List of LEE and Non-LEE genes/proteins (EPEC O127:H6 strain E2348/69)


LEE locus genes/proteins
(based on Pallen 2005 and updated)

Protein name

(new)

 

Uniprot code

Other names

MW (Da)

pI

GRAVY

PTMs

Localization

 

Domain

 

Quaternary Structure

 

 

Secretion mechanism

 

Effect of deletion
mutation on secretion*

Effect on
pedestal
formation#/
Virulence&

Known
Interactions in Bacterium

Known
Interactions in Host
Homologues Known
function
Predicted
function
Protein
existence
Refs

rorf1

B7UMC9_ECO27

 

31053.97

6.14

 

 

U

PF06977

Beta_propeller (C-terminal) by homology

U

+

+/+

●EspD

 

●YjiK

-

2

espG1

B7UMC8_ECO27

 

43918.57

5.21

 

 

Host Cytoplasm

PF06872

T3S

+

+/+    

●VirA-Shigella

●Translocated effector
● Disassemble microtubules to induce RhoGTPase-mediated cytokeletal rearrangements that promote bacterial attachment, entry, or movement within the cytoplasm [20] ● activating the host cell protease calpain [87]

-

13,
19,
20

Ler

B7UMC6_ECO27

Orf1

15134.21

5.91

 

C

PF00816

dimers and soluble aggregates of up to 50000 kDa [78]                   

No

No expression

-

●HNS (heterodimer?) ● StpA (heterodimer?) ● DNA

No

●HNS ●StpA

●Positive regulator of T3SS

-

13, 11, 78

escE

B7UMC5_ECO27

 Orf2

8449.89

 6.10

 

 

C                                                          

 

 

 

●Orf29 [ref]

●SepL - C-terminus

 

●YscE ● PscE ● SsaE ●CV2595 ●YPO0259

Functionally important conserved residues can be identified by scrutiny of homologues

-

13

cesAB

B7UMC4_ECO27

Orf3

12298.10

9.45

 

 

C

 

No

±EspA, EspB

-

●EspA (CS/NMR/2H/AP) [1, 2, 3, 86]
● EspB (2H) [2]

-

●NleF effector (B7UR63_ECO27)

●Chaperone EspA

●Chaperone EspB

+ P

1,
2,
3,
9,
13

orf4

B7UMC3_ECO27

L0051

23465.08

7.64

 

C

 

No

-

-    

●YPO0264 ● CV2589, STM1410
(Q8ZPP3_SALTY
Q0WK43_YERPE

Functionally important conserved residues can be identified by scrutiny of homologues

-

13

escL

B7UMC2_ECO27

orf5

27179.76

8.44

 

peripheral inner membrane protein

 

No

-

-

●EspA ● EscN [85]
● EscQ [85]

-

●YscL-Yersinia (by function) ● FliH

Binds to and regulates activity of ATPase EscN

13, 21, 85

escR

B7UMC1_ECO27

 

24382.43

5.48

 

 

IM

PF00813

Sec?

-

-

●EscR ● EscR ● EscS ●EscU, ●Sep
●EspD

 

●YscR

-

2

escS

B7UMC0_ECO27

 

9920.96

5.36

 

 

IM

PF01313

Sec?

-

-

●EscR

 

YscS

-

2

escT

B7UMB9_ECO27

 

28745.27

4.92

 

 

IM

PF01311

 

Sec?

-

-    

YscT -Yersini
FliR - flagellum

Physically associated in the basal body with EscU in a 1:1 ratio; C-terminus is cytoplasmic 17

-

17

escU

B7UMB8_ECO27

 

39177.29

9.27

 

cleaved at NPTH motif [18]

IM

PF01312

Sec?

-

- ●EscR  

YscU -Yersin
FlhB - flagellu
Spa40 -Shigella

Substrate specificity switching 18

-

2,
17,
18

etgA

B7UMB7_ECO27

rOrf3 

17103.65

8.96

 

 

P

PF01464

Sec

±

± ●EscI  

lytic transglycosylase IagB, IpgF

●Lytic transglycosylase needed to open gap in peptidoglycan for assembly of secretion system [22]; potential drug target.
● Muramidase activity of EtgA is not critical but has a significant contribution to the efficiency of the T3S process [77]

22,
77

grIR

B7UMB6_ECO27

 

13944.04

4.83

 

 

C

 

 

No

+

+

●Grl
●GrlA

-

Bongori regulator

Negative regulator of TTSS

Co-operates with GrlA

-

grIA  

B7UMB5_ECO27

 

16052.49

9.71

 

 

C

PF07180

 

No

No expression

-

●GrlR

 

Bongori regulator, CaiF

Positive regulator of TTSS

Co-operates with GrlR

-

cesD

B7UMB4_ECO27

 

17502.84

6.94

 

 

C

PF07720

 

No

-

±

●EspD (FWB)[4]
● EscD (2H) [2]

 

●SycD -Yersinia ● Other TPR chaperones

Chaperone EspD

-

2,
4

escC

B7UMB3_ECO27

Secretin

56225.89

8.10

 

 

OM

PF00263 PF03958

12–14
subunits "ring"

Sec?

--

     

●EscD

T3S basal body

Interacts with peptidoglycan [23], Dsb-dependent domain missing

-

23

sepD

B7UMB2_ECO27

 

17563.07

7.00

 

 

 

 

No

- (translocators are not secreted)

-

●SepL

 

Switches translocator

Works in concert with SepL

-

escJ

B7UMB1_ECO27

 

20756.91

5.53 

 

Palmitoylated at C19 (by analogy to PrgK) [10]

ΙΜ

PF01514

24 subunit ‘ring’ 1yj7

Sec

-

-    

●YscJ

●Essential molecular platform for T3SS assembly

EscD and EscJ form ring-like structure in inner membrane [24, 25]

-

10, 24, 25,

escI

B7UMB0_ECO27

 rOrf8-rod

15258.41

5.22 

 

 

 

PF09392

T3S?

-

●EscU

 

●MxiH, MxiI

T3S

Forms inner rod within base of needle complex[27, 28, 29, 30].

-

27,
28,
29,
30

EspZ

B7UMA9_ECO27

SepZ

9391.86

4.99

 

 

 

PF06066

T3S

+

+

●EscR

 

●Translocated effector
● Contributes to host cell survival mechanisms [31]

-

31,
32

Mpc

B7UMA08_ECO27

Orf12- multiple point controller

13942.02

4.74

 

 

 

 

No

-

-

●Ler

 

●SsaM

Interacts with Ler-suppresses LEE expression [12]

Might play a role in switching translocator

-

12

escN

B7UMA6_ECO27

 

48858.45

5.99

 

 

Peripheral inner membrane protein

PF00006

2OBL

No

-

-

●Ces
● Tir ●EscL [85] ●EscQ [85]

-

●YscN-Yersinia ● HrcN-Pseudominas ● BscN-Bordetella
● InvC-Salmonella
● SsaN - Salmonela

ATPAse Forms hexameric complex on the inner membrane

+ P

2,
5, 82, 85

EscA

B7UMA5_ECO27

Orf15

14659.78

9.56

 

 

 

 

 

No

 -

-    

T3S

essential for T3S;localized to the periplasm;associated with inner membrane via N-terminal 19 aa;interacts with EscC

ref

EscP

B7UMA4_ECO27

Orf16

16579.01

9.27

 

 

 

PF06523

 

No

±

±    

Needle length control 13
Trigger the substrate switch 14

-

13,
14
ref

escV

B7UMA7_ECO27

 

75155.16

5.66

 

 

IM

PF00771

 

Sec?

-

-    

●LcrD -Yersinia
● FlhA - flagellum

T3S

C-terminal cytoplasmic domain might play a role in gene regulation 15, 16

-

15,
16

sepQ

B7UMA3_ECO27

escQ-C-ring like

34962.85

4.79

 

 

 

PF06622

 

No

-

-    

●YscQ (by fubction) ● FliN domain in the C terminus[13]

T3S

●Forms ring within basal body [33]; interacts with EscL [34]

-

33,
34

espH

B7UMA2_ECO27

 

19022.51

9.48

 -0,37

 

 

 

 

T3S

+

+    

●Translocated effector

-

cesF

B7UMA1_ECO27

 

14058.11

4.57 

 

 

C

PF06704

 

No

±

+

●EspF [84]

 

●Chaperone EspF

-

84

map

B7UMA0_ECO27

 

22568.69

9.08

-0,404

 

 

PF03278

 

T3S

+

●CesT

 

●IpgB2 ● EspM ● EspT

●Mitochondrial dysfunction [35]
● Induces transient filopodia formation [36]

●Translocated effector

-

35,
36,
37,
38

tir

B7UM99_ECO27

 

56509.78

4.92

-0,417

●pY474 by host kinases [39, 40, 42] ●pY454 by host kinases [41] ●pS436, pS437 by host kinases [43]

Host CM

PF07489 PF03549 PF07490

 

T3S

-

●CesT

●Tir, Map, and EspH collaborate to organize the assembly and disassembly of actin filopodia and pedestals (Kenny et al., 2002; Tu et al., 2003)
● Intimin

● N-terminal and C-terminal domains remain intracellular and interact with numerous signalling, adapter and cytoskeletal proteins.
● Function dependent on its phosphorylation sites, a GTPase activating protein (GAP)-like motif and a polyproline region.

●Translocated effector

2,
5-
7
,
39-
48

cesT

CEST_

ECO27

17706.94

4.44

 

 

C

PF05932

1K3E

-

± 

-

●CesT (2H) [2]
● Map (2H/AP) [2]
● Tir (2H/AP/CL) [5, 6, 7]
● EspF (2H) [2]
● EscN (AP) [5]
● SepL (FWB) [8]

-

●SrcA -Salmonela Many

Chaperone Tir and Map

●Possible regulatory role, by analogy with ExsC? ● Probably influences the translocation of EspH, EspZ, and some non-LEE effectors [83]

+ P

2,
5,
6,
7,
8, 46, 83, 89

Intimin

EAE_ ECO27

Eae

102352.53

 

8.84

-0,394

 

OM

PF02369 PF02368 PF07979 PF01476

1E5U 1F00
1F02

Self

+

-  

●Tir

Adhesin (intimin)

+ P

44,
47,
48

escD

B7UM96_ECO27

 

45314.32

6.96

-0,091

 

 

 

 

 

-

-    

●YscD

T3S

sepL

B7UM95_ECO27

 

39987.85

4.76

-0,204

C (weak interaction IM)

PF07201

No

-

-

●SepD

 

●MxiC

Switches translocator

●Single protein mediating effects of YopN and TyeA; internal interaction between YopN- and TyeA-like moieties; also a translocated effector?

2,
8,
49,
50

espA

B7UM94_ECO27

20468.89 

4.52

-0,191

 

Bacterial cell surface

PF0343

T3S

+

-

●CesAB

 

●Flagelin (C-terminal coiled-coil domain)

Translocator

●Half-flagellin model (see text); dimerizes before polymerizes; lacks D0 and D3 domains

-

1-3, 51,
52

espD

B7UM93_ECO27

O88127_ECOLI

39499.40

 

5.13

-0,003

 

PF04888

T3S

-

●EspD

 

●YopB

Translocator

-

2,
54

espB

EAEB_ECO27

EaeB

33140.81

5.24

-0,188

 

Secreted: Host Cytosol-Membrane

PD454109

T3S

+

-

●CesAB [2]

●SERPINA1 [80]
● a-catenin [81]

●YopD

●Translocator ● Effector - Binds to myosins that interact with actin filaments and mediate essential processes (e.g.microvillus formation ,phagocytosis). Inhibits the interaction of myosins with actin [55, 56]

-

2,
55,
56, 80, 81

cesD2

B7UM91_ECO27

 

15831.97

5.23 

-0,332

C

PF09621

 

No

±

+

●EspD

 

●LcrR

Chaperone EspD

-

escF

B7UM90_ECO27

 

8127.21

4.32

-0,190

 

PF09392

 

T3S

-

-

●EscJ

 

●YscF

Major Needle component

-

57

orf29

B7UM89_ECO27

CesA2

10311.95

5.83

0,142

PF06287

No

-

-

●EscE(Orf2) ● EspA

 

●YPO0261 ● SsaH
● CV2586

●T3S?. ● EspA chaperone? [58]

Functionally important conserved residues can be identified by scrutiny of homologues, Needle component like SsaH? Is that why it binds EspA?

-

58

espF

B7UM88_ECO27

 

20977.68

10,61 

-0,339

 

PF04806

 

T3S

+

+

●CesF

 

●Translocated effector
●Mitochondrial dysfunction [60, 61]
● Microvilli effacement [62] ● TJ disruption, apoptosis [63] ● Epithelial transporter inhibition [64] ●Antiphagocytosis ● Membrane remodeling [65]
● Actin-pedestal maturation
● Nucleolus disruption

●Map and EspF synergise in TJ-disrupting activity proven in vivo [62, 63, 79]

-

2,
59-70, 79


Non- LEE Effectors (based on [Iguchi 2009], [Dean and Kenny, 2009] and modified)

Protein name
(new)

Uniprot code

Pathogenicity

island

Other names

MW (Da)

pI

GRAVY PTMs Localization Domain

Quaternary Structure

Secretion

Mechanism

Effect of deletion
mutation on secretion*

Effect on
pedestal
formation# /virulence&

Known
Interactions in Bacterium/
method/Ref

 Known
Interactions in Host/
method/Ref

Homologues/
organism
Known
function
Predicted
function
Protein
existence
Refs

EspG2

B7UH72_ECO27

  IE5

 

42.730

  5,76

       

 

T3S    

 

           

EspJ

B7ULW8_ECO27

  PP2

 

24.583

  9,67

       

 

T3S    

 

    ● inhibits phagocytosis [88]     88

EspL

B7UI20_ECO27

  IE6

 

62.188

  6,33

       

 

T3S    

 

           

NleA

/EspI

B7UR60_ECO27

  PP6

 

47.478

  5,27

       

 

T3S    

 

    targets Golgi aparratus/Binds PDZ domain-containing proteins [91]     91

NleB1

B7UNX3_ECO27

  IE6

 

38.056

  5,96

       

 

T3S    

 

           

NleB2

B7UI21_ECO27

  PP4

 

37.627

  5,52

       

 

T3S    

 

           

NleC

B7UNX4_ECO27

  PP4

 

37.226

  4,67

       

 

T3S    

 

           

NleD

B7UNX6_ECO27

 PP4

 

25.951

  5,78

       

 

T3S    

 

           
NleE1
IE6  

26.057

5,78           T3S                  

NleE2

B7UP11_ECO27

  IE2

 

19.723

  5,62

       

 

T3S    

 

           

NleF

B7UR63_ECO27

  PP6

 

21.388

  4,94

       

 

T3S    

 

           

NleG/

NleI

B7UNX2_ECO27

  PP4

 

20.331

  5,34

       

 

T3S    

 

           

NleH1

B7ULW4_ECO27

PP2 

 

32.482

  5,34

       

 

T3S    

 

           

NleH2

B7UR62_ECO27

  PP6

 

33.683

  5,54

       

 

T3S    

 

           

Other proteins of the EPEC secretome and virulence factors

Protein name (new)

Uniprot code

Pathogenicity island

Other names

MW (Da)

pI

GRAVY

PTMs Localization Domain Quaternary Structure

Secretion

Mechanism

Effect of deletion
mutation on secretion*

Effect on
pedestal
formation# /virulence&

Known
Interactions in Bacterium/
method/Ref

    Known
Interactions in
Host/
method/Ref

Homologues/
organism
Known
function
Predicted
function
Protein
existence

  Refs

EspC

IE5
140.782 5.51           Sec  

 

      Autotransporter/
Serine protease
     
FliC
B7USU2_ECO27  

 

56.301             Fla                  
FliD
B7USU3_ECO27  

 

48.496             Fla                  
FlgK
B7UP96_ECO27  
57.844             Fla                  

Efa1/

LifA

IE6
Lymphostatin
365.953             Sec/T5S  

 

 
Rho-GTPase
  Multi-domain protein:
Glucosyl transferase/
YopT-like protease/
adhesin? Toxin that specifically inhibits lymphocyte proliferation and interleukin 2 (IL-2), IL-4, and gamma interferon production in response to a variety of stimuli-disruption of intestinal epithelial-barrier function via the modulation of Rho GTPase activities
   

 Klapproth,2000

Babbin 2009

Efa1/

LifA-

like

B7UP10_ECO27  IE2
Lymphostatin
298.303             Sec/T5S  

 

 
Rho-GTPase
  Multi-domain protein:
Glucosyl transferase/
YopT-like protease/
adhesin? Toxin that specifically inhibits lymphocyte proliferation and interleukin 2 (IL-2), IL-4, and gamma interferon production in response to a variety of stimuli-disruption of intestinal epithelial-barrier function via the modulation of Rho GTPase activities
   

 Klapproth,2000

Babbin 2009

Stevens 2004

BfpA
BFPA_ECO27  
Bfp, Bundle-forming pilin
20.270             Pil  
      Major repeating bundle-forming pilus (BFP) subunit. Is required for EPEC localized adherence      
BfpB BFPB_ECO27  
Bundle-forming pilus B
58.372                         Is absolutely required for pilus biogenesis, and for EPEC localized adherence and autoaggregation. Acts at a step in the BFP biogenic pathway after production and processing of the structural pilus subunit BfpA      
Lom1 B7ULW1_ECO27 PP2
Predicted outer membrane Lom
21.706       outer membrane protein PF06316   Sec/Bam                  
Lom2   PP4
        outer membrane protein     Sec/Bam                  
Lom3 B7UR56_ECO27 PP6
Predicted outer membrane Lom
21.787       outer membrane protein PF06316   Sec/Bam                  
PagC B7UI17_ECO27 IE6
20.307       outer membrane protein PF06316   Sec/Bam                  
YghJ B7UI41_ECO27  
168.101       inner membrane PF13322   T2S