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HMA, heavy metal-associated domain superfamily

SCOP classification
Root:   SCOP hierarchy in SUPERFAMILY [ 0] (11)
Class:   Alpha and beta proteins (a+b) [ 53931] (376)
Fold:   Ferredoxin-like [ 54861] (59)
Superfamily:   HMA, heavy metal-associated domain [ 55008]
Families:   HMA, heavy metal-associated domain [ 55009] (8)


Superfamily statistics
Genomes (2,750) Uniprot 2014_06 PDB chains (SCOP 1.75)
Domains 18,999 71,444 21
Proteins 14,379 54,999 20


Functional annotation
General category Processes_IC
Detailed category Ion metabolism and transport

Document:
Function annotation of SCOP domain superfamilies

Gene Ontology (high-quality)

(show details)
GO termFDR (singleton)FDR (all)SDFO levelAnnotation (direct or inherited)
Biological Process (BP)biological regulation0.0034540.1116Least InformativeInherited
Biological Process (BP)single-organism cellular process0.15931Least InformativeInherited
Biological Process (BP)ion transport0.00011080.000000000000001945Moderately InformativeDirect
Biological Process (BP)regulation of biological quality0.00000096750.0000000006213Moderately InformativeDirect
Biological Process (BP)ion homeostasis0.000000000012930InformativeDirect
Biological Process (BP)metal ion transport00.001374InformativeInherited
Biological Process (BP)transition metal ion transport00Highly InformativeDirect
Biological Process (BP)transition metal ion homeostasis00.0000000000003149Highly InformativeDirect
Molecular Function (MF)binding0.0015170.01056Least InformativeInherited
Molecular Function (MF)metal ion binding0.0000000050380Moderately InformativeDirect
Molecular Function (MF)copper ion binding0.0000000000000013940Highly InformativeDirect

Document: GO annotation of SCOP domains

Gene Ontology (high-coverage)

(show details)
GO term FDR (all) SDFO level Annotation (direct or inherited)
Biological Process (BP) response to stimulus 0.0003985 Least Informative Direct
Biological Process (BP) biological regulation 0.1116 Least Informative Inherited
Biological Process (BP) single-organism cellular process 1 Least Informative Inherited
Biological Process (BP) ion transport 0.000000000000001945 Moderately Informative Direct
Biological Process (BP) regulation of biological quality 0.0000000006213 Moderately Informative Direct
Biological Process (BP) cellular response to stress 0.3379 Moderately Informative Inherited
Biological Process (BP) cellular response to chemical stimulus 0.4725 Moderately Informative Inherited
Biological Process (BP) cellular localization 1 Moderately Informative Inherited
Biological Process (BP) response to metal ion 0 Informative Direct
Biological Process (BP) ion homeostasis 0 Informative Direct
Biological Process (BP) transmembrane transport 0.07072 Informative Inherited
Biological Process (BP) response to oxidative stress 0.001215 Informative Inherited
Biological Process (BP) metal ion transport 0.001374 Informative Inherited
Biological Process (BP) cellular chemical homeostasis 0.1362 Informative Inherited
Biological Process (BP) transition metal ion transport 0 Highly Informative Direct
Biological Process (BP) pigmentation 0.000003051 Highly Informative Direct
Biological Process (BP) response to copper ion 0.0000008106 Highly Informative Direct
Biological Process (BP) transition metal ion homeostasis 0.0000000000003149 Highly Informative Direct
Biological Process (BP) inorganic cation transmembrane transport 0.00000008852 Highly Informative Direct
Biological Process (BP) detoxification 0 Highly Informative Direct
Molecular Function (MF) binding 0.01056 Least Informative Inherited
Molecular Function (MF) hydrolase activity 0.2348 Least Informative Inherited
Molecular Function (MF) transporter activity 0.00000002355 Moderately Informative Direct
Molecular Function (MF) hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides 0.0001154 Moderately Informative Direct
Molecular Function (MF) metal ion binding 0 Moderately Informative Direct
Molecular Function (MF) molecular function regulator 0.002414 Moderately Informative Inherited
Molecular Function (MF) enzyme activator activity 0.0000017 Informative Direct
Molecular Function (MF) ATPase activity 0.000001809 Informative Direct
Molecular Function (MF) metal ion transmembrane transporter activity 0 Informative Direct
Molecular Function (MF) active transmembrane transporter activity 0.0185 Informative Inherited
Molecular Function (MF) copper ion binding 0 Highly Informative Direct
Molecular Function (MF) ATPase coupled ion transmembrane transporter activity 0.00000000000001997 Highly Informative Direct
Cellular Component (CC) intracellular organelle part 0.04896 Least Informative Inherited
Cellular Component (CC) membrane 0.005609 Least Informative Inherited
Cellular Component (CC) intracellular membrane-bounded organelle 0.08091 Least Informative Inherited
Cellular Component (CC) cytoplasmic part 0.005035 Least Informative Inherited
Cellular Component (CC) vesicle 0.08428 Moderately Informative Inherited
Cellular Component (CC) Golgi apparatus 0.0000000006234 Informative Direct
Cellular Component (CC) endosome 0.03434 Informative Inherited
Cellular Component (CC) late endosome 0.0006117 Highly Informative Direct
Cellular Component (CC) cell-cell junction 0.0000579 Highly Informative Direct
Cellular Component (CC) symplast 0.000001243 Highly Informative Direct

Document: GO annotation of SCOP domains

Enzyme Commission (EC)

(show details)
EC termFDR (all)SDEO levelAnnotation (direct or inherited)
Enzyme Commission (EC)Acting on acid anhydrides0Least InformativeDirect
Enzyme Commission (EC)Oxidoreductases0.3102Least InformativeInherited
Enzyme Commission (EC)Acting on acid anhydrides; catalyzing transmembran0InformativeDirect
Enzyme Commission (EC)Oxidizing metal ions0InformativeDirect
Enzyme Commission (EC)Copper-exporting ATPase0Highly InformativeDirect
Enzyme Commission (EC)Mercury(II) reductase0Highly InformativeDirect
Enzyme Commission (EC)Cu(+) exporting ATPase0Highly InformativeDirect
Enzyme Commission (EC)Cadmium-exporting ATPase0Highly InformativeDirect
Enzyme Commission (EC)Zinc-exporting ATPase0.000000000000008737Highly InformativeDirect

Document: EC annotation of SCOP domains

Disease Ontology (DO)

(show details) Document: DO annotation of SCOP domains

Mouse Phenotype (MP)

(show details)
MP termFDR (all)SDMP levelAnnotation (direct or inherited)
Mammalian Phenotype (MP)abnormal homeostasis0Least InformativeDirect
Mammalian Phenotype (MP)cellular phenotype0Least InformativeDirect
Mammalian Phenotype (MP)nervous system phenotype0.07325Least InformativeInherited
Mammalian Phenotype (MP)liver/biliary system phenotype0.0047Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal metabolism0.005943Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal brain morphology0.01158Moderately InformativeInherited
Mammalian Phenotype (MP)reproductive system phenotype0.01697Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal ion homeostasis0InformativeDirect
Mammalian Phenotype (MP)abnormal enzyme/coenzyme activity0.00002184InformativeDirect
Mammalian Phenotype (MP)abnormal female reproductive system physiology0.0007657InformativeDirect
Mammalian Phenotype (MP)abnormal mineral level0.9492Highly InformativeInherited

Document: MP annotation of SCOP domains

Yeast Phenotype (YP)

(show details)
YP termFDR (all)SDYP levelAnnotation (direct or inherited)
Yeast Phenotype (YP)resistance to chemicals0Least InformativeDirect
Yeast Phenotype (YP)metabolism and growth0Least InformativeDirect
Yeast Phenotype (YP)alkaline pH resistance0.000003693Highly InformativeDirect

Document: YP annotation of SCOP domains

Xenopus Anatomy (XA)

(show details) Document: XA annotation of SCOP domains

Arabidopsis Plant Ontology (AP)

(show details) Document: AP annotation of SCOP domains

Enzyme Commission (EC)

(show details)
EC termFDR (all)SDEC levelAnnotation (direct or inherited)
Enzyme Commission (EC)Hydrolases0Least InformativeDirect
Enzyme Commission (EC)Oxidoreductases0.3902Least InformativeInherited
Enzyme Commission (EC)Acting on acid anhydrides0Moderately InformativeDirect
Enzyme Commission (EC)Oxidizing metal ions0Highly InformativeDirect
Enzyme Commission (EC)Acting on acid anhydrides; catalyzing transmembrane movement of substances0Highly InformativeDirect

Document: EC annotation of SCOP domains

UniProtKB KeyWords (KW)

(show details)
KW termFDR (all)SDKW levelAnnotation (direct or inherited)
Biological processTransport0Least InformativeDirect
Biological processIon transport0Moderately InformativeDirect
Cellular componentMembrane0Least InformativeDirect
Cellular componentGolgi apparatus0.000001598Moderately InformativeDirect
Cellular componentCell membrane0.000001993Moderately InformativeDirect
Cellular componentPeriplasm0.000002122InformativeDirect
DomainTransmembrane0.0000000000001409Least InformativeDirect
DomainRedox-active center0.0000003434InformativeDirect
Molecular functionMetal-binding0Least InformativeDirect
Molecular functionMagnesium0.000000000001072Least InformativeDirect
Molecular functionNucleotide-binding0.716Least InformativeInherited
Molecular functionZinc1Least InformativeInherited
Molecular functionFlavoprotein0.05113Moderately InformativeInherited
Molecular functionCopper0InformativeDirect
Molecular functionFAD0.00001673InformativeDirect
Molecular functionCadmium0Highly InformativeDirect
Molecular functionMercury0Highly InformativeDirect
Molecular functionZinc transport0.000000003022Highly InformativeDirect
Post-translational modificationHydrolase0Least InformativeDirect
Post-translational modificationChaperone0InformativeDirect
Post-translational modificationMethylation0.00000000003241Moderately InformativeDirect
Post-translational modificationPrenylation0InformativeDirect

Document: KW annotation of SCOP domains

InterPro annotation
Cross references IPR006121 SSF55008 Protein matches
Abstract

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 [PubMed8091505].

A conserved domain has been found in a number of these heavy metal transport or detoxification proteins [PubMed8091505]. 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 [PubMed9437429]. This fold is common to other domains and is classified as "ferredoxin-like".


InterPro database


PDBeMotif information about ligands, sequence and structure motifs
Cross references PDB entries
Ligand binding statistics
Nucleic-acid binding statistics
Occurrence of secondary structure elements
Occurrence of small 3D structural motifs

PDBeMotif resource

Jump to [ Top of page · SCOP classification · InterPro annotation · PDBeMotif links · Functional annotation · Gene Ontology (high-quality) · Gene Ontology (high-coverage) · Enzyme Commission (EC) · Disease Ontology (DO) · Mouse Phenotype (MP) · Yeast Phenotype (YP) · Xenopus Anatomy (XA) · Arabidopsis Plant Ontology (AP) · Enzyme Commission (EC) · UniProtKB KeyWords (KW) ]

Internal database links

Browse genome assignments for this superfamily. The SUPERFAMILY hidden Markov model library has been used to carry out SCOP domain assignments to all genomes at the superfamily level.


Alignments of sequences to 15 models in this superfamily are available by clicking on the 'Alignments' icon above. PDB sequences less than 40% identical are shown by default, but any other sequence(s) may be aligned. Select PDB sequences, genome sequences, or paste in or upload your own sequences.


Browse and view proteins in genomes which have different domain combinations including a HMA, heavy metal-associated domain domain.


Examine the distribution of domain superfamilies, or families, across the major taxonomic kingdoms or genomes within a kingdom. This gives an immediate impression of how superfamilies, or families, are restricted to certain kingdoms of life.


Explore domain occurrence network where nodes represent genomes and edges are domain architectures (shared between genomes) containing the superfamily of interest.

There are 15 hidden Markov models representing the HMA, heavy metal-associated domain superfamily. Information on how the models are built, and plots showing hydrophobicity, match emmission probabilities and insertion/deletion probabilities can be inspected.


Jump to [ Top of page · SCOP classification · InterPro annotation · PDBeMotif links · Functional annotation · Gene Ontology (high-quality) · Gene Ontology (high-coverage) · Enzyme Commission (EC) · Disease Ontology (DO) · Mouse Phenotype (MP) · Yeast Phenotype (YP) · Xenopus Anatomy (XA) · Arabidopsis Plant Ontology (AP) · Enzyme Commission (EC) · UniProtKB KeyWords (KW) · Internal database links ]