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SMAD/FHA domain superfamily

SCOP classification
Root:   SCOP hierarchy in SUPERFAMILY [ 0] (11)
Class:   All beta proteins [ 48724] (174)
Fold:   SMAD/FHA domain [ 49878]
Superfamily:   SMAD/FHA domain [ 49879] (4)
Families:   SMAD domain [ 49880] (4)
  FHA domain [ 49885] (11)
  Interferon regulatory factor 3 (IRF3), transactivation domain [ 101630]
  EssC N-terminal domain-like [ 141143]


Superfamily statistics
Genomes (1,762) Uniprot 2018_03 genome PDB chains (SCOP 1.75)
Domains 17,190 79,873 38
Proteins 16,412 75,224 37


Functional annotation
General category Regulation
Detailed category DNA-binding

Document:
Function annotation of SCOP domain superfamilies

Enzyme Commission (EC)

(show details)
EC termFDR (all)SDEO levelAnnotation (direct or inherited)
Enzyme Commission (EC)Oxidoreductases0.1289Least InformativeInherited
Enzyme Commission (EC)Protein-serine/threonine kinases0.000000000000007375Moderately InformativeDirect
Enzyme Commission (EC)Acting on paired donors, with incorporation or red0.00000000823Moderately InformativeDirect
Enzyme Commission (EC)With NADH or NADPH as one donor, and incorporation0.000000000001841InformativeDirect

Document: EC annotation of SCOP domains

Disease Ontology (DO)

(show details)
DO termFDR (all)SDDO levelAnnotation (direct or inherited)
Disease Ontology (DO)disease by infectious agent0.00033Moderately InformativeDirect
Disease Ontology (DO)genetic disease0.0383Moderately InformativeInherited
Disease Ontology (DO)autosomal dominant disease0.0007026InformativeDirect

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 head0.1873Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of nervous system morphology0.2207Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the cardiovascular system0.4904Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the vasculature0.2943Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal peripheral nervous system morphology0.3912Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of cardiovascular system morphology0.6Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal oral cavity morphology1Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal systemic arterial morphology0.1694InformativeInherited
Phenotypic Abnormality (PA)Abnormal palate morphology0.2519InformativeInherited
Phenotypic Abnormality (PA)Abnormal lip morphology0.3836InformativeInherited
Phenotypic Abnormality (PA)Bifid uvula0.0007022Highly InformativeDirect
Phenotypic Abnormality (PA)Abnormal myelination0.05266Highly InformativeInherited
Phenotypic Abnormality (PA)Oral cleft0.2232Highly InformativeInherited
Phenotypic Abnormality (PA)Abnormal aortic morphology0.241Highly InformativeInherited

Document: HP annotation of SCOP domains

Mouse Phenotype (MP)

(show details)
MP termFDR (all)SDMP levelAnnotation (direct or inherited)
Mammalian Phenotype (MP)cellular phenotype0.05162Least InformativeInherited
Mammalian Phenotype (MP)mortality/aging0.1461Least InformativeInherited
Mammalian Phenotype (MP)immune system phenotype0.2899Least InformativeInherited
Mammalian Phenotype (MP)cardiovascular system phenotype0.4437Least InformativeInherited
Mammalian Phenotype (MP)hematopoietic system phenotype0.4803Least InformativeInherited
Mammalian Phenotype (MP)neoplasm0.001878Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal blood cell morphology/development0.007914Moderately InformativeInherited
Mammalian Phenotype (MP)embryo phenotype0.02691Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal metabolism0.05209Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal blood cell morphology0.07468Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal digestive system morphology0.1213Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal leukocyte physiology0.1405Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal cell morphology0.151Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal mononuclear cell morphology0.1539Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal immune serum protein physiology0.2105Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal professional antigen presenting cell physiology0.2401Moderately InformativeInherited
Mammalian Phenotype (MP)reproductive system phenotype0.2514Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal induced morbidity/mortality0.2559Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal cardiovascular system physiology0.2996Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal gland morphology0.5743Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal hematopoietic cell number0.7731Moderately InformativeInherited
Mammalian Phenotype (MP)increased gland tumor incidence0.0001682InformativeDirect
Mammalian Phenotype (MP)increased carcinoma incidence0.0002096InformativeDirect
Mammalian Phenotype (MP)chromosomal instability0.0002903InformativeDirect
Mammalian Phenotype (MP)abnormal response to radiation0.002803InformativeInherited
Mammalian Phenotype (MP)abnormal germ cell morphology0.009764InformativeInherited
Mammalian Phenotype (MP)abnormal B cell differentiation0.01163InformativeInherited
Mammalian Phenotype (MP)abnormal interferon secretion0.0385InformativeInherited
Mammalian Phenotype (MP)abnormal extraembryonic tissue morphology0.06532InformativeInherited
Mammalian Phenotype (MP)abnormal sensitivity to induced morbidity/mortality0.08228InformativeInherited
Mammalian Phenotype (MP)abnormal internal female genitalia morphology0.1199InformativeInherited
Mammalian Phenotype (MP)abnormal female reproductive gland morphology0.2InformativeInherited
Mammalian Phenotype (MP)abnormal embryo development0.2255InformativeInherited
Mammalian Phenotype (MP)abnormal fertility/fecundity0.4073InformativeInherited
Mammalian Phenotype (MP)hemorrhage0.691InformativeInherited
Mammalian Phenotype (MP)increased gonad tumor incidence0.000001959Highly InformativeDirect
Mammalian Phenotype (MP)abnormal embryonic epiblast morphology0.00002551Highly InformativeDirect
Mammalian Phenotype (MP)abnormal cumulus expansion0.00002686Highly InformativeDirect
Mammalian Phenotype (MP)decreased interferon-alpha secretion0.0001576Highly InformativeDirect
Mammalian Phenotype (MP)abnormal oocyte number0.0004301Highly InformativeDirect
Mammalian Phenotype (MP)abnormal digestive system development0.0004303Highly InformativeDirect
Mammalian Phenotype (MP)absent primordial germ cells0.0007229Highly InformativeDirect
Mammalian Phenotype (MP)abnormal gastrulation0.002318Highly InformativeInherited
Mammalian Phenotype (MP)premature aging0.004479Highly InformativeInherited
Mammalian Phenotype (MP)decreased dendritic cell number0.005529Highly InformativeInherited
Mammalian Phenotype (MP)internal hemorrhage0.3395Highly InformativeInherited

Document: MP annotation of SCOP domains

Worm Phenotype (WP)

(show details)
WP termFDR (all)SDWP levelAnnotation (direct or inherited)
Worm Phenotype (WP)organism behavior variant0.0007165Least InformativeDirect
Worm Phenotype (WP)cell development variant0.002909Least InformativeInherited
Worm Phenotype (WP)organ system morphology variant0.003931Least InformativeInherited
Worm Phenotype (WP)organism environmental stimulus response variant0.004008Least InformativeInherited
Worm Phenotype (WP)cell morphology variant0.2454Least InformativeInherited
Worm Phenotype (WP)nervous system morphology variant0.00005983Moderately InformativeDirect
Worm Phenotype (WP)pericellular component development variant0.001954Moderately InformativeInherited
Worm Phenotype (WP)drug response variant0.08154Moderately InformativeInherited
Worm Phenotype (WP)body region morphology variant0.08321Moderately InformativeInherited
Worm Phenotype (WP)organism segment morphology variant0.08321Moderately InformativeInherited
Worm Phenotype (WP)developmental morphology variant0.08351Moderately InformativeInherited
Worm Phenotype (WP)adult body morphology variant0.08379Moderately InformativeInherited
Worm Phenotype (WP)body morphology variant0.09058Moderately InformativeInherited
Worm Phenotype (WP)feeding behavior variant0.2513Moderately InformativeInherited
Worm Phenotype (WP)movement variant0.5994Moderately InformativeInherited
Worm Phenotype (WP)velocity of movement variant0.000173InformativeDirect
Worm Phenotype (WP)directionality variant0.0004071InformativeDirect
Worm Phenotype (WP)body bend variant0.0005734InformativeDirect
Worm Phenotype (WP)aldicarb response variant0.0008123InformativeDirect
Worm Phenotype (WP)tail morphology variant0.001411InformativeInherited
Worm Phenotype (WP)male morphology variant0.0017InformativeInherited
Worm Phenotype (WP)axon outgrowth variant0.003725InformativeInherited
Worm Phenotype (WP)localized movement variant0.003776InformativeInherited
Worm Phenotype (WP)body posture variant0.01001InformativeInherited
Worm Phenotype (WP)forward locomotion variant0.01325InformativeInherited
Worm Phenotype (WP)sensillum morphology variant0.02672InformativeInherited
Worm Phenotype (WP)foraging behavior variant0.04656InformativeInherited
Worm Phenotype (WP)neuron morphology variant0.09894InformativeInherited
Worm Phenotype (WP)small0.1902InformativeInherited
Worm Phenotype (WP)locomotion reduced0.7644InformativeInherited
Worm Phenotype (WP)cuticle development variant0.00000101Highly InformativeDirect
Worm Phenotype (WP)cuticle physiology variant0.000003122Highly InformativeDirect
Worm Phenotype (WP)male nervous system development variant0.00001868Highly InformativeDirect
Worm Phenotype (WP)social behavior variant0.00002015Highly InformativeDirect
Worm Phenotype (WP)short0.00002935Highly InformativeDirect
Worm Phenotype (WP)axon branching variant0.00003256Highly InformativeDirect
Worm Phenotype (WP)roaming variant0.00004335Highly InformativeDirect
Worm Phenotype (WP)coiling frequency0.00005646Highly InformativeDirect
Worm Phenotype (WP)forward locomotion decreased0.00006232Highly InformativeDirect
Worm Phenotype (WP)body posture amplitude variant0.0001054Highly InformativeDirect
Worm Phenotype (WP)male tail morphology variant0.0001078Highly InformativeDirect
Worm Phenotype (WP)backward point velocity variant0.0001084Highly InformativeDirect
Worm Phenotype (WP)amplitude of sinusoidal movement variant0.0002347Highly InformativeDirect
Worm Phenotype (WP)frequency of body bend variant0.0002567Highly InformativeDirect
Worm Phenotype (WP)dauer development variant0.0004454Highly InformativeDirect
Worm Phenotype (WP)cell fusion variant0.0007533Highly InformativeDirect
Worm Phenotype (WP)path curvature variant0.06275Highly InformativeInherited
Worm Phenotype (WP)male ray morphology variant0.2416Highly InformativeInherited
Worm Phenotype (WP)body posture wavelength variant0.3812Highly 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)decreased occurrence of cell division0.00001973Highly 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)multi-tissue structure0.09029Least InformativeInherited
Fly Anatomy (FA)stem cell0.0119Moderately InformativeInherited
Fly Anatomy (FA)gonad0.07462Moderately InformativeInherited
Fly Anatomy (FA)germarium0.03265InformativeInherited
Fly Anatomy (FA)germline cell0.07363InformativeInherited
Fly Anatomy (FA)female germline stem cell0.0007386Highly InformativeDirect

Document: FA annotation of SCOP domains

Zebrafish Anatomy (ZA)

(show details)
ZA termFDR (all)SDZA levelAnnotation (direct or inherited)
Zebrafish Anatomy (ZA)cell0.04905Least InformativeInherited
Zebrafish Anatomy (ZA)multi-tissue structure0.0932Least InformativeInherited
Zebrafish Anatomy (ZA)nervous system0.2101Least InformativeInherited
Zebrafish Anatomy (ZA)portion of tissue0.02209Moderately InformativeInherited
Zebrafish Anatomy (ZA)central nervous system0.06414Moderately InformativeInherited
Zebrafish Anatomy (ZA)hematopoietic system0.000000737InformativeDirect
Zebrafish Anatomy (ZA)hematopoietic cell0.0001826InformativeDirect
Zebrafish Anatomy (ZA)primary germ layer0.03785InformativeInherited
Zebrafish Anatomy (ZA)embryonic structure0.2593InformativeInherited
Zebrafish Anatomy (ZA)mononuclear phagocyte0.000000006141Highly InformativeDirect
Zebrafish Anatomy (ZA)professional antigen presenting cell0.00000000988Highly InformativeDirect
Zebrafish Anatomy (ZA)intermediate cell mass of mesoderm0.0000005211Highly InformativeDirect
Zebrafish Anatomy (ZA)floor plate0.00003052Highly InformativeDirect
Zebrafish Anatomy (ZA)neurogenic placode0.0004855Highly InformativeDirect

Document: ZA annotation of SCOP domains

Xenopus Anatomy (XA)

(show details)
XA termFDR (all)SDXA levelAnnotation (direct or inherited)
Xenopus ANatomical entity (XAN)trunk0.1739Least InformativeInherited
Xenopus ANatomical entity (XAN)tissue0.3816Least InformativeInherited
Xenopus ANatomical entity (XAN)cavitated compound organ0.7731Least InformativeInherited
Xenopus ANatomical entity (XAN)anatomical system1Least InformativeInherited
Xenopus ANatomical entity (XAN)viscus0.1472Moderately InformativeInherited
Xenopus ANatomical entity (XAN)cardiovascular system0.00637InformativeInherited

Document: XA annotation of SCOP domains

Arabidopsis Plant Ontology (AP)

(show details)
AP termFDR (all)SDAP levelAnnotation (direct or inherited)
Plant structure DEvelopment stage (PDE)F mature embryo stage0Least InformativeDirect

Document: AP annotation of SCOP domains

Enzyme Commission (EC)

(show details)
EC termFDR (all)SDEC levelAnnotation (direct or inherited)
Enzyme Commission (EC)Hydrolases0.08685Least InformativeInherited
Enzyme Commission (EC)Transferring phosphorus-containing groups0.1303Least InformativeInherited
Enzyme Commission (EC)Oxidoreductases0.5463Least InformativeInherited
Enzyme Commission (EC)Lyases1Least InformativeInherited
Enzyme Commission (EC)Aminoacyltransferases0Moderately InformativeDirect
Enzyme Commission (EC)Protein-serine/threonine kinases0.00000000000104Moderately InformativeDirect
Enzyme Commission (EC)Carbon-oxygen lyases0.4813Moderately InformativeInherited
Enzyme Commission (EC)RING-type E3 ubiquitin transferase0InformativeDirect
Enzyme Commission (EC)Non-specific serine/threonine protein kinase5.074e-16InformativeDirect
Enzyme Commission (EC)Acting on paired donors, with incorporation or reduction of molecular oxygen. The oxygen incorporate0.00000003152InformativeDirect
Enzyme Commission (EC)With reduced iron-sulfur protein as one donor, and incorporation of one atom of oxygen0Highly InformativeDirect
Enzyme Commission (EC)Exodeoxyribonucleases producing 5'-phosphomonoesters0Highly InformativeDirect
Enzyme Commission (EC)DNA-(apurinic or apyrimidinic site) lyase0.00005568Highly InformativeDirect

Document: EC annotation of SCOP domains

InterPro annotation
Cross references IPR008984 SSF49879 Protein matches
Abstract

FHA and SMAD (MH2) domains share a common structure consisting of a sandwich of eleven beta strands in two sheets with Greek key topology. Forkhead-associated (FHA) domains were originally identified as a sequence profile of about 75 amino acids, whereas the full-length domain is closer to about 150 amino acids. FHA domains are found in transcription factors, kinesin motors, and in a variety of other signalling molecules in organisms ranging from eubacteria to humans. FHA domains are protein-protein interaction domains that are specific for phosphoproteins. FHA-containing proteins function in maintaining cell-cycle checkpoints, DNA repair and transcriptional regulation. FHA domain proteins include the Chk2/Rad53/Cds1 family of proteins that contain one or more FHA domains, as well as a Ser/Thr kinase domain [PubMed11106755, PubMed12121644, PubMed12049740].

SMAD domain proteins are found in a range of species from nematodes to humans. These highly conserved proteins contain an N-terminal MH1 domain that contacts DNA, and is separated by a short linker region from the C-terminal MH2 domain, the later showing a striking similarity to FHA domains. SMAD proteins mediate signalling by the TGF-beta/activin/BMP-2/4 cytokines from receptor Ser/Thr protein kinases at the cell surface to the nucleus. SMAD proteins fall into three functional classes: the receptor-regulated SMADs (R-SMADs), including SMAD1, -2, -3, -5, and -8, each of which is involved in a ligand-specific signalling pathway [PubMed11779503]; the comediator SMADs (co-SMADs), including SMAD4, which interact with R-SMADs to participate in signalling [PubMed9214508]; and the inhibitory SMADs (I-SMADs), including SMAD6 and -7, which block the activation of R-SMADs and Co-SMADs, thereby negatively regulating signalling pathways [PubMed11483516].


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 · Enzyme Commission (EC) · Disease Ontology (DO) · Human Phenotype (HP) · Mouse Phenotype (MP) · Worm Phenotype (WP) · Fly Phenotype (FP) · Fly Anatomy (FA) · Zebrafish Anatomy (ZA) · Xenopus Anatomy (XA) · Arabidopsis Plant Ontology (AP) · Enzyme Commission (EC) ]

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 27 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/FHA 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 27 hidden Markov models representing the SMAD/FHA 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 · Enzyme Commission (EC) · Disease Ontology (DO) · Human Phenotype (HP) · Mouse Phenotype (MP) · Worm Phenotype (WP) · Fly Phenotype (FP) · Fly Anatomy (FA) · Zebrafish Anatomy (ZA) · Xenopus Anatomy (XA) · Arabidopsis Plant Ontology (AP) · Enzyme Commission (EC) · Internal database links ]