1NHK,1F6T,1NUE


Conserved Protein Domain Family
NDPk
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cd00595: NDPk 
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Nucleoside diphosphate kinases (NDP kinases, NDPks): NDP kinases, responsible for the synthesis of nucleoside triphosphates (NTPs), are involved in numerous regulatory processes associated with proliferation, development, and differentiation. They are vital for DNA/RNA synthesis, cell division, macromolecular metabolism and growth. The enzymes generate NTPs or their deoxy derivatives by terminal (gamma) phosphotransfer from an NTP such as ATP or GTP to any nucleoside diphosphate (NDP) or its deoxy derivative. The sequence of NDPk has been highly conserved through evolution. There is a single histidine residue conserved in all known NDK isozymes, which is involved in the catalytic mechanism. The first confirmed metastasis suppressor gene was the NDP kinase protein encoded by the nm23 gene. Unicellular organisms generally possess only one gene encoding NDP kinase, while most multicellular organisms possess not only an ortholog that provides most of the NDP kinase enzymatic activity but also multiple divergent paralogous genes. The human genome codes for at least nine NDP kinases and can be classified into two groups, Groups I and II, according to their genomic architecture and distinct enzymatic activity. Group I isoforms (A-D) are well-conserved, catalytically active, and share 58-88% identity between each other, while Group II are more divergent, with only NDPk6 shown to be active. NDP kinases exist in two different quaternary structures; all known eukaryotic enzymes are hexamers, while some bacterial enzymes are tetramers, as in Myxococcus. The hexamer can be viewed as trimer of dimers, while tetramers are dimers of dimers, with the dimerization interface conserved.
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Statistics
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PSSM-Id: 238335
Aligned: 10 rows
Threshold Bit Score: 197.962
Created: 7-Mar-2002
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
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active sitemultimer
Conserved site includes 11 residues -Click on image for an interactive view with Cn3D
Feature 1:active site [active site]
Evidence:
  • Comment:NDKs possess the active site motif N-x-x-H-[GA]-S-D.
  • Comment:His residue is phosphorylated during catalysis
  • Structure:1NUE_A: Homo sapiens NDP kinase complexed with GDP
  • Citation:PMID 8747457
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Sequence Alignment
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Format: Row Display: Color Bits: Type Selection: 
Feature 1            #                                        #        #                      
1NHK_R      3 ERTLSIIKPDGLek-gvIGKIISRFEekGLKPvAIRLQhlSQAQAEGFYavhk-arpFFKDLVQFMIsgPVVLMVLEGe- 79  Myxococcus xanthus
12232627   12 QLTLALIKPDAVahpliLEAVHQQILsnKFLIvRMRELlwRKEDCQRFYrehe-grfFYQRLVEFMAsgPIRAYILAHk- 89  human
1F6T_A      9 ERTFLAVKPDGVar-glVGEIIARYEkkGFVLvGLKQLvpTKDLAESHYaehk-erpFFGGLVSFITsgPVVAMVFEGk- 85  Dictyostelium disc...
1NUE_A      4 ERTFIAIKPDGVqr-glVGEIIKRFEqkGFRLvAMKFLraSEEHLKQHYidlk-drpFFPGLVKYMNsgPVVAMVWEGl- 80  human
Q9Y5B8    238 NCTCCIVKPHAVse-glLGKILMAIRdaGFEIsAMQMFnmDRVNVEEFYevykgvvtEYHDMVTEMYsgPCVAMEIQQn- 315 human
AAH70973  159 SYTVAIIKPDAVah-gkTDEIIMKIQesGFEIlANEERtmTESEAREFYqhra-geeKFQELIQFMSsgPCHILIISKse 236 African clawed frog
3914118    13 EKTLAIIKPDIVd---kEEEIQDIILrsGFTIvQRRKLrlSPEQCSNFYveky-gkmFFPNLTAYMSsgPLVAMILARh- 87  human
AAH70973  314 ERTLALIRPEILke--rKDEILQSIKdaGFSIaMQKEVmlTEHQVQEFYkehi-nedYYPALLKQMTsgPVLALALVKd- 389 African clawed frog
Q9Y5B8     92 EKTLALIKPDAIs---kAGEIIEIINkaGFTItKLKMMmlSRKEALDFHvdhq-srpFFNELIQFITtgPIIAMEILRd- 166 human
Q715S9    449 QSTLALIKPHVShk--eRMEILKAIRdaRFELtQMKEMhlTPEHASKVYfkit-gkdFYKNVLDVLSsgMSVVMILTKw- 524 Norway rat

Feature 1              #     #             #          #  # ##       #     
1NHK_R     80 ---nAVLANRDIMGATnpa---qaAEGTIRKDFAtsi-dkNTVHGSDslENAKIEIAYFF 132 Myxococcus xanthus
12232627   90 ---dAIQLWRTLMGPTrvfrarhvAPDSIRGSFGltd-trNTTHGSDsvVSASREIAAFF 145 human
1F6T_A     86 ---gVVASARLMIGVTnpl---asAPGSIRGDFGvdv-grNIIHGSDsvESANREIALWF 138 Dictyostelium discoideum
1NUE_A     81 ---nVVKTGRVMLGETnpa---dsKPGTIRGDFCiqv-grNIIHGSDsvKSAEKEISLWF 133 human
Q9Y5B8    316 ---nATKTFREFCGPAdpeiarhlRPGTLRAIFGktk-iqNAVHCTDlpEDGLLEVQYFF 371 human
AAH70973  237 ededVIPAWREFIGPTdveiakkeKPESLRAQYGtev-lyNAVHGSNdrEQASRELAFFF 295 African clawed frog
3914118    88 ---kAISYWLELLGPNnslvaketHPDSLRAIYGtdd-lrNALHGSNdfAAAEREIRFMF 143 human
AAH70973  390 ---nAVGHWRNMLGPAslsqalseAPDSLRAQFApsdsetNQLHGSSttEEAKKEINFFF 446 African clawed frog
Q9Y5B8    167 ---dAICEWKRLLGPAnsgvartdASESIRALFGtdg-irNAAHGPDsfASAAREMELFF 222 human
Q715S9    525 ---nAVGEWRRMMGPVdpeeakllSPNSLRARYGidv-lrNAVHGASnmSEAATAISNVF 580 Norway rat

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