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SMAD MH1 domain superfamily

SCOP classification
Root:   SCOP hierarchy in SUPERFAMILY [ 0] (11)
Class:   Alpha and beta proteins (a+b) [ 53931] (376)
Fold:   SMAD MH1 domain [ 56365]
Superfamily:   SMAD MH1 domain [ 56366]
Families:   SMAD MH1 domain [ 56367]


Superfamily statistics
Genomes (146) Uniprot 2017_06 genome PDB chains (SCOP 1.75)
Domains 1,211 2,903 2
Proteins 1,204 2,887 2


Functional annotation
General category Regulation
Detailed category DNA-binding

Document:
Function annotation of SCOP domain superfamilies

Gene Ontology (high-coverage)

(show details)
GO term FDR (all) SDFO level Annotation (direct or inherited)
Biological Process (BP) multicellular organismal process 0 Least Informative Direct
Biological Process (BP) response to stimulus 0 Least Informative Direct
Biological Process (BP) biological regulation 0 Least Informative Direct
Biological Process (BP) single-organism cellular process 0.6627 Least Informative Inherited
Biological Process (BP) cellular component organization or biogenesis 0.00884 Least Informative Inherited
Biological Process (BP) macromolecule metabolic process 0.7675 Least Informative Inherited
Biological Process (BP) primary metabolic process 1 Least Informative Inherited
Biological Process (BP) organonitrogen compound metabolic process 0.7832 Least Informative Inherited
Biological Process (BP) reproduction 0.0000002295 Moderately Informative Direct
Biological Process (BP) cell communication 0 Moderately Informative Direct
Biological Process (BP) response to endogenous stimulus 0 Moderately Informative Direct
Biological Process (BP) response to organic substance 0.000000004508 Moderately Informative Direct
Biological Process (BP) regulation of gene expression 0.000005916 Moderately Informative Direct
Biological Process (BP) regulation of macromolecule biosynthetic process 0.0000000001498 Moderately Informative Direct
Biological Process (BP) regulation of nucleobase-containing compound metabolic process 0.0000002101 Moderately Informative Direct
Biological Process (BP) cell differentiation 0.0000000000009981 Moderately Informative Direct
Biological Process (BP) regulation of cellular biosynthetic process 0.000000371 Moderately Informative Direct
Biological Process (BP) single organism signaling 0 Moderately Informative Direct
Biological Process (BP) regulation of developmental process 0.000001374 Moderately Informative Direct
Biological Process (BP) regulation of multicellular organismal process 0.000002343 Moderately Informative Direct
Biological Process (BP) multi-organism process 0.0001336 Moderately Informative Direct
Biological Process (BP) cellular response to chemical stimulus 0 Moderately Informative Direct
Biological Process (BP) regulation of response to stimulus 1 Moderately Informative Inherited
Biological Process (BP) positive regulation of metabolic process 1 Moderately Informative Inherited
Biological Process (BP) regulation of signaling 0.6781 Moderately Informative Inherited
Biological Process (BP) positive regulation of cellular process 0.1962 Moderately Informative Inherited
Biological Process (BP) regulation of molecular function 0.6733 Moderately Informative Inherited
Biological Process (BP) regulation of biological quality 0.2321 Moderately Informative Inherited
Biological Process (BP) anatomical structure morphogenesis 0.4462 Moderately Informative Inherited
Biological Process (BP) negative regulation of metabolic process 0.07042 Moderately Informative Inherited
Biological Process (BP) immune system process 0.008565 Moderately Informative Inherited
Biological Process (BP) negative regulation of cellular process 0.1266 Moderately Informative Inherited
Biological Process (BP) regulation of cell communication 0.8872 Moderately Informative Inherited
Biological Process (BP) regulation of cellular component organization 0.3246 Moderately Informative Inherited
Biological Process (BP) animal organ development 0.06649 Moderately Informative Inherited
Biological Process (BP) response to external stimulus 0.3768 Moderately Informative Inherited
Biological Process (BP) cellular protein modification process 0.02089 Moderately Informative Inherited
Biological Process (BP) regulation of protein metabolic process 1 Moderately Informative Inherited
Biological Process (BP) tissue development 0.03158 Moderately Informative Inherited
Biological Process (BP) regulation of transcription from RNA polymerase II promoter 0.000000009549 Informative Direct
Biological Process (BP) movement of cell or subcellular component 0.00004493 Informative Direct
Biological Process (BP) cell surface receptor signaling pathway 0.0000000000000376 Informative Direct
Biological Process (BP) embryo development 0.0000331 Informative Direct
Biological Process (BP) post-embryonic development 0.0000102 Informative Direct
Biological Process (BP) animal organ morphogenesis 0.0001927 Informative Direct
Biological Process (BP) hemopoiesis 0.0003542 Informative Direct
Biological Process (BP) regulation of growth 0.00006083 Informative Direct
Biological Process (BP) locomotion 0.0000006252 Informative Direct
Biological Process (BP) regulation of cellular component biogenesis 0.0001013 Informative Direct
Biological Process (BP) generation of neurons 0.0000002024 Informative Direct
Biological Process (BP) positive regulation of developmental process 0.000000392 Informative Direct
Biological Process (BP) positive regulation of multicellular organismal process 0.00002193 Informative Direct
Biological Process (BP) negative regulation of multicellular organismal process 0.000004028 Informative Direct
Biological Process (BP) circulatory system development 0.0000005861 Informative Direct
Biological Process (BP) positive regulation of cellular component organization 0.05593 Informative Inherited
Biological Process (BP) positive regulation of macromolecule biosynthetic process 0.9086 Informative Inherited
Biological Process (BP) positive regulation of gene expression 1 Informative Inherited
Biological Process (BP) positive regulation of cellular biosynthetic process 1 Informative Inherited
Biological Process (BP) positive regulation of nucleobase-containing compound metabolic process 1 Informative Inherited
Biological Process (BP) negative regulation of response to stimulus 0.1044 Informative Inherited
Biological Process (BP) negative regulation of cell communication 0.02346 Informative Inherited
Biological Process (BP) negative regulation of signaling 0.07733 Informative Inherited
Biological Process (BP) cell development 0.393 Informative Inherited
Biological Process (BP) regulation of protein modification process 0.118 Informative Inherited
Biological Process (BP) cellular component morphogenesis 0.01069 Informative Inherited
Biological Process (BP) regulation of nervous system development 0.4474 Informative Inherited
Biological Process (BP) regulation of cell differentiation 0.02351 Informative Inherited
Biological Process (BP) developmental process involved in reproduction 0.04783 Informative Inherited
Biological Process (BP) multicellular organism reproduction 0.1043 Informative Inherited
Biological Process (BP) single organism reproductive process 0.007417 Informative Inherited
Biological Process (BP) multi-organism reproductive process 0.01029 Informative Inherited
Biological Process (BP) epithelium development 0.113 Informative Inherited
Biological Process (BP) phosphorylation 0.00104 Informative Inherited
Biological Process (BP) regulation of anatomical structure morphogenesis 0.09584 Informative Inherited
Biological Process (BP) regulation of phosphorylation 0.587 Informative Inherited
Biological Process (BP) negative regulation of cellular protein metabolic process 0.254 Informative Inherited
Biological Process (BP) anatomical structure formation involved in morphogenesis 0.8382 Informative Inherited
Biological Process (BP) kidney development 0.0005017 Highly Informative Direct
Biological Process (BP) enzyme linked receptor protein signaling pathway 0 Highly Informative Direct
Biological Process (BP) heart development 0.000000006545 Highly Informative Direct
Biological Process (BP) cell proliferation 0.0001742 Highly Informative Direct
Biological Process (BP) post-embryonic animal morphogenesis 0.0000007117 Highly Informative Direct
Biological Process (BP) negative regulation of protein modification process 0.000139 Highly Informative Direct
Biological Process (BP) tube morphogenesis 0.00002983 Highly Informative Direct
Biological Process (BP) positive regulation of growth 0.000006729 Highly Informative Direct
Biological Process (BP) regulation of developmental growth 0.0002367 Highly Informative Direct
Biological Process (BP) appendage development 0.000002036 Highly Informative Direct
Biological Process (BP) regulation of binding 0.00004164 Highly Informative Direct
Biological Process (BP) response to growth factor 0 Highly Informative Direct
Biological Process (BP) regulation of transmembrane receptor protein serine/threonine kinase signaling pathway 0 Highly Informative Direct
Biological Process (BP) regulation of cellular response to growth factor stimulus 0.0000000003953 Highly Informative Direct
Biological Process (BP) plasma membrane bounded cell projection organization 0.0000002673 Highly Informative Direct
Biological Process (BP) positive regulation of transcription from RNA polymerase II promoter 1 Highly Informative Inherited
Biological Process (BP) neuron development 0.08492 Highly Informative Inherited
Biological Process (BP) myeloid cell differentiation 0.002854 Highly Informative Inherited
Biological Process (BP) positive regulation of cellular component biogenesis 0.002747 Highly Informative Inherited
Biological Process (BP) positive regulation of nervous system development 0.008937 Highly Informative Inherited
Biological Process (BP) cell morphogenesis involved in differentiation 0.00926 Highly Informative Inherited
Biological Process (BP) germ cell development 0.03254 Highly Informative Inherited
Biological Process (BP) female gamete generation 0.07396 Highly Informative Inherited
Biological Process (BP) muscle tissue development 0.02213 Highly Informative Inherited
Biological Process (BP) morphogenesis of an epithelium 0.3352 Highly Informative Inherited
Biological Process (BP) epithelial cell differentiation 0.006758 Highly Informative Inherited
Biological Process (BP) negative regulation of phosphate metabolic process 0.004049 Highly Informative Inherited
Biological Process (BP) gastrulation 0.001411 Highly Informative Inherited
Molecular Function (MF) binding 0.00000000003344 Least Informative Direct
Molecular Function (MF) nucleic acid binding 0 Moderately Informative Direct
Molecular Function (MF) DNA binding 0 Informative Direct
Molecular Function (MF) transcription factor activity, sequence-specific DNA binding 0.00003813 Informative Direct
Molecular Function (MF) signal transducer activity 0.00000000005195 Informative Direct
Molecular Function (MF) protein dimerization activity 0.0008101 Informative Direct
Molecular Function (MF) chromatin binding 0.0001399 Highly Informative Direct
Molecular Function (MF) transcription factor binding 0.0001353 Highly Informative Direct
Molecular Function (MF) protein heterodimerization activity 0.0000009169 Highly Informative Direct
Cellular Component (CC) intracellular membrane-bounded organelle 0.0000000000006276 Least Informative Direct
Cellular Component (CC) protein complex 0.0000005733 Least Informative Direct

Document: GO annotation of SCOP domains

UniProtKB KeyWords (KW)

(show details)
KW termFDR (all)SDKW levelAnnotation (direct or inherited)
Biological processTranscription regulation0Moderately InformativeDirect
Cellular componentNucleus0Least InformativeDirect
Cellular componentCytoplasm0.0000000903Least InformativeDirect
Molecular functionMetal-binding0Least InformativeDirect
Molecular functionZinc0Least InformativeDirect
Post-translational modificationDNA-binding0Moderately InformativeDirect
Post-translational modificationDevelopmental protein0.0000538Moderately InformativeDirect
Post-translational modificationAcetylation0.00000000000933Least InformativeDirect
Post-translational modificationPhosphoprotein0.0000005054Least InformativeDirect
Post-translational modificationUbl conjugation0Moderately InformativeDirect
Post-translational modificationIsopeptide bond0.000002105Moderately InformativeDirect

Document: KW annotation of SCOP domains

InterPro annotation
Cross references IPR013019 SSF56366 Protein matches
Abstract

Smad proteins are signal transducers and transcriptional comodulators of the TGF-beta superfamily of ligands, which play a central role in regulating a broad range of cellular responses, including cell growth, differentiation, and specification of developmental fate, in diverse organisms from C. elegans to humans. Ligand binding to specific transmembrane receptor kinases induces receptor oligomerization and phosphorylation of the receptor specific Smad protein (R-Smad) in the cytoplasm. The R-Smad proteins regulate distinct signaling pathways. Smad1, 5 and 8 mediate the signals of bone morphogenetic proteins (BMPs), while Smad2 and 3 mediate the signals of activins and TGF-betas. Upon ligand stimulation, R-Smad proteins are phosphorylated at the conserved C-terminal tail sequence, SS*xS* (where S* denotes a site of phosphorylation). The phosphorylated states of R-Smad proteins form heteromeric complexes with Smad4 and are translocated into the nucleus. In the nucleus, the heteromeric complexes function as gene-specific transcription activators by binding to promoters and interacting with transcriptional coactivators. Smad6 and Smad7 are inhibitory Smad proteins that inhibit TGF-beta signaling by interfering with either receptor-mediated phosphorylation or hetero-oligomerization between Smad4 and R-Smad proteins. Smad proteins comprise two conserved MAD homology domains, one in the N-terminus (MH1) and one in the C-terminus (MH2), separated by a more variable, proline-rich linker region. The MH1 domain has a role in DNA binding and negatively regulates the functions of MH2 domain, whereas the MH2 domain is responsible for transactivation and mediates phosphorylation-triggered heteromeric assembly between Smad4 and R-Smad [PubMed9741623, PubMed11779503].

The MH1 domain adopts a compact globular fold, with four alpha helices, six short beta strands, and five loops. The N-terminal half of the sequence consists of three alpha helices, and the C-terminal half contains all six beta strands, which form two small beta sheets and one beta hairpin. The fourth alpha helix is located in the hydrophobic core of the molecule, surrounded by the N-terminal three alpha helices on one side and by the two small beta sheets and the beta hairpin on the other side. These secondary structural elements are connected with five intervening surface loops. The MH1 domain employs a novel DNA-binding motif, an 11-residue beta-hairpin formed by strands B2 and B3, to contact DNA in the major groove. Two residues in the L3 loop and immediately preceding strand B2 also contribute significantly to DNA recognition. The beta hairpin appears to protrude outward from the globular MH1 core [PubMed9741623].


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-coverage) · 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 1 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 SMAD MH1 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 1 hidden Markov models representing the SMAD MH1 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-coverage) · UniProtKB KeyWords (KW) · Internal database links ]