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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 0 38
Proteins 16,412 0 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 agent0.0003222Moderately InformativeDirect
Disease Ontology (DO)genetic disease0.03816Moderately InformativeInherited
Disease Ontology (DO)autosomal dominant disease0.0006953InformativeDirect

Document: DO annotation of SCOP domains

Human Phenotype (HP)

(show details)
HP termFDR (all)SDHP levelAnnotation (direct or inherited)
Phenotypic Abnormality (PA)Abnormality of nervous system morphology0.1213Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the head0.1893Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of metabolism/homeostasis0.3148Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of upper lip0.1076InformativeInherited
Phenotypic Abnormality (PA)Abnormality of circulating protein level0.2037InformativeInherited
Phenotypic Abnormality (PA)Abnormal peripheral myelination0.000928Highly InformativeDirect
Phenotypic Abnormality (PA)Cleft upper lip0.06815Highly InformativeInherited

Document: HP annotation of SCOP domains

Mouse Phenotype (MP)

(show details)
MP termFDR (all)SDMP levelAnnotation (direct or inherited)
Mammalian Phenotype (MP)cellular phenotype0.05205Least InformativeInherited
Mammalian Phenotype (MP)mortality/aging0.1459Least InformativeInherited
Mammalian Phenotype (MP)immune system phenotype0.2908Least InformativeInherited
Mammalian Phenotype (MP)cardiovascular system phenotype0.4449Least InformativeInherited
Mammalian Phenotype (MP)hematopoietic system phenotype0.4819Least InformativeInherited
Mammalian Phenotype (MP)neoplasm0.001888Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal blood cell morphology/development0.00795Moderately InformativeInherited
Mammalian Phenotype (MP)embryo phenotype0.02694Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal metabolism0.05215Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal blood cell morphology0.07504Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal digestive system morphology0.1216Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal leukocyte physiology0.141Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal cell morphology0.1509Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal mononuclear cell morphology0.1545Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal immune serum protein physiology0.2099Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal professional antigen presenting cell physiology0.24Moderately InformativeInherited
Mammalian Phenotype (MP)reproductive system phenotype0.2518Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal induced morbidity/mortality0.2564Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal cardiovascular system physiology0.3004Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal gland morphology0.5741Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal hematopoietic cell number0.7729Moderately InformativeInherited
Mammalian Phenotype (MP)increased gland tumor incidence0.0001681InformativeDirect
Mammalian Phenotype (MP)increased carcinoma incidence0.0002106InformativeDirect
Mammalian Phenotype (MP)chromosomal instability0.0002908InformativeDirect
Mammalian Phenotype (MP)abnormal response to radiation0.002797InformativeInherited
Mammalian Phenotype (MP)abnormal germ cell morphology0.009747InformativeInherited
Mammalian Phenotype (MP)abnormal B cell differentiation0.01162InformativeInherited
Mammalian Phenotype (MP)abnormal interferon secretion0.03847InformativeInherited
Mammalian Phenotype (MP)abnormal extraembryonic tissue morphology0.06549InformativeInherited
Mammalian Phenotype (MP)abnormal sensitivity to induced morbidity/mortality0.08253InformativeInherited
Mammalian Phenotype (MP)abnormal internal female genitalia morphology0.1202InformativeInherited
Mammalian Phenotype (MP)abnormal female reproductive gland morphology0.2InformativeInherited
Mammalian Phenotype (MP)abnormal embryo development0.2249InformativeInherited
Mammalian Phenotype (MP)abnormal fertility/fecundity0.4067InformativeInherited
Mammalian Phenotype (MP)hemorrhage0.691InformativeInherited
Mammalian Phenotype (MP)increased gonad tumor incidence0.000001966Highly InformativeDirect
Mammalian Phenotype (MP)abnormal germ layer development0.000006084Highly InformativeDirect
Mammalian Phenotype (MP)abnormal embryonic epiblast morphology0.00002558Highly InformativeDirect
Mammalian Phenotype (MP)abnormal cumulus expansion0.00002692Highly InformativeDirect
Mammalian Phenotype (MP)decreased interferon-alpha secretion0.000158Highly InformativeDirect
Mammalian Phenotype (MP)abnormal digestive system development0.000429Highly InformativeDirect
Mammalian Phenotype (MP)abnormal oocyte number0.0004303Highly InformativeDirect
Mammalian Phenotype (MP)absent primordial germ cells0.0007205Highly InformativeDirect
Mammalian Phenotype (MP)premature aging0.004489Highly InformativeInherited
Mammalian Phenotype (MP)decreased dendritic cell number0.005518Highly 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 variant0.0005403Least InformativeDirect
Worm Phenotype (WP)organ system morphology variant0.003657Least InformativeInherited
Worm Phenotype (WP)organism environmental stimulus response variant0.005159Least InformativeInherited
Worm Phenotype (WP)nervous system morphology variant0.00003478Moderately InformativeDirect
Worm Phenotype (WP)pericellular component development variant0.001967Moderately InformativeInherited
Worm Phenotype (WP)chemical response variant0.05716Moderately InformativeInherited
Worm Phenotype (WP)organism segment morphology variant0.07269Moderately InformativeInherited
Worm Phenotype (WP)feeding behavior variant0.2764Moderately InformativeInherited
Worm Phenotype (WP)movement variant0.6591Moderately InformativeInherited
Worm Phenotype (WP)velocity of movement variant0.0001682InformativeDirect
Worm Phenotype (WP)aldicarb response variant0.0007553InformativeDirect
Worm Phenotype (WP)male morphology variant0.001702InformativeInherited
Worm Phenotype (WP)localized movement variant0.003583InformativeInherited
Worm Phenotype (WP)tail morphology variant0.005278InformativeInherited
Worm Phenotype (WP)body posture variant0.01088InformativeInherited
Worm Phenotype (WP)forward locomotion variant0.01126InformativeInherited
Worm Phenotype (WP)sensillum morphology variant0.03123InformativeInherited
Worm Phenotype (WP)foraging behavior variant0.05133InformativeInherited
Worm Phenotype (WP)locomotor coordination variant0.05501InformativeInherited
Worm Phenotype (WP)body length variant0.5InformativeInherited
Worm Phenotype (WP)locomotion reduced0.7863InformativeInherited
Worm Phenotype (WP)cuticle development variant0.0000009031Highly InformativeDirect
Worm Phenotype (WP)cuticle physiology variant0.000003021Highly InformativeDirect
Worm Phenotype (WP)male nervous system development variant0.00001815Highly InformativeDirect
Worm Phenotype (WP)social behavior variant0.00002148Highly InformativeDirect
Worm Phenotype (WP)short0.0000255Highly InformativeDirect
Worm Phenotype (WP)roaming variant0.00004079Highly InformativeDirect
Worm Phenotype (WP)coiling frequency0.00005499Highly InformativeDirect
Worm Phenotype (WP)forward locomotion decreased0.00006065Highly InformativeDirect
Worm Phenotype (WP)body posture amplitude variant0.0001027Highly InformativeDirect
Worm Phenotype (WP)male tail morphology variant0.0001049Highly InformativeDirect
Worm Phenotype (WP)backward point velocity variant0.0001055Highly InformativeDirect
Worm Phenotype (WP)nose movement variant0.0001897Highly InformativeDirect
Worm Phenotype (WP)amplitude of sinusoidal movement variant0.0002234Highly InformativeDirect
Worm Phenotype (WP)frequency of body bend variant0.00025Highly InformativeDirect
Worm Phenotype (WP)male nervous system morphology variant0.0002558Highly InformativeDirect
Worm Phenotype (WP)dauer development variant0.0004426Highly InformativeDirect
Worm Phenotype (WP)path curvature variant0.06294Highly InformativeInherited
Worm Phenotype (WP)body posture wavelength variant0.3852Highly 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 division0.00004073InformativeDirect
Fly Phenotype (FP)cell number defective0.0008835InformativeDirect

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 structure0.08353Least InformativeInherited
Fly Anatomy (FA)anterior-posterior subdivision of organism1Least InformativeInherited
Fly Anatomy (FA)stem cell0.01072Moderately InformativeInherited
Fly Anatomy (FA)thoracic segment0.04703Moderately InformativeInherited
Fly Anatomy (FA)gonad0.07393Moderately InformativeInherited
Fly Anatomy (FA)pupa0.01296InformativeInherited
Fly Anatomy (FA)larval thoracic segment0.01508InformativeInherited
Fly Anatomy (FA)ovariole0.02544InformativeInherited
Fly Anatomy (FA)germline cell0.07067InformativeInherited
Fly Anatomy (FA)imaginal precursor0.08967InformativeInherited
Fly Anatomy (FA)female germline stem cell0.0005437Highly InformativeDirect
Fly Anatomy (FA)wing disc0.0008143Highly InformativeDirect

Document: FA annotation of SCOP domains

Zebrafish Anatomy (ZA)

(show details)
ZA termFDR (all)SDZA levelAnnotation (direct or inherited)
Zebrafish Anatomy (ZA)cell0.04555Least InformativeInherited
Zebrafish Anatomy (ZA)multi-tissue structure0.08985Least InformativeInherited
Zebrafish Anatomy (ZA)nervous system0.2026Least InformativeInherited
Zebrafish Anatomy (ZA)portion of tissue0.02004Moderately InformativeInherited
Zebrafish Anatomy (ZA)central nervous system0.05918Moderately InformativeInherited
Zebrafish Anatomy (ZA)hematopoietic system0.000000476InformativeDirect
Zebrafish Anatomy (ZA)hematopoietic cell0.0001863InformativeDirect
Zebrafish Anatomy (ZA)immune system0.02337InformativeInherited
Zebrafish Anatomy (ZA)mononuclear phagocyte0.000000002757Highly InformativeDirect
Zebrafish Anatomy (ZA)professional antigen presenting cell0.000000004045Highly InformativeDirect
Zebrafish Anatomy (ZA)intermediate cell mass of mesoderm0.0000007481Highly InformativeDirect
Zebrafish Anatomy (ZA)floor plate0.00003289Highly InformativeDirect
Zebrafish Anatomy (ZA)embryonic structure0.2538Highly InformativeInherited

Document: ZA annotation of SCOP domains

Xenopus Anatomy (XA)

(show details)
XA termFDR (all)SDXA levelAnnotation (direct or inherited)
Xenopus ANatomical entity (XAN)trunk0.1622Least InformativeInherited
Xenopus ANatomical entity (XAN)tissue0.3266Least InformativeInherited
Xenopus ANatomical entity (XAN)cavitated compound organ0.7657Least InformativeInherited
Xenopus ANatomical entity (XAN)viscus0.1464Moderately InformativeInherited
Xenopus ANatomical entity (XAN)cardiovascular system0.00401InformativeInherited

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)Transferring phosphorus-containing groups0.1153Least InformativeInherited
Enzyme Commission (EC)Hydrolases0.1373Least InformativeInherited
Enzyme Commission (EC)Oxidoreductases0.5909Least InformativeInherited
Enzyme Commission (EC)Lyases1Least InformativeInherited
Enzyme Commission (EC)Protein-serine/threonine kinases0.0000000000009665Moderately InformativeDirect
Enzyme Commission (EC)Acyltransferases0.00000001434Moderately InformativeDirect
Enzyme Commission (EC)Carbon-oxygen lyases0.4677Moderately InformativeInherited
Enzyme Commission (EC)RING-type E3 ubiquitin transferase0InformativeDirect
Enzyme Commission (EC)Non-specific serine/threonine protein kinase4.978e-16InformativeDirect
Enzyme Commission (EC)Acting on paired donors, with incorporation or reduction of molecular oxygen. The oxygen incorporate0.00000002182InformativeDirect
Enzyme Commission (EC)Exodeoxyribonucleases producing 5'-phosphomonoesters0Highly InformativeDirect
Enzyme Commission (EC)DNA-(apurinic or apyrimidinic site) lyase0.00005325Highly InformativeDirect

Document: EC annotation of SCOP domains

UniProtKB KeyWords (KW)

(show details)
KW termFDR (all)SDKW levelAnnotation (direct or inherited)
Biological processCell cycle0Moderately InformativeDirect
Biological processDNA damage0Moderately InformativeDirect
Biological processUbl conjugation pathway0.000000001292Moderately InformativeDirect
Biological processTranscription regulation0.0000004336Moderately InformativeDirect
Biological processImmunity0.00001947Moderately InformativeDirect
Biological processVirulence0.0006467Moderately InformativeDirect
Biological processDifferentiation0.0007545Moderately InformativeDirect
Biological processMitosis0.0000000000004368InformativeDirect
Biological processMeiosis0.00000000003892InformativeDirect
Biological processInnate immunity0.00000002981InformativeDirect
Biological processAngiogenesis0.000003259InformativeDirect
Biological processCell adhesion0.0007237InformativeDirect
Biological processAbscisic acid biosynthesis0Highly InformativeDirect
Biological processAntiviral defense0.000000000001461Highly InformativeDirect
Cellular componentNucleus0Least InformativeDirect
Cellular componentCytoplasm1Least InformativeInherited
Cellular componentCytoskeleton0Moderately InformativeDirect
Cellular componentMicrotubule0InformativeDirect
Cellular componentChromosome0.00000000000002051InformativeDirect
Cellular componentTelomere0.0000001764Highly InformativeDirect
DiseaseDisease mutation0.0006565Least InformativeDirect
DiseaseNeurodegeneration0.000768Highly InformativeDirect
DomainCoiled coil0Moderately InformativeDirect
DomainZinc-finger0.00000000002049Moderately InformativeDirect
Molecular functionZinc0Least InformativeDirect
Post-translational modificationTransferase1Least InformativeInherited
Post-translational modificationDNA-binding0Moderately InformativeDirect
Post-translational modificationActivator0.00000001546Moderately InformativeDirect
Post-translational modificationDevelopmental protein0.000002361Moderately InformativeDirect
Post-translational modificationKinase0.04303Moderately InformativeInherited
Post-translational modificationSerine/threonine-protein kinase0.000000003855InformativeDirect
Post-translational modificationChromatin regulator0.0000001311InformativeDirect
Post-translational modificationPhosphoprotein0Least InformativeDirect
Post-translational modificationAcetylation0.00005531Least InformativeDirect
Post-translational modificationUbl conjugation0Moderately InformativeDirect
Post-translational modificationIsopeptide bond0.000000000000002417Moderately InformativeDirect
Post-translational modificationADP-ribosylation0.000001677InformativeDirect

Document: KW 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) · UniProtKB KeyWords (KW) ]

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 19 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 19 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) · UniProtKB KeyWords (KW) · Internal database links ]