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 (2,145) Uniprot 2013_05 PDB chains (SCOP 1.75)
Domains 14,622 32,219 21
Proteins 10,773 24,978 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)localization0.00025320Least InformativeDirect
Biological Process (BP)single-organism cellular process0.12780.001947Least InformativeInherited
Biological Process (BP)response to stimulus0.1750.04726Least InformativeInherited
Biological Process (BP)ion transport2.458e-070Moderately InformativeDirect
Biological Process (BP)homeostatic process2.361e-067.535e-07Moderately InformativeDirect
Biological Process (BP)response to oxidative stress0.00017265.347e-07InformativeDirect
Biological Process (BP)cellular cation homeostasis0.20740.001386InformativeInherited
Biological Process (BP)metal ion transport9.971e-110.002864InformativeInherited
Biological Process (BP)transition metal ion transport6.629e-130Highly InformativeDirect
Molecular Function (MF)binding0.0036380.007518Least InformativeInherited
Molecular Function (MF)cation binding6.288e-107.431e-10Moderately InformativeDirect
Molecular Function (MF)transition metal ion binding0.014593.078e-06InformativeInherited
Molecular Function (MF)copper ion binding6.715e-160Highly 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 0.1849 Least Informative Inherited
Biological Process (BP) protein metabolic process 0.5551 Least Informative Inherited
Biological Process (BP) cellular macromolecule metabolic process 1 Least Informative Inherited
Biological Process (BP) developmental process 0.5915 Least Informative Inherited
Biological Process (BP) multicellular organismal process 0.8121 Least Informative Inherited
Biological Process (BP) organic cyclic compound metabolic process 0.3293 Least Informative Inherited
Biological Process (BP) cellular aromatic compound metabolic process 0.3603 Least Informative Inherited
Biological Process (BP) single-organism metabolic process 0.09299 Least Informative Inherited
Biological Process (BP) heterocycle metabolic process 0.4709 Least Informative Inherited
Biological Process (BP) nitrogen compound metabolic process 0.6458 Least Informative Inherited
Biological Process (BP) regulation of cellular process 1 Least Informative Inherited
Biological Process (BP) regulation of metabolic process 0.8647 Least Informative Inherited
Biological Process (BP) cellular component organization or biogenesis 0.9887 Least Informative Inherited
Biological Process (BP) response to stimulus 0.04726 Least Informative Inherited
Biological Process (BP) single-organism cellular process 0.001947 Least Informative Inherited
Biological Process (BP) ion transport 0 Moderately Informative Direct
Biological Process (BP) homeostatic process 7.535e-07 Moderately Informative Direct
Biological Process (BP) organic hydroxy compound metabolic process 0.0001535 Moderately Informative Direct
Biological Process (BP) carbohydrate derivative metabolic process 0.0003312 Moderately Informative Direct
Biological Process (BP) cellular amino acid metabolic process 0.0004367 Moderately Informative Direct
Biological Process (BP) negative regulation of cellular process 0.8326 Moderately Informative Inherited
Biological Process (BP) signal transduction 0.7627 Moderately Informative Inherited
Biological Process (BP) cellular component biogenesis 0.1883 Moderately Informative Inherited
Biological Process (BP) cellular response to chemical stimulus 0.2869 Moderately Informative Inherited
Biological Process (BP) cellular macromolecule biosynthetic process 0.04887 Moderately Informative Inherited
Biological Process (BP) organ development 0.09043 Moderately Informative Inherited
Biological Process (BP) single-organism developmental process 1 Moderately Informative Inherited
Biological Process (BP) immune system process 0.05459 Moderately Informative Inherited
Biological Process (BP) nucleobase-containing small molecule metabolic process 0.002261 Moderately Informative Inherited
Biological Process (BP) regulation of molecular function 0.1857 Moderately Informative Inherited
Biological Process (BP) regulation of cellular metabolic process 0.8041 Moderately Informative Inherited
Biological Process (BP) small molecule biosynthetic process 0.01078 Moderately Informative Inherited
Biological Process (BP) organic cyclic compound biosynthetic process 0.02828 Moderately Informative Inherited
Biological Process (BP) aromatic compound biosynthetic process 0.03549 Moderately Informative Inherited
Biological Process (BP) organonitrogen compound biosynthetic process 0.03023 Moderately Informative Inherited
Biological Process (BP) cellular response to stress 0.02644 Moderately Informative Inherited
Biological Process (BP) cell differentiation 0.865 Moderately Informative Inherited
Biological Process (BP) nervous system development 0.5592 Moderately Informative Inherited
Biological Process (BP) anatomical structure morphogenesis 0.402 Moderately Informative Inherited
Biological Process (BP) cellular protein modification process 0.09704 Moderately Informative Inherited
Biological Process (BP) cellular localization 0.2786 Moderately Informative Inherited
Biological Process (BP) organophosphate metabolic process 0.01119 Moderately Informative Inherited
Biological Process (BP) phosphate-containing compound metabolic process 0.2711 Moderately Informative Inherited
Biological Process (BP) tissue development 0.2308 Moderately Informative Inherited
Biological Process (BP) organelle organization 0.6438 Moderately Informative Inherited
Biological Process (BP) response to oxygen-containing compound 0.1724 Moderately Informative Inherited
Biological Process (BP) response to oxidative stress 5.347e-07 Informative Direct
Biological Process (BP) transmembrane transport 0 Informative Direct
Biological Process (BP) response to inorganic substance 2.465e-10 Informative Direct
Biological Process (BP) cellular biogenic amine metabolic process 9.572e-08 Informative Direct
Biological Process (BP) immune effector process 1.063e-05 Informative Direct
Biological Process (BP) organic hydroxy compound biosynthetic process 1.108e-05 Informative Direct
Biological Process (BP) mitochondrion organization 3.61e-05 Informative Direct
Biological Process (BP) purine nucleoside metabolic process 0.0001195 Informative Direct
Biological Process (BP) ribonucleoside metabolic process 0.0001829 Informative Direct
Biological Process (BP) hematopoietic or lymphoid organ development 0.000426 Informative Direct
Biological Process (BP) single-organism behavior 0.0007371 Informative Direct
Biological Process (BP) ribose phosphate metabolic process 0.0008088 Informative Direct
Biological Process (BP) negative regulation of molecular function 0.0008586 Informative Direct
Biological Process (BP) apoptotic process 0.002572 Informative Inherited
Biological Process (BP) cellular response to oxygen-containing compound 0.004858 Informative Inherited
Biological Process (BP) cellular component morphogenesis 0.05883 Informative Inherited
Biological Process (BP) tissue morphogenesis 0.003056 Informative Inherited
Biological Process (BP) organ morphogenesis 0.01438 Informative Inherited
Biological Process (BP) positive regulation of catalytic activity 0.001246 Informative Inherited
Biological Process (BP) cell activation 0.002656 Informative Inherited
Biological Process (BP) negative regulation of cell death 0.006864 Informative Inherited
Biological Process (BP) regulation of apoptotic process 1 Informative Inherited
Biological Process (BP) metal ion transport 0.002864 Informative Inherited
Biological Process (BP) tube development 0.001217 Informative Inherited
Biological Process (BP) generation of neurons 0.08754 Informative Inherited
Biological Process (BP) anatomical structure formation involved in morphogenesis 0.01064 Informative Inherited
Biological Process (BP) central nervous system development 0.005952 Informative Inherited
Biological Process (BP) peptidyl-amino acid modification 0.001299 Informative Inherited
Biological Process (BP) cell projection organization 0.1074 Informative Inherited
Biological Process (BP) nucleoside triphosphate metabolic process 0.008008 Informative Inherited
Biological Process (BP) purine nucleotide metabolic process 0.05356 Informative Inherited
Biological Process (BP) cellular cation homeostasis 0.001386 Informative Inherited
Biological Process (BP) immune response 0.004207 Informative Inherited
Biological Process (BP) cardiovascular system development 0.00437 Informative Inherited
Biological Process (BP) transition metal ion transport 0 Highly Informative Direct
Biological Process (BP) superoxide metabolic process 1.546e-12 Highly Informative Direct
Biological Process (BP) ion transmembrane transport 2.845e-10 Highly Informative Direct
Biological Process (BP) diol metabolic process 1.98e-09 Highly Informative Direct
Biological Process (BP) leukocyte activation involved in immune response 1.195e-08 Highly Informative Direct
Biological Process (BP) phenol-containing compound metabolic process 4.604e-08 Highly Informative Direct
Biological Process (BP) response to toxic substance 8.679e-08 Highly Informative Direct
Biological Process (BP) lung development 3.616e-07 Highly Informative Direct
Biological Process (BP) peptidyl-lysine modification 3.75e-07 Highly Informative Direct
Biological Process (BP) connective tissue development 8.697e-07 Highly Informative Direct
Biological Process (BP) lymphocyte differentiation 9.348e-07 Highly Informative Direct
Biological Process (BP) extracellular matrix organization 1.167e-06 Highly Informative Direct
Biological Process (BP) T cell activation 1.883e-06 Highly Informative Direct
Biological Process (BP) negative regulation of neuron death 2.296e-06 Highly Informative Direct
Biological Process (BP) response to superoxide 2.305e-06 Highly Informative Direct
Biological Process (BP) tryptophan metabolic process 5.05e-06 Highly Informative Direct
Biological Process (BP) apoptotic signaling pathway 8.747e-06 Highly Informative Direct
Biological Process (BP) locomotory behavior 1.031e-05 Highly Informative Direct
Biological Process (BP) cellular response to reactive oxygen species 1.162e-05 Highly Informative Direct
Biological Process (BP) regulation of neuron apoptotic process 1.645e-05 Highly Informative Direct
Biological Process (BP) purine ribonucleoside triphosphate metabolic process 3.061e-05 Highly Informative Direct
Biological Process (BP) skeletal system development 5.525e-05 Highly Informative Direct
Biological Process (BP) epidermis development 0.0001174 Highly Informative Direct
Biological Process (BP) negative regulation of apoptotic process 0.003898 Highly Informative Inherited
Biological Process (BP) hair cycle process 0.5269 Highly Informative Inherited
Molecular Function (MF) hydrolase activity 0.0004751 Least Informative Direct
Molecular Function (MF) binding 0.007518 Least Informative Inherited
Molecular Function (MF) cation binding 7.431e-10 Moderately Informative Direct
Molecular Function (MF) transporter activity 0 Moderately Informative Direct
Molecular Function (MF) transition metal ion binding 3.078e-06 Informative Direct
Molecular Function (MF) nucleoside-triphosphatase activity 1.486e-11 Informative Direct
Molecular Function (MF) metal ion transmembrane transporter activity 6.534e-05 Informative Direct
Molecular Function (MF) active transmembrane transporter activity 0.0001596 Informative Direct
Molecular Function (MF) inorganic cation transmembrane transporter activity 0.006357 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 1.153e-12 Highly Informative Direct
Cellular Component (CC) membrane 4.66e-07 Least Informative Direct
Cellular Component (CC) intracellular membrane-bounded organelle 0.1822 Least Informative Inherited
Cellular Component (CC) intracellular organelle part 0.3518 Least Informative Inherited
Cellular Component (CC) cytoplasmic part 0.008675 Least Informative Inherited
Cellular Component (CC) vesicle 4.544e-05 Moderately Informative Direct
Cellular Component (CC) Golgi apparatus 6.186e-08 Informative Direct
Cellular Component (CC) cell junction 0.0003904 Informative Direct
Cellular Component (CC) neuron part 0.009412 Informative Inherited
Cellular Component (CC) trans-Golgi network 0 Highly Informative Direct
Cellular Component (CC) symplast 1.169e-06 Highly Informative Direct
Cellular Component (CC) cell body 4.271e-05 Highly Informative Direct
Cellular Component (CC) cell-cell junction 4.557e-05 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 ATPase8.737e-15Highly 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)alkaline pH resistance6.238e-06Highly 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)Oxidoreductases0.3082Least 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 processAntiport8.618e-06Highly InformativeDirect
Cellular componentMembrane0Least InformativeDirect
Cellular componentCell membrane3.721e-07Moderately InformativeDirect
Cellular componentGolgi apparatus2.159e-06Moderately InformativeDirect
Cellular componentPeriplasm7.843e-07InformativeDirect
DomainTransmembrane6.413e-16Least InformativeDirect
DomainRedox-active center2.037e-07InformativeDirect
Molecular functionMetal-binding0Least InformativeDirect
Molecular functionNucleotide-binding2.972e-06Least InformativeDirect
Molecular functionMagnesium0Moderately InformativeDirect
Molecular functionCopper0InformativeDirect
Molecular functionFAD1.89e-05InformativeDirect
Molecular functionFlavoprotein0.0002704InformativeDirect
Molecular functionCadmium0Highly InformativeDirect
Molecular functionMercury0Highly InformativeDirect
Post-translational modificationHydrolase0Least InformativeDirect
Post-translational modificationChaperone0InformativeDirect
Post-translational modificationPhosphoprotein2.19e-15Least 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 ]