SUPERFAMILY 1.75 HMM library and genome assignments server

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 (2,745) Uniprot 2014_06 PDB chains (SCOP 1.75)
Domains 18,965 71,444 21
Proteins 14,367 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)localization0.000053730Least InformativeDirect
Biological Process (BP)single-organism cellular process0.24670.531Least InformativeInherited
Biological Process (BP)response to stimulus0.18570.04761Least InformativeInherited
Biological Process (BP)ion transport0.000000034880.000000000000007248Moderately InformativeDirect
Biological Process (BP)regulation of biological quality0.0000017310.00000000001455Moderately InformativeDirect
Biological Process (BP)metal ion transport0.0000000000019640.000005809InformativeDirect
Biological Process (BP)cation homeostasis0.0000000000077640InformativeDirect
Biological Process (BP)response to oxidative stress0.00021910.000006487InformativeDirect
Biological Process (BP)transition metal ion transport0.0000000000000032510Highly InformativeDirect
Biological Process (BP)transition metal ion homeostasis0.0000000000000032510.000000000003103Highly InformativeDirect
Molecular Function (MF)binding0.0014570.0136Least InformativeInherited
Molecular Function (MF)cation binding0.0000000012620Moderately 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) regulation of cellular process 1 Least Informative Inherited
Biological Process (BP) single-organism cellular process 0.531 Least Informative Inherited
Biological Process (BP) cellular component organization or biogenesis 0.9679 Least Informative Inherited
Biological Process (BP) positive regulation of biological process 0.2227 Least Informative Inherited
Biological Process (BP) organic cyclic compound metabolic process 0.4717 Least Informative Inherited
Biological Process (BP) regulation of metabolic process 0.3791 Least Informative Inherited
Biological Process (BP) developmental process 0.44 Least Informative Inherited
Biological Process (BP) single-organism metabolic process 0.5553 Least Informative Inherited
Biological Process (BP) biosynthetic process 0.2526 Least Informative Inherited
Biological Process (BP) cellular aromatic compound metabolic process 0.4976 Least Informative Inherited
Biological Process (BP) heterocycle metabolic process 0.6258 Least Informative Inherited
Biological Process (BP) nitrogen compound metabolic process 0.7947 Least Informative Inherited
Biological Process (BP) protein metabolic process 0.5976 Least Informative Inherited
Biological Process (BP) cellular macromolecule metabolic process 1 Least Informative Inherited
Biological Process (BP) multicellular organismal process 0.8336 Least Informative Inherited
Biological Process (BP) response to stimulus 0.04761 Least Informative Inherited
Biological Process (BP) ion transport 0.000000000000007248 Moderately Informative Direct
Biological Process (BP) regulation of biological quality 0.00000000001455 Moderately Informative Direct
Biological Process (BP) positive regulation of molecular function 0.00001141 Moderately Informative Direct
Biological Process (BP) regulation of catalytic activity 0.0001242 Moderately Informative Direct
Biological Process (BP) cellular amino acid metabolic process 0.0004763 Moderately Informative Direct
Biological Process (BP) organic hydroxy compound metabolic process 0.0008603 Moderately Informative Direct
Biological Process (BP) cellular response to stress 0.03895 Moderately Informative Inherited
Biological Process (BP) tissue development 0.2856 Moderately Informative Inherited
Biological Process (BP) cell differentiation 0.9547 Moderately Informative Inherited
Biological Process (BP) negative regulation of metabolic process 0.1858 Moderately Informative Inherited
Biological Process (BP) cellular component biogenesis 0.2522 Moderately Informative Inherited
Biological Process (BP) carbohydrate derivative metabolic process 0.00179 Moderately Informative Inherited
Biological Process (BP) immune system process 0.07997 Moderately Informative Inherited
Biological Process (BP) negative regulation of cellular process 0.949 Moderately Informative Inherited
Biological Process (BP) positive regulation of metabolic process 0.006915 Moderately Informative Inherited
Biological Process (BP) organic cyclic compound biosynthetic process 0.054 Moderately Informative Inherited
Biological Process (BP) organonitrogen compound biosynthetic process 0.02375 Moderately Informative Inherited
Biological Process (BP) cellular response to chemical stimulus 0.4522 Moderately Informative Inherited
Biological Process (BP) macromolecular complex subunit organization 0.05351 Moderately Informative Inherited
Biological Process (BP) organ development 0.1211 Moderately Informative Inherited
Biological Process (BP) anatomical structure morphogenesis 0.5537 Moderately Informative Inherited
Biological Process (BP) nervous system development 0.5747 Moderately Informative Inherited
Biological Process (BP) response to oxygen-containing compound 0.2816 Moderately Informative Inherited
Biological Process (BP) cellular protein modification process 0.09128 Moderately Informative Inherited
Biological Process (BP) cellular localization 1 Moderately Informative Inherited
Biological Process (BP) aromatic compound biosynthetic process 0.0657 Moderately Informative Inherited
Biological Process (BP) phosphate-containing compound metabolic process 0.4601 Moderately Informative Inherited
Biological Process (BP) organophosphate metabolic process 0.03514 Moderately Informative Inherited
Biological Process (BP) nucleobase-containing small molecule metabolic process 0.02585 Moderately Informative Inherited
Biological Process (BP) cellular macromolecule biosynthetic process 0.07173 Moderately Informative Inherited
Biological Process (BP) regulation of nucleobase-containing compound metabolic process 0.8099 Moderately Informative Inherited
Biological Process (BP) regulation of phosphorus metabolic process 0.1052 Moderately Informative Inherited
Biological Process (BP) signal transduction 0.8055 Moderately Informative Inherited
Biological Process (BP) metal ion transport 0.000005809 Informative Direct
Biological Process (BP) cation homeostasis 0 Informative Direct
Biological Process (BP) response to oxidative stress 0.000006487 Informative Direct
Biological Process (BP) cellular chemical homeostasis 0.000436 Informative Direct
Biological Process (BP) response to inorganic substance 0.000000000574 Informative Direct
Biological Process (BP) cellular biogenic amine metabolic process 0.00000009024 Informative Direct
Biological Process (BP) immune effector process 0.00001427 Informative Direct
Biological Process (BP) organic hydroxy compound biosynthetic process 0.00003258 Informative Direct
Biological Process (BP) mitochondrion organization 0.00004433 Informative Direct
Biological Process (BP) leukocyte activation 0.00009402 Informative Direct
Biological Process (BP) regulation of nucleoside metabolic process 0.0001406 Informative Direct
Biological Process (BP) regulation of purine nucleotide metabolic process 0.0004365 Informative Direct
Biological Process (BP) hematopoietic or lymphoid organ development 0.0009762 Informative Direct
Biological Process (BP) ion transmembrane transport 0.001127 Informative Inherited
Biological Process (BP) apoptotic process 0.004126 Informative Inherited
Biological Process (BP) cellular component morphogenesis 0.06818 Informative Inherited
Biological Process (BP) tissue morphogenesis 0.003276 Informative Inherited
Biological Process (BP) negative regulation of catalytic activity 0.001732 Informative Inherited
Biological Process (BP) nucleoside monophosphate metabolic process 0.007052 Informative Inherited
Biological Process (BP) purine ribonucleoside metabolic process 0.001823 Informative Inherited
Biological Process (BP) purine ribonucleotide metabolic process 0.002487 Informative Inherited
Biological Process (BP) negative regulation of cell death 0.01207 Informative Inherited
Biological Process (BP) regulation of apoptotic process 1 Informative Inherited
Biological Process (BP) organ morphogenesis 0.01544 Informative Inherited
Biological Process (BP) epithelium development 0.04184 Informative Inherited
Biological Process (BP) tube development 0.002571 Informative Inherited
Biological Process (BP) generation of neurons 0.1104 Informative Inherited
Biological Process (BP) anatomical structure formation involved in morphogenesis 0.01158 Informative Inherited
Biological Process (BP) central nervous system development 0.00801 Informative Inherited
Biological Process (BP) cellular response to oxygen-containing compound 0.007618 Informative Inherited
Biological Process (BP) peptidyl-amino acid modification 0.002814 Informative Inherited
Biological Process (BP) cell projection organization 0.06034 Informative Inherited
Biological Process (BP) single-organism intracellular transport 1 Informative Inherited
Biological Process (BP) nucleoside triphosphate metabolic process 0.03659 Informative Inherited
Biological Process (BP) immune response 0.006189 Informative Inherited
Biological Process (BP) cardiovascular system development 0.005009 Informative Inherited
Biological Process (BP) transition metal ion transport 0 Highly Informative Direct
Biological Process (BP) transition metal ion homeostasis 0.000000000003103 Highly Informative Direct
Biological Process (BP) response to transition metal nanoparticle 0 Highly Informative Direct
Biological Process (BP) superoxide metabolic process 0.000000000003663 Highly Informative Direct
Biological Process (BP) alpha-beta T cell activation 0.0000000006282 Highly Informative Direct
Biological Process (BP) leukocyte activation involved in immune response 0.00000001841 Highly Informative Direct
Biological Process (BP) response to toxic substance 0.00000003019 Highly Informative Direct
Biological Process (BP) T cell differentiation 0.0000002895 Highly Informative Direct
Biological Process (BP) respiratory tube development 0.0000005183 Highly Informative Direct
Biological Process (BP) peptidyl-lysine modification 0.0000006798 Highly Informative Direct
Biological Process (BP) phenol-containing compound metabolic process 0.0000008558 Highly Informative Direct
Biological Process (BP) connective tissue development 0.000001238 Highly Informative Direct
Biological Process (BP) extracellular matrix organization 0.000002928 Highly Informative Direct
Biological Process (BP) tryptophan metabolic process 0.000003227 Highly Informative Direct
Biological Process (BP) negative regulation of neuron death 0.00000472 Highly Informative Direct
Biological Process (BP) response to superoxide 0.00001044 Highly Informative Direct
Biological Process (BP) respiratory system development 0.00001638 Highly Informative Direct
Biological Process (BP) locomotory behavior 0.00001775 Highly Informative Direct
Biological Process (BP) cellular response to reactive oxygen species 0.00001809 Highly Informative Direct
Biological Process (BP) epidermis development 0.00001933 Highly Informative Direct
Biological Process (BP) regulation of neuron apoptotic process 0.00002122 Highly Informative Direct
Biological Process (BP) skeletal system development 0.00008202 Highly Informative Direct
Biological Process (BP) neuron projection development 0.005485 Highly Informative Inherited
Biological Process (BP) cell projection morphogenesis 0.006308 Highly Informative Inherited
Biological Process (BP) cell morphogenesis involved in differentiation 0.02944 Highly Informative Inherited
Biological Process (BP) hair cycle process 0.3338 Highly Informative Inherited
Molecular Function (MF) binding 0.0136 Least Informative Inherited
Molecular Function (MF) hydrolase activity 0.001513 Least Informative Inherited
Molecular Function (MF) cation binding 0 Moderately Informative Direct
Molecular Function (MF) transporter activity 0 Moderately Informative Direct
Molecular Function (MF) enzyme regulator activity 0.00000003441 Moderately Informative Direct
Molecular Function (MF) metal ion transmembrane transporter activity 0 Informative Direct
Molecular Function (MF) enzyme activator activity 0.00000000001054 Informative Direct
Molecular Function (MF) nucleoside-triphosphatase activity 0.0000000001149 Informative Direct
Molecular Function (MF) hydrolase activity, acting on acid anhydrides, catalyzing transmembrane movement of substances 0.0000000002703 Informative Direct
Molecular Function (MF) active transmembrane transporter activity 0.0007158 Informative Direct
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 0.00000000006159 Highly Informative Direct
Cellular Component (CC) cytoplasmic part 0.0005899 Least Informative Direct
Cellular Component (CC) membrane 0.000004825 Least Informative Direct
Cellular Component (CC) intracellular organelle part 0.001901 Least Informative Inherited
Cellular Component (CC) intracellular membrane-bounded organelle 0.1371 Least Informative Inherited
Cellular Component (CC) vesicle 0.003443 Moderately Informative Inherited
Cellular Component (CC) Golgi apparatus 0.0000000003466 Informative Direct
Cellular Component (CC) cell junction 0.000837 Informative Direct
Cellular Component (CC) trans-Golgi network 0 Highly Informative Direct
Cellular Component (CC) symplast 0.0000006955 Highly Informative Direct
Cellular Component (CC) cell body 0.0001296 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 resistance0.000003852Highly 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)Oxidoreductases0.3778Least 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 processAntiport0.00003792Highly InformativeDirect
Cellular componentMembrane0Least InformativeDirect
Cellular componentCell membrane0.0000001143Moderately InformativeDirect
Cellular componentGolgi apparatus0.000003448Moderately InformativeDirect
Cellular componentPeriplasm0.0000009367InformativeDirect
DomainTransmembrane0Least InformativeDirect
DomainRedox-active center0.0000001293InformativeDirect
Molecular functionMetal-binding0Least InformativeDirect
Molecular functionNucleotide-binding0.000004965Least InformativeDirect
Molecular functionATP-binding0Moderately InformativeDirect
Molecular functionMagnesium0Moderately InformativeDirect
Molecular functionFlavoprotein0.0006922Moderately InformativeDirect
Molecular functionCopper0InformativeDirect
Molecular functionFAD0.0000003535InformativeDirect
Molecular functionCadmium0Highly InformativeDirect
Molecular functionMercury0Highly InformativeDirect
Post-translational modificationHydrolase0Least InformativeDirect
Post-translational modificationChaperone0InformativeDirect
Post-translational modificationPhosphoprotein0.000000002585Least 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 ]