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181  structures 8199  species 0  interactions 56698  sequences 394  architectures

Family: HMA (PF00403)

Summary: Heavy-metal-associated domain

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This is the Wikipedia entry entitled "HMA domain". More...

HMA domain Edit Wikipedia article

Heavy-metal-associated domain
PDB 1mwz EBI.jpg
solution structure of the n-terminal domain of znta in the zn(ii)-form
Identifiers
SymbolHMA
PfamPF00403
InterProIPR006121
PROSITEPDOC00804
SCOP22hqi / SCOPe / SUPFAM
TCDB9.A.2

In molecular biology, the HMA domain (heavy-metal-associated domain) is a conserved protein domain found in a number of heavy metal transport or detoxification proteins.[1]

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's and Menke's diseases.[1]

The HMA domain, contains two conserved cysteines that are probably involved in metal binding. The fourth HMA domain of the Menke's copper transporting ATPase shows a well-defined structure comprising a four-stranded antiparallel beta-sheet and two alpha helices packed in an alpha-beta sandwich fold.[2] This fold is common to other domains and is classified as "ferredoxin-like".


References

  1. ^ a b Bull PC, Cox DW (1994). "Wilson disease and Menkes disease: new handles on heavy-metal transport". Trends Genet. 10 (7): 246–52. PMID 8091505. {{cite journal}}: Unknown parameter |month= ignored (help)
  2. ^ Gitschier J, Moffat B, Reilly D, Wood WI, Fairbrother WJ (1998). "Solution structure of the fourth metal-binding domain from the Menkes copper-transporting ATPase". Nat. Struct. Biol. 5 (1): 47–54. PMID 9437429. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
This article incorporates text from the public domain Pfam and InterPro: IPR006121

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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Literature references

  1. Rosenzweig AC, Huffman DL, Hou MY, Wernimont AK, Pufahl RA, O'Halloran TV; , Structure Fold Des 1999;7:605-617.: Crystal structure of the Atx1 metallochaperone protein at 1.02 A resolution. PUBMED:10404590 EPMC:10404590


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR006121

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's and Menke's diseases [ PUBMED:8091505 ].

A conserved domain has been found in a number of these heavy metal transport or detoxification proteins [ PUBMED:8091505 ]. The domain, which has been termed Heavy-Metal-Associated (HMA), contains two conserved cysteines that are probably involved in metal binding.

Structure solution of the fourth HMA domain of the Menke's copper transporting ATPase shows a well-defined structure comprising a four-stranded antiparallel beta-sheet and two alpha helices packed in an alpha-beta sandwich fold [ PUBMED:9437429 ]. This fold is common to other domains and is classified as "ferredoxin-like".

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan HMA (CL0704), which has the following description:

This superfamily includes families that are involved in heavy metals transport or in detoxification pathways. The Heavy-Metal -Associated (HMA) domain contains two conserved Cys and a common structure comprising a four-stranded antiparallel beta-sheet and two alpha-helices packed in an alpha-beta sandwich fold.

The clan contains the following 2 members:

HMA HMA_2

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(48)
Full
(56698)
Representative proteomes UniProt
(181538)
RP15
(7259)
RP35
(25810)
RP55
(51379)
RP75
(80570)
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PP/heatmap 1            

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(48)
Full
(56698)
Representative proteomes UniProt
(181538)
RP15
(7259)
RP35
(25810)
RP55
(51379)
RP75
(80570)
Alignment:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(48)
Full
(56698)
Representative proteomes UniProt
(181538)
RP15
(7259)
RP35
(25810)
RP55
(51379)
RP75
(80570)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Prosite
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Finn RD , Griffiths-Jones SR
Number in seed: 48
Number in full: 56698
Average length of the domain: 60.7 aa
Average identity of full alignment: 25 %
Average coverage of the sequence by the domain: 17.62 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 24.8 24.8
Trusted cut-off 24.8 24.8
Noise cut-off 24.7 24.7
Model length: 62
Family (HMM) version: 29
Download: download the raw HMM for this family

Species distribution

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Selections

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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the HMA domain has been found. There are 181 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A044UQF2 View 3D Structure Click here
A0A044VA77 View 3D Structure Click here
A0A077ZAF2 View 3D Structure Click here
A0A077ZJJ6 View 3D Structure Click here
A0A077ZKP7 View 3D Structure Click here
A0A096RFC0 View 3D Structure Click here
A0A0D2EZG3 View 3D Structure Click here
A0A0D2G7M0 View 3D Structure Click here
A0A0D2GBG6 View 3D Structure Click here
A0A0D2GRS3 View 3D Structure Click here
A0A0D2GUW6 View 3D Structure Click here
A0A0D2H243 View 3D Structure Click here
A0A0H3GJB4 View 3D Structure Click here
A0A0H3GYK0 View 3D Structure Click here
A0A0H3H5J8 View 3D Structure Click here
A0A0K0E6L3 View 3D Structure Click here
A0A0K0EJT2 View 3D Structure Click here
A0A0N4UIX7 View 3D Structure Click here
A0A0N7KES2 View 3D Structure Click here
A0A0P0UZA6 View 3D Structure Click here
A0A0P0VRA1 View 3D Structure Click here
A0A0P0VTT2 View 3D Structure Click here
A0A0P0W6H8 View 3D Structure Click here
A0A0P0WEB4 View 3D Structure Click here
A0A0P0X004 View 3D Structure Click here
A0A0R0EEE4 View 3D Structure Click here
A0A0R0EQL9 View 3D Structure Click here
A0A0R0FIF7 View 3D Structure Click here
A0A0R0FWJ2 View 3D Structure Click here
A0A0R0FWR5 View 3D Structure Click here
A0A0R0FZ47 View 3D Structure Click here
A0A0R0FZQ3 View 3D Structure Click here
A0A0R0FZY9 View 3D Structure Click here
A0A0R0G3D4 View 3D Structure Click here
A0A0R0GKD7 View 3D Structure Click here
A0A0R0HGB3 View 3D Structure Click here
A0A0R0HQB9 View 3D Structure Click here
A0A0R0I422 View 3D Structure Click here
A0A0R0I8C0 View 3D Structure Click here
A0A0R0IEH2 View 3D Structure Click here