Reviewed, UniProtKB/Swiss-Prot O76003 (GLRX3_HUMAN)

Names and origin

Protein names

Recommended name:
    Glutaredoxin-3
Alternative name(s):
    Thioredoxin-like protein 2
    PKC-interacting cousin of thioredoxin
    PKC-theta-interacting protein
      Short name=PKCq-interacting protein

Gene names

Name:	GLRX3
Synonyms:	PICOT, TXNL2
ORF Names:	HUSSY-22

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	335 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	May play a role in regulating the function of the thioredoxin system.
Subunit structure	Interacts weakly with PKC-theta. Ref.1
Subcellular location	Cytoplasm › cell cortex. Note: Under the plasma membrane. After PMA stimulation, GLRX3/TXNL2 and PRKCQ/PKC-theta translocate to a more extended submembrane area. Ref.1
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.
Domain	The thioredoxin domain lacks the two redox-active cysteines. This strongly suggests that it lacks thioredoxin activity.
Sequence similarities	Contains 2 glutaredoxin domains. Contains 1 thioredoxin domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Domain	Repeat
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	cell redox homeostasis Inferred from electronic annotation. Source: InterPro
Cellular component	cell cortex Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	electron carrier activity Inferred from electronic annotation. Source: InterPro protein binding Ref.1 Inferred from physical interaction. Source: IntAct protein disulfide oxidoreductase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PRKCQ	Q04759	2	EBI-374781,EBI-374762
RGS20	O76081	1	EBI-374781,EBI-1052678

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 335

334

Glutaredoxin-3

PRO_0000120019

Regions

Domain

2 – 117

116

Thioredoxin

Domain

144 – 236

93

Glutaredoxin 1

Domain

237 – 335

99

Glutaredoxin 2

Amino acid modifications

Modified residue

2

1

N-acetylalanine By similarity

Natural variations

Natural variant

21

1

Q → H: dbSNP rs13991. Ref.1 Ref.3 Ref.6

VAR_016875

Natural variant

123

1

P → S: dbSNP rs2274217. Ref.1 Ref.3 Ref.6

VAR_016876

Experimental info

Sequence conflict

2

1

A → E in CAA09375. Ref.2

Sequence conflict

67

1

K → R in BAG51067. Ref.3

Sequence conflict

210

1

I → T in BAG51059. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

335

Helix Strand Turn

Details...

Beta strand

14 – 16

3

Helix

19 – 28

10

Beta strand

31 – 39

9

Helix

45 – 59

15

Beta strand

63 – 69

7

Turn

70 – 72

3

Helix

74 – 80

7

Beta strand

84 – 102

19

Helix

105 – 116

12

Sequences

	Sequence		Length	Mass (Da)
	O76003-1 [UniParc]. Last modified September 26, 2003. Version 2. Checksum: 46D644413D9EDFDA	FASTA	335	37,432
	10 20 30 40 50 60 MAAGAAEAAV AAVEEVGSAG QFEELLRLKA KSLLVVHFWA PWAPQCAQMN EVMAELAKEL 70 80 90 100 110 120 PQVSFVKLEA EGVPEVSEKY EISSVPTFLF FKNSQKIDRL DGAHAPELTK KVQRHASSGS 130 140 150 160 170 180 FLPSANEHLK EDLNLRLKKL THAAPCMLFM KGTPQEPRCG FSKQMVEILH KHNIQFSSFD 190 200 210 220 230 240 IFSDEEVRQG LKAYSSWPTY PQLYVSGELI GGLDIIKELE ASEELDTICP KAPKLEERLK 250 260 270 280 290 300 VLTNKASVML FMKGNKQEAK CGFSKQILEI LNSTGVEYET FDILEDEEVR QGLKAYSNWP 310 320 330 TYPQLYVKGE LVGGLDIVKE LKENGELLPI LRGEN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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." Witte S., Villalba M., Bi K., Liu Y., Isakov N., Altman A. J. Biol. Chem. 275:1902-1909(2000) [PubMed: 10636891] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, INTERACTION WITH PKC-THETA, VARIANTS HIS-21 AND SER-123. Tissue: Liver, Spleen and T-cell lymphoma.
[2]	"Characterization of 16 novel human genes showing high similarity to yeast sequences." Stanchi F., Bertocco E., Toppo S., Dioguardi R., Simionati B., Cannata N., Zimbello R., Lanfranchi G., Valle G. Yeast 18:69-80(2001) [PubMed: 11124703] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Melanocyte.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS HIS-21 AND SER-123.
[4]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS HIS-21 AND SER-123. Tissue: Bone marrow and Urinary bladder.
[7]	Lubec G., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 59-79; 115-130; 218-231; 246-253; 309-319 AND 323-332. Tissue: Fetal brain cortex.
[8]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[9]	"The solution structure of the thioredoxin domain of human thioredoxin-like protein 2." RIKEN structural genomics initiative (RSGI) Submitted (APR-2007) to the PDB data bank Cited for: STRUCTURE BY NMR OF 1-119.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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. Translation: CAC40691.1.
CH471066 Genomic DNA. Translation: EAW49152.1.
BC005289 mRNA. Translation: AAH05289.1.
BC014372 mRNA. Translation: AAH14372.2.

IPI

IPI00008552.

RefSeq

NP_006532.2.

UniGene

Hs.42644

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2DIY	NMR	-	A	1-117	[»]

SMR

O76003. Positions 239-335.

ModBase

Search...

Protein-protein interaction databases

IntAct

O76003. 12 interactions.

2-D gel databases

REPRODUCTION-2DPAGE

IPI00008552.

Proteomic databases

PeptideAtlas

O76003.

PRIDE

O76003.

Genome annotation databases

Ensembl

ENSG00000108010. Homo sapiens. [Contig view]

GeneID

10539.

KEGG

hsa:10539.

UCSC

uc001lkm.1. human.

Organism-specific databases

GeneCards

GC10P131826.

H-InvDB

HIX0009315.

HGNC

HGNC:15987. GLRX3.

PharmGKB

PA38075.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

O76003.

HOVERGEN

O76003.

OMA

O76003. EYETFDI.

Gene expression databases

ArrayExpress

O76003.

Bgee

O76003.

CleanEx

HS_GLRX3.

GermOnline

ENSG00000108010. Homo sapiens.

Family and domain databases

InterPro

IPR002109. Glutaredoxin.
IPR004480. Glutredox-rel.
IPR017936. Thioredoxin-like.
IPR017937. Thioredoxin_CS.
IPR013766. Thioredoxin_domain.
IPR012335. Thioredoxin_fold.
[Graphical view]

Gene3D

G3DSA:3.40.30.10. Thioredoxin_fold. 3 hits.

PANTHER

PTHR10293. Glutredox-rel. 1 hit.

Pfam

PF00462. Glutaredoxin. 2 hits.
PF00085. Thioredoxin. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00365. Glutredox-rel. 2 hits.

PROSITE

PS51354. GLUTAREDOXIN_2. 2 hits.
PS00194. THIOREDOXIN_1. False negative.
PS51352. THIOREDOXIN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

39985.

PMAP-CutDB

O76003.

Entry information

Entry name

GLRX3_HUMAN

Accession

Primary (citable) accession number: O76003
Secondary accession number(s): B3KMP7 , B3KMQ5, Q5JV01, Q96CE0, Q9P1B0, Q9P1B1

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2003
Last sequence update:	September 26, 2003
Last modified:	July 7, 2009
This is version 92 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)