P0A9K9 (SLYD_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
FKBP-type peptidyl-prolyl cis-trans isomerase SlyD
Short name=PPIase
EC=5.2.1.8

Alternative name(s):
Histidine-rich protein
Metallochaperone SlyD
Rotamase
Sensitivity to lysis protein D
WHP

Gene names

Name:	slyD
Ordered Locus Names:	b3349, JW3311

Organism

Escherichia coli (strain K12) [Reference proteome] [HAMAP]

Taxonomic identifier

83333 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacteriales › Enterobacteriaceae › Escherichia › Escherichia coli

Protein attributes

Sequence length	196 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Folding helper with both chaperone and peptidyl-prolyl cis-trans isomerase (PPIase) activities. Chaperone activity prevents aggregation of unfolded or partially folded proteins and promotes their correct folding. PPIases catalyze the cis-trans isomerization of Xaa-Pro bonds of peptides, which accelerates slow steps of protein folding and thus shortens the lifetime of intermediates. Both strategies lower the concentration of intermediates and increase the productivity and yield of the folding reaction. SlyD could be involved in Tat-dependent translocation, by binding to the Tat-type signal of folded proteins. The PPIase substrate specificity, carried out with synthetic peptides of the 'suc-Ala-Xaa-Pro-Phe-4NA' type (where Xaa is the AA tested), was found to be Phe > Ala > Leu. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.14 Required for lysis of phiX174 infected cells by stabilizing the hydrophobic viral lysis protein E and allowing it to accumulate to the levels required to exert its lytic effect. May act by a chaperone-like mechanism. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.14 Also involved in hydrogenase metallocenter assembly, probably by participating in the nickel insertion step. This function in hydrogenase biosynthesis requires chaperone activity and the presence of the metal-binding domain, but not PPIase activity. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.14
Catalytic activity	Peptidylproline (omega=180) = peptidylproline (omega=0). Ref.9
Enzyme regulation	PPIase activity is inhibited by binding of nickel ions to the C-terminal metal-binding region and/or the C-terminal part of the PPIase domain. Folding activity is inhibited by FK506 and by permanently unfolded proteins, irrespective of their proline content. Ref.6 Ref.9
Subunit structure	Monomer. Binds to a broad range of unrelated Tat signal sequences. Interacts with the hydrogenase nickel incorporation protein HypB. Ref.8 Ref.11 Ref.12
Subcellular location	Cytoplasm.
Domain	The N-terminal region consists of two globular folded domains that contain prolyl isomerase and chaperone activities. Ref.9 Ref.10 Ref.12 Ref.13 Ref.14 The C-terminal region binds up to 7 nickel ions in a non-cooperative manner. Can also bind zinc with high affinity, and copper or cobalt with lower affinity. No binding detectable for ferrous, ferric, magnesium and calcium ions. Binding of nickel causes conformational rearrangements in the PPIase domain, modulating its isomerase activity. This region is also important for hydrogenase biosynthesis. Ref.9 Ref.10 Ref.12 Ref.13 Ref.14
Miscellaneous	The activity of SlyD is considerably smaller than the one found in other PPIases with the same substrate.
Sequence similarities	Belongs to the FKBP-type PPIase family. Contains 1 PPIase FKBP-type domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Ligand	Cobalt Copper Metal-binding Nickel Zinc
Molecular function	Chaperone Isomerase Rotamase
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	protein maturation by protein folding Inferred from mutant phenotype Ref.8. Source: EcoliWiki protein refolding Inferred from direct assay Ref.9. Source: EcoCyc protein stabilization Inferred from mutant phenotype PubMed 17971396. Source: EcoliWiki response to heat Inferred from expression pattern PubMed 17971396. Source: EcoliWiki
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell membrane Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	FK506 binding Inferred from Biological aspect of Ancestor. Source: RefGenome cobalt ion binding Inferred from direct assay PubMed 22047179. Source: EcoCyc copper ion binding Inferred from direct assay PubMed 22047179. Source: EcoCyc nickel cation binding Inferred from direct assay Ref.13Ref.12PubMed 22047179Ref.1. Source: EcoCyc peptidyl-prolyl cis-trans isomerase activity Inferred from direct assay Ref.6. Source: EcoCyc unfolded protein binding Inferred from direct assay Ref.14. Source: EcoCyc zinc ion binding Inferred from direct assay PubMed 22047179Ref.1. Source: EcoCyc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
hypB	P0AAN3	3	EBI-369251,EBI-558261

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 196

196

FKBP-type peptidyl-prolyl cis-trans isomerase SlyD

PRO_0000075355

Regions

Domain

1 – 95

95

PPIase FKBP-type

Region

1 – 69

69

PPIase first part

Region

76 – 120

45

IF-chaperone

Region

129 – 151

23

PPIase second part

Region

152 – 196

45

Metal-binding

Compositional bias

141 – 146

6

Glu-rich (acidic)

Compositional bias

148 – 179

32

His-rich (basic)

Compositional bias

166 – 194

29

Gly-rich

Sites

Metal binding

167

1

Nickel Potential

Metal binding

168

1

Nickel Potential

Metal binding

184

1

Nickel Potential

Metal binding

185

1

Nickel Potential

Metal binding

193

1

Nickel Potential

Metal binding

195

1

Nickel Potential

Experimental info

Mutagenesis

42

1

I → S: Decrease in PPIase activity, but has little impact on chaperone activity and interaction with HypB. Almost complete loss of PPIase activity; when associated with Y-132. Ref.10 Ref.12

Mutagenesis

132

1

F → Y: Almost complete loss of PPIase activity, but has little impact on chaperone activity and interaction with HypB; when associated with S-42. Ref.10 Ref.12

Mutagenesis

167 – 168

2

CC → AA: Reduces nickel-binding capacity. Ref.12

Mutagenesis

184 – 185

2

CC → AA: Reduces nickel-binding capacity. Ref.12

Secondary structure

1

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196

Helix Strand Turn

Details...

Beta strand

7 – 17

11

Turn

18 – 20

3

Beta strand

22 – 25

4

Beta strand

28 – 30

3

Beta strand

32 – 35

4

Helix

44 – 49

6

Beta strand

50 – 52

3

Beta strand

57 – 63

7

Turn

64 – 66

3

Beta strand

67 – 69

3

Beta strand

75 – 80

6

Helix

81 – 84

4

Beta strand

95 – 100

6

Beta strand

103 – 112

10

Beta strand

114 – 121

8

Beta strand

129 – 141

13

Helix

145 – 149

5

Beta strand

158 – 160

3

Beta strand

177 – 182

6

Sequences

	Sequence		Length	Mass (Da)
	P0A9K9 [UniParc]. Last modified July 19, 2005. Version 1. Checksum: 46DCC7C7ECD61DBA	FASTA	196	20,853
	10 20 30 40 50 60 MKVAKDLVVS LAYQVRTEDG VLVDESPVSA PLDYLHGHGS LISGLETALE GHEVGDKFDV 70 80 90 100 110 120 AVGANDAYGQ YDENLVQRVP KDVFMGVDEL QVGMRFLAET DQGPVPVEIT AVEDDHVVVD 130 140 150 160 170 180 GNHMLAGQNL KFNVEVVAIR EATEEELAHG HVHGAHDHHH DHDHDGCCGG HGHDHGHEHG 190 GEGCCGGKGN GGCGCH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"An Escherichia coli protein consisting of a domain homologous to FK506-binding proteins (FKBP) and a new metal binding motif." Wuelfing C., Lomardero J., Plueckthun A. J. Biol. Chem. 269:2895-2901(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-35 AND 141-146. Strain: K12 / ATCC 35607 / JM83.
[2]	"slyD, a host gene required for phi X174 lysis, is related to the FK506-binding protein family of peptidyl-prolyl cis-trans-isomerases." Roof W.D., Horne S.M., Young K.D., Young R. J. Biol. Chem. 269:2902-2910(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: K12 / CS109.
[3]	"Escherichia coli and other species of the Enterobacteriaceae encode a protein similar to the family of Mip-like FK506-binding proteins." Horne S.M., Young K.D. Arch. Microbiol. 163:357-365(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: K12 / CS109.
[4]	"The complete genome sequence of Escherichia coli K-12." Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., Shao Y. Science 277:1453-1474(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / MG1655 / ATCC 47076.
[5]	"Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110." Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T. Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[6]	"The Escherichia coli SlyD is a metal ion-regulated peptidyl-prolyl cis/trans-isomerase." Hottenrott S., Schumann T., Plueckthun A., Fischer G., Rahfeld J.-U. J. Biol. Chem. 272:15697-15701(1997) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-10, ENZYME REGULATION, CHARACTERIZATION. Strain: BL21.
[7]	"The Escherichia coli FKBP-type PPIase SlyD is required for the stabilization of the E lysis protein of bacteriophage phi X174." Bernhardt T.G., Roof W.D., Young R. Mol. Microbiol. 45:99-108(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN LYSIS OF PHIX174 INFECTED CELLS.
[8]	"A role for SlyD in the Escherichia coli hydrogenase biosynthetic pathway." Zhang J.W., Butland G., Greenblatt J.F., Emili A., Zamble D.B. J. Biol. Chem. 280:4360-4366(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN HYDROGENASE METALLOCENTER ASSEMBLY, INTERACTION WITH HYPB. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[9]	"SlyD proteins from different species exhibit high prolyl isomerase and chaperone activities." Scholz C., Eckert B., Hagn F., Schaarschmidt P., Balbach J., Schmid F.X. Biochemistry 45:20-33(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS A CHAPERONE AND A PPIASE, CATALYTIC ACTIVITY, ENZYME REGULATION, DOMAIN.
[10]	"The peptidyl-prolyl isomerase activity of SlyD is not required for maturation of Escherichia coli hydrogenase." Zhang J.W., Leach M.R., Zamble D.B. J. Bacteriol. 189:7942-7944(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN HYDROGENASE METALLOCENTER ASSEMBLY, DOMAIN, MUTAGENESIS OF ILE-42 AND PHE-132.
[11]	"DnaK plays a pivotal role in Tat targeting of CueO and functions beside SlyD as a general Tat signal binding chaperone." Graubner W., Schierhorn A., Bruser T. J. Biol. Chem. 282:7116-7124(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH TAT SIGNAL SEQUENCES. Strain: K12 / MC4100 / JA176.
[12]	"The Ni(II)-binding properties of the metallochaperone SlyD." Kaluarachchi H., Sutherland D.E., Young A., Pickering I.J., Stillman M.J., Zamble D.B. J. Am. Chem. Soc. 131:18489-18500(2009) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT, NICKEL-BINDING, DOMAIN, MUTAGENESIS OF 167-CYS-CYS-168 AND 184-CYS-CYS-185.
[13]	"The interaction of the Escherichia coli protein SlyD with nickel ions illuminates the mechanism of regulation of its peptidyl-prolyl isomerase activity." Martino L., He Y., Hands-Taylor K.L., Valentine E.R., Kelly G., Giancola C., Conte M.R. FEBS J. 276:4529-4544(2009) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR, NICKEL-BINDING, DOMAIN.
[14]	"NMR solution structure of SlyD from Escherichia coli: spatial separation of prolyl isomerase and chaperone function." Weininger U., Haupt C., Schweimer K., Graubner W., Kovermann M., Bruser T., Scholz C., Schaarschmidt P., Zoldak G., Schmid F.X., Balbach J. J. Mol. Biol. 387:295-305(2009) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 1-165, FUNCTION AS A CHAPERONE, DOMAIN, BINDING TO UNFOLDED PROTEINS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z21496 Genomic DNA. Translation: CAA79705.1.
L13261 Unassigned DNA. Translation: AAA18574.1.
L28082 Genomic DNA. Translation: AAC41458.1.
U18997 Genomic DNA. Translation: AAA58146.1.
U00096 Genomic DNA. Translation: AAC76374.1.
AP009048 Genomic DNA. Translation: BAE77942.1.

PIR

A49987.

RefSeq

NP_417808.1. NC_000913.2.
YP_492083.1. NC_007779.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2K8I	NMR	-	A	1-165	[»]
2KFW	NMR	-	A	1-196	[»]

ProteinModelPortal

P0A9K9.

SMR

P0A9K9. Positions 1-148.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31853N.

IntAct

P0A9K9. 119 interactions.

MINT

MINT-1223693.

STRING

511145.b3349.

Proteomic databases

PaxDb

P0A9K9.

PRIDE

P0A9K9.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAC76374; AAC76374; b3349.
BAE77942; BAE77942; BAE77942.

GeneID

12931688.
947859.

KEGG

ecj:Y75_p3827.
eco:b3349.

PATRIC

32122130. VBIEscCol129921_3442.

Organism-specific databases

EchoBASE

EB1614.

EcoGene

EG11663. slyD.

Phylogenomic databases

eggNOG

COG1047.

HOGENOM

HOG000154889.

KO

K03775.

OMA

HMLAGQT.

ProtClustDB

PRK10737.

Enzyme and pathway databases

BioCyc

EcoCyc:EG11663-MONOMER.
ECOL316407:JW3311-MONOMER.
MetaCyc:EG11663-MONOMER.

Gene expression databases

Genevestigator

P0A9K9.

Family and domain databases

InterPro

IPR023566. PPIase_FKBP.
IPR001179. PPIase_FKBP_dom.
[Graphical view]

PANTHER

PTHR10516. PTHR10516. 1 hit.

Pfam

PF00254. FKBP_C. 1 hit.
[Graphical view]

PROSITE

PS50059. FKBP_PPIASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P0A9K9.

Entry information

Entry name

SLYD_ECOLI

Accession

Primary (citable) accession number: P0A9K9
Secondary accession number(s): P30856, Q2M714

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2005
Last sequence update:	July 19, 2005
Last modified:	May 1, 2013
This is version 73 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program