SMAD/FHA domain (IPR008984)

Short name: SMAD_FHA_domain

Domain relationships


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 [PMID: 11106755, PMID: 12121644, PMID: 12049740].

SMAD (Mothers against decapentaplegic (MAD) homolog) 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 [PMID: 11779503]; the comediator SMADs (co-SMADs), including SMAD4, which interact with R-SMADs to participate in signalling [PMID: 9214508]; 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 [PMID: 11483516].

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 [PMID: 14555996], and the N-terminal domain of EssC protein in Staphylococcus aureus.

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0005515 protein binding

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.