1QWU,3CZN,1HWW


Conserved Protein Domain Family
GH38N_AMII_GMII_SfManIII_like

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cd10809: GH38N_AMII_GMII_SfManIII_like 
Click on image for an interactive view with Cn3D
N-terminal catalytic domain of Golgi alpha-mannosidase II, Spodoptera frugiperda Sf9 alpha-mannosidase III, and similar proteins; glycoside hydrolase family 38 (GH38)
This subfamily is represented by Golgi alpha-mannosidase II (GMII, also known as mannosyl-oligosaccharide 1,3- 1,6-alpha mannosidase, EC 3.2.1.114, Man2A1), a monomeric, membrane-anchored class II alpha-mannosidase existing in the Golgi apparatus of eukaryotes. GMII plays a key role in the N-glycosylation pathway. It catalyzes the hydrolysis of the terminal both alpha-1,3-linked and alpha-1,6-linked mannoses from the high-mannose oligosaccharide GlcNAc(Man)5(GlcNAc)2 to yield GlcNAc(Man)3(GlcNAc)2(GlcNAc, N-acetylglucosmine), which is the committed step of complex N-glycan synthesis. GMII is activated by zinc or cobalt ions and is strongly inhibited by swainsonine. Inhibition of GMII provides a route to block cancer-induced changes in cell surface oligosaccharide structures. GMII has a pH optimum of 5.5-6.0, which is intermediate between those of acidic (lysosomal alpha-mannosidase) and neutral (ER/cytosolic alpha-mannosidase) enzymes. GMII is a retaining glycosyl hydrolase of family GH38 that employs a two-step mechanism involving the formation of a covalent glycosyl enzyme complex; two carboxylic acids positioned within the active site act in concert: one as a catalytic nucleophile and the other as a general acid/base catalyst. This subfamily also includes human alpha-mannosidase 2x (MX, also known as mannosyl-oligosaccharide 1,3- 1,6-alpha mannosidase, EC 3.2.1.114, Man2A2). MX is enzymatically and functionally very similar to GMII, and is thought to also function in the N-glycosylation pathway. Also found in this subfamily is class II alpha-mannosidase encoded by Spodoptera frugiperda Sf9 cell. This alpha-mannosidase is an integral membrane glycoprotein localized in the Golgi apparatus. It shows high sequence homology with mammalian Golgi alpha-mannosidase II(GMII). It can hydrolyze p-nitrophenyl alpha-D-mannopyranoside (pNP-alpha-Man), and it is inhibited by swainsonine. However, the Sf9 enzyme is stimulated by cobalt and can hydrolyze (Man)5(GlcNAc)2 to (Man)3(GlcNAc)2, but it cannot hydrolyze GlcNAc(Man)5(GlcNAc)2, which is distinct from that of GMII. Thus, this enzyme has been designated as Sf9 alpha-mannosidase III (SfManIII). It probably functions in an alternate N-glycan processing pathway in Sf9 cells.
Statistics
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PSSM-Id: 212120
Aligned: 24 rows
Threshold Bit Score: 567.664
Created: 19-Aug-2010
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 17 residues -Click on image for an interactive view with Cn3D
Feature 1:active site [active site]
Evidence:
  • Structure:3CZN; Drosophila melanogaster Golgi Alpha-Mannosidase II (D204A nucleophile mutant) binds GnMan5Gn/Zn2+ in the active site, contacts at 4A
    View structure with Cn3D
  • Comment:Drosophila melanogaster Golgi Alpha-Mannosidase II (3CZN) contains an active site made up of three sugar-binding subsites (the catalytic, holding, and anchor sites) and a Zn2+ binding site
  • Structure:1QWU; Drosophila melanogaster Golgi alpha-mannosidase II (D341N mutant) binds 5-F-guloside/Zn2+ in the active site, contacts at 4A.
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                   # #  #                                                                
1QWU_A         80 KLKVFVVPHSHNDPGWIQTFEEYYQhDTKHILSNALRHLHDNpEMKFIWAEISYFARFYHDLg--ENKKLQMKSIVKNGQ 157  fruit fly
3CZN_A         80 KLKVFVVPHSHNDPGWIQTFEEYYQhDTKHILSNALRHLHDNpEMKFIWAEISYFARFYHDLg--ENKKLQMKSIVKNGQ 157  fruit fly
XP_002575281  159 PLEVFIVPFSHQDPGWIKTLEKYFVtETKPNLDATLNILNEKeESRFVYSEVSFLDLWINTLs--EEQKQSFKRLLLNGH 236  Schistosoma m...
CBY15331      165 KLQIILMPHSHNDPGWVKTLDTYYTgQTRTILKVIVDALSKNpLRKFIWAETVFLNMWFDDQtvtQDYKTRFTSLLKAGQ 244  Oikopleura di...
NP_001021474  136 KLKVYVLPFTHVDPGWLETFERYTK-STNQILDNMHQFMMKNeKMRFMWAEFVFFERWWSLQn--EQVKEDVKKLVTEGR 212  nematode
EGD74845      237 PLNVFIIPHSHNDPGWIMTLDEYYRkQTSQILTLMTQTLSQEpTVKFVWAEISYLSMWWKDQs--SNVRETFKRMVHSGQ 314  Salpingoeca s...
EFX84714       32 SLKVVVLPHSHVDPGWLKTFENYYAqSTHSILDNLVTKLTQHkNMTFIWTEISFFALWWESAl--PAKRRQVQKLVEEKR 109  common water ...
NP_650494     167 PLKIIVVPHSHNDPGWLKTFTNYFQsDSRQILNLLVTKMQEYtDMTFIWSEISFLQLWWDQAh--PTKQRALKRLIDAGR 244  fruit fly
EGD82499      423 PLEVILMPHTHVDPGWIRTFDDYYQkQTKAILDTVTDFLAARpFRKFIWAEISFLQAWWHDAt--PDRRRTFRNLVRRGQ 500  Salpingoeca s...
GAA48315      133 PLEVFLVPHSHQDPGWVMTLEEYFRtKTKKCLDSTLKVLESRpDARFSYAEISFFSMWVAGLt--EDEKNRVKKLLNNGQ 210  Clonorchis si...
Feature 1                                                       # #                     #         
1QWU_A        158 LEFVTGGWVMPDEANSHWRNVLLQLTEGQTWLKQFMNVTPTASWAIDPFGHSPTMPYILQKSGFKNMLIQRTHYSVKKEL 237  fruit fly
3CZN_A        158 LEFVTGGWVMPDEANSHWRNVLLQLTEGQTWLKQFMNVTPTASWAIAPFGHSPTMPYILQKSGFKNMLIQRTHYSVKKEL 237  fruit fly
XP_002575281  237 WEIVSGGWVMPDEAVTHYYSIIDQFIEGHHWLLEHFDYRPNVTWSIDSFGQSSTMPYLAKKLGFSQMIINRVHYEVKKYL 316  Schistosoma m...
CBY15331      245 IEIVTGGWVMTEEAPSHYFAMSDQLIEGHQWLKKHFDYHPKNGYNCDTFGASPTTAYLNHLAGIDHMLIQRTHYVVKKNF 324  Oikopleura di...
NP_001021474  213 LELATGSWVMTDEANPYFPVSVDNIVEGFQFIHKNFGIKPQTMWSNDPFGYSNSVPYLFKKSGVHRTVINRIHHKLKQTL 292  nematode
EGD74845      315 IEIVTGGWVMPDEANSHYFALVDQLIEGHKWVEENLGVRPESGWSIDPFGHSPTMAYILKRADFKGMLIQRIHYEVKRML 394  Salpingoeca s...
EFX84714      110 LEFTSATWVMVDEATPHLYSMLDQMIEGHQWLKSHLGVSPKSAWTVDPFGHGPVAPYLLHAAGLQNTVVQRIHYGWKRWM 189  common water ...
NP_650494     245 IEITTGGWVMTDEANVHIYPMLDQLIEGHQWLKNNLNVTPKVGWSIDPFGHGSTVPYLLSGANFEGTIIQRIHYAWKQWF 324  fruit fly
EGD82499      501 MEIVTGGWVMTEEACSHYFSMVDQLIEGQIWVNETFGVVPATGWSVDPFGHTPTMAFINSKAGLKGMVIDRIHWRLKQQM 580  Salpingoeca s...
GAA48315      211 LEVVSGGWVMTDEAAGHHYAMLDQLIEGHQWLLENFDYRPNVSWSIDPFGHSPTMAYLNRKMRFSAMVLQRVHYEVKKYL 290  Clonorchis si...
Feature 1                                           # #   #     #         #          ##           
1QWU_A        238 AQQRQLEFLWRQIWDnk-----gdTALFTHMMPFYSYDIPHTCGPDPKVCCQFDFKRmg--sfGLSCPWKVPPr------ 304  fruit fly
3CZN_A        238 AQQRQLEFLWRQIWDnk-----gdTALFTHMMPFYSYDIPHTCGPDPKVCCQFDFKRmg--sfGLSCPWKVPPr------ 304  fruit fly
XP_002575281  317 ASRKALEFMWHQPWDaa-----gsHSILVHMFPFFSYDVPHTCGPEPAVCCQFDFIRt----eKYGCPWRKLPv------ 381  Schistosoma m...
CBY15331      325 AEKNILEFNWRQSFDns-----gsDETFTHMMPFYSYDVPHTCGPDPSVCCQFDFRRlrkvspPVTCPWRKEPi------ 393  Oikopleura di...
NP_001021474  293 QSQKAIPFKWRQYFDat-----geDDVLTQILPYTHYDILNSCGSDASVCCEFDFKRm----tHWSCPGPKPEk------ 357  nematode
EGD74845      395 AEKKQLEFMWRQDFDvg-----kdTSMYTHMMPFYSYDVPHTCGPEPAICCQFDFARmr--ggRYSCPWRKPPl------ 461  Salpingoeca s...
EFX84714      190 ADRQVSDFYWKLPWEtp-----grDSVLCHNFPYDIYTTKHSCGPNPKTCLGYDFRNv----rGEYNEFTMNSs------ 254  common water ...
NP_650494     325 ARQQSGDFIWKPYWRsrkdkdseaGSLLTHNMPFDIYSIKGSCGPHPFICLNFDFRKi----pGEYTEYSVKAq------ 394  fruit fly
EGD82499      581 QQRNELVFRWQQDWDtt-----anTAVLTHTLPFYLYDVHYTCGPDYAVCCQLDFGLay--fkKKLTPQCAEFgakttvr 653  Salpingoeca s...
GAA48315      291 AKRQSLEFSWRQYWDnn-----ghTEILAHMMPFYSYDVPHTCGPEPAVCCQFDFARl----qRFKCPWKIQPq------ 355  Clonorchis si...
Feature 1                                                  ## #                                   
1QWU_A        305 tISDQNVAARSDLLVDQWKKKAELYRT------NVLLIPLGDNFRFkqNTEWDVQRVNYERLFEHINSqa-hFNVQAQFG 377  fruit fly
3CZN_A        305 tISDQNVAARSDLLVDQWKKKAELYRT------NVLLIPLGDDFRFkqNTEWDVQRVNYERLFEHINSqa-hFNVQAQFG 377  fruit fly
XP_002575281  382 fIDDSNVAVRADMLADQYRKKATLYNNn-----GLVLIPLGDDFRYqsTHEWNVQLDNYNKLIQHINSnp-sYRMKIHFS 455  Schistosoma m...
CBY15331      394 eITKTNVAERARILLDQYRKKSKLYAKgtksntRVVLTLLGDDFRYdsDAEAEAQFTNYEKLFEYINNnp-qMNAEAKFG 472  Oikopleura di...
NP_001021474  358 -ITNANVAAKAEKLVNQLEKMSEMYKA------PVILMMHGDDFRFdmIEEWNQQHDNFIPVFDEINKg---SRVEIRFG 427  nematode
EGD74845      462 eITPDNVAERAALLLDQYRKKAQLYAT------NNVLIPLGDDFRYdnQQEIDAQIRNYKRLISYMNAhp-eLHVNIKFA 534  Salpingoeca s...
EFX84714      255 pITRTNIQSKAEVLLEQYAKTGSLTRH------NIVLALVGDDFRYdhDIEWDQQYTNYQNLFNYINArkeiYKTEIGFG 328  common water ...
NP_650494     395 fITDDNLESKAQLLLEQYARTASLFPH------NVALIPVGDDFRYnkDREVDQQYQNYKKLIDHIMAnrrlYNADIRFG 468  fruit fly
EGD82499      654 pIIPGYEQNAALQLIEQYRKQALLFKN------NVVLHPIGGDFRYtsHQEIAAQLDSYTRIMKYINSqp-eLNVNVRFG 726  Salpingoeca s...
GAA48315      356 vITQNNVAERARLLADQYRKKAMLFDNd-----GLLLVPLGDDFRYlsEEEWGLQMDNYGRLIQHFNSnp-eYRIKVRFA 429  Clonorchis si...
Feature 1                                                        #    
1QWU_A        378 TLQEYFDAVHQAERAgq------aeFPTLSGDFFTYADRs----DNYWSGYY 419  fruit fly
3CZN_A        378 TLQEYFDAVHQAERAgq------aeFPTLSGDFFTYADRs----DNYWSGYY 419  fruit fly
XP_002575281  456 TLSNYFHALNERVNKmnst--mstlFPSLSGDFFTYADRq----HDYWSGYY 501  Schistosoma mansoni
CBY15331      473 TLADYFELVDKARPIs--------eNPSITGDFFSYADRt----TNYWTGFF 512  Oikopleura dioica
NP_001021474  428 TFTDYFNDLEKWYSNnkd-----sePPTVSGDFFPYMCAl----GDYWTGYY 470  nematode
EGD74845      535 TLGEYFDAVRKATNAhte----tpsLPTLSGDFFSYADRn----DNYWTGYF 578  Salpingoeca sp. ATCC50818
EFX84714      329 TLTDYFDAIRGRVDN----------FPTLKGDFFPYSDIfsegrPAYWTGYF 370  common water flea
NP_650494     469 TPSDYFEAIKERMKDht------pgFPTFKGDFFVYSDIfsegrPAYWSGYF 514  fruit fly
EGD82499      727 TLRDYFNAIEDKATPt--------tYPTLTGHFMPYSDRr----DHYWTGFY 766  Salpingoeca sp. ATCC50818
GAA48315      430 TVSDYFNALHQRLKTrtnephlateMAQLTGDLFTYADRd----HDYWSGYF 477  Clonorchis sinensis

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