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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 disease0.001681Moderately InformativeInherited
Disease Ontology (DO)hypersensitivity reaction type II disease0.01664Moderately InformativeInherited
Disease Ontology (DO)connective tissue disease0.04608Moderately InformativeInherited
Disease Ontology (DO)nephritis0.00001076InformativeDirect
Disease Ontology (DO)rheumatic disease0.0001816InformativeDirect
Disease Ontology (DO)collagen disease0.0002184InformativeDirect

Document: DO annotation of SCOP domains

Human Phenotype (HP)

(show details)
HP termFDR (all)SDHP levelAnnotation (direct or inherited)
Mode of Inheritance (MI)Autosomal dominant inheritance0Least InformativeDirect
Phenotypic Abnormality (PA)Abnormality of the cardiovascular system0Least InformativeDirect
Phenotypic Abnormality (PA)Abnormality of the vasculature0Moderately InformativeDirect
Phenotypic Abnormality (PA)Abnormality of cardiovascular system physiology0Moderately InformativeDirect
Phenotypic Abnormality (PA)Abnormality of cardiovascular system morphology0.3364Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal systemic arterial morphology0.0009924InformativeDirect
Phenotypic Abnormality (PA)Aortic aneurysm0.000006964Highly InformativeDirect
Phenotypic Abnormality (PA)Abnormal aortic valve physiology0.00002402Highly InformativeDirect
Phenotypic Abnormality (PA)Hypertension0.0006324Highly 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 phenotype0.006491Least InformativeInherited
Mammalian Phenotype (MP)growth/size/body region phenotype0.01157Least InformativeInherited
Mammalian Phenotype (MP)abnormal homeostasis0.01194Least InformativeInherited
Mammalian Phenotype (MP)nervous system phenotype0.02865Least InformativeInherited
Mammalian Phenotype (MP)abnormal heart morphology0Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal craniofacial morphology0.000002218Moderately InformativeDirect
Mammalian Phenotype (MP)neoplasm0.00003993Moderately InformativeDirect
Mammalian Phenotype (MP)embryo phenotype0.00006429Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal digestive system morphology0.00008044Moderately InformativeDirect
Mammalian Phenotype (MP)reproductive system phenotype0.0001334Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal nervous system development0.0001862Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal gland morphology0.0001969Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal cell morphology0.003838Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal hormone level0.01286Moderately InformativeInherited
Mammalian Phenotype (MP)integument phenotype0.05572Moderately InformativeInherited
Mammalian Phenotype (MP)prenatal lethality0.143Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal cardiovascular system physiology0.3187Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal germ cell morphology0.000002494InformativeDirect
Mammalian Phenotype (MP)increased carcinoma incidence0.00000281InformativeDirect
Mammalian Phenotype (MP)abnormal fertility/fecundity0.00001322InformativeDirect
Mammalian Phenotype (MP)increased gland tumor incidence0.0007459InformativeDirect
Mammalian Phenotype (MP)abnormal prenatal growth/weight/body size0.002761InformativeInherited
Mammalian Phenotype (MP)abnormal internal female genitalia morphology0.003961InformativeInherited
Mammalian Phenotype (MP)abnormal pituitary hormone level0.006686InformativeInherited
Mammalian Phenotype (MP)abnormal skin physiology0.01255InformativeInherited
Mammalian Phenotype (MP)abnormal female reproductive gland morphology0.08448InformativeInherited
Mammalian Phenotype (MP)abnormal embryo development0.08678InformativeInherited
Mammalian Phenotype (MP)abnormal heart ventricle morphology0.7733InformativeInherited
Mammalian Phenotype (MP)hemorrhage0.8611InformativeInherited
Mammalian Phenotype (MP)increased gonad tumor incidence0.000000000732Highly InformativeDirect
Mammalian Phenotype (MP)absent primordial germ cells0.000000009682Highly InformativeDirect
Mammalian Phenotype (MP)abnormal cumulus expansion0.00000004037Highly InformativeDirect
Mammalian Phenotype (MP)abnormal follicle stimulating hormone level0.0000004188Highly InformativeDirect
Mammalian Phenotype (MP)decreased litter size0.000003531Highly InformativeDirect
Mammalian Phenotype (MP)abnormal gastrulation0.000005666Highly InformativeDirect
Mammalian Phenotype (MP)abnormal embryonic epiblast morphology0.00001171Highly InformativeDirect
Mammalian Phenotype (MP)abnormal oocyte number0.00001404Highly InformativeDirect
Mammalian Phenotype (MP)embryonic lethality during organogenesis0.00004201Highly InformativeDirect
Mammalian Phenotype (MP)abnormal keratinocyte physiology0.00005881Highly InformativeDirect
Mammalian Phenotype (MP)premature aging0.00007881Highly InformativeDirect
Mammalian Phenotype (MP)abnormal heart development0.0003935Highly InformativeDirect
Mammalian Phenotype (MP)abnormal circulating gonadotropin level0.0007437Highly InformativeDirect
Mammalian Phenotype (MP)ventricular septal defect0.0007752Highly InformativeDirect
Mammalian Phenotype (MP)abnormal digestive system development0.0008907Highly InformativeDirect
Mammalian Phenotype (MP)internal hemorrhage0.002081Highly InformativeInherited
Mammalian Phenotype (MP)increased alimentary system tumor incidence0.01626Highly InformativeInherited
Mammalian Phenotype (MP)abnormal primitive streak morphology0.03844Highly 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 variant0.0001364Least InformativeDirect
Worm Phenotype (WP)cell development variant0.0002452Least InformativeDirect
Worm Phenotype (WP)organism environmental stimulus response variant0.0004186Least InformativeDirect
Worm Phenotype (WP)nervous system morphology variant0.0000001531Moderately InformativeDirect
Worm Phenotype (WP)pericellular component development variant0.00004882Moderately InformativeDirect
Worm Phenotype (WP)organism segment morphology variant0.0002837Moderately InformativeDirect
Worm Phenotype (WP)level of transgene expression variant0.04681Moderately InformativeInherited
Worm Phenotype (WP)gametogenesis variant0.3338Moderately InformativeInherited
Worm Phenotype (WP)movement variant0.4651Moderately InformativeInherited
Worm Phenotype (WP)sensillum morphology variant0.000000008106InformativeDirect
Worm Phenotype (WP)transgene expression reduced0.0000006048InformativeDirect
Worm Phenotype (WP)male morphology variant0.000004518InformativeDirect
Worm Phenotype (WP)velocity of movement variant0.000005733InformativeDirect
Worm Phenotype (WP)body width variant0.00005096InformativeDirect
Worm Phenotype (WP)localized movement variant0.0007607InformativeDirect
Worm Phenotype (WP)dauer arrest variant0.001025InformativeInherited
Worm Phenotype (WP)tail morphology variant0.001293InformativeInherited
Worm Phenotype (WP)body posture variant0.002466InformativeInherited
Worm Phenotype (WP)locomotor coordination variant0.009215InformativeInherited
Worm Phenotype (WP)foraging behavior variant0.01036InformativeInherited
Worm Phenotype (WP)body length variant0.5915InformativeInherited
Worm Phenotype (WP)male nervous system development variant0.00000003672Highly InformativeDirect
Worm Phenotype (WP)cuticle development variant0.00000007445Highly InformativeDirect
Worm Phenotype (WP)male tail morphology variant0.0000002272Highly InformativeDirect
Worm Phenotype (WP)male nervous system morphology variant0.0000005834Highly InformativeDirect
Worm Phenotype (WP)short0.000001167Highly InformativeDirect
Worm Phenotype (WP)roaming variant0.000001729Highly InformativeDirect
Worm Phenotype (WP)coiling frequency0.000002218Highly InformativeDirect
Worm Phenotype (WP)body posture amplitude variant0.000003763Highly InformativeDirect
Worm Phenotype (WP)backward point velocity variant0.000003851Highly InformativeDirect
Worm Phenotype (WP)nose movement variant0.000006361Highly InformativeDirect
Worm Phenotype (WP)amplitude of sinusoidal movement variant0.000007315Highly InformativeDirect
Worm Phenotype (WP)frequency of body bend variant0.000008061Highly InformativeDirect
Worm Phenotype (WP)dauer development variant0.00001565Highly InformativeDirect
Worm Phenotype (WP)germline proliferation variant0.00003216Highly InformativeDirect

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)neuroanatomy defective0Moderately InformativeDirect
Fly Phenotype (FP)size defective0InformativeDirect
Fly Phenotype (FP)cell number defective0InformativeDirect
Fly Phenotype (FP)decreased occurrence of cell division0.00003942Highly InformativeDirect

Document: FP annotation of SCOP domains

Fly Anatomy (FA)

(show details)
FA termFDR (all)SDFA levelAnnotation (direct or inherited)
Fly Anatomy (FA)embryo0Least InformativeDirect
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)thoracic segment0Moderately InformativeDirect
Fly Anatomy (FA)adult segment0Moderately InformativeDirect
Fly Anatomy (FA)adult thorax0Moderately InformativeDirect
Fly Anatomy (FA)developing embryonic structure0Moderately InformativeDirect
Fly Anatomy (FA)peripheral nervous system0Moderately InformativeDirect
Fly Anatomy (FA)neuron0Moderately InformativeDirect
Fly Anatomy (FA)late embryo0Moderately InformativeDirect
Fly Anatomy (FA)adult integumentary system0Moderately InformativeDirect
Fly Anatomy (FA)appendage0Moderately InformativeDirect
Fly Anatomy (FA)acellular anatomical structure0Moderately InformativeDirect
Fly Anatomy (FA)tagmatic subdivision of integument0Moderately InformativeDirect
Fly Anatomy (FA)multi-cell-component structure0.007439Moderately InformativeInherited
Fly Anatomy (FA)gonad0.02275Moderately InformativeInherited
Fly Anatomy (FA)ganglion0.04594Moderately InformativeInherited
Fly Anatomy (FA)stem cell0.04708Moderately InformativeInherited
Fly Anatomy (FA)central nervous system0.08953Moderately InformativeInherited
Fly Anatomy (FA)head0.3435Moderately InformativeInherited
Fly Anatomy (FA)abdominal segment0InformativeDirect
Fly Anatomy (FA)larval thoracic segment0InformativeDirect
Fly Anatomy (FA)imaginal disc0InformativeDirect
Fly Anatomy (FA)digestive system0InformativeDirect
Fly Anatomy (FA)wing blade0InformativeDirect
Fly Anatomy (FA)supraesophageal ganglion0.001202InformativeInherited
Fly Anatomy (FA)synaptic neuropil0.001314InformativeInherited
Fly Anatomy (FA)neuromere0.001903InformativeInherited
Fly Anatomy (FA)cell component0.007015InformativeInherited
Fly Anatomy (FA)ovariole0.009114InformativeInherited
Fly Anatomy (FA)germline cell0.0236InformativeInherited
Fly Anatomy (FA)wing disc0Highly InformativeDirect
Fly Anatomy (FA)wing vein0Highly InformativeDirect
Fly Anatomy (FA)female germline stem cell0.000004047Highly InformativeDirect
Fly Anatomy (FA)bouton0.0004786Highly 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)cell0.05847Least InformativeInherited
Zebrafish Anatomy (ZA)multi-tissue structure0.09726Least InformativeInherited
Zebrafish Anatomy (ZA)portion of tissue0.03268Moderately InformativeInherited
Zebrafish Anatomy (ZA)central nervous system0.1115Moderately InformativeInherited
Zebrafish Anatomy (ZA)hematopoietic system0.000125InformativeDirect
Zebrafish Anatomy (ZA)hematopoietic cell0.1056InformativeInherited
Zebrafish Anatomy (ZA)immune system0.1328InformativeInherited
Zebrafish Anatomy (ZA)floor plate0.00000002684Highly InformativeDirect
Zebrafish Anatomy (ZA)intermediate cell mass of mesoderm0.000003198Highly InformativeDirect
Zebrafish Anatomy (ZA)mononuclear phagocyte0.00003617Highly InformativeDirect
Zebrafish Anatomy (ZA)professional antigen presenting cell0.00004933Highly 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)nervous system0Least 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)ectoderm0Moderately InformativeDirect
Xenopus ANatomical entity (XAN)brain0Moderately InformativeDirect
Xenopus ANatomical entity (XAN)multi-tissue structure0Moderately InformativeDirect
Xenopus ANatomical entity (XAN)sensory system0.0002874Moderately InformativeDirect
Xenopus ANatomical entity (XAN)viscus0.1426Moderately InformativeInherited
Xenopus ANatomical entity (XAN)cardiovascular system0.0000005698InformativeDirect
Xenopus ANatomical entity (XAN)surface structure0.0001178InformativeDirect
Xenopus ANatomical entity (XAN)eye0.0001504InformativeDirect
Xenopus ANatomical entity (XAN)pharyngeal region0.0002081InformativeDirect
Xenopus ANatomical entity (XAN)anatomical direction0.0003018InformativeDirect
Xenopus ANatomical entity (XAN)vestibuloauditory system0.03125InformativeInherited
Xenopus ANatomical entity (XAN)otic vesicle0.0002742Highly InformativeDirect
Xenopus ANatomical entity (XAN)animal hemisphere0.0003428Highly InformativeDirect
Xenopus ANatomical entity (XAN)non-neural ectoderm0.0007804Highly 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 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 · 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 ]