2AFF,4EGX,1G6G,1GXC,1LGP,1MZK,1QU5,1WLN,2JPE,2JQJ,2PIE,2W3O,3GQS,3HUF,3HX1,3POA,3UOT,3VPY,4A0E,4H87,4JON,4YM4,5A8I,5DJO,6A8W,6AR0,6CCD,6I2P,2FF4,3ELV,5YYZ,6HC1,2N84,2FEZ,5LQW,5YYX,6HBZ


Conserved Protein Domain Family
FHA

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cd00060: FHA 
Click on image for an interactive view with Cn3D
forkhead associated (FHA) domain superfamily
Forkhead-associated (FHA) domains are small phosphopeptide recognition modules mostly found in eubacteria and eukaryotes. It is about 95-120 residues long that fold into an 11-stranded beta-sandwich. FHA domains can mediate the recognition of phosphorylated and non-phosphorylated substrates, as well as protein oligomerization. They specifically recognize threonine phosphorylation (pThr) accompanying activation of protein serine/threonine kinases. FHA domains show diverse ligand specificity. They may recognize the pTXXD motif, the pTXXI/L motif, and TQ clusters (singly and multiply phosphorylated). In eukaryotes, FHA superfamily members include forkhead-type transcription factors, as well as other signaling proteins, such as many regulatory proteins, kinases, phosphatases, motor proteins called kinesins, and metabolic enzymes. Many of them localize to the nucleus, where they participate in establishing or maintaining cell cycle checkpoints, DNA repair, or transcriptional regulation. FHA domains play important roles in human diseases, particularly in relation to DNA damage responses and cancers. In bacteria, FHA domain-containing proteins may participate in injection of viral proteins into host cells, transmembrane transporters, and cell division. FHA domain-containing proteins rarely include more than one copy of the domain. The only exception in eukaryotes is the checkpoint kinase Rad53 from Saccharomyces cerevisiae, which harbors two FHA domains (FHA1 and FHA2) flanking a central kinase domain. The two FHA domains recognize different phosphorylated targets and function independently from one another. In contrast, Mycobacterium tuberculosis ABC transporter Rv1747 contains two FHA domains but only one of them is essential for protein function.
Statistics
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PSSM-Id: 438714
Aligned: 734 rows
Threshold Bit Score: 37.2549
Created: 1-Nov-2000
Updated: 17-Oct-2022
Structure
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Program:
Drawing:
Aligned Rows:
 
phosphopeptide
Conserved site includes 7 residues -Click on image for an interactive view with Cn3D
Feature 1:phosphopeptide binding site [polypeptide binding site]
Evidence:
  • Comment:GR at the C terminus of strand beta3, SRxH just preceding beta5, and motif SxNG in the beta6-beta7 turn indicate a canonical mode of pThr recognition.
  • Structure:2PIE; Homo sapiens RNF8 in complex with its optimal phosphopeptide, contacts at 4A
  • Structure:3UOT; Homo sapiens MDC1 in complex with a phosphorylated peptide from the MDC1 N-terminus, contacts at 4A
  • Comment:Conserved residues are involved in binding directly to the ligand backbone and phosphate group. Non-conserved residues may determine binding specificity.
  • Comment:some members lack the conserved residues that are required for binding phosphothreonine
  • Structure:4YM4; Homo sapiens TIFA in complex with its Thr9 phosphorylated N-terminal peptide 1-15, contacts at 4A
  • Structure:1GXC; Homo sapiens CHK2 in complex with a synthetic phosphopeptide, contacts at 4A
  • Structure:3HUF; Schizosaccharomyces pombe Nbs1 in complex with Ctp1, contacts at 4A

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                                       ##               
2AFF_A         6 RLVTIKrsg----------------------------vdgPHFPLSl-----------sTCLFGRGiecdi----riqlp 42  human
2PIE_A        11 CLRRVGms-------------------------------aGWLLLEdg----------cEVTVGRGfgvtyqlvskicpl 49  human
AAD47812      40 LILISTttpa---------------------------aigKAYRLDq-----------gEHIIGRGsdvtv----riddh 77  Myxococcus xant...
KMQ52860       5 AMQELV----------------------------------FQFPLDg-----------dDRYIGRGtsshm----rlngm 35  Chitinispirillu...
WP_054358619  67 VLEFEDd--------------------------------pGVVAVDq-----------pRVTIGRHsdddi----rvkdv 99  Prosthecomicrob...
OAI53363      33 QLFLEDcgvaegfdiq---------------isvqgrpdvHTIHVDd-----------aFAFIGRDeecav----rlaga 82  Planctomyces sp...
PNV85911       3 KLELALqnl-----------------------------vlKEYVLSdg----------aKLSIGRHsendi----vlkdm 39  Desulfobacterac...
WP_106012982  48 YLLGQKsd-------------------------------gSTISLPly----------hTTNIGKArsndl----rinnp 82  Fastidiosipila ...
WP_120320021  38 DVRVSTdpstsrtprrrks---------aaapadpavgsgQTAAADgs----------iRTRLGRDadndi----vladl 94  Catellatospora ...
WP_145817380  95 VLTFRPdgapaapptgtgsvqpgpstqvrpsgpgpgaeppPGGRFAagrvpsasyraadRVRIGRApdndi----vlddl 170 Micromonospora ...
Feature 1          ## #                       ##                                         
2AFF_A        43 VVSKQHCKIEIHe-QEAILHNFss----tNPTQVNGSVIde--pVRLKhGDVITIId---------RSFRYE 98  human
2PIE_A        50 MISRNHCVLKQNpeGQWTIMDNks----lNGVWLNRARLeplrvYSIHqGDYIQLGvplenkenaeYEYEVT 117 human
AAD47812      78 GVSRKHARVVRAgdGACHVTDLds----tNGTLLNGVPVs---tAELMeGDRLQIGt--------vTVFRFS 134 Myxococcus xanthus DZ2
KMQ52860      36 GISEKHAVLRCDp-RNPWISDNns----tFGIHLNGVPVs---qSALKsGAVLTVGl---------QQFRVD 90  Chitinispirillum alkali...
WP_054358619 100 TVSRHHAVLQMNaqGLFEIHNQtagrsepNPLLVNGVYRe---hAELAdGDLVTIGg---------VTFRFR 159 Prosthecomicrobium hirs...
OAI53363      83 DIGRHHAYLQAVa-GQFVVVDLgs----rTGIRQNGRAVr---tALLSsGETVEVGp---------YTLRVS 137 Planctomyces sp. SCGC A...
PNV85911      40 GVSRYHATVEGRg-QKLLVLDTgs----kNGTIVNGTKVe---sAELHhGDIVRIGk--------nCTIKVS 95  Desulfobacteraceae bact...
WP_106012982  83 DISRHHAVIYRYd-NNWFIRPQnm----sAQFSVNGEPVkg--eTQLKnGDYIDFYv---------SKFAFV 138 Fastidiosipila sanguinis
WP_120320021  95 QASRHHAELRRLg-DAFHIVDLgs----rNGTFLNGRQVqk--aTLMHaGDIVSIGr---------HELLFD 150 Catellatospora citrea
WP_145817380 171 LVSRHHADLVRDg-AGFRVIDLgt----rNGTYVNGRQVe---qAALSgGDLLSFGh---------HQMVFD 225 Micromonospora sagamiensis

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