P0A006 (ARSC_STAAU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein ArsC

Alternative name(s):
Arsenate reductase
EC=1.20.4.-
Arsenical pump modifier
Low molecular weight protein-tyrosine-phosphatase
EC=3.1.3.48

Gene names

Name:

arsC

Encoded on

Plasmid pI258 Ref.1 Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.8

Organism

Staphylococcus aureus

Taxonomic identifier

1280 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Firmicutes › Bacilli › Bacillales › Staphylococcaceae › Staphylococcus

Protein attributes

Sequence length	131 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Reduces arsenate [As(V)] to arsenite [As(III)] and dephosphorylates tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates. Could switch between different functions in different circumstances. HAMAP-Rule MF_01624
Catalytic activity	Protein tyrosine phosphate + H2O = protein tyrosine + phosphate. HAMAP-Rule MF_01624 Arsenate + thioredoxin = arsenite + thioredoxin disulfide + H2O. HAMAP-Rule MF_01624
Enzyme regulation	Inhibited by arsenite (mixed inhibitor). HAMAP-Rule MF_01624
Subunit structure	Monomer.
Post-translational modification	Cys-89 performs a nucleophilic attack on a Cys-10-Cys-82 intermediate, forming another disulfide intermediate with Cys-82. HAMAP-Rule MF_01624
Miscellaneous	Cys-10 is essential for both reductase and phosphatase reactions. HAMAP-Rule MF_01624
Sequence similarities	Belongs to the low molecular weight phosphotyrosine protein phosphatase superfamily. ArsC family.
Biophysicochemical properties	Kinetic parameters: Arsenate is the physiological substrate. KM=146 mM for para-nitrophenyl phosphate (reduced form only) Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 KM=68 µM for arsenate KM=0.8 µM for arsenate (below 1mM arsenate) KM=2 mM for arsenate (above 1mM arsenate) KM=13 mM for selenate Vmax=200 nmol/min/mg enzyme (below 1 mM arsenate) Vmax=450 nmol/min/mg enzyme (above 1 mM arsenate) pH dependence: Optimum pH is 8.
Mass spectrometry	Molecular mass is 14810.5 Da from positions 1 - 131. Determined by ESI. Ref.4 Molecular mass is 14812 Da from positions 1 - 131. Determined by ESI. Ref.6

Ontologies

Keywords
Biological process	Arsenical resistance
Domain	Redox-active center
Molecular function	Hydrolase Oxidoreductase
PTM	Disulfide bond
Technical term	3D-structure Plasmid
Gene Ontology (GO)
Biological_process	peptidyl-tyrosine dephosphorylation Inferred from electronic annotation. Source: GOC response to arsenic-containing substance Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	arsenate reductase (thioredoxin) activity Inferred from electronic annotation. Source: HAMAP protein tyrosine phosphatase activity Inferred from electronic annotation. Source: HAMAP
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 131

131

Protein ArsC HAMAP-Rule MF_01624

PRO_0000162523

Sites

Active site

10

1

Nucleophile; for reductase activity and phosphatase activity

Active site

82

1

Nucleophile; for reductase activity

Active site

89

1

Nucleophile; for reductase activity

Amino acid modifications

Disulfide bond

10 ↔ 82

Redox-active; alternate HAMAP-Rule MF_01624

Disulfide bond

82 ↔ 89

Redox-active; alternate HAMAP-Rule MF_01624

Natural variations

Natural variant

2

1

D → T in strain: SW18, SW4, SW24 and SW1.

Natural variant

24 – 33

10

GKEILGEGWN → AKQILAKDWD in strain: SW18.

Natural variant

24 – 31

8

GKEILGEG → AKQILADD in strain: SW24 and SW1.

Natural variant

24 – 31

8

GKEILGEG → AKQILAED in strain: SW4.

Natural variant

56

1

D → G in strain: SW18, SW4, SW24 and SW1.

Natural variant

65

1

D → N in strain: SW24 and SW1.

Natural variant

70 – 76

7

DILKQSD → NIIKNSN in strain: SW18, SW4, SW24 and SW1.

Natural variant

87

1

N → V in strain: SW18, SW4, SW24 and SW1.

Natural variant

91

1

I → S in strain: SW4, SW24 and SW1.

Natural variant

91

1

I → T in strain: SW18.

Natural variant

94

1

P → T in strain: SW18, SW4, SW24 and SW1.

Natural variant

110

1

E → P in strain: SW18, SW4, SW24 and SW1.

Natural variant

123

1

L → I in strain: SW4, SW24 and SW1.

Natural variant

123

1

L → V in strain: SW18.

Natural variant

127

1

K → N in strain: SW18, SW4, SW24 and SW1.

Natural variant

130

1

L → S in strain: SW18, SW4, SW24 and SW1.

Experimental info

Mutagenesis

10

1

C → S: Loss of reductase and phosphatase activities. Loss of reductase and phosphatase activities; when associated with A-15. Ref.5

Mutagenesis

15

1

C → A: Decrease in substrate affinity of reductase. Substrate affinity of phosphatase identical to wild-type. Loss of reductase and phosphatase activities; when associated with S-10. Ref.5

Mutagenesis

16

1

R → K: Loss of reductase activity. Ref.8

Mutagenesis

17

1

S → A: 5-fold decrease in catalytic efficiency. Ref.8

Mutagenesis

82

1

C → S: Loss of reductase activity. Increase in substrate affinity of phosphatase. Ref.5

Mutagenesis

89

1

C → A: Loss of reductase activity. Ref.5 Ref.8

Mutagenesis

89

1

C → L: Decrease in substrate affinity of phosphatase. Leads to a reductase locked in the C-10/C-82 intermediate form. Ref.5 Ref.8

Mutagenesis

105

1

D → A: 55-fold decrease in substrate affinity of reductase. Ref.8

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

131

Helix Strand Turn

Details...

Beta strand

4 – 15

12

Helix

16 – 27

12

Turn

29 – 31

3

Beta strand

32 – 40

9

Helix

46 – 54

9

Helix

69 – 74

6

Beta strand

76 – 80

5

Helix

83 – 88

6

Beta strand

96 – 100

5

Helix

111 – 129

19

Sequences

	Sequence		Length	Mass (Da)
	P0A006 [UniParc]. Last modified February 15, 2005. Version 1. Checksum: 03871148DC433A18	FASTA	131	14,813
	10 20 30 40 50 60 MDKKTIYFIC TGNSCRSQMA EGWGKEILGE GWNVYSAGIE THGVNPKAIE AMKEVDIDIS 70 80 90 100 110 120 NHTSDLIDND ILKQSDLVVT LCSDADNNCP ILPPNVKKEH WGFDDPAGKE WSEFQRVRDE 130 IKLAIEKFKL R

References

[1]	"Regulation and expression of the arsenic resistance operon from Staphylococcus aureus plasmid pI258." Ji G., Silver S. J. Bacteriol. 174:3684-3694(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Characterization of a collection of clinical Staphylococcus aureus wound isolates." Tibor L., Cramton S.E., Goetz F., Hunt T.K. Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: SW1, SW18, SW24 and SW4.
[3]	"Reduction of arsenate to arsenite by the ArsC protein of the arsenic resistance operon of Staphylococcus aureus plasmid pI258." Ji G., Silver S. Proc. Natl. Acad. Sci. U.S.A. 89:9474-9478(1992) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[4]	"Arsenate reductase of Staphylococcus aureus plasmid pI258." Ji G., Garber E.A.E., Armes L.G., Chen C.-M., Fuchs J.A., Silver S. Biochemistry 33:7294-7299(1994) [PubMed] [Europe PMC] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES, MASS SPECTROMETRY.
[5]	"The essential catalytic redox couple in arsenate reductase from Staphylococcus aureus." Messens J., Hayburn G., Desmyter A., Laus G., Wyns L. Biochemistry 38:16857-16865(1999) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF CYS-10; CYS-15; CYS-82; CYS-89 AND 10-CYS--CYS-15, BIOPHYSICOCHEMICAL PROPERTIES.
[6]	"Kinetics and active site dynamics of Staphylococcus aureus arsenate reductase." Messens J., Martins J.C., Brosens E., Van Belle K., Jacobs D.M., Willem R., Wyns L. J. Biol. Inorg. Chem. 7:146-156(2002) [PubMed] [Europe PMC] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES, MASS SPECTROMETRY, STRUCTURE BY NMR.
[7]	"Arsenate reductase from S. aureus plasmid pI258 is a phosphatase drafted for redox duty." Zegers I., Martins J.C., Willem R., Wyns L., Messens J. Nat. Struct. Biol. 8:843-847(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.12 ANGSTROMS) OF REDUCED AND OXIDIZED FORM OF MUTANT CYS-10--CYS-15, BIOPHYSICOCHEMICAL PROPERTIES.
[8]	"All intermediates of the arsenate reductase mechanism, including an intramolecular dynamic disulfide cascade." Messens J., Martins J.C., Van Belle K., Brosens E., Desmyter A., De Gieter M., Wieruszeski J.-M., Willem R., Wyns L., Zegers I. Proc. Natl. Acad. Sci. U.S.A. 99:8506-8511(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF WILD-TYPE, MUTANT CYS-15 IN COMPLEX WITH ARSENITE AND CYS-89, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ARG-16; SER-17; CYS-89 AND ASP-105, STRUCTURE BY NMR OF MUTANT CYS-82 AND CYS-89.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M86824 Genomic DNA. Translation: AAA25638.1.
AY194061 Genomic DNA. Translation: AAP32334.1.
AY194062 Genomic DNA. Translation: AAP32338.1.
AY194064 Genomic DNA. Translation: AAP32346.1.
AY194065 Genomic DNA. Translation: AAP32350.1.

PIR

A53641.
D41903.

RefSeq

YP_001573918.1. NC_010077.1.
YP_001715971.1. NC_010419.1.
YP_006937217.1. NC_013292.1.
YP_006937607.1. NC_013319.1.
YP_006937727.1. NC_013322.1.
YP_006937753.1. NC_013323.1.
YP_006938161.1. NC_013333.1.
YP_006938435.1. NC_013340.1.
YP_006938641.1. NC_013347.1.
YP_006938712.1. NC_013349.1.
YP_006938775.1. NC_013352.1.
YP_006939395.1. NC_018965.1.
YP_006940871.1. NC_019009.1.
YP_536862.1. NC_007931.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1JF8	X-ray	1.12	A	1-131	[»]
1JFV	X-ray	2.00	A	1-131	[»]
1LJL	X-ray	2.01	A	1-131	[»]
1LJU	X-ray	1.40	A	1-131	[»]
1LK0	X-ray	1.60	A/B	1-131	[»]
1RXE	X-ray	1.70	A	1-131	[»]
1RXI	X-ray	1.50	A	1-131	[»]
2CD7	X-ray	1.50	A	1-131	[»]
2FXI	X-ray	1.80	A	1-131	[»]

ProteinModelPortal

P0A006.

SMR

P0A006. Positions 2-131.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

13874340.
13874755.
13874878.
13874905.
13875324.
13875605.
13875818.
13875891.
13875956.
13876308.
13877846.
3978621.
5759819.
6155824.

Phylogenomic databases

ProtClustDB

PRK13530.

Enzyme and pathway databases

BioCyc

MetaCyc:MONOMER-10862.

Family and domain databases

HAMAP

MF_01624. Arsenate_reduct.

InterPro

IPR014064. Arsenate_reductase_ArsC.
IPR023485. Ptyr_pPase_SF.
IPR017867. Tyr_phospatase_low_mol_wt.
[Graphical view]

PANTHER

PTHR11717. PTHR11717. 1 hit.

Pfam

PF01451. LMWPc. 1 hit.
[Graphical view]

SMART

SM00226. LMWPc. 1 hit.
[Graphical view]

SUPFAM

SSF52788. Tyr_Pase_low_mol_wt. 1 hit.

TIGRFAMs

TIGR02691. arsC_pI258_fam. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

P0A006.

Entry information

Entry name

ARSC_STAAU

Accession

Primary (citable) accession number: P0A006
Secondary accession number(s): P30330 , Q6Y0M0, Q6Y0M4, Q6Y0N2, Q8GQH3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 15, 2005
Last sequence update:	February 15, 2005
Last modified:	April 3, 2013
This is version 63 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program