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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 agent0.0003293Moderately InformativeDirect
Disease Ontology (DO)genetic disease0.03828Moderately InformativeInherited
Disease Ontology (DO)autosomal dominant disease0.0007023InformativeDirect

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 system0.3667Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the eye0.865Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the head0.9446Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of cardiovascular system morphology0.4569Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the vasculature0.5876Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal eye physiology0.6987Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal oral cavity morphology1Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal systemic arterial morphology0.1614InformativeInherited
Phenotypic Abnormality (PA)Abnormality of eye movement0.2056InformativeInherited
Phenotypic Abnormality (PA)Abnormal morphology of the great vessels0.2708InformativeInherited
Phenotypic Abnormality (PA)Abnormal lip morphology0.5168InformativeInherited
Phenotypic Abnormality (PA)Aortic dissection0.0002768Highly InformativeDirect
Phenotypic Abnormality (PA)Cleft upper lip0.04298Highly InformativeInherited

Document: HP annotation of SCOP domains

Mouse Phenotype (MP)

(show details)
MP termFDR (all)SDMP levelAnnotation (direct or inherited)
Mammalian Phenotype (MP)cellular phenotype0.05139Least InformativeInherited
Mammalian Phenotype (MP)mortality/aging0.1462Least InformativeInherited
Mammalian Phenotype (MP)immune system phenotype0.2903Least InformativeInherited
Mammalian Phenotype (MP)cardiovascular system phenotype0.4435Least InformativeInherited
Mammalian Phenotype (MP)hematopoietic system phenotype0.4808Least InformativeInherited
Mammalian Phenotype (MP)neoplasm0.001868Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal blood cell morphology/development0.007896Moderately InformativeInherited
Mammalian Phenotype (MP)embryo phenotype0.02702Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal metabolism0.05215Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal blood cell morphology0.07491Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal reproductive system physiology0.1077Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal digestive system morphology0.1212Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal leukocyte physiology0.1404Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal cell morphology0.1504Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal mononuclear cell morphology0.1542Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal reproductive system morphology0.1721Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal immune serum protein physiology0.2096Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal professional antigen presenting cell physiology0.2388Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal induced morbidity/mortality0.2557Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal cardiovascular system physiology0.2995Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal gland morphology0.574Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal hematopoietic cell number0.7721Moderately InformativeInherited
Mammalian Phenotype (MP)increased gland tumor incidence0.000169InformativeDirect
Mammalian Phenotype (MP)increased carcinoma incidence0.0002095InformativeDirect
Mammalian Phenotype (MP)chromosomal instability0.00029InformativeDirect
Mammalian Phenotype (MP)abnormal response to radiation0.002789InformativeInherited
Mammalian Phenotype (MP)abnormal germ cell morphology0.009678InformativeInherited
Mammalian Phenotype (MP)abnormal B cell differentiation0.01163InformativeInherited
Mammalian Phenotype (MP)abnormal interferon secretion0.03819InformativeInherited
Mammalian Phenotype (MP)abnormal extraembryonic tissue morphology0.0651InformativeInherited
Mammalian Phenotype (MP)abnormal sensitivity to induced morbidity/mortality0.08227InformativeInherited
Mammalian Phenotype (MP)abnormal internal female genitalia morphology0.1199InformativeInherited
Mammalian Phenotype (MP)abnormal female reproductive gland morphology0.2007InformativeInherited
Mammalian Phenotype (MP)abnormal embryo development0.2261InformativeInherited
Mammalian Phenotype (MP)abnormal fertility/fecundity0.4073InformativeInherited
Mammalian Phenotype (MP)hemorrhage0.6911InformativeInherited
Mammalian Phenotype (MP)increased gonad tumor incidence0.000001957Highly InformativeDirect
Mammalian Phenotype (MP)abnormal embryonic epiblast morphology0.00002547Highly InformativeDirect
Mammalian Phenotype (MP)decreased interferon-alpha secretion0.0001575Highly InformativeDirect
Mammalian Phenotype (MP)abnormal oocyte number0.000429Highly InformativeDirect
Mammalian Phenotype (MP)abnormal digestive system development0.0004294Highly InformativeDirect
Mammalian Phenotype (MP)abnormal gastrulation0.002345Highly InformativeInherited
Mammalian Phenotype (MP)premature aging0.004471Highly InformativeInherited
Mammalian Phenotype (MP)decreased dendritic cell number0.005294Highly InformativeInherited
Mammalian Phenotype (MP)decreased primordial germ cell number0.01496Highly InformativeInherited
Mammalian Phenotype (MP)abnormal ovarian follicle morphology0.01579Highly InformativeInherited
Mammalian Phenotype (MP)absent germ cells0.1697Highly InformativeInherited
Mammalian Phenotype (MP)internal hemorrhage0.3396Highly 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 variant0.0002805Least InformativeDirect
Worm Phenotype (WP)cell development variant0.002979Least InformativeInherited
Worm Phenotype (WP)organ system morphology variant0.00524Least InformativeInherited
Worm Phenotype (WP)organism metabolism processing variant0.02159Least InformativeInherited
Worm Phenotype (WP)cell morphology variant0.2574Least InformativeInherited
Worm Phenotype (WP)larval development variant0.8104Least InformativeInherited
Worm Phenotype (WP)nervous system morphology variant0.00007186Moderately InformativeDirect
Worm Phenotype (WP)pericellular component development variant0.00218Moderately InformativeInherited
Worm Phenotype (WP)organism segment morphology variant0.08029Moderately InformativeInherited
Worm Phenotype (WP)body region morphology variant0.08142Moderately InformativeInherited
Worm Phenotype (WP)neuron development variant0.2809Moderately InformativeInherited
Worm Phenotype (WP)feeding behavior variant0.2908Moderately InformativeInherited
Worm Phenotype (WP)movement variant0.6932Moderately InformativeInherited
Worm Phenotype (WP)velocity of movement variant0.0002191InformativeDirect
Worm Phenotype (WP)directionality variant0.0004526InformativeDirect
Worm Phenotype (WP)body bend variant0.0006936InformativeDirect
Worm Phenotype (WP)male morphology variant0.001832InformativeInherited
Worm Phenotype (WP)localized movement variant0.003642InformativeInherited
Worm Phenotype (WP)axon outgrowth variant0.004305InformativeInherited
Worm Phenotype (WP)tail morphology variant0.00601InformativeInherited
Worm Phenotype (WP)forward locomotion variant0.01273InformativeInherited
Worm Phenotype (WP)body posture variant0.01302InformativeInherited
Worm Phenotype (WP)sensillum morphology variant0.02407InformativeInherited
Worm Phenotype (WP)lipid metabolism variant0.0442InformativeInherited
Worm Phenotype (WP)small0.05165InformativeInherited
Worm Phenotype (WP)foraging behavior variant0.05927InformativeInherited
Worm Phenotype (WP)neuron morphology variant0.1094InformativeInherited
Worm Phenotype (WP)locomotion reduced0.7359InformativeInherited
Worm Phenotype (WP)dauer larva physiology variant1InformativeInherited
Worm Phenotype (WP)cuticle development variant0.0000019Highly InformativeDirect
Worm Phenotype (WP)male nervous system development variant0.00002241Highly InformativeDirect
Worm Phenotype (WP)social behavior variant0.00002318Highly InformativeDirect
Worm Phenotype (WP)short0.00003311Highly InformativeDirect
Worm Phenotype (WP)roaming variant0.00004862Highly InformativeDirect
Worm Phenotype (WP)coiling frequency variant0.00006309Highly InformativeDirect
Worm Phenotype (WP)forward locomotion decreased0.00006443Highly InformativeDirect
Worm Phenotype (WP)fat content reduced0.0001153Highly InformativeDirect
Worm Phenotype (WP)male tail morphology variant0.0001167Highly InformativeDirect
Worm Phenotype (WP)body posture amplitude variant0.0001198Highly InformativeDirect
Worm Phenotype (WP)backward point velocity variant0.0001198Highly InformativeDirect
Worm Phenotype (WP)dauer development variant0.0001346Highly InformativeDirect
Worm Phenotype (WP)pericellular component physiology variant0.0001941Highly InformativeDirect
Worm Phenotype (WP)amplitude of sinusoidal movement variant0.0002627Highly InformativeDirect
Worm Phenotype (WP)dye filling defect0.0002935Highly InformativeDirect
Worm Phenotype (WP)frequency of body bend variant0.0003068Highly InformativeDirect
Worm Phenotype (WP)cell fusion variant0.0009022Highly InformativeDirect
Worm Phenotype (WP)path curvature variant0.05723Highly InformativeInherited
Worm Phenotype (WP)male ray morphology variant0.2338Highly InformativeInherited
Worm Phenotype (WP)body posture wavelength variant0.3683Highly 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 division0.00002021Highly 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 structure0.08064Least InformativeInherited
Fly Anatomy (FA)cell0.5191Least InformativeInherited
Fly Anatomy (FA)stem cell0.01143Moderately InformativeInherited
Fly Anatomy (FA)female-specific anatomical entity0.02922Moderately InformativeInherited
Fly Anatomy (FA)gonad0.06746Moderately InformativeInherited
Fly Anatomy (FA)germarium0.03123InformativeInherited
Fly Anatomy (FA)germline cell0.0678InformativeInherited
Fly Anatomy (FA)female germline stem cell0.0006637Highly InformativeDirect

Document: FA annotation of SCOP domains

Zebrafish Anatomy (ZA)

(show details)
ZA termFDR (all)SDZA levelAnnotation (direct or inherited)
Zebrafish Anatomy (ZA)multi-tissue structure0.07731Least InformativeInherited
Zebrafish Anatomy (ZA)compound organ0.08813Least InformativeInherited
Zebrafish Anatomy (ZA)cell0.1156Least InformativeInherited
Zebrafish Anatomy (ZA)nervous system0.1771Least InformativeInherited
Zebrafish Anatomy (ZA)portion of tissue0.01777Moderately InformativeInherited
Zebrafish Anatomy (ZA)central nervous system0.03957Moderately InformativeInherited
Zebrafish Anatomy (ZA)cardiovascular system0.3997Moderately InformativeInherited
Zebrafish Anatomy (ZA)hematopoietic system0.000003214InformativeDirect
Zebrafish Anatomy (ZA)hematopoietic cell0.0001811InformativeDirect
Zebrafish Anatomy (ZA)primary germ layer0.05387InformativeInherited
Zebrafish Anatomy (ZA)blood vasculature0.06683InformativeInherited
Zebrafish Anatomy (ZA)mononuclear phagocyte0.00000003837Highly InformativeDirect
Zebrafish Anatomy (ZA)professional antigen presenting cell0.00000005636Highly InformativeDirect
Zebrafish Anatomy (ZA)intermediate cell mass of mesoderm0.0000009367Highly InformativeDirect
Zebrafish Anatomy (ZA)floor plate0.00003779Highly InformativeDirect
Zebrafish Anatomy (ZA)vein0.0004104Highly InformativeDirect
Zebrafish Anatomy (ZA)neurogenic placode0.0007199Highly InformativeDirect

Document: ZA annotation of SCOP domains

Xenopus Anatomy (XA)

(show details)
XA termFDR (all)SDXA levelAnnotation (direct or inherited)
Xenopus ANatomical entity (XAN)trunk0.2708Least InformativeInherited
Xenopus ANatomical entity (XAN)tissue0.355Least InformativeInherited
Xenopus ANatomical entity (XAN)cavitated compound organ0.7462Least InformativeInherited
Xenopus ANatomical entity (XAN)viscus0.147Moderately InformativeInherited
Xenopus ANatomical entity (XAN)cardiovascular system0.01041InformativeInherited

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)Hydrolases0.08389Least InformativeInherited
Enzyme Commission (EC)Transferring phosphorus-containing groups0.131Least InformativeInherited
Enzyme Commission (EC)Oxidoreductases0.5524Least InformativeInherited
Enzyme Commission (EC)Lyases1Least InformativeInherited
Enzyme Commission (EC)Aminoacyltransferases0Moderately InformativeDirect
Enzyme Commission (EC)Protein-serine/threonine kinases0.000000000001123Moderately InformativeDirect
Enzyme Commission (EC)Carbon-oxygen lyases0.4811Moderately InformativeInherited
Enzyme Commission (EC)RING-type E3 ubiquitin transferase0InformativeDirect
Enzyme Commission (EC)Non-specific serine/threonine protein kinase5.111e-16InformativeDirect
Enzyme Commission (EC)Acting on paired donors, with incorporation or reduction of molecular oxygen. The oxygen incorporate0.00000005667InformativeDirect
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) lyase0.00005547Highly 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 ]