Q86SX6 (GLRX5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glutaredoxin-related protein 5, mitochondrial

Alternative name(s):
Monothiol glutaredoxin-5

Gene names

Name:	GLRX5
Synonyms:	C14orf87

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	157 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	Monothiol glutaredoxin involved in the biogenesis of iron-sulfur clusters. Required for normal iron homeostasis. Required for normal regulation of hemoglobin synthesis by the iron-sulfur protein ACO1.
Subunit structure	Homodimer Probable. Ref.9
Subcellular location	Mitochondrion By similarity.
Involvement in disease	Anemia, sideroblastic, pyridoxine-refractory, autosomal recessive (PRARSA) [MIM:205950]: A form of sideroblastic anemia not responsive to pyridoxine. 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7
Sequence similarities	Belongs to the glutaredoxin family. Monothiol subfamily. Contains 1 glutaredoxin domain.
Sequence caution	The sequence CAD62364.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Domain	Redox-active center Transit peptide
Ligand	2Fe-2S Iron Iron-sulfur Metal-binding
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell redox homeostasis Inferred from electronic annotation. Source: InterPro hemopoiesis Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	mitochondrion Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from direct assay. Source: HPA
Molecular_function	2 iron, 2 sulfur cluster binding Inferred from electronic annotation. Source: UniProtKB-KW electron carrier activity Inferred from electronic annotation. Source: InterPro metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein disulfide oxidoreductase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 31

31

Mitochondrion Potential

Chain

32 – 157

126

Glutaredoxin-related protein 5, mitochondrial

PRO_0000141650

Regions

Domain

42 – 145

104

Glutaredoxin

Region

97 – 101

5

Glutathione binding

Region

122 – 123

2

Glutathione binding

Compositional bias

8 – 11

4

Poly-Ala

Compositional bias

16 – 23

8

Poly-Gly

Compositional bias

33 – 40

8

Poly-Gly

Sites

Metal binding

67

1

Iron-sulfur (2Fe-2S); shared with dimeric partner

Binding site

59

1

Glutathione

Binding site

109

1

Glutathione; via amide nitrogen and carbonyl oxygen

Natural variations

Natural variant

146

1

A → T. Ref.1 Ref.6
Corresponds to variant rs11628901 [ dbSNP | Ensembl ].

VAR_026125

Secondary structure

1

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157

Helix Strand Turn

Details...

Helix

42 – 51

10

Beta strand

52 – 60

9

Beta strand

62 – 67

6

Helix

68 – 79

12

Beta strand

86 – 89

4

Helix

94 – 104

11

Beta strand

111 – 114

4

Beta strand

117 – 120

4

Helix

122 – 131

10

Helix

133 – 140

8

Turn

146 – 148

3

Sequences

	Sequence		Length	Mass (Da)
	Q86SX6 [UniParc]. Last modified February 1, 2005. Version 2. Checksum: 5E6873BD5DE91F86	FASTA	157	16,628
	10 20 30 40 50 60 MSGSLGRAAA ALLRWGRGAG GGGLWGPGVR AAGSGAGGGG SAEQLDALVK KDKVVVFLKG 70 80 90 100 110 120 TPEQPQCGFS NAVVQILRLH GVRDYAAYNV LDDPELRQGI KDYSNWPTIP QVYLNGEFVG 130 140 150 GCDILLQMHQ NGDLVEELKK LGIHSALLDE KKDQDSK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Deficiency of glutaredoxin 5 reveals Fe-S clusters are required for vertebrate haem synthesis." The Tuebingen 2000 screen consortium Wingert R.A., Galloway J.L., Barut B., Foott H., Fraenkel P., Axe J.L., Weber G.J., Dooley K., Davidson A.J., Schmid B., Paw B.H., Shaw G.C., Kingsley P., Palis J., Schubert H., Chen O., Kaplan J., Zon L.I. Nature 436:1035-1039(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT THR-146.
[2]	Erratum The Tuebingen 2000 screen consortium Wingert R.A., Galloway J.L., Barut B., Foott H., Fraenkel P., Axe J.L., Weber G.J., Dooley K., Davidson A.J., Schmid B., Paw B.H., Shaw G.C., Kingsley P., Palis J., Schubert H., Chen O., Kaplan J. Nature 437:920-920(2005)
[3]	"Biological function of human glutaredoxin 3 (Grx 3), a novel mitochondrial monothiol Grx." Kurosawa N., Isobe M., Saito M. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Full-length cDNA libraries and normalization." Li W.B., Gruber C., Jessee J., Polayes D. Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: B-cell.
[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 (JUL-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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT THR-146. Tissue: Skin and Testis.
[7]	"The human counterpart of zebrafish shiraz shows sideroblastic-like microcytic anemia and iron overload." Camaschella C., Campanella A., De Falco L., Boschetto L., Merlini R., Silvestri L., Levi S., Iolascon A. Blood 110:1353-1358(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN PRARSA.
[8]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]	"The crystal structure of human GLRX5: iron-sulfur cluster co-ordination, tetrameric assembly and monomer activity." Johansson C., Roos A.K., Montano S.J., Sengupta R., Filippakopoulos P., Guo K., von Delft F., Holmgren A., Oppermann U., Kavanagh K.L. Biochem. J. 433:303-311(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 35-150 IN COMPLEX WITH GLUTATHIONE AND IRON-SULFUR CLUSTER, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00333763.

RefSeq

NP_057501.2. NM_016417.2.

UniGene

Hs.532683.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2WUL	X-ray	2.40	A/B/C/D	35-150	[»]

ProteinModelPortal

Q86SX6.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q86SX6. 1 interaction.

STRING

9606.ENSP00000328570.

PTM databases

PhosphoSite

Q86SX6.

Polymorphism databases

DMDM

83288163.

Proteomic databases

PaxDb

Q86SX6.

PeptideAtlas

Q86SX6.

PRIDE

Q86SX6.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000331334; ENSP00000328570; ENSG00000182512.

GeneID

51218.

KEGG

hsa:51218.

UCSC

uc001yem.1. human.

Organism-specific databases

CTD

51218.

GeneCards

GC14P096001.

HGNC

HGNC:20134. GLRX5.

HPA

HPA042465.

MIM

205950. phenotype.
609588. gene.

neXtProt

NX_Q86SX6.

Orphanet

255132. Autosomal recessive pyridoxine-refractory sideroblastic anemia.

PharmGKB

PA134992547.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0278.

HOGENOM

HOG000095211.

HOVERGEN

HBG051012.

InParanoid

Q86SX6.

KO

K07390.

OMA

DPQLRQG.

OrthoDB

EOG4RV2SS.

PhylomeDB

Q86SX6.

Gene expression databases

Bgee

Q86SX6.

CleanEx

HS_GLRX5.

Genevestigator

Q86SX6.

GermOnline

ENSG00000182512. Homo sapiens.

Family and domain databases

Gene3D

3.40.30.10. 1 hit.

InterPro

IPR002109. Glutaredoxin.
IPR004480. Monothiol_GRX-rel.
IPR012336. Thioredoxin-like_fold.
[Graphical view]

PANTHER

PTHR10293. PTHR10293. 1 hit.

Pfam

PF00462. Glutaredoxin. 1 hit.
[Graphical view]

SUPFAM

SSF52833. Thiordxn-like_fd. 1 hit.

TIGRFAMs

TIGR00365. TIGR00365. 1 hit.

PROSITE

PS51354. GLUTAREDOXIN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q86SX6.

GenomeRNAi

51218.

NextBio

54294.

SOURCE

Search...

Entry information

Entry name

GLRX5_HUMAN

Accession

Primary (citable) accession number: Q86SX6
Secondary accession number(s): Q0X088 , Q3YML0, Q86WY3, Q8IZ54

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 2005
Last sequence update:	February 1, 2005
Last modified:	May 1, 2013
This is version 89 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.