4AW6,2YPT,4IL3


Conserved Protein Domain Family
M48A_Zmpste24p_like

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cd07343: M48A_Zmpste24p_like 
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Peptidase M48 subfamily A, a type 1 CaaX endopeptidase
This family contains peptidase family M48 subfamily A which includes a number of well-characterized genes such as those found in humans (ZMPSTE24, also known as farnesylated protein-converting enzyme 1 or FACE-1 or Hs Ste24), Taenia solium metacestode (TsSte24p), Arabidopsis (AtSte24) and yeast (Ste24p). Ste24p contains the zinc metalloprotease motif (HEXXH), likely exposed on the cytoplasmic side. It is thought to be intimately associated with the endoplasmic reticulum (ER), regardless of whether its genes possess the conventional signal motif (KKXX) in the C-terminal. Proteins in this family proteolytically remove the C-terminal three residues of farnesylated proteins. Ste24p is involved in the post-translational processing of prelamin A to mature lamin A, a major component of the nuclear envelope. ZmpSte24 deficiency causes an accumulation of prelamin A leading to lipodystrophy and other disease phenotypes, while mutations in this gene or in that encoding its substrate, prelamin A, result in a series of human inherited diseases known as laminopathies, the most severe of which are Hutchinson Gilford progeria syndrome (HGPS) and restrictive dermopathy (RD) which arise due to unsuccessful maturation of prelamin A. Two forms of mandibuloacral dysplasia, a condition that causes a variety of abnormalities involving bone development, skin pigmentation, and fat distribution, are caused by mutations in two different genes; mutations in the LMNA gene, which normally provides instructions for making lamin A and lamin C, cause mandibuloacral dysplasia with A-type lipodystrophy (MAD-A), and mutations in the ZMPSTE24 gene cause mandibuloacral dysplasia with B-type lipodystrophy (MAD-B). Within cells, these genes are involved in maintaining the structure of the nucleus and may play a role in many cellular processes. Certain HIV protease inhibitors have been shown to inhibit the enzymatic activity of ZMPSTE24, but not enzymes involved in prelamin A processing.
Statistics
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PSSM-Id: 320702
View PSSM: cd07343
Aligned: 371 rows
Threshold Bit Score: 240.461
Threshold Setting Gi: 325948658
Created: 4-Mar-2009
Updated: 18-Aug-2016
Structure
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Program:
Drawing:
Aligned Rows:
 
Zn binding siteactive site
Conserved site includes 4 residues -Click on image for an interactive view with Cn3D
Feature 1:Zn binding site [ion binding site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                         
4AW6_A         21 GAVLLFSWTVYLWETFLAQRQRRIYKttthvppelgqimdsetfeksRLYQLDKSTFSFWSGLYSETEGTLILLFggipy 100
4IL3_A         17 LIISAFSIAQFSFESYLTYRQYQKLSetklppvled-eiddetfhksRNYSRAKAKFSIFSDIYNLAQKLVFIKYdffpk 95
gi 330752627   25 NIFIVLVIFNFLFTTVLEYLNDKNWNdnipdd---------fkdfydAKSYLKAKNYKISRGKLSSVSSSVSFVFtiaml 95
gi 441436665    8 TIVLIIITADFLLEQVLEYINLRSAKddipdd---------iaafydRNEYKRSREYQRTLTRFSFLTATFSFIVsflll 78
gi 496562801    8 YLLIGILSVNFISSKFLNWLNIRRKEngipkt---------megyldTEKLTKANEYQRVNFNFSLVASFFSFGLtilfl 78
gi 684288920    9 IGILAFVAIDFLIGTLLNYLNEKSNQqplseq---------vsqiydLTGYNKSLEYGTTKYKFGLFTSVVSTIVillai 79
gi 695124721    8 YIILGILSFDFILEQFFDYLNLKHQKtdlpee---------lkdiysEEEFKKAQDYYKANANFSFLSSTLSFLLiiivi 78
gi 748178107   10 TIILFLVMAGFVFDTFLSWLNLRSQPddipds---------vaafydREKYRKSLEYHRHRTNFSFVTSTFSFLLsvaml 80
gi 1000268996   8 QIILGIALLSYAFDQLLDYLNLKALRkdipee---------iatfynPEKYNRSLDYQRTQARFSFITAAFGFILsftml 78
gi 595616369   28 IILISLVALGYLLESALDWLNYTYLKkpylpq---------lsgiltEEKYSETVRYQQERKRFGFITATYSFVLmlvml 98
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                         
4AW6_A        101 lwrlsg---rfcgyagfgpeYEITQSLVFLLLATLFSALAGLPWSLYNTFVIEEKHGFNqqTLGFFMKDAIKKFVVTQCI 177
4IL3_A         96 iwhmavtlsnavlpvrfhmvSTVAQSLCFLGLLSSMSTLVDLPLSYYSHFVLEEKFGFNklTVKLWITDMIKSLTLAYAI 175
gi 330752627   96 yffgfg---flsdiatsfsdSVILQSSLFFMILYLFNFVIGIPFSYYSTFVIEEKFGFNktNLKTFISDKIKGLFISSAL 172
gi 441436665   79 itggfg---yidellrpffeNEIYLALSYFGILFLASDLLNTPFEIYQTFVIEEKYGFNktTPKIFIMDKLKGYLLTIAI 155
gi 496562801   79 asgffg---wldaflsqftiHPLWLPALYFAVLYLGSDLMGIPFDYYHTFVIEQRFGFNntSMGTFLSDKLKGYLLSIVI 155
gi 684288920   80 vlgwfa---wldaslrevirSDLMVTVSFVGILIVLAAITGLPTSYYATFVIEEKFGFNktTKKLFIADNIKQTLLSLAL 156
gi 695124721   79 ltgtfg---wldkqlsfkfqNPTTLALVFFGILFFVSDIINIPFSLYKTFVIEEKFGFNktTIKTYVLDKLKGYLIGGVL 155
gi 748178107   81 yfggfg---lldswlrpvihNDILLALIFFGVLAIASDILTLPFQLYSTFVIEEKYGFNktTISTFIGDKLKGYAVGTIL 157
gi 1000268996  79 atggfg---widslvrphfpNEIVLALIFFGVIMIASDLLTLPFQWYSTFVIEEKFGFNktTPKTFIADKIKGYALGAIV 155
gi 595616369   99 ltggfg---wldeqlrewtqHPILLALLYFGMLMLAADILSLPFQLYSTFRIEESWGFNktSVRTFWLDKLKGYGLGALL 175
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                         
4AW6_A        178 LLPVSSLLLYIIkiggdyFFIYAWLFTLVVSLVLVTIYADYIAPLFDKFTPLpEGKLKEEIEVMAKSIDFPL-TKVYVVE 256
4IL3_A        176 GGPILYLFLKIFdkfptdFLWYIMVFLFVVQILAMTIIPVFIMPLFNKFTPLeDGELKKSIESLADRVGFPL-DKIFVID 254
gi 330752627  173 IVGLTSLAIFIIesfssgYWLWLWLGLSSLMIFLNMFYADLIVPIFNKLTPLeDGELRKKIEAYSNKVGYSLkNIFVIDG 252
gi 441436665  156 GGLLIGLLLYLIlnigesFWVYFWVVAALFILFVNMFYTSLVLPLFNKLTPLgEGELKTAIENYSRKVNFPLdNIFVIDG 235
gi 496562801  156 GGSLLLTFLLLVnymgvdFWWQFWLVTGVFMVLVNGLFSSYILPLFNKLTPLeEGELRQAILSYASKAGFPLeNVFVIDG 235
gi 684288920  157 GLPLIGLIAWIYqelnslFWLVGWLLISVFSLFMFIFGTRIFLPLFNKLKPLpAGELRDEVEAYCQSQGFPLsKLWEMDA 236
gi 695124721  156 GGLLIWLFIFMVtsigpgFWLYFWIILSVVMLIINMFYTSIFVPLFNKLTPLeAGDLRNSIEEYSKTNNFSLtNIFVIDG 235
gi 748178107  158 GGGLISLLIYLIqligpdFWILFSLIAAVLILLINMFYTTIFLPLFNKLTPLeDGELKTKIESFSKTVGFPLdNVFVMDG 237
gi 1000268996 156 GGGLLALLIYLIqwigpdFWIWFGMVAALFILIVNMFYTTLILPLFNKLTPLaEGDLKTAITTYAKQVDFPLeNIFVMDG 235
gi 595616369  176 GGLLLSLLLWLVlelgqnFWLYFWGVLILFMLGANVFYTSLILPLFNKLRPLtAGALKTALETYSQKINFPLkNIYVIDG 255
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        #
4AW6_A        257 GSKRssHSNAYFYGFFKn-KRIVLFDTLLEeysvlnkdiqedsgmeprneeegnseeikakvknkkqgcknEEVLAVLGH 335
4IL3_A        255 GSKRssHSNAYFTGLPFtsKRIVLFDTLVNsn-------------------------------------stDEITAVLAH 297
gi 330752627  253 SKRSs-KANAFFSGLGPr-KTIALYDTLIKkh-------------------------------------sdEELVSVLAH 293
gi 441436665  236 SKRSk-KANAFFSGIGKr-KKIVLYDTLIEnh-------------------------------------stDELVAILAH 276
gi 496562801  236 SKRSs-KANAFFSGFGKr-KKVVLYDTLIAqh-------------------------------------stDELVAVLAH 276
gi 684288920  237 SKRSt-KLNAFFSGMGKv-KIIGLYDTLIQkl-------------------------------------ttKEVVAVLAH 277
gi 695124721  236 SKRSs-KANAFFSGIGPk-KKVVLYDTLINnh-------------------------------------skEELVAVLAH 276
gi 748178107  238 SKRSn-KANAFFSGIGRk-KKIVLYDTLIAnh-------------------------------------ntDELVAVLAH 278
gi 1000268996 236 SKRSa-KANAFFSGIGKk-KKIVLYDTLINnh-------------------------------------ttDELVAVLAH 276
gi 595616369  256 SKRSs-KANAFFAGLGKq-KKIVLYDTLIEkh-------------------------------------teEEIVAVLAH 296
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1            #                                                                            
4AW6_A        336 ELGHWKLGHTVKNIIISQMNSFLCFFLFAVligrkelfaa-------------fgfydsqptlIGLLIIFQfifsPYNEV 402
4IL3_A        298 EIGHWQKNHIVNMVIFSQLHTFLIFSLFTSiyrnssfyntfgffveksssgfvdpvitkefpiIIGFMLFNdlltPLECA 377
gi 330752627  294 EVGHFKKKHILLSMIITICQLGVMCYLFEIcmsfemiansl------------gssamnfhigIIAFSFLYs---PIGLI 358
gi 441436665  277 EVGHFKKKHIIGSFIFSILQIGIMLFIMSRmiynenlslal------------gaeqmgvhlnLLAFGILYs---PISKV 341
gi 496562801  277 EIGHYKKRHIVTNLVLGILQTGLILFVLAQlifseslslal------------ggsemavhlnLVGFTMLFs---PLSAL 341
gi 684288920  278 EVGHYKRKHVYTMFLFSNVQTLILFALMGWllgnpnlaral------------gseipsfhlsLISFVLLFs---PLSTI 342
gi 695124721  277 EIGHFKKKHIITGLILGIIQTGFMLFLLSYfifnknlseal------------gadhlaihinLIAFGILYt---PISHI 341
gi 748178107  279 EVGHYKKKHIIFGYILSVIQVVFTLFILSLmvqsenvslal------------ggtqsaihlnLLAFGILFs---PISGL 343
gi 1000268996 277 EVGHFKKKHIILTYLISILQVFFVLFVLSTmvfneklsaal------------ggsqqaihlnLIAFTILFs---PISGI 341
gi 595616369  297 EAGHYKKRHILKGFVLSVLQSGLMLFLLSRfigsetltlalggtpl--ggtpleagllplhlnLIGFGLLYs---PISML 371
                         410       420       430       440       450       460       470
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
Feature 1                     #                                             #            
4AW6_A        403 LSFCLTVLSRRFEFQADAFAKKLGka--kdLYSALIKLNKDNLGFPvSDWLFSMWHYSHPPLlERLQALKT 471
4IL3_A        378 MQFIMSLISRTHEYQADAYAKKLGyk--qnLCRALIDLQIKNLSTMnVDPLYSSYHYSHPTLaERLTALDY 446
gi 330752627  359 IGILMNILSRKNEFEADEYAKLTYdg--naLSQALKKLSVDSLSNLyPHPLYVFVHYSHPPLiKRLNALNK 427
gi 441436665  342 LGIISNVISRKNEFEADAYAGTTYgg--saLAASLKKLSVDNLSNLyPHPAYVFMYYSHPPLlKRLGALKN 410
gi 496562801  342 IGVGMNILSRKHEFEADAFAKSTFdg--qpLATALKKLSVNNLTNLnPHPWYVFMNYSHPPLlQRLAKLET 410
gi 684288920  343 LGLIANSFSRFNEYQADQFSIDTYpgarehLHSALKKLSVESLKDLnPHPMYVKVNYSHPPIlERLANLKS 413
gi 695124721  342 TGLLMNIISRKNEYEADRFAAVTYss--iaLQEALKKLSSKNLSNLtPHPAYVFMHYSHPPLlYRLRALKQ 410
gi 748178107  344 TGLFMSMYSRKNEFEADAYAKETFsg--paLASALKKLSVDNLSDLyPHPLYVFFHYSHPPLlKRLAVIDQ 412
gi 1000268996 342 TGLLMSMLSRKNEFEADAYAKNTFdg--taLANALKKLSVDTLSNLyPHPWYVFFHYSHPPLlKRLQALEL 410
gi 595616369  372 LGLFMNSLSRKHEYQADAYAAQTYga--epLQEALRKLSVLNLSQPlPHPWYVWVHYSHPPLlYRLDALEK 440

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