGEN
Length:335
Mass (Da):37,432
Last modified:September 26, 2003 - v2
Checksum:i46D644413D9EDFDA
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti2A → E in CAA09375 (PubMed:11124703).Curated1
Sequence conflicti67K → R in BAG51067 (PubMed:14702039).Curated1
Sequence conflicti210I → T in BAG51059 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01687521Q → H3 PublicationsCorresponds to variant dbSNP:rs13991Ensembl.1
Natural variantiVAR_016876123P → S3 PublicationsCorresponds to variant dbSNP:rs2274217Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF118649 mRNA. Translation: AAF28841.1.
AF118652 mRNA. Translation: AAF28844.1.
AJ010841 mRNA. Translation: CAA09375.1.
AK022131 mRNA. Translation: BAG51067.1.
AK021926 mRNA. Translation: BAG51059.1.
AL139123 Genomic DNA. No translation available.
CH471066 Genomic DNA. Translation: EAW49152.1.
CH471066 Genomic DNA. Translation: EAW49154.1.
CH471066 Genomic DNA. Translation: EAW49155.1.
BC005289 mRNA. Translation: AAH05289.1.
BC014372 mRNA. Translation: AAH14372.2.
CCDSiCCDS7661.1.
RefSeqiNP_001186797.1. NM_001199868.1.
NP_006532.2. NM_006541.4.
UniGeneiHs.42644.

Genome annotation databases

EnsembliENST00000331244; ENSP00000330836; ENSG00000108010.
ENST00000368644; ENSP00000357633; ENSG00000108010.
ENST00000481034; ENSP00000435445; ENSG00000108010.
GeneIDi10539.
KEGGihsa:10539.
UCSCiuc001lkm.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiGLRX3_HUMAN
AccessioniPrimary (citable) accession number: O76003
Secondary accession number(s): B3KMP7
, B3KMQ5, D3DRG2, Q5JV01, Q96CE0, Q9P1B0, Q9P1B1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 26, 2003
Last sequence update: September 26, 2003
Last modified: November 22, 2017
This is version 177 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: 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