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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 (2,744) Uniprot 2014_06 PDB chains (SCOP 1.75)
Domains 18,955 71,444 21
Proteins 14,358 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)localization0.000041130Least InformativeDirect
Biological Process (BP)single-organism cellular process0.058520.003666Least InformativeInherited
Biological Process (BP)response to stimulus0.18620.04512Least InformativeInherited
Biological Process (BP)ion transport0.000000015250Moderately InformativeDirect
Biological Process (BP)regulation of biological quality0.0000017730.00000000001852Moderately InformativeDirect
Biological Process (BP)metal ion transport0.0000000000019950.0004013InformativeDirect
Biological Process (BP)cation homeostasis0.000000000010660InformativeDirect
Biological Process (BP)response to oxidative stress0.00021870.000005301InformativeDirect
Biological Process (BP)transition metal ion transport0.0000000000000032580Highly InformativeDirect
Biological Process (BP)transition metal ion homeostasis0.0000000000000063810.000000000005252Highly InformativeDirect
Molecular Function (MF)binding0.0013730.01134Least InformativeInherited
Molecular Function (MF)cation binding0.0000000012510Moderately InformativeDirect
Molecular Function (MF)copper ion binding00Highly 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) localization 0 Least Informative Direct
Biological Process (BP) biosynthetic process 0.2513 Least Informative Inherited
Biological Process (BP) protein metabolic process 0.5742 Least Informative Inherited
Biological Process (BP) cellular macromolecule metabolic process 1 Least Informative Inherited
Biological Process (BP) developmental process 0.4404 Least Informative Inherited
Biological Process (BP) multicellular organismal process 0.9047 Least Informative Inherited
Biological Process (BP) regulation of cellular process 1 Least Informative Inherited
Biological Process (BP) regulation of metabolic process 0.3234 Least Informative Inherited
Biological Process (BP) heterocycle metabolic process 0.6044 Least Informative Inherited
Biological Process (BP) organic cyclic compound metabolic process 0.4518 Least Informative Inherited
Biological Process (BP) cellular aromatic compound metabolic process 0.476 Least Informative Inherited
Biological Process (BP) cellular component organization or biogenesis 1 Least Informative Inherited
Biological Process (BP) nitrogen compound metabolic process 0.7727 Least Informative Inherited
Biological Process (BP) single-organism metabolic process 0.06977 Least Informative Inherited
Biological Process (BP) response to stimulus 0.04512 Least Informative Inherited
Biological Process (BP) single-organism cellular process 0.003666 Least Informative Inherited
Biological Process (BP) ion transport 0 Moderately Informative Direct
Biological Process (BP) regulation of biological quality 0.00000000001852 Moderately Informative Direct
Biological Process (BP) positive regulation of molecular function 0.00001112 Moderately Informative Direct
Biological Process (BP) regulation of catalytic activity 0.0001211 Moderately Informative Direct
Biological Process (BP) cellular amino acid metabolic process 0.0005205 Moderately Informative Direct
Biological Process (BP) organic hydroxy compound metabolic process 0.0006233 Moderately Informative Direct
Biological Process (BP) negative regulation of cellular process 0.9036 Moderately Informative Inherited
Biological Process (BP) carbohydrate derivative metabolic process 0.001322 Moderately Informative Inherited
Biological Process (BP) signal transduction 0.798 Moderately Informative Inherited
Biological Process (BP) cellular component biogenesis 0.241 Moderately Informative Inherited
Biological Process (BP) cellular response to chemical stimulus 0.4437 Moderately Informative Inherited
Biological Process (BP) cellular macromolecule biosynthetic process 0.0709 Moderately Informative Inherited
Biological Process (BP) organ development 0.1266 Moderately Informative Inherited
Biological Process (BP) single-organism developmental process 1 Moderately Informative Inherited
Biological Process (BP) immune system process 0.08034 Moderately Informative Inherited
Biological Process (BP) organic cyclic compound biosynthetic process 0.04784 Moderately Informative Inherited
Biological Process (BP) aromatic compound biosynthetic process 0.0578 Moderately Informative Inherited
Biological Process (BP) organonitrogen compound biosynthetic process 0.02486 Moderately Informative Inherited
Biological Process (BP) cellular response to stress 0.03721 Moderately Informative Inherited
Biological Process (BP) cell differentiation 0.9425 Moderately Informative Inherited
Biological Process (BP) nervous system development 0.5536 Moderately Informative Inherited
Biological Process (BP) anatomical structure morphogenesis 0.5521 Moderately Informative Inherited
Biological Process (BP) cellular protein modification process 0.08952 Moderately Informative Inherited
Biological Process (BP) cellular localization 0.2508 Moderately Informative Inherited
Biological Process (BP) nucleobase-containing small molecule metabolic process 0.00881 Moderately Informative Inherited
Biological Process (BP) organophosphate metabolic process 0.02952 Moderately Informative Inherited
Biological Process (BP) phosphate-containing compound metabolic process 0.4 Moderately Informative Inherited
Biological Process (BP) tissue development 0.2815 Moderately Informative Inherited
Biological Process (BP) organelle organization 0.7505 Moderately Informative Inherited
Biological Process (BP) regulation of phosphate metabolic process 0.06001 Moderately Informative Inherited
Biological Process (BP) response to oxygen-containing compound 0.2673 Moderately Informative Inherited
Biological Process (BP) metal ion transport 0.0004013 Informative Direct
Biological Process (BP) cation homeostasis 0 Informative Direct
Biological Process (BP) response to oxidative stress 0.000005301 Informative Direct
Biological Process (BP) cellular chemical homeostasis 0.0006247 Informative Direct
Biological Process (BP) transmembrane transport 0 Informative Direct
Biological Process (BP) response to inorganic substance 0.0000000005375 Informative Direct
Biological Process (BP) cellular biogenic amine metabolic process 0.00000009255 Informative Direct
Biological Process (BP) immune effector process 0.00001389 Informative Direct
Biological Process (BP) organic hydroxy compound biosynthetic process 0.00002163 Informative Direct
Biological Process (BP) mitochondrion organization 0.00004317 Informative Direct
Biological Process (BP) leukocyte activation 0.00009489 Informative Direct
Biological Process (BP) tube development 0.0008286 Informative Direct
Biological Process (BP) hematopoietic or lymphoid organ development 0.000974 Informative Direct
Biological Process (BP) apoptotic process 0.004119 Informative Inherited
Biological Process (BP) cellular response to oxygen-containing compound 0.0073 Informative Inherited
Biological Process (BP) cellular component morphogenesis 0.06603 Informative Inherited
Biological Process (BP) tissue morphogenesis 0.003347 Informative Inherited
Biological Process (BP) negative regulation of catalytic activity 0.03405 Informative Inherited
Biological Process (BP) purine ribonucleoside metabolic process 0.001167 Informative Inherited
Biological Process (BP) purine ribonucleotide metabolic process 0.001638 Informative Inherited
Biological Process (BP) organ morphogenesis 0.01544 Informative Inherited
Biological Process (BP) negative regulation of cell death 0.006657 Informative Inherited
Biological Process (BP) regulation of apoptotic process 1 Informative Inherited
Biological Process (BP) generation of neurons 0.1081 Informative Inherited
Biological Process (BP) anatomical structure formation involved in morphogenesis 0.01086 Informative Inherited
Biological Process (BP) central nervous system development 0.007571 Informative Inherited
Biological Process (BP) peptidyl-amino acid modification 0.002691 Informative Inherited
Biological Process (BP) cell projection organization 0.14 Informative Inherited
Biological Process (BP) nucleoside triphosphate metabolic process 0.02797 Informative Inherited
Biological Process (BP) nucleoside monophosphate metabolic process 0.004825 Informative Inherited
Biological Process (BP) single-organism behavior 0.001294 Informative Inherited
Biological Process (BP) immune response 0.006329 Informative Inherited
Biological Process (BP) cardiovascular system development 0.005085 Informative Inherited
Biological Process (BP) transition metal ion transport 0 Highly Informative Direct
Biological Process (BP) transition metal ion homeostasis 0.000000000005252 Highly Informative Direct
Biological Process (BP) superoxide metabolic process 0.000000000003478 Highly Informative Direct
Biological Process (BP) alpha-beta T cell activation 0.0000000007099 Highly Informative Direct
Biological Process (BP) hair follicle development 0.000000003397 Highly Informative Direct
Biological Process (BP) leukocyte activation involved in immune response 0.00000001886 Highly Informative Direct
Biological Process (BP) response to toxic substance 0.00000002662 Highly Informative Direct
Biological Process (BP) phenol-containing compound metabolic process 0.00000006016 Highly Informative Direct
Biological Process (BP) T cell differentiation 0.0000003064 Highly Informative Direct
Biological Process (BP) respiratory tube development 0.0000005177 Highly Informative Direct
Biological Process (BP) peptidyl-lysine modification 0.0000006796 Highly Informative Direct
Biological Process (BP) connective tissue development 0.00000115 Highly Informative Direct
Biological Process (BP) extracellular matrix organization 0.000003008 Highly Informative Direct
Biological Process (BP) tryptophan metabolic process 0.000003035 Highly Informative Direct
Biological Process (BP) negative regulation of neuron death 0.000004374 Highly Informative Direct
Biological Process (BP) response to superoxide 0.00001022 Highly Informative Direct
Biological Process (BP) respiratory system development 0.00001626 Highly Informative Direct
Biological Process (BP) locomotory behavior 0.00001646 Highly Informative Direct
Biological Process (BP) cellular response to reactive oxygen species 0.00001706 Highly Informative Direct
Biological Process (BP) regulation of neuron apoptotic process 0.00002042 Highly Informative Direct
Biological Process (BP) ATP metabolic process 0.00005558 Highly Informative Direct
Biological Process (BP) skeletal system development 0.00008135 Highly Informative Direct
Biological Process (BP) neuron projection development 0.005405 Highly Informative Inherited
Biological Process (BP) cell part morphogenesis 0.006784 Highly Informative Inherited
Biological Process (BP) cell morphogenesis involved in differentiation 0.02915 Highly Informative Inherited
Biological Process (BP) negative regulation of apoptotic process 0.003302 Highly Informative Inherited
Molecular Function (MF) binding 0.01134 Least Informative Inherited
Molecular Function (MF) hydrolase activity 0.001497 Least Informative Inherited
Molecular Function (MF) cation binding 0 Moderately Informative Direct
Molecular Function (MF) transporter activity 0 Moderately Informative Direct
Molecular Function (MF) hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides 0.0000000003581 Moderately Informative Direct
Molecular Function (MF) nucleoside-triphosphatase activity 0.0000000001178 Informative Direct
Molecular Function (MF) hydrolase activity, acting on acid anhydrides, catalyzing transmembrane movement of substances 0.0000000002717 Informative Direct
Molecular Function (MF) metal ion transmembrane transporter activity 0.000003518 Informative Direct
Molecular Function (MF) active transmembrane transporter activity 0.0006645 Informative Direct
Molecular Function (MF) inorganic cation transmembrane transporter activity 0.009618 Informative Inherited
Molecular Function (MF) copper ion binding 0 Highly Informative Direct
Molecular Function (MF) transition metal ion transmembrane transporter activity 0 Highly Informative Direct
Molecular Function (MF) ATPase activity, coupled to transmembrane movement of ions 0.00000000005683 Highly Informative Direct
Cellular Component (CC) membrane 0.000004341 Least Informative Direct
Cellular Component (CC) intracellular membrane-bounded organelle 0.1768 Least Informative Inherited
Cellular Component (CC) intracellular organelle part 0.4494 Least Informative Inherited
Cellular Component (CC) cytoplasmic part 0.002441 Least Informative Inherited
Cellular Component (CC) vesicle 0.003215 Moderately Informative Inherited
Cellular Component (CC) Golgi apparatus 0.00000009419 Informative Direct
Cellular Component (CC) cell junction 0.0008526 Informative Direct
Cellular Component (CC) trans-Golgi network 0 Highly Informative Direct
Cellular Component (CC) symplast 0.0000007099 Highly Informative Direct
Cellular Component (CC) cell body 0.0001302 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)abnormal ion homeostasis0InformativeDirect
Mammalian Phenotype (MP)abnormal mineral homeostasis0InformativeDirect

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 resistance0.000003843Highly InformativeDirect

Document: YP 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)Oxidoreductases0.3721Least 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
Biological processAntiport0.0000382Highly InformativeDirect
Cellular componentMembrane0Least InformativeDirect
Cellular componentCell membrane0.0000001041Moderately InformativeDirect
Cellular componentGolgi apparatus0.000003339Moderately InformativeDirect
Cellular componentPeriplasm0.0000009173InformativeDirect
DomainTransmembrane0Least InformativeDirect
DomainRedox-active center0.0000001317InformativeDirect
Molecular functionMetal-binding0Least InformativeDirect
Molecular functionNucleotide-binding0.000005407Least InformativeDirect
Molecular functionATP-binding0Moderately InformativeDirect
Molecular functionMagnesium0Moderately InformativeDirect
Molecular functionFlavoprotein0.0006988Moderately InformativeDirect
Molecular functionCopper0InformativeDirect
Molecular functionFAD0.0000003531InformativeDirect
Molecular functionCadmium0Highly InformativeDirect
Molecular functionMercury0Highly InformativeDirect
Post-translational modificationHydrolase0Least InformativeDirect
Post-translational modificationChaperone0InformativeDirect
Post-translational modificationPhosphoprotein0.000000002467Least InformativeDirect

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) · 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) · Arabidopsis Plant Ontology (AP) · Enzyme Commission (EC) · UniProtKB KeyWords (KW) · Internal database links ]