SPRINT Home UMBER Home Contents Standard Search Advanced Search Relation Search

==SPRINT==> PRINTS View



  selected as


PR00941

Identifier
CDATPASE  [View Relations]  [View Alignment]  
Accession
PR00941
No. of Motifs
9
Creation Date
27-JUL-1998  (UPDATE 10-JUN-1999)
Title
Cadmium-transporting ATPase signature
Database References

PROSITE; PS00154 ATPASE_E1_E2; PS01047 HMA
BLOCKS; BL00154; BL01047
INTERPRO; IPR001366
PDB; 1AFI; 1AFJ
SCOP; 1AFI; 1AFJ
Literature References
1. BULL, P.C. AND COX, D.W. 
Wilson disease and Menkes disease - new handles on heavy-metal transport.
TRENDS GENET. 10 246-252 (1994).
 
2. STEELE, R.A. AND OPELLA, S.J.
Structures of the reduced and mercury-bound forms of MerP, the periplasmic
protein from the bacterial mercury detoxification system. 
BIOCHEMISTRY 36 6885-6895 (1997). 

Documentation
Proteins that transport heavy metals in micro-organisms and mammals share
similarities in their sequences and structures. These proteins provide an
important focus for research, some being involved in bacterial resistance
to toxic metals, such as lead and cadmium, while others are involved in
inherited human syndromes, such as Wilson and Menkes diseases [1].
 
A conserved 30-residue domain has been found in a number of these heavy
metal transport or detoxification proteins [1]. The domain, which has been
termed Heavy-Metal-Associated (HMA), contains two conserved cysteines that
are probably involved in metal binding. 
 
The HMA domain has been identified in the N-terminal regions of a variety
of cation-transporting ATPases (E1-E2 ATPases): the human copper ATPases 
involved in Menkes and Wilson diseases (ATP7A and ATP7B) each contain 6 
tandem copies; a chromosomal Staphylococcus aureus cadA contains two copies;
and the copper ATPases CCC2 from budding yeast, copA from Enterococcus 
faecalis, synA from Synechococcus, and cadmium ATPases cadA from Bacillus 
firmus and plasmid pI258 from Staphylococcus aureus contain a single copy.
Other ATPases that contain the HMA domain include: fixI from Rhizobium 
meliloti; pacS from Synechococcus strain PCC 7942; Mycobacterium leprae 
ctpA and ctpB; and Escherichia coli hypothetical protein yhhO. In addition,
the domain has been found in bacterial mercuric reductase; the copP copper-
binding protein of Helicobacter pylori; and in bacterial mercuric transport
proteins.
 
The structure of the mercuric ion-binding protein MerP from Shigella
flexneri has been determined. The fold has been classed as a ferredoxin-like
alpha-beta sandwich, having a beta-alpha beta-beta alpha-beta architecture,
with the two alpha-helices overlaying a four-stranded anti-parallel beta-
sheet [2]. Structural differences between the reduced and mercury-bound 
forms of merP are localised to the metal-binding loop containing the 
consensus sequence GMTCXXC, the two cysteines of which are involved in
bi-coordination of Hg(2+) [2].
 
Cadmium-transporting ATPase is an integral membrane protein that contains 
a single copy of the HMA domain and is predicted to contain 4 transmembrane
(TM) domains. The protein, which functions as an electroneutral antiporter,
ejecting one Cd(2+) and accumulating two protons via an energy-dependent
efflux mechanism, catalyses the reaction:
 
		ATP + H(2)O = ADP + orthophosphate
 
CDATPASE is a 9-element fingerprint that provides a signature for cadmium-
transporting ATPases. The fingerprint was derived from an initial alignment
of 5 sequences: the motifs were drawn from conserved regions spanning the
N-terminal portion of the alignment, motifs 1 and 2 encoding the HMA domain
- motif 1 includes the C-terminal residues of strand 1 and the first metal-
binding cysteine; motif 2 spans helix 1 and strand 2; and motif 3 spans 
strand 3 and helix 2. A single iteration on OWL30.2 was required to reach 
convergence, no further sequences being identified beyond the starting set. 
Three partial matches were found (E70041, LPU494983, F69869), all of which 
are heavy-metal transporting ATPase homologues that match 2 motifs.
 
An update on SPTR37_9f identified a true set of 5 sequences, and 6
partial matches.
Summary Information
   5 codes involving  9 elements
0 codes involving 8 elements
0 codes involving 7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
4 codes involving 2 elements
Composite Feature Index
9555555555
8000000000
7000000000
6000000000
5000000000
4000000000
3000000000
2030001121
123456789
True Positives
CADA_BACFI    CADA_LISMO    CADA_STAAU    CADD_STAAU    
P94888
True Positive Partials
Codes involving 2 elements
COPA_ENTHR O31688 O32219 O32220
Sequence Titles
CADA_BACFI  PROBABLE CADMIUM-TRANSPORTING ATPASE (EC 3.6.1.-) (CADMIUM EFFLUX ATPASE) - BACILLUS FIRMUS. 
CADA_LISMO PROBABLE CADMIUM-TRANSPORTING ATPASE (EC 3.6.1.-) (CADMIUM EFFLUX ATPASE) - LISTERIA MONOCYTOGENES.
CADA_STAAU PROBABLE CADMIUM-TRANSPORTING ATPASE (EC 3.6.1.-) (CADMIUM EFFLUX ATPASE) - STAPHYLOCOCCUS AUREUS.
CADD_STAAU PROBABLE CADMIUM-TRANSPORTING ATPASE (EC 3.6.1.-) (CADMIUM EFFLUX ATPASE) - STAPHYLOCOCCUS AUREUS.
P94888 CADMIUM RESISTANCE PROTEIN - LACTOCOCCUS LACTIS.

COPA_ENTHR COPPER/POTASSIUM-TRANSPORTING ATPASE A (EC 3.6.1.36) - ENTEROCOCCUS HIRAE.
O31688 YKVW PROTEIN - BACILLUS SUBTILIS.
O32219 YVGW PROTEIN - BACILLUS SUBTILIS.
O32220 YVGX PROTEIN - BACILLUS SUBTILIS.
Scan History
OWL30_2    1  50   NSINGLE    
SPTR37_9f 2 69 NSINGLE
Initial Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
YRVDGLSCTN LISCADTNP 7 7 -
YRIEGLSCTN LLU789671 10 10 -
YRVEGFSCAN CADD_STAAU 15 15 -
YRVQGFTCAN CADA_STAAU 16 16 -
YRVQGFTCAN CADA_BACFI 16 16 -

Motif 2 width=22
Element Seqn Id St Int Rpt
AGKFEKNVKQLAGVQDAKVNFG CADD_STAAU 104 79 -
AGKFEKNVKQLPGVTSATVNFG LLU789671 21 1 -
AAKFERNVKEIEGVTEAIVNFG LISCADTNP 18 1 -
AGKFEKNVKQLSGVEDAKVNFG CADA_BACFI 27 1 -
AGKFEKNVKKIPGVQDAKVNFG CADA_STAAU 27 1 -

Motif 3 width=24
Element Seqn Id St Int Rpt
ASKIDVYGNASVEELEKAGAFENL CADA_STAAU 49 0 -
ASKIDVYGNASVEELEKAGAFENL CADD_STAAU 126 0 -
ASKITVTGEASIQQVEQAGAFEHL LISCADTNP 40 0 -
ASKISVEGQTTIEELEEAGAFENL LLU789671 43 0 -
ASKIAVYGNATIEELEKAGAFENL CADA_BACFI 49 0 -

Motif 4 width=18
Element Seqn Id St Int Rpt
GEDNLVTSMLFVSSIVIG CADD_STAAU 203 53 -
GEDFYLTNALFIFAIFIG LISCADTNP 109 45 -
GEDHLLTKALYILAIIIG LLU789671 109 42 -
GEDNLVTSMLFVGSIVIG CADA_STAAU 126 53 -
GEENIVTTLLFLASMFIG CADA_BACFI 123 50 -

Motif 5 width=13
Element Seqn Id St Int Rpt
GGYSLFKVGFQNL CADA_STAAU 143 -1 -
GGFDLFKEGFSDL LLU789671 126 -1 -
GGYSLFKEGFKNL LISCADTNP 126 -1 -
GGYSLFKVGFQNL CADD_STAAU 220 -1 -
GGLSLFKVGLQNL CADA_BACFI 140 -1 -

Motif 6 width=21
Element Seqn Id St Int Rpt
RFSMDRSRQSIRSLMDIAPKE CADA_STAAU 197 41 -
RFSMDKARQSIRSLMDIAPKE LLU789671 180 41 -
RYSMDKARQSIRSLMDIAPKE LISCADTNP 180 41 -
RFSMDRARQSIRSLMDIAPKE CADD_STAAU 274 41 -
RFSMDRARQSIRSLMDIAPKE CADA_BACFI 194 41 -

Motif 7 width=17
Element Seqn Id St Int Rpt
EALVRRSGTDRMVHVDD LISCADTNP 200 -1 -
EALIRRNNVEQLVSVDK LLU789671 200 -1 -
EALVRRNGQEIMIHVDD CADD_STAAU 294 -1 -
EALVKRNGQEIMIHVDD CADA_BACFI 214 -1 -
EALVRRNGQEIIIHVDD CADA_STAAU 217 -1 -

Motif 8 width=17
Element Seqn Id St Int Rpt
DDEVFAGTLNEEGILEV LLU789671 261 44 -
DDSVFAGTLNEEGLLEV LISCADTNP 261 44 -
DDEVFAGTLNEEGLLEV CADD_STAAU 355 44 -
DDEVFAGTLNEEGLIEV CADA_STAAU 278 44 -
DNEVFAGTLNEEGLLEV CADA_BACFI 275 44 -

Motif 9 width=15
Element Seqn Id St Int Rpt
TKKVTDTTIAKIIHL LLU789671 280 2 -
TKRVEDTTISKIIHL LISCADTNP 280 2 -
TKLVEDTTISKIIHL CADA_BACFI 294 2 -
TKYVEDTTITKIIHL CADA_STAAU 297 2 -
TKYVEDTTISKIIHL CADD_STAAU 374 2 -
Final Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
YRVEGFSCAN CADD_STAAU 15 15 -
YRVQGFTCAN CADA_STAAU 16 16 -
YRVQGFTCAN CADA_BACFI 16 16 -
YRVDGLSCTN CADA_LISMO 7 7 -
YRIEGLSCTN P94888 10 10 -

Motif 2 width=22
Element Seqn Id St Int Rpt
AGKFEKNVKQLAGVQDAKVNFG CADD_STAAU 104 79 -
AGKFEKNVKKIPGVQDAKVNFG CADA_STAAU 27 1 -
AGKFEKNVKQLSGVEDAKVNFG CADA_BACFI 27 1 -
AAKFERNVKEIEGVTEAIVNFG CADA_LISMO 18 1 -
AGKFEKNVKQLPGVTSATVNFG P94888 21 1 -

Motif 3 width=24
Element Seqn Id St Int Rpt
ASKIDVYGNASVEELEKAGAFENL CADD_STAAU 126 0 -
ASKIDVYGNASVEELEKAGAFENL CADA_STAAU 49 0 -
ASKIAVYGNATIEELEKAGAFENL CADA_BACFI 49 0 -
ASKITVTGEASIQQVEQAGAFEHL CADA_LISMO 40 0 -
ASKISVEGQTTIEELEEAGAFENL P94888 43 0 -

Motif 4 width=18
Element Seqn Id St Int Rpt
GEDNLVTSMLFVSSIVIG CADD_STAAU 203 53 -
GEDNLVTSMLFVGSIVIG CADA_STAAU 126 53 -
GEENIVTTLLFLASMFIG CADA_BACFI 123 50 -
GEDFYLTNALFIFAIFIG CADA_LISMO 109 45 -
GEDHLLTKALYILAIIIG P94888 109 42 -

Motif 5 width=13
Element Seqn Id St Int Rpt
GGYSLFKVGFQNL CADD_STAAU 220 -1 -
GGYSLFKVGFQNL CADA_STAAU 143 -1 -
GGLSLFKVGLQNL CADA_BACFI 140 -1 -
GGYSLFKEGFKNL CADA_LISMO 126 -1 -
GGFDLFKEGFSDL P94888 126 -1 -

Motif 6 width=21
Element Seqn Id St Int Rpt
RFSMDRARQSIRSLMDIAPKE CADD_STAAU 274 41 -
RFSMDRSRQSIRSLMDIAPKE CADA_STAAU 197 41 -
RFSMDRARQSIRSLMDIAPKE CADA_BACFI 194 41 -
RYSMDKARQSIRSLMDIAPKE CADA_LISMO 180 41 -
RFSMDKARQSIRSLMDIAPKE P94888 180 41 -

Motif 7 width=17
Element Seqn Id St Int Rpt
EALVRRNGQEIMIHVDD CADD_STAAU 294 -1 -
EALVRRNGQEIIIHVDD CADA_STAAU 217 -1 -
EALVKRNGQEIMIHVDD CADA_BACFI 214 -1 -
EALVRRSGTDRMVHVDD CADA_LISMO 200 -1 -
EALIRRNNVEQLVSVDK P94888 200 -1 -

Motif 8 width=17
Element Seqn Id St Int Rpt
DDEVFAGTLNEEGLLEV CADD_STAAU 355 44 -
DDEVFAGTLNEEGLIEV CADA_STAAU 278 44 -
DNEVFAGTLNEEGLLEV CADA_BACFI 275 44 -
DDSVFAGTLNEEGLLEV CADA_LISMO 261 44 -
DDEVFAGTLNEEGILEV P94888 261 44 -

Motif 9 width=15
Element Seqn Id St Int Rpt
TKYVEDTTISKIIHL CADD_STAAU 374 2 -
TKYVEDTTITKIIHL CADA_STAAU 297 2 -
TKLVEDTTISKIIHL CADA_BACFI 294 2 -
TKRVEDTTISKIIHL CADA_LISMO 280 2 -
TKKVTDTTIAKIIHL P94888 280 2 -