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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 system0.1136Least InformativeInherited
Phenotypic Abnormality (PA)Abnormal cardiovascular system physiology0.01131Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the vasculature0.03128Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of cardiovascular system morphology0.3074Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal systemic arterial morphology0.004128InformativeInherited
Phenotypic Abnormality (PA)Abnormal morphology of the great vessels0.006695InformativeInherited
Phenotypic Abnormality (PA)Aortic dissection0.0000004086Highly InformativeDirect
Phenotypic Abnormality (PA)Aortic aneurysm0.00004953Highly InformativeDirect
Phenotypic Abnormality (PA)Abnormal aortic valve physiology0.0001334Highly 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 phenotype0.006443Least InformativeInherited
Mammalian Phenotype (MP)growth/size/body region phenotype0.01157Least InformativeInherited
Mammalian Phenotype (MP)abnormal homeostasis0.01189Least InformativeInherited
Mammalian Phenotype (MP)nervous system phenotype0.02868Least InformativeInherited
Mammalian Phenotype (MP)abnormal heart morphology0Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal craniofacial morphology0.000002239Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal reproductive system physiology0.00003352Moderately InformativeDirect
Mammalian Phenotype (MP)neoplasm0.00003976Moderately InformativeDirect
Mammalian Phenotype (MP)embryo phenotype0.00006434Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal digestive system morphology0.00008017Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal nervous system development0.0001856Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal gland morphology0.0001954Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal cell morphology0.003819Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal hormone level0.01288Moderately InformativeInherited
Mammalian Phenotype (MP)integument phenotype0.05586Moderately InformativeInherited
Mammalian Phenotype (MP)prenatal lethality0.1428Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal reproductive system morphology0.1495Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal cardiovascular system physiology0.3189Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal germ cell morphology0.000002459InformativeDirect
Mammalian Phenotype (MP)increased carcinoma incidence0.000002804InformativeDirect
Mammalian Phenotype (MP)abnormal fertility/fecundity0.00001323InformativeDirect
Mammalian Phenotype (MP)increased gland tumor incidence0.0007487InformativeDirect
Mammalian Phenotype (MP)abnormal prenatal growth/weight/body size0.002763InformativeInherited
Mammalian Phenotype (MP)abnormal internal female genitalia morphology0.003945InformativeInherited
Mammalian Phenotype (MP)abnormal pituitary hormone level0.006558InformativeInherited
Mammalian Phenotype (MP)abnormal skin physiology0.01252InformativeInherited
Mammalian Phenotype (MP)abnormal female reproductive gland morphology0.08486InformativeInherited
Mammalian Phenotype (MP)abnormal embryo development0.08705InformativeInherited
Mammalian Phenotype (MP)abnormal heart ventricle morphology0.7735InformativeInherited
Mammalian Phenotype (MP)hemorrhage0.8611InformativeInherited
Mammalian Phenotype (MP)increased gonad tumor incidence0.0000000007307Highly InformativeDirect
Mammalian Phenotype (MP)abnormal follicle stimulating hormone level0.0000003943Highly InformativeDirect
Mammalian Phenotype (MP)decreased litter size0.000003591Highly InformativeDirect
Mammalian Phenotype (MP)abnormal gastrulation0.000005755Highly InformativeDirect
Mammalian Phenotype (MP)abnormal embryonic epiblast morphology0.00001169Highly InformativeDirect
Mammalian Phenotype (MP)abnormal oocyte number0.000014Highly InformativeDirect
Mammalian Phenotype (MP)embryonic lethality during organogenesis0.00004185Highly InformativeDirect
Mammalian Phenotype (MP)abnormal keratinocyte physiology0.00005867Highly InformativeDirect
Mammalian Phenotype (MP)premature aging0.00007858Highly InformativeDirect
Mammalian Phenotype (MP)abnormal heart development0.0003942Highly InformativeDirect
Mammalian Phenotype (MP)abnormal ovarian follicle morphology0.0004298Highly InformativeDirect
Mammalian Phenotype (MP)abnormal circulating gonadotropin level0.000712Highly InformativeDirect
Mammalian Phenotype (MP)ventricular septal defect0.0007723Highly InformativeDirect
Mammalian Phenotype (MP)abnormal digestive system development0.0008891Highly InformativeDirect
Mammalian Phenotype (MP)internal hemorrhage0.002071Highly InformativeInherited
Mammalian Phenotype (MP)decreased primordial germ cell number0.002342Highly InformativeInherited
Mammalian Phenotype (MP)increased alimentary system tumor incidence0.01629Highly 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 variant0.0001724Least InformativeDirect
Worm Phenotype (WP)cell development variant0.0002886Least InformativeDirect
Worm Phenotype (WP)larval development variant0.7231Least InformativeInherited
Worm Phenotype (WP)nervous system morphology variant0.0000002743Moderately InformativeDirect
Worm Phenotype (WP)pericellular component development variant0.00005458Moderately InformativeDirect
Worm Phenotype (WP)organism segment morphology variant0.0003254Moderately InformativeDirect
Worm Phenotype (WP)body region morphology variant0.0003311Moderately InformativeDirect
Worm Phenotype (WP)germ cell development variant0.004202Moderately InformativeInherited
Worm Phenotype (WP)level of transgene expression variant0.0524Moderately InformativeInherited
Worm Phenotype (WP)movement variant0.3922Moderately InformativeInherited
Worm Phenotype (WP)sensillum morphology variant0.00000001385InformativeDirect
Worm Phenotype (WP)transgene expression reduced0.0000008969InformativeDirect
Worm Phenotype (WP)male morphology variant0.000004943InformativeDirect
Worm Phenotype (WP)velocity of movement variant0.000007227InformativeDirect
Worm Phenotype (WP)directionality variant0.00001354InformativeDirect
Worm Phenotype (WP)body bend variant0.00001963InformativeDirect
Worm Phenotype (WP)localized movement variant0.0007809InformativeDirect
Worm Phenotype (WP)tail morphology variant0.00151InformativeInherited
Worm Phenotype (WP)lipid metabolism variant0.00201InformativeInherited
Worm Phenotype (WP)body posture variant0.002165InformativeInherited
Worm Phenotype (WP)foraging behavior variant0.009116InformativeInherited
Worm Phenotype (WP)small0.09929InformativeInherited
Worm Phenotype (WP)dauer larva physiology variant1InformativeInherited
Worm Phenotype (WP)male nervous system development variant0.00000004598Highly InformativeDirect
Worm Phenotype (WP)cuticle development variant0.0000001378Highly InformativeDirect
Worm Phenotype (WP)male tail morphology variant0.0000002564Highly InformativeDirect
Worm Phenotype (WP)fat content reduced0.0000004088Highly InformativeDirect
Worm Phenotype (WP)short0.000001464Highly InformativeDirect
Worm Phenotype (WP)roaming variant0.000002018Highly InformativeDirect
Worm Phenotype (WP)coiling frequency variant0.000002511Highly InformativeDirect
Worm Phenotype (WP)body posture amplitude variant0.000004321Highly InformativeDirect
Worm Phenotype (WP)backward point velocity variant0.000004321Highly InformativeDirect
Worm Phenotype (WP)amplitude of sinusoidal movement variant0.000008454Highly InformativeDirect
Worm Phenotype (WP)frequency of body bend variant0.000009656Highly InformativeDirect
Worm Phenotype (WP)cell fusion variant0.00001857Highly InformativeDirect
Worm Phenotype (WP)dauer development variant0.00002955Highly InformativeDirect
Worm Phenotype (WP)germline proliferation variant0.00003295Highly InformativeDirect
Worm Phenotype (WP)male ray morphology variant0.04283Highly 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)cell0Least InformativeDirect
Fly Anatomy (FA)organism subdivision0Least InformativeDirect
Fly Anatomy (FA)multi-tissue structure0Least InformativeDirect
Fly Anatomy (FA)organ system subdivision0Least InformativeDirect
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 structure0.007231Moderately InformativeInherited
Fly Anatomy (FA)female-specific anatomical entity0.01047Moderately InformativeInherited
Fly Anatomy (FA)gonad0.02104Moderately InformativeInherited
Fly Anatomy (FA)stem cell0.04654Moderately InformativeInherited
Fly Anatomy (FA)central nervous system0.08856Moderately InformativeInherited
Fly Anatomy (FA)abdominal segment0InformativeDirect
Fly Anatomy (FA)larval segment0InformativeDirect
Fly Anatomy (FA)imaginal disc0InformativeDirect
Fly Anatomy (FA)wing0InformativeDirect
Fly Anatomy (FA)cuticular specialization0InformativeDirect
Fly Anatomy (FA)gut section0InformativeDirect
Fly Anatomy (FA)synaptic neuropil domain0.0005608InformativeDirect
Fly Anatomy (FA)germarium0.001357InformativeInherited
Fly Anatomy (FA)cell component0.009835InformativeInherited
Fly Anatomy (FA)germline cell0.02244InformativeInherited
Fly Anatomy (FA)larval mesothoracic segment0Highly InformativeDirect
Fly Anatomy (FA)wing vein0Highly InformativeDirect
Fly Anatomy (FA)female germline stem cell0.000004773Highly InformativeDirect
Fly Anatomy (FA)bouton0.0006085Highly InformativeDirect
Fly Anatomy (FA)egg0.0009899Highly 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)cell0.0631Least InformativeInherited
Zebrafish Anatomy (ZA)portion of tissue0Moderately InformativeDirect
Zebrafish Anatomy (ZA)central nervous system0.1024Moderately InformativeInherited
Zebrafish Anatomy (ZA)hematopoietic system0.000152InformativeDirect
Zebrafish Anatomy (ZA)hematopoietic cell0.1049InformativeInherited
Zebrafish Anatomy (ZA)floor plate0.0000000194Highly InformativeDirect
Zebrafish Anatomy (ZA)intermediate cell mass of mesoderm0.000007707Highly InformativeDirect
Zebrafish Anatomy (ZA)mononuclear phagocyte0.00009989Highly InformativeDirect
Zebrafish Anatomy (ZA)professional antigen presenting cell0.0001241Highly 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 system0.0004632Moderately InformativeDirect
Xenopus ANatomical entity (XAN)viscus0.1448Moderately InformativeInherited
Xenopus ANatomical entity (XAN)cardiovascular system0.000001255InformativeDirect
Xenopus ANatomical entity (XAN)surface structure0.0002069InformativeDirect
Xenopus ANatomical entity (XAN)eye0.0002419InformativeDirect
Xenopus ANatomical entity (XAN)anatomical direction0.0003427InformativeDirect
Xenopus ANatomical entity (XAN)animal hemisphere0.0004944InformativeDirect
Xenopus ANatomical entity (XAN)mesoderm0.0005846InformativeDirect
Xenopus ANatomical entity (XAN)pharyngeal region0.0005993InformativeDirect
Xenopus ANatomical entity (XAN)vestibuloauditory system0.04502InformativeInherited
Xenopus ANatomical entity (XAN)tail bud0.00001102Highly 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 ]