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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 2018_03 genome PDB chains (SCOP 1.75)
Domains 1,211 3,495 2
Proteins 1,204 3,477 2


Functional annotation
General category Regulation
Detailed category DNA-binding

Document:
Function annotation of SCOP domain superfamilies

Disease Ontology (DO)

(show details)
DO termFDR (all)SDDO levelAnnotation (direct or inherited)
Disease Ontology (DO)organ system cancer0Least InformativeDirect
Disease Ontology (DO)urinary system disease0.001714Moderately InformativeInherited
Disease Ontology (DO)hypersensitivity reaction type II disease0.01674Moderately InformativeInherited
Disease Ontology (DO)connective tissue disease0.04624Moderately InformativeInherited
Disease Ontology (DO)nephritis0.00001116InformativeDirect
Disease Ontology (DO)rheumatic disease0.0001831InformativeDirect
Disease Ontology (DO)collagen disease0.0002205InformativeDirect

Document: DO annotation of SCOP domains

Human Phenotype (HP)

(show details)
HP termFDR (all)SDHP levelAnnotation (direct or inherited)
Phenotypic Abnormality (PA)Abnormality of the cardiovascular system0.1108Least InformativeInherited
Phenotypic Abnormality (PA)Abnormal cardiovascular system physiology0.01081Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the vasculature0.02931Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of cardiovascular system morphology0.3064Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal systemic arterial morphology0.004012InformativeInherited
Phenotypic Abnormality (PA)Abnormal aortic valve physiology0.0001246Highly InformativeDirect
Phenotypic Abnormality (PA)Dilatation0.0002043Highly InformativeDirect
Phenotypic Abnormality (PA)Abnormal aortic morphology0.0009191Highly InformativeDirect

Document: HP annotation of SCOP domains

Mouse Phenotype (MP)

(show details)
MP termFDR (all)SDMP levelAnnotation (direct or inherited)
Mammalian Phenotype (MP)cardiovascular system phenotype0Least InformativeDirect
Mammalian Phenotype (MP)mortality/aging0Least InformativeDirect
Mammalian Phenotype (MP)cellular phenotype0.006446Least InformativeInherited
Mammalian Phenotype (MP)growth/size/body region phenotype0.01157Least InformativeInherited
Mammalian Phenotype (MP)abnormal homeostasis0.01187Least InformativeInherited
Mammalian Phenotype (MP)nervous system phenotype0.02863Least InformativeInherited
Mammalian Phenotype (MP)abnormal heart morphology0Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal craniofacial morphology0.000002246Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal reproductive system physiology0.0000336Moderately InformativeDirect
Mammalian Phenotype (MP)neoplasm0.00003983Moderately InformativeDirect
Mammalian Phenotype (MP)embryo phenotype0.00006442Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal digestive system morphology0.00008028Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal nervous system development0.0001856Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal gland morphology0.0001955Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal cell morphology0.003816Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal hormone level0.01288Moderately InformativeInherited
Mammalian Phenotype (MP)integument phenotype0.05589Moderately InformativeInherited
Mammalian Phenotype (MP)prenatal lethality0.1427Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal reproductive system morphology0.1495Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal cardiovascular system physiology0.3193Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal germ cell morphology0.000002465InformativeDirect
Mammalian Phenotype (MP)increased carcinoma incidence0.00000281InformativeDirect
Mammalian Phenotype (MP)abnormal fertility/fecundity0.00001325InformativeDirect
Mammalian Phenotype (MP)increased gland tumor incidence0.0007485InformativeDirect
Mammalian Phenotype (MP)abnormal prenatal growth/weight/body size0.002761InformativeInherited
Mammalian Phenotype (MP)abnormal internal female genitalia morphology0.003944InformativeInherited
Mammalian Phenotype (MP)abnormal pituitary hormone level0.006554InformativeInherited
Mammalian Phenotype (MP)abnormal skin physiology0.01251InformativeInherited
Mammalian Phenotype (MP)abnormal female reproductive gland morphology0.08487InformativeInherited
Mammalian Phenotype (MP)abnormal embryo development0.08707InformativeInherited
Mammalian Phenotype (MP)abnormal heart ventricle morphology0.774InformativeInherited
Mammalian Phenotype (MP)hemorrhage0.8612InformativeInherited
Mammalian Phenotype (MP)increased gonad tumor incidence0.0000000007297Highly InformativeDirect
Mammalian Phenotype (MP)abnormal follicle stimulating hormone level0.0000003953Highly InformativeDirect
Mammalian Phenotype (MP)decreased litter size0.0000036Highly InformativeDirect
Mammalian Phenotype (MP)abnormal gastrulation0.000005771Highly InformativeDirect
Mammalian Phenotype (MP)abnormal embryonic epiblast morphology0.0000117Highly InformativeDirect
Mammalian Phenotype (MP)abnormal oocyte number0.00001402Highly InformativeDirect
Mammalian Phenotype (MP)embryonic lethality during organogenesis0.00004195Highly InformativeDirect
Mammalian Phenotype (MP)abnormal keratinocyte physiology0.00005876Highly InformativeDirect
Mammalian Phenotype (MP)premature aging0.00007866Highly InformativeDirect
Mammalian Phenotype (MP)abnormal heart development0.0003964Highly InformativeDirect
Mammalian Phenotype (MP)abnormal ovarian follicle morphology0.0004301Highly InformativeDirect
Mammalian Phenotype (MP)abnormal circulating gonadotropin level0.0007114Highly InformativeDirect
Mammalian Phenotype (MP)ventricular septal defect0.0007729Highly InformativeDirect
Mammalian Phenotype (MP)abnormal digestive system development0.0008882Highly InformativeDirect
Mammalian Phenotype (MP)internal hemorrhage0.002071Highly InformativeInherited
Mammalian Phenotype (MP)decreased primordial germ cell number0.002341Highly InformativeInherited
Mammalian Phenotype (MP)increased alimentary system tumor incidence0.01628Highly InformativeInherited
Mammalian Phenotype (MP)abnormal primitive streak morphology0.0384Highly InformativeInherited
Mammalian Phenotype (MP)absent germ cells0.2341Highly InformativeInherited

Document: MP annotation of SCOP domains

Worm Phenotype (WP)

(show details)
WP termFDR (all)SDWP levelAnnotation (direct or inherited)
Worm Phenotype (WP)organism metabolism processing variant0Least InformativeDirect
Worm Phenotype (WP)organism behavior variant0Least InformativeDirect
Worm Phenotype (WP)organ system morphology variant0.0001549Least InformativeDirect
Worm Phenotype (WP)cell development variant0.0002937Least InformativeDirect
Worm Phenotype (WP)organism environmental stimulus response variant0.0005188Least InformativeDirect
Worm Phenotype (WP)larval development variant1Least InformativeInherited
Worm Phenotype (WP)nervous system morphology variant0.0000002156Moderately InformativeDirect
Worm Phenotype (WP)body region morphology variant0.00002456Moderately InformativeDirect
Worm Phenotype (WP)organism segment morphology variant0.00002456Moderately InformativeDirect
Worm Phenotype (WP)developmental morphology variant0.00002467Moderately InformativeDirect
Worm Phenotype (WP)adult body morphology variant0.00002477Moderately InformativeDirect
Worm Phenotype (WP)body morphology variant0.00002744Moderately InformativeDirect
Worm Phenotype (WP)pericellular component development variant0.00004974Moderately InformativeDirect
Worm Phenotype (WP)germ cell development variant0.00519Moderately InformativeInherited
Worm Phenotype (WP)level of transgene expression variant0.06105Moderately InformativeInherited
Worm Phenotype (WP)movement variant0.3781Moderately InformativeInherited
Worm Phenotype (WP)locomotion variant0.6052Moderately InformativeInherited
Worm Phenotype (WP)sensillum morphology variant0.00000001186InformativeDirect
Worm Phenotype (WP)transgene expression reduced0.0000008397InformativeDirect
Worm Phenotype (WP)tail morphology variant0.000003843InformativeDirect
Worm Phenotype (WP)male morphology variant0.000004675InformativeDirect
Worm Phenotype (WP)velocity of movement variant0.000006595InformativeDirect
Worm Phenotype (WP)fat content variant0.00001146InformativeDirect
Worm Phenotype (WP)directionality variant0.00001274InformativeDirect
Worm Phenotype (WP)body bend variant0.00001742InformativeDirect
Worm Phenotype (WP)localized movement variant0.0003003InformativeDirect
Worm Phenotype (WP)body posture variant0.001534InformativeInherited
Worm Phenotype (WP)foraging behavior variant0.006262InformativeInherited
Worm Phenotype (WP)small0.1InformativeInherited
Worm Phenotype (WP)male nervous system development variant0.00000003897Highly InformativeDirect
Worm Phenotype (WP)cuticle development variant0.00000008433Highly InformativeDirect
Worm Phenotype (WP)male tail morphology variant0.0000002413Highly InformativeDirect
Worm Phenotype (WP)fat content reduced0.000000357Highly InformativeDirect
Worm Phenotype (WP)short0.000001359Highly InformativeDirect
Worm Phenotype (WP)roaming variant0.000001885Highly InformativeDirect
Worm Phenotype (WP)coiling frequency0.000002353Highly InformativeDirect
Worm Phenotype (WP)body posture amplitude variant0.000003981Highly InformativeDirect
Worm Phenotype (WP)backward point velocity variant0.000004076Highly InformativeDirect
Worm Phenotype (WP)amplitude of sinusoidal movement variant0.000007902Highly InformativeDirect
Worm Phenotype (WP)frequency of body bend variant0.000008534Highly InformativeDirect
Worm Phenotype (WP)dauer development variant0.00001106Highly InformativeDirect
Worm Phenotype (WP)cell fusion variant0.00001527Highly InformativeDirect
Worm Phenotype (WP)germline proliferation variant0.00003052Highly InformativeDirect
Worm Phenotype (WP)dauer arrest variant0.0006324Highly InformativeDirect
Worm Phenotype (WP)male ray morphology variant0.04296Highly InformativeInherited

Document: WP annotation of SCOP domains

Fly Phenotype (FP)

(show details)
FP termFDR (all)SDFP levelAnnotation (direct or inherited)
Fly Phenotype (FP)increased mortality0Least InformativeDirect
Fly Phenotype (FP)lethal0Moderately InformativeDirect
Fly Phenotype (FP)size defective0InformativeDirect
Fly Phenotype (FP)neuroanatomy defective0InformativeDirect
Fly Phenotype (FP)cell number defective0InformativeDirect
Fly Phenotype (FP)decreased cell number0Highly InformativeDirect
Fly Phenotype (FP)decreased occurrence of cell division0Highly InformativeDirect

Document: FP annotation of SCOP domains

Fly Anatomy (FA)

(show details)
FA termFDR (all)SDFA levelAnnotation (direct or inherited)
Fly Anatomy (FA)larva0Least InformativeDirect
Fly Anatomy (FA)adult0Least InformativeDirect
Fly Anatomy (FA)nervous system0Least InformativeDirect
Fly Anatomy (FA)multi-tissue structure0Least InformativeDirect
Fly Anatomy (FA)organ system subdivision0Least InformativeDirect
Fly Anatomy (FA)somatic cell0Least InformativeDirect
Fly Anatomy (FA)anterior-posterior subdivision of organism1Least InformativeInherited
Fly Anatomy (FA)thorax0Moderately InformativeDirect
Fly Anatomy (FA)adult tagma0Moderately InformativeDirect
Fly Anatomy (FA)adult segment0Moderately InformativeDirect
Fly Anatomy (FA)peripheral nervous system0Moderately InformativeDirect
Fly Anatomy (FA)neuron0Moderately InformativeDirect
Fly Anatomy (FA)adult integumentary system0Moderately InformativeDirect
Fly Anatomy (FA)appendage0Moderately InformativeDirect
Fly Anatomy (FA)acellular anatomical structure0Moderately InformativeDirect
Fly Anatomy (FA)region of integument0Moderately InformativeDirect
Fly Anatomy (FA)multi-cell-component structure0.007525Moderately InformativeInherited
Fly Anatomy (FA)gonad0.02266Moderately InformativeInherited
Fly Anatomy (FA)stem cell0.04572Moderately InformativeInherited
Fly Anatomy (FA)central nervous system0.08707Moderately InformativeInherited
Fly Anatomy (FA)abdominal segment0InformativeDirect
Fly Anatomy (FA)larval segment0InformativeDirect
Fly Anatomy (FA)wing blade0InformativeDirect
Fly Anatomy (FA)cuticular specialization0InformativeDirect
Fly Anatomy (FA)gut section0InformativeDirect
Fly Anatomy (FA)synaptic neuropil0.001453InformativeInherited
Fly Anatomy (FA)cell component0.008993InformativeInherited
Fly Anatomy (FA)ovariole0.009059InformativeInherited
Fly Anatomy (FA)germline cell0.02266InformativeInherited
Fly Anatomy (FA)larval mesothoracic segment0Highly InformativeDirect
Fly Anatomy (FA)imaginal disc0Highly InformativeDirect
Fly Anatomy (FA)wing vein0Highly InformativeDirect
Fly Anatomy (FA)female germline stem cell0.000005391Highly InformativeDirect
Fly Anatomy (FA)bouton0.0006224Highly InformativeDirect

Document: FA annotation of SCOP domains

Zebrafish Anatomy (ZA)

(show details)
ZA termFDR (all)SDZA levelAnnotation (direct or inherited)
Zebrafish Anatomy (ZA)nervous system0Least InformativeDirect
Zebrafish Anatomy (ZA)organism subdivision0Least InformativeDirect
Zebrafish Anatomy (ZA)multi-tissue structure0Least InformativeDirect
Zebrafish Anatomy (ZA)cell0.06262Least InformativeInherited
Zebrafish Anatomy (ZA)portion of tissue0Moderately InformativeDirect
Zebrafish Anatomy (ZA)central nervous system0.1023Moderately InformativeInherited
Zebrafish Anatomy (ZA)hematopoietic system0.000147InformativeDirect
Zebrafish Anatomy (ZA)surface structure0.1027InformativeInherited
Zebrafish Anatomy (ZA)hematopoietic cell0.1053InformativeInherited
Zebrafish Anatomy (ZA)floor plate0.00000002256Highly InformativeDirect
Zebrafish Anatomy (ZA)intermediate cell mass of mesoderm0.000008992Highly InformativeDirect
Zebrafish Anatomy (ZA)mononuclear phagocyte0.00007529Highly InformativeDirect
Zebrafish Anatomy (ZA)professional antigen presenting cell0.00009538Highly InformativeDirect
Zebrafish Anatomy (ZA)median fin fold0.0009967Highly InformativeDirect

Document: ZA annotation of SCOP domains

Xenopus Anatomy (XA)

(show details)
XA termFDR (all)SDXA levelAnnotation (direct or inherited)
Xenopus ANatomical entity (XAN)embryo0Least InformativeDirect
Xenopus ANatomical entity (XAN)head0Least InformativeDirect
Xenopus ANatomical entity (XAN)trunk0Least InformativeDirect
Xenopus ANatomical entity (XAN)tissue0Least InformativeDirect
Xenopus ANatomical entity (XAN)cavitated compound organ0Least InformativeDirect
Xenopus ANatomical entity (XAN)anatomical system1Least InformativeInherited
Xenopus ANatomical entity (XAN)ectoderm0Moderately InformativeDirect
Xenopus ANatomical entity (XAN)brain0Moderately InformativeDirect
Xenopus ANatomical entity (XAN)multi-tissue structure0Moderately InformativeDirect
Xenopus ANatomical entity (XAN)sensory system0.0004304Moderately InformativeDirect
Xenopus ANatomical entity (XAN)viscus0.1445Moderately InformativeInherited
Xenopus ANatomical entity (XAN)cardiovascular system0.000001394InformativeDirect
Xenopus ANatomical entity (XAN)eye0.0001894InformativeDirect
Xenopus ANatomical entity (XAN)surface structure0.0002044InformativeDirect
Xenopus ANatomical entity (XAN)anatomical direction0.0003457InformativeDirect
Xenopus ANatomical entity (XAN)animal hemisphere0.00051InformativeDirect
Xenopus ANatomical entity (XAN)mesoderm0.0005528InformativeDirect
Xenopus ANatomical entity (XAN)pharyngeal region0.0005756InformativeDirect
Xenopus ANatomical entity (XAN)vestibuloauditory system0.05131InformativeInherited
Xenopus ANatomical entity (XAN)tail bud0.00001175Highly InformativeDirect
Xenopus ANatomical entity (XAN)otic vesicle0.0005396Highly InformativeDirect

Document: XA 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 · Disease Ontology (DO) · Human Phenotype (HP) · Mouse Phenotype (MP) · Worm Phenotype (WP) · Fly Phenotype (FP) · Fly Anatomy (FA) · Zebrafish Anatomy (ZA) · Xenopus Anatomy (XA) ]

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 3 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 3 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 · Disease Ontology (DO) · Human Phenotype (HP) · Mouse Phenotype (MP) · Worm Phenotype (WP) · Fly Phenotype (FP) · Fly Anatomy (FA) · Zebrafish Anatomy (ZA) · Xenopus Anatomy (XA) · Internal database links ]