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{
"metadata": {
"accession": "IPR008984",
"entry_id": null,
"type": "homologous_superfamily",
"go_terms": [
{
"identifier": "GO:0005515",
"name": "protein binding",
"category": {
"code": "F",
"name": "molecular_function"
}
}
],
"source_database": "interpro",
"member_databases": {
"ssf": {
"SSF49879": "SMAD/FHA domain"
}
},
"integrated": null,
"hierarchy": {
"accession": "IPR008984",
"name": "SMAD/FHA domain superfamily",
"type": "Homologous_superfamily",
"children": []
},
"name": {
"name": "SMAD/FHA domain superfamily",
"short": "SMAD_FHA_dom_sf"
},
"description": [
{
"text": "<p>FHA and SMAD (MH2) domains share a common structure consisting of a sandwich of eleven β-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 [[cite:PUB00010677], [cite:PUB00010678], [cite:PUB00010679]].</p>\n\n<p>SMAD (Mothers against decapentaplegic (MAD) homologue) 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 [[cite:PUB00010680]]; the comediator SMADs (co-SMADs), including SMAD4, which interact with R-SMADs to participate in signalling [[cite:PUB00010681]]; 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 [[cite:PUB00010682]].</p>\n\n<p>Domains with this fold are also found as the transactivation domain of interferon regulatory factor 3 (IRF3), which has a weak homology to SMAD domains [[cite:PUB00030421]], and the N-terminal domain of EssC protein in Staphylococcus aureus.</p>",
"llm": false,
"checked": false,
"updated": false
}
],
"wikipedia": null,
"literature": {
"PUB00010677": {
"PMID": 11106755,
"ISBN": null,
"volume": "6",
"issue": "5",
"year": 2000,
"title": "The molecular basis of FHA domain:phosphopeptide binding specificity and implications for phospho-dependent signaling mechanisms.",
"URL": null,
"raw_pages": "1169-82",
"medline_journal": "Mol Cell",
"ISO_journal": "Mol. Cell",
"authors": [
"Durocher D",
"Taylor IA",
"Sarbassova D",
"Haire LF",
"Westcott SL",
"Jackson SP",
"Smerdon SJ",
"Yaffe MB."
],
"DOI_URL": "http://dx.doi.org/10.1016/S1097-2765(00)00114-3"
},
"PUB00010678": {
"PMID": 12121644,
"ISBN": null,
"volume": "10",
"issue": "7",
"year": 2002,
"title": "Crystal structure of the FHA domain of the Chfr mitotic checkpoint protein and its complex with tungstate.",
"URL": null,
"raw_pages": "891-9",
"medline_journal": "Structure",
"ISO_journal": "Structure",
"authors": [
"Stavridi ES",
"Huyen Y",
"Loreto IR",
"Scolnick DM",
"Halazonetis TD",
"Pavletich NP",
"Jeffrey PD."
],
"DOI_URL": "http://dx.doi.org/10.1016/S0969-2126(02)00776-1"
},
"PUB00010679": {
"PMID": 12049740,
"ISBN": null,
"volume": "9",
"issue": "5",
"year": 2002,
"title": "Structural and functional versatility of the FHA domain in DNA-damage signaling by the tumor suppressor kinase Chk2.",
"URL": null,
"raw_pages": "1045-54",
"medline_journal": "Mol Cell",
"ISO_journal": "Mol. Cell",
"authors": [
"Li J",
"Williams BL",
"Haire LF",
"Goldberg M",
"Wilker E",
"Durocher D",
"Yaffe MB",
"Jackson SP",
"Smerdon SJ."
],
"DOI_URL": "http://dx.doi.org/10.1016/S1097-2765(02)00527-0"
},
"PUB00010680": {
"PMID": 11779503,
"ISBN": null,
"volume": "8",
"issue": "6",
"year": 2001,
"title": "Crystal structure of a phosphorylated Smad2. Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-beta signaling.",
"URL": null,
"raw_pages": "1277-89",
"medline_journal": "Mol Cell",
"ISO_journal": "Mol. Cell",
"authors": [
"Wu JW",
"Hu M",
"Chai J",
"Seoane J",
"Huse M",
"Li C",
"Rigotti DJ",
"Kyin S",
"Muir TW",
"Fairman R",
"Massague J",
"Shi Y."
],
"DOI_URL": "http://dx.doi.org/10.1016/S1097-2765(01)00421-X"
},
"PUB00010681": {
"PMID": 9214508,
"ISBN": null,
"volume": "388",
"issue": "6637",
"year": 1997,
"title": "A structural basis for mutational inactivation of the tumour suppressor Smad4.",
"URL": null,
"raw_pages": "87-93",
"medline_journal": "Nature",
"ISO_journal": "Nature",
"authors": [
"Shi Y",
"Hata A",
"Lo RS",
"Massague J",
"Pavletich NP."
],
"DOI_URL": "http://dx.doi.org/10.1038/40431"
},
"PUB00010682": {
"PMID": 11483516,
"ISBN": null,
"volume": "20",
"issue": "15",
"year": 2001,
"title": "Promoting bone morphogenetic protein signaling through negative regulation of inhibitory Smads.",
"URL": null,
"raw_pages": "4132-42",
"medline_journal": "EMBO J",
"ISO_journal": "EMBO J.",
"authors": [
"Itoh F",
"Asao H",
"Sugamura K",
"Heldin CH",
"ten Dijke P",
"Itoh S."
],
"DOI_URL": "http://dx.doi.org/10.1093/emboj/20.15.4132"
},
"PUB00030421": {
"PMID": 14555996,
"ISBN": null,
"volume": "10",
"issue": "11",
"year": 2003,
"title": "Crystal structure of IRF-3 reveals mechanism of autoinhibition and virus-induced phosphoactivation.",
"URL": null,
"raw_pages": "913-21",
"medline_journal": "Nat Struct Biol",
"ISO_journal": "Nat. Struct. Biol.",
"authors": [
"Qin BY",
"Liu C",
"Lam SS",
"Srinath H",
"Delston R",
"Correia JJ",
"Derynck R",
"Lin K."
],
"DOI_URL": "http://dx.doi.org/10.1038/nsb1002"
}
},
"set_info": null,
"overlaps_with": [
{
"accession": "IPR000253",
"name": "Forkhead-associated (FHA) domain",
"type": "domain"
},
{
"accession": "IPR001132",
"name": "SMAD domain",
"type": "domain"
},
{
"accession": "IPR050923",
"name": "Cellular Process Regulator and RNA Processing Protein",
"type": "family"
},
{
"accession": "IPR032030",
"name": "YscD, cytoplasmic domain",
"type": "domain"
},
{
"accession": "IPR017855",
"name": "SMAD-like domain superfamily",
"type": "homologous_superfamily"
},
{
"accession": "IPR061279",
"name": "Afadin, forkhead associated domain",
"type": "domain"
},
{
"accession": "IPR041388",
"name": "PNK, FHA domain",
"type": "domain"
},
{
"accession": "IPR019471",
"name": "Interferon regulatory factor-3",
"type": "domain"
},
{
"accession": "IPR048204",
"name": "Oxoglutarate dehydrogenase inhibitor",
"type": "family"
},
{
"accession": "IPR047398",
"name": "Forkhead box protein K2, forkhead associated domain",
"type": "domain"
},
{
"accession": "IPR049779",
"name": "Kinesin-like protein KIF1A, forkhead associated domain",
"type": "domain"
},
{
"accession": "IPR047289",
"name": "Aprataxin, forkhead associated domain",
"type": "domain"
}
],
"counters": {
"subfamilies": 0,
"domain_architectures": 0,
"interactions": 4,
"matches": 195923,
"pathways": 285,
"proteins": 189024,
"proteomes": 13771,
"sets": 0,
"structural_models": {
"alphafold": 131180,
"bfvd": 19
},
"structures": 177,
"taxa": 27342
},
"entry_annotations": {},
"cross_references": {},
"is_llm": false,
"is_reviewed_llm": false,
"is_updated_llm": false,
"representative_structure": {
"accession": "3kt9",
"name": "Aprataxin FHA Domain"
}
}
}
