A conserved domain of about 70 amino acid residues has been found  in a
number of proteins that transport or detoxify heavy metals. This domain
contains two conserved cysteines that could be involved in the binding of
these metals. The domain has been termed Heavy-Metal-Associated (HMA).
Solution structure of the fourth HMA domain of the Menkes copper-transporting
ATPase shows a well defined structure comprising a four-stranded antiparallel
β-sheet and two α helices packed in an α-β sandwich fold
(see <PDB:1AW0>) . This fold is common to other domains and is classified
Some of the proteins containing an HMA domain are listed below.
A variety of cation transport ATPases (E1-E2 ATPases) (see <PDOC00139>).
The human copper ATPAses ATP7A and ATP7B which are respectively involved in
Menke's and Wilson's diseases. ATP7A and ATP7B both contain 6 tandem copies
of the HMA domain. The copper ATPases CCC2 from budding yeast, copA from
Enterococcus faecalis and synA from Synechococcus contain one copy of the
HMA domain. The cadmium ATPases cadA from Bacillus firmus and from plasmid
pI258 from Staphylococcus aureus also contain a single HMA domain, while
a chromosomal Staphylococcus aureus cadA contains two copies. Other, less
characterized ATPases that contain the HMA domain are: fixI from Rhizobium
meliloti, pacS from Synechococcus strain PCC 7942), Mycobacterium leprae
ctpA and ctpB and Escherichia coli hypothetical protein yhhO. In all these
ATPases the HMA domain(s) are located in the N-terminal section.
Mercuric reductase (EC 188.8.131.52) (gene merA) which is generally encoded by
plasmids carried by mercury-resistant Gram-negative bacteria. Mercuric
reductase is a class-1 pyridine nucleotide-disulphide oxidoreductase (see
<PDOC00073>). There is generally one HMA domain (with the exception of a
chromosomal merA from Bacillus strain RC607 which has two) in the N-
terminal part of merA.
Mercuric transport protein periplasmic component (gene merP), also encoded
by plasmids carried by mercury-resistant Gram-negative bacteria. It seems
to be a mercury scavenger that specifically binds to one Hg(2+) ion and
which passes it to the mercuric reductase via the merT protein. The N-
terminal half of merP is a HMA domain.
Helicobacter pylori copper-binding protein copP.
Yeast protein ATX1 , which could act in the transport and/or
partitioning of copper.
The profile we developed spans the complete domain. The pattern is centered on
the two metal-binding residues.
PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and
distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives
(CC BY-NC-ND 4.0) License, see prosite_license.html.