The domain within your query sequence starts at position 524 and ends at position 581; the E-value for the FHA domain shown below is 1.39e-8.

VTRVGREDAERRQDIVLSGHFIKEEHCIFRSDSRGGGEAVVTLEPCEGADTYVNGKKV

FHA

Forkhead associated domain

• SMART accession number: SM00240
• Description: Found in eukaryotic and prokaryotic proteins. Putative nuclear signalling domain.
• Interpro abstract (IPR000253):

  The forkhead-associated (FHA) domain [ (PUBMED:7482699) ] is a phosphopeptide recognition domain found in many regulatory proteins. It displays specificity for phosphothreonine-containing epitopes but will also recognise phosphotyrosine with relatively high affinity. It spans approximately 80-100 amino acid residues folded into an 11-stranded beta sandwich, which sometimes contain small helical insertions between the loops connecting the strands [ (PUBMED:11911881) ].

  To date, genes encoding FHA-containing proteins have been identified in eubacterial and eukaryotic but not archaeal genomes. The domain is present in a diverse range of proteins, such as kinases, phosphatases, kinesins, transcription factors, RNA-binding proteins and metabolic enzymes which partake in many different cellular processes - DNA repair, signal transduction, vesicular transport and protein degradation are just a few examples.

• GO function: protein binding (GO:0005515)

There are 73373 FHA domains in 68942 proteins in SMART's nrdb database.

Cellular role (predicted cellular role)

Cellular role: signalling

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Durocher D, Henckel J, Fersht AR, Jackson SP
• The FHA domain is a modular phosphopeptide recognition motif.
• Mol Cell. 1999; 4: 387-94

FHA domains are conserved sequences of 65-100 amino acid residues found principally within eukaryotic nuclear proteins, but which also exist in certain prokaryotes. The FHA domain is thought to mediate protein-protein interactions, but its mode of action has yet to be elucidated. Here, we show that the two highly divergent FHA domains of Saccharomyces cerevisiae Rad53p, a protein kinase involved in cell cycle checkpoint control, possess phosphopeptide-binding specificity. We also demonstrate that other FHA domains bind peptides in a phospho-dependent manner. These findings indicate that the FHA domain is a phospho-specific protein-protein interaction motif and have important implications for mechanisms of intracellular signaling in both eukaryotes and prokaryotes.

• Sun Z, Hsiao J, Fay DS, Stern DF
• Rad53 FHA domain associated with phosphorylated Rad9 in the DNA damage checkpoint.
• Science. 1998; 281: 272-4

The Rad53 protein kinase of Saccharomyces cerevisiae is required for checkpoints that prevent cell division in cells with damaged or incompletely replicated DNA. The Rad9 protein was phosphorylated in response to DNA damage, and phosphorylated Rad9 interacted with the COOH-terminal forkhead homology-associated (FHA) domain of Rad53. Inactivation of this domain abolished DNA damage-dependent Rad53 phosphorylation, G2/M cell cycle phase arrest, and increase of RNR3 transcription but did not affect replication inhibition-dependent Rad53 phosphorylation. Thus, Rad53 integrates DNA damage signals by coupling with phosphorylated Rad9. The hitherto uncharacterized FHA domain appears to be a modular protein-binding domain.

• Hofmann K, Bucher P
• The FHA domain: a putative nuclear signalling domain found in protein kinases and transcription factors.
• Trends Biochem Sci. 1995; 20: 347-9

Disease (disease genes where sequence variants are found in this domain)

SwissProt sequences and OMIM curated human diseases associated with missense mutations within the FHA domain.

Protein	Disease
Serine/threonine-protein kinase Chk2 (O96017) (SMART)	OMIM:604373: Li-Fraumeni syndrome OMIM:151623:

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
17.14	map04110	Cell cycle
17.14	map04115	p53 signaling pathway
11.43	map00230	Purine metabolism
8.57	map04520	Adherens junction
8.57	map04530	Tight junction
8.57	map04670	Leukocyte transendothelial migration
4.29	map04111	Cell cycle - yeast
4.29	map00380	Tryptophan metabolism
4.29	map00550	Peptidoglycan biosynthesis
2.86	map00562	Inositol phosphate metabolism
2.86	map03090	Type II secretion system
2.86	map00632	Benzoate degradation via CoA ligation
1.43	map00790	Folate biosynthesis
1.43	map03070	Type III secretion system
1.43	map00500	Starch and sucrose metabolism
1.43	map00906	Carotenoid biosynthesis - General
1.43	map04914	Progesterone-mediated oocyte maturation

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with FHA domain which could be assigned to a KEGG orthologous group, and not all proteins containing FHA domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of FHA domains in PDB

PDB code	Title
1dmz	A REFINED NMR STRUCTURE OF A NEW PHOPHOPEPTIDE-BINDING DOMAIN CONTAINING THE FHA2 OF RAD53
1fhq	REFINED SOLUTION STRUCTURE OF THE FHA2 DOMAIN OF RAD53
1fhr	SOLUTION STRUCTURE OF THE FHA2 DOMAIN OF RAD53 COMPLEXED WITH A PHOSPHOTYROSYL PEPTIDE
1g3g	NMR STRUCTURE OF THE FHA1 DOMAIN OF YEAST RAD53
1g6g	X-RAY STRUCTURE OF THE N-TERMINAL FHA DOMAIN FROM S. CEREVISIAE RAD53P IN COMPLEX WITH A PHOSPHOTHREONINE PEPTIDE AT 1.6 A RESOLUTION
1gxc	FHA domain from human Chk2 kinase in complex with a synthetic phosphopeptide
1j4k	SOLUTION STRUCTURE OF THE FHA2 DOMAIN OF RAD53 COMPLEXED WITH A PHOSPHOTYROSYL PEPTIDE DERIVED FROM RAD9
1j4l	SOLUTION STRUCTURE OF THE FHA2 DOMAIN OF RAD53 COMPLEXED WITH A PHOSPHOTHREONYL PEPTIDE DERIVED FROM RAD9
1j4o	REFINED NMR STRUCTURE OF THE FHA1 DOMAIN OF YEAST RAD53
1j4p	NMR STRUCTURE OF THE FHA1 DOMAIN OF RAD53 IN COMPLEX WITH A RAD9-DERIVED PHOSPHOTHREONINE (AT T155) PEPTIDE
1j4q	NMR STRUCTURE OF THE FHA1 DOMAIN OF RAD53 IN COMPLEX WITH A RAD9-DERIVED PHOSPHOTHREONINE (AT T192) PEPTIDE
1k2m	Solution Structure of the FHA2 Domain of Rad53 Complexed with a Phosphotyrosyl Peptide Derived from Rad9
1k2n	Solution Structure of the FHA2 domain of Rad53 Complexed with a Phosphothreonyl Peptide Derived from Rad9
1k3j	Refined NMR Structure of the FHA1 Domain of Yeast Rad53
1k3n	NMR Structure of the FHA1 Domain of Rad53 in Complex with a Rad9-derived Phosphothreonine (at T155) Peptide
1k3q	NMR structure of the FHA1 Domain of Rad53 in Complex with a Rad9-derived Phosphothreonine (at T192) Peptide
1lgp	Crystal structure of the FHA domain of the Chfr mitotic checkpoint protein complexed with tungstate
1lgq	Crystal structure of the FHA domain of the Chfr mitotic checkpoint protein
1mzk	NMR structure of kinase-interacting FHA domain of kinase associated protein phosphatase, KAPP in Arabidopsis
1qu5	NMR STRUCTURE OF A NEW PHOSPHOTYROSINE BINDING DOMAIN CONTAINING THE FHA2 DOMAIN OF RAD 53
1r21	Solution Structure of human Ki67 FHA Domain
1uht	Solution Structure of The FHA Domain of Arabidopsis thaliana Hypothetical Protein
1wln	Solution structure of the FHA domain of mouse Afadin 6
2a0t	NMR structure of the FHA1 domain of Rad53 in complex with a biological relevant phosphopeptide derived from Madt1
2aff	The solution structure of the Ki67FHA/hNIFK(226-269)3P complex
2csw	Solution structure of the FHA domain of human ubiquitin ligase protein RNF8
2eh0	Solution structure of the FHA domain from human Kinesin-like protein KIF1B
2fez	Mycobacterium tuberculosis EmbR
2ff4	Mycobacterium tuberculosis EmbR in complex with low affinity phosphopeptide
2g1l	Crystal structure of the FHA domain of human kinesin family member C
2jkd	Structure of the yeast Pml1 splicing factor and its integration into the RES complex
2jpe	FHA domain of NIPP1
2jqi	NMR Structure of the Rad53 FHA1 domain in complex with a phosphothreonien peptide derived from Rad53 SCD1
2jqj	NMR structure of yeast Dun1 FHA domain
2jql	NMR structure of the yeast Dun1 FHA domain in complex with a doubly phosphorylated (pT) peptide derived from Rad53 SCD1
2kb3	NMR Structure of the phosphorylated form of OdhI, pOdhI.
2kb4	NMR structure of the unphosphorylated form of OdhI, OdhI.
2kfu	PknB-phosphorylated Rv1827
2kkl	Solution NMR structure of FHA domain of Mb1858 from Mycobacterium bovis. Northeast Structural Genomics Consortium Target MbR243C (24-155).
2lc1	Rv0020c_FHA Structure
2n84	2N84
2pie	Crystal structure of the FHA domain of RNF8 in complex with its optimal phosphopeptide
2xt9	Crystal structure of Mycobacterium smegmatis alpha-ketoglutarate decarboxylase in complex with GarA
3els	Crystal Structure of Yeast Pml1p, Residues 51-204
3elv	Crystal Structure of Full-Length Yeast Pml1p
3fm8	Crystal structure of full length centaurin alpha-1 bound with the FHA domain of KIF13B (CAPRI target)
3gqs	Crystal structure of the FHA domain of CT664 protein from Chlamydia trachomatis
3hue	Structure of the S. pombe Nbs1 FHA-BRCT1-BRCT2 domains
3huf	Structure of the S. pombe Nbs1-Ctp1 complex
3hx1	Crystal structure of the Slr1951 protein from Synechocystis sp. Northeast Structural Genomics Consortium Target SgR167A
3i0m	Structure of the S. pombe Nbs1 FHA/BRCT-repeat domain
3i0n	Structure of the S. pombe Nbs1 FHA/BRCT-repeat domain
3i6u	Structure and Activation Mechanism of the CHK2 DNA-Damage Checkpoint Kinase
3i6w	Structure and Activation Mechanism of the CHK2 DNA-Damage Checkpoint Kinase
3mdb	Crystal structure of the ternary complex of full length centaurin alpha-1, KIF13B FHA domain, and IP4
3oun	Crystal structure of the FhaA FHA domain complexed with the intracellular domain of Rv3910
3po8	Structural and functional analysis of phosphothreonine-dependent FHA domain interactions
3poa	Structural and functional analysis of phosphothreonine-dependent FHA domain interactions
3umz	Crystal Structure of the human MDC1 FHA Domain
3un0	Crystal Structure of MDC1 FHA Domain
3unm	Crystal Structure of The Human MDC1 FHA Domain
3unn	Monomeric structure of the human MDC1 FHA domain in complex with an MDC1 phospho-T4 peptide
3uot	Crystal Structure of MDC1 FHA Domain in Complex with a Phosphorylated Peptide from the MDC1 N-terminus
3va1	Crystal structure of the mammalian MDC1 FHA domain
3va4	Crystal structure of the mammalian MDC1 FHA domain complexed with CHK2 pThr68 peptide
3vpy	Crystal structure of Arabidopsis DDL FHA domain
4egx	Crystal structure of KIF1A CC1-FHA tandem
4ejq	Crystal structure of KIF1A C-CC1-FHA
4h87	Crystal structure of a FHA domain of kanadaptin (SLC4A1AP) from Homo sapiens at 1.55 A resolution
4jon	Crystal structure of a centrosomal protein 170kDa, transcript variant beta (CEP170) from Homo sapiens at 2.15 A resolution (PSI Community Target, Sundstrom)
4qcj	4QCJ
4ym4	4YM4
4zgi	4ZGI
5a8i	5A8I
5djo	5DJO
5gm6	5GM6
5lqw	5LQW
5t2s	5T2S

Links (links to other resources describing this domain)

• PFAM: FHA
• INTERPRO: IPR000253
• PROSITE: FHA_DOMAIN