2DUK,2FVV,3MCF,5LTU


Conserved Protein Domain Family
NUDIX_DIPP2_like_Nudt4

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cd04666: NUDIX_DIPP2_like_Nudt4 
diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase type 2 and similar proteins
Diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase type 2 (DIPP2), also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 4; Nudt4, and other proteins including DIPP1/Nudt3, DIPP3a;APS2/Nudt10 and DIPP3beta;APS1/Nudt11. DIPP regulates the turnover of diphosphoinositol polyphosphates. The turnover of these high-energy diphosphoinositol polyphosphates represents a molecular switching activity with important regulatory consequences. Molecular switching by diphosphoinositol polyphosphates may contribute to regulating intracellular trafficking. Several alternatively spliced transcript variants have been described, but the full-length nature of some variants has not been determined. Isoforms DIPP2alpha and DIPP2beta are distinguishable from each other solely by DIPP2beta possessing one additional amino acid due to intron boundary skidding in alternate splicing. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance & "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.
Statistics
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PSSM-Id: 467551
Aligned: 121 rows
Threshold Bit Score: 89.8965
Created: 6-Dec-2006
Updated: 27-Apr-2023
Structure
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Program:
Drawing:
Aligned Rows:
 
NUDIX motifputative metal
Conserved site includes 23 residues -Click on image for an interactive view with Cn3D
Feature 1:NUDIX motif [structural motif]
Evidence:
  • Comment:G[X5]E[X7]REUXEEXGU, where U is a bulky aliphatic residue (usually Ile, Leu, or Val).
  • Comment:The NUDIX motif contains many of the active site residues of NUDIX hydrolases.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                       #######  ################     
2DUK_A     11 KRAACLCFRse------------------qeDEVLLVSSSRypdQWIVPGGGMEPEE--EPGGAAVREVYEEAGVKGk-- 68  house mouse
EDP45438    9 QVVVILAVKqdttq------------skedrILVCLVKSRKhenKWVLPKGGVEKNE--TVEEAAVRELWEEAGIRTks- 73  Malassezia globosa...
EEY70202   62 RLLACIVISrrhv---------------dtsDEFLLISSSKhptQWILPKGGWETDE--TVVESALREADEEAGISGe-- 122 Phytophthora infes...
CBN77384   19 LVAGCLPVTp--------------------dGRLVLIGSVKh-tDWILPKGGWDTDE--TAAEAAVREAYEEAGVKGl-- 73  Ectocarpus silicul...
EFP78199   19 QVAVAVAYRsktah------------dgmpqIEYLLVSSRKhlgSWVLPKGGVEKEEvsDHGLAALREAWEEGGIRGk-- 84  Puccinia graminis ...
EGG20148    4 DQSGTIPIRikkiklqdengdvsgrlqvcgqFQMLMITNSStgsERVFPKGSVKKSE--SLKKAAKRETMEECGIKGkil 81  Dictyostelium fasc...
EHY66379   55 PFVGCIPIKd---------------------GKIFLINGRTn-kKLIFPKGGIERGE--EGYYSAGKEALEEAGLIGni- 109 Nematocida sp. 1 E...
EIM23112   19 IVCGAVPINyl-------------------tNQILLISSRKhkgNWVLPKGGYELSDv-RLETAASREAFEEAGVIGq-- 76  Wallemia sebi CBS ...
EIW83992   13 VVCCAIPIQra-------------------aGKVLLITSRKrqdLWVLPKGGYEASDv-QLEAAASREALEEAGVRGk-- 70  Coniophora puteana...
ELA41796   11 TIVGAIPILd--------------------dQKILFVKSRHe--NWIFPKGGVKKSE--KSYDAATREAFEEGGVIGqv- 65  Vittaforma corneae...
Feature 1                                                                                     
2DUK_A     69 -lGRLLGIFEnqd----------------------rkhRTYVYVLTVt----eILEDWEDSvn---igRKREWFKVEDAI 118 house mouse
EDP45438   74 -lRPSWTEARnrvshadrrphskcpkeligtdkmvpktMYELEELSVtd--deMMDEWPEMh-----eRERQFFRWEEAK 145 Malassezia globosa...
EEY70202  123 -vVGALGTLDfasqq-------------------gkpcRFYGFRLEVr----qVFEDWAENt------RRRKWVSLDEAR 172 Phytophthora infes...
CBN77384   74 -vTADLGPHEivssr-------------------gnksRAAMFALLVs----dVLDEWPEKhrrrkvdRERRVLAGPERC 129 Ectocarpus silicul...
EFP78199   85 -lGDRLHVSSdpkahraiq----------kikifipraEYSFWLIKVdegeagVSSSWPEEh-----eRERRWVRRQEAI 148 Puccinia graminis ...
EGG20148   82 nrEPPIVVTDtsk-----------------------gsIIHYYPMLVt----kKKKEWDEMd-----kRQRIWVPLDQCL 129 Dictyostelium fasc...
EHY66379  110 -dKAPFAMIH----------------------------GIYWYVLEVt----kVLPEWNEKh-----eRLRIEMDPENVL 151 Nematocida sp. 1 E...
EIM23112   77 -vRNLVLSIDdkrpiktlt----------dndpfipraRYHFFEISVd----eLSTQWPESn-----eRDRCWCSFGEAL 136 Wallemia sebi CBS ...
EIW83992   71 -iERYVTTINsp------------------------stIYHFYEMKVe----rMEADWQESr-----eRIREWFTYDEAR 116 Coniophora puteana...
ELA41796   66 -eLEPFCVKK----------------------------GVSFYVLSVa----tILDSYPESq-----eRQRTIMKMMDAL 107 Vittaforma corneae...
Feature 1                              
2DUK_A    119 KVLqc--------hkPVHAEYLEKL 135 house mouse
EDP45438  146 ELVaw---------rEGMRELMDKS 161 Malassezia globosa CBS 7966
EEY70202  173 ELLqh---------rPELVEMVERA 188 Phytophthora infestans T30-4
CBN77384  130 RCNtslsvsqppeerGDESDLTREW 154 Ectocarpus siliculosus
EFP78199  149 DLVqw--------rqDGAVDALMKV 165 Puccinia graminis f. sp. tritici CRL 75-36-700-3
EGG20148  130 SQSdql------qfkPYIHQAILSL 148 Dictyostelium fasciculatum
EHY66379  152 YHSevra-----vtkNVVKELILQE 171 Nematocida sp. 1 ERTm2
EIM23112  137 NRVsw---------rDEQRAALLAC 152 Wallemia sebi CBS 633.66
EIW83992  117 RRVgw---------kPELREGLDRA 132 Coniophora puteana RWD-64-598 SS2
ELA41796  108 ENTevae-----yvrEIVKEYIRKR 127 Vittaforma corneae ATCC 50505

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