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Conserved domains on  [gi|530377543|ref|XP_005262981|]
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N-acylethanolamine-hydrolyzing acid amidase isoform X8 [Homo sapiens]

Protein Classification

NAAA-beta and Ntn_AC_NAAA domain-containing protein( domain architecture ID 10634631)

NAAA-beta and Ntn_AC_NAAA domain-containing protein

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
Ntn_AC_NAAA cd01903
AC_NAAA This conserved domain includes two closely related proteins, acid ceramidase (AC, also ...
117-324 1.12e-124

AC_NAAA This conserved domain includes two closely related proteins, acid ceramidase (AC, also known as N-acylsphingosine amidohydrolase), and N-acylethanolamine-hydrolyzing acid amidase (NAAA). AC catalyzes the hydrolysis of ceramide to sphingosine and fatty acid. Ceramide is required for the biosynthesis of most sphingolipids and plays an important role in many signal transduction pathways by inducing apoptosis and/or arresting cell growth. An inherited deficiency of AC activity leads to the lysosomal storage disorder known as Farber disease. AC is considered a "rheostat" important for maintaining the proper intracellular levels of these lipids since hydrolysis of ceramide is the only source of sphingosine in cells. NAAA is a eukaryotic glycoprotein that hydrolyzes bioactive N-acylethanolamines, including anandamide (an endocannabinoid) and N-palmitoylethanolamine (an anti-inflammatory and neuroprotective substance), to fatty acids and ethanolamine at acidic pH. NAAA shows structural and functional similarity to acid ceramidase, but lacks the ceramide-hydrolyzing activity of AC.


:

Pssm-ID: 238886  Cd Length: 231  Bit Score: 356.58  E-value: 1.12e-124
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377543 117 NLAYESSVFCTSIVAQDSRGHIYHGRNLDYPFGNVLRKLTVDVQFLKNGQIAFTGTTFIGYVGLWTGQSPHKFTVSGDER 196
Cdd:cd01903    1 NIFYEIFTFCTSIVAQDSNGTIYHARNLDFGFFEELSKLTVNVDFQRNGKIVFKGTTFAGYVGLLTGQKPGKFSLTINER 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377543 197 DKGWWWENAI-AALFRRHIPVSWLIRATLSESENFEAAVGKLAKTPLIADVYYIVGGTSPREGVVITRNRDGPADIWPLD 275
Cdd:cd01903   81 FSLDGGYNGIlALLKKDGIPVSWLIRETLENATSYEDAVEKLSTTPILAPAYFIVGGVKPGEGVVITRNRDSVADVYPLD 160
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 530377543 276 PLNGAWFRVETNYDHWKPAPKEDDRRTSAIKALNATGQANLSLEALFQM 324
Cdd:cd01903  161 LKNGTWFLVQTNYDRWKPPPFLDDRRTPAIKCMNALGQANISFKTLYDV 209
NAAA-beta pfam15508
beta subunit of N-acylethanolamine-hydrolyzing acid amidase; NAAA-beta is a family of ...
32-91 3.03e-12

beta subunit of N-acylethanolamine-hydrolyzing acid amidase; NAAA-beta is a family of vertebral sequences that form the beta subunit of vertebral N-acylethanolamine-hydrolyzing acid amidase, a member of the choloylglycine hydrolase acid ceramidase family. The alpha subunit is represented by family CBAH, pfam02275.


:

Pssm-ID: 464754  Cd Length: 63  Bit Score: 60.72  E-value: 3.03e-12
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 530377543   32 AAPRFNVSLDSVPELRWLPVLRHYD--LDLVRAAMAQVIGDRVPKWVHVLIGKVVLELERFL 91
Cdd:pfam15508   2 PVPWYVINLDLPPEERWTQVAKDYKpeIKSLIPALKDLLKSLVPGKLVPLVDKLAADLLRYL 63
 
Name Accession Description Interval E-value
Ntn_AC_NAAA cd01903
AC_NAAA This conserved domain includes two closely related proteins, acid ceramidase (AC, also ...
117-324 1.12e-124

AC_NAAA This conserved domain includes two closely related proteins, acid ceramidase (AC, also known as N-acylsphingosine amidohydrolase), and N-acylethanolamine-hydrolyzing acid amidase (NAAA). AC catalyzes the hydrolysis of ceramide to sphingosine and fatty acid. Ceramide is required for the biosynthesis of most sphingolipids and plays an important role in many signal transduction pathways by inducing apoptosis and/or arresting cell growth. An inherited deficiency of AC activity leads to the lysosomal storage disorder known as Farber disease. AC is considered a "rheostat" important for maintaining the proper intracellular levels of these lipids since hydrolysis of ceramide is the only source of sphingosine in cells. NAAA is a eukaryotic glycoprotein that hydrolyzes bioactive N-acylethanolamines, including anandamide (an endocannabinoid) and N-palmitoylethanolamine (an anti-inflammatory and neuroprotective substance), to fatty acids and ethanolamine at acidic pH. NAAA shows structural and functional similarity to acid ceramidase, but lacks the ceramide-hydrolyzing activity of AC.


Pssm-ID: 238886  Cd Length: 231  Bit Score: 356.58  E-value: 1.12e-124
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377543 117 NLAYESSVFCTSIVAQDSRGHIYHGRNLDYPFGNVLRKLTVDVQFLKNGQIAFTGTTFIGYVGLWTGQSPHKFTVSGDER 196
Cdd:cd01903    1 NIFYEIFTFCTSIVAQDSNGTIYHARNLDFGFFEELSKLTVNVDFQRNGKIVFKGTTFAGYVGLLTGQKPGKFSLTINER 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377543 197 DKGWWWENAI-AALFRRHIPVSWLIRATLSESENFEAAVGKLAKTPLIADVYYIVGGTSPREGVVITRNRDGPADIWPLD 275
Cdd:cd01903   81 FSLDGGYNGIlALLKKDGIPVSWLIRETLENATSYEDAVEKLSTTPILAPAYFIVGGVKPGEGVVITRNRDSVADVYPLD 160
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 530377543 276 PLNGAWFRVETNYDHWKPAPKEDDRRTSAIKALNATGQANLSLEALFQM 324
Cdd:cd01903  161 LKNGTWFLVQTNYDRWKPPPFLDDRRTPAIKCMNALGQANISFKTLYDV 209
NAAA-beta pfam15508
beta subunit of N-acylethanolamine-hydrolyzing acid amidase; NAAA-beta is a family of ...
32-91 3.03e-12

beta subunit of N-acylethanolamine-hydrolyzing acid amidase; NAAA-beta is a family of vertebral sequences that form the beta subunit of vertebral N-acylethanolamine-hydrolyzing acid amidase, a member of the choloylglycine hydrolase acid ceramidase family. The alpha subunit is represented by family CBAH, pfam02275.


Pssm-ID: 464754  Cd Length: 63  Bit Score: 60.72  E-value: 3.03e-12
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 530377543   32 AAPRFNVSLDSVPELRWLPVLRHYD--LDLVRAAMAQVIGDRVPKWVHVLIGKVVLELERFL 91
Cdd:pfam15508   2 PVPWYVINLDLPPEERWTQVAKDYKpeIKSLIPALKDLLKSLVPGKLVPLVDKLAADLLRYL 63
C45_proenzyme NF040521
C45 family autoproteolytic acyltransferase/hydolase; Members of this family include hydrolases ...
59-266 3.27e-11

C45 family autoproteolytic acyltransferase/hydolase; Members of this family include hydrolases and N-acyltransferases, and belong to the Ntn (N-terminal nucleophile) hydrolase family. Members have an invariant Cys residue (Cys-103 in XP_002569112.1) required both for autoproteolytic processing into alpha and beta chains and for activity. The family is described by MEROPs as a cysteine protease, family C45, because of its autoproteolytic activity. Characterized members include TAN from Drosophila, which removes beta-alanine from both carcinine and N-beta-alanyl dopamine, and isopenicillin-N N-acyltransferase from various fungi. The latter has been heavily studied because of its role in penicillin biosynthesis.


Pssm-ID: 468523 [Multi-domain]  Cd Length: 312  Bit Score: 63.08  E-value: 3.27e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377543  59 LVRAAMAQVIGDRVPKWVHV-------LIGKVVLELERFLPQpFTGEIRGMCDFMNLSLADCLLVNLAYE---SSVFCTS 128
Cdd:NF040521  14 LLKELIRDLYLALLRAWGLVswrelrdFAKEFLAALEAFAPE-LWEELEGIADGLGLPFEDVLALNARTEilaAPDGCST 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377543 129 IVAQDSRGHIYHGRNLDYPFGnvLRKLTVDVQFLKNGQIAFtgtTFIGYVGLWTGQS----PHKFTVSGDERDKGWWWEN 204
Cdd:NF040521  93 FAVLGEDGEPILARNYDWHPE--LYDGCLLLTIRPDGGPRY---ASIGYAGLLPGRTdgmnEAGLAVTLNFLDGRKLPGV 167
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 530377543 205 AiaalfrrhIPVSWLIRATLSESENFEAAVGKLAKTPLIADVYYIVGG---------TSPREGVVITRNRD 266
Cdd:NF040521 168 G--------VPVHLLARAILENCKTVDEAIALLKEIPRASSFNLTLADasgraasveASPDRVVVVRPEDG 230
CBAH pfam02275
Linear amide C-N hydrolases, choloylglycine hydrolase family; This family includes several ...
126-316 7.46e-09

Linear amide C-N hydrolases, choloylglycine hydrolase family; This family includes several hydrolases which cleave carbon-nitrogen bonds, other than peptide bonds, in linear amides. These include choloylglycine hydrolase (conjugated bile acid hydrolase, CBAH) EC:3.5.1.24, penicillin acylase EC:3.5.1.11 and acid ceramidase EC:3.5.1.23. This domain forms the alpha-subunit for members from vertebral species, see family NAAA-beta, pfam15508.


Pssm-ID: 396726  Cd Length: 316  Bit Score: 55.98  E-value: 7.46e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377543  126 CTSIVAQDSRGHIYHGRNLDYPFGN----VLRKLTVDVQFLKNGQIAFTGTTFIGyVGLWTGQSPhKFTVSGDERDKGww 201
Cdd:pfam02275   1 CTSITLETKKGNLLFGRNMDFGISYgeevIITPRNYKLVFEKLGNMLVTKYAVIG-MGTDVGSYP-LFYDGLNEKGLG-- 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377543  202 wenaIAALF--------------RRHIPVSWLIRATLSESENFEAAVGKLAKTPLIADVYYIVGGTSPR---------EG 258
Cdd:pfam02275  77 ----IAGLYfpgyafyskgpkkdKVNIQPGELILWVLGNFTSVEEVKELLTKLNIVNEALDILGGKAPLhwiisdasgES 152
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 530377543  259 VVItRNRDGPADIWPLDPL----NGAWFRVETNYDHWK-------PAPKEDDRRTSAIKalNATGQANL 316
Cdd:pfam02275 153 IVI-EPRKEGLKVYDNEVGvmtnSPTFDWHLTNLNNYTglrpnqpQNFFMGDLDLTPFG--QGTGGLGL 218
 
Name Accession Description Interval E-value
Ntn_AC_NAAA cd01903
AC_NAAA This conserved domain includes two closely related proteins, acid ceramidase (AC, also ...
117-324 1.12e-124

AC_NAAA This conserved domain includes two closely related proteins, acid ceramidase (AC, also known as N-acylsphingosine amidohydrolase), and N-acylethanolamine-hydrolyzing acid amidase (NAAA). AC catalyzes the hydrolysis of ceramide to sphingosine and fatty acid. Ceramide is required for the biosynthesis of most sphingolipids and plays an important role in many signal transduction pathways by inducing apoptosis and/or arresting cell growth. An inherited deficiency of AC activity leads to the lysosomal storage disorder known as Farber disease. AC is considered a "rheostat" important for maintaining the proper intracellular levels of these lipids since hydrolysis of ceramide is the only source of sphingosine in cells. NAAA is a eukaryotic glycoprotein that hydrolyzes bioactive N-acylethanolamines, including anandamide (an endocannabinoid) and N-palmitoylethanolamine (an anti-inflammatory and neuroprotective substance), to fatty acids and ethanolamine at acidic pH. NAAA shows structural and functional similarity to acid ceramidase, but lacks the ceramide-hydrolyzing activity of AC.


Pssm-ID: 238886  Cd Length: 231  Bit Score: 356.58  E-value: 1.12e-124
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377543 117 NLAYESSVFCTSIVAQDSRGHIYHGRNLDYPFGNVLRKLTVDVQFLKNGQIAFTGTTFIGYVGLWTGQSPHKFTVSGDER 196
Cdd:cd01903    1 NIFYEIFTFCTSIVAQDSNGTIYHARNLDFGFFEELSKLTVNVDFQRNGKIVFKGTTFAGYVGLLTGQKPGKFSLTINER 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377543 197 DKGWWWENAI-AALFRRHIPVSWLIRATLSESENFEAAVGKLAKTPLIADVYYIVGGTSPREGVVITRNRDGPADIWPLD 275
Cdd:cd01903   81 FSLDGGYNGIlALLKKDGIPVSWLIRETLENATSYEDAVEKLSTTPILAPAYFIVGGVKPGEGVVITRNRDSVADVYPLD 160
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 530377543 276 PLNGAWFRVETNYDHWKPAPKEDDRRTSAIKALNATGQANLSLEALFQM 324
Cdd:cd01903  161 LKNGTWFLVQTNYDRWKPPPFLDDRRTPAIKCMNALGQANISFKTLYDV 209
Ntn_CGH_like cd01935
Choloylglycine hydrolase (CGH)_like. This family of choloylglycine hydrolase-like proteins ...
126-326 2.89e-42

Choloylglycine hydrolase (CGH)_like. This family of choloylglycine hydrolase-like proteins includes conjugated bile acid hydrolase (CBAH), penicillin V acylase (PVA), acid ceramidase (AC), and N-acylethanolamine-hydrolyzing acid amidase (NAAA) which cleave non-peptide carbon-nitrogen bonds in bile salt constituents. These enzymes have an N-terminal nucleophilic cysteine, as do other members of the Ntn hydrolase family to which they belong. This nucleophilic cysteine is exposed by post-translational prossessing of the precursor protein.


Pssm-ID: 238910  Cd Length: 229  Bit Score: 145.96  E-value: 2.89e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377543 126 CTSIVAQDSRGHIYHGRNLDYPFGNVLRKLTVDVQFLKNGQI---------AFTGTTFIGYVGLWTGQSPHKFTVSGDER 196
Cdd:cd01935    1 CTSIVAQTKDGGVYLGRNMDFSFDYELRLLVFPRGYQRNGQTgdkskwyakYGSGGTSAGYIGLVDGMNEKGLSVSLLYF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377543 197 DKGWWWENAIAAlFRRHIPVSWLIRATLSESENFEAAVGKLAKTPLI----------ADVYYIVGGTSpREGVVITRNRD 266
Cdd:cd01935   81 PGYAYYPAGIKE-GKDGLPAFELIRWVLENCDSVEEVKEALKKIPIVdfpiplggpaAPLHYILSDKS-GDSAVIEPIDG 158
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377543 267 GPADIWPLdplngaWFRVETNYDHWKPAPkedDRRTSAIKALNATGQANLSLEALFQMIF 326
Cdd:cd01935  159 GLKIYDNP------WFGVMTNHPTFDWHL---PRRFVRVAYLKNTAQKNKETVEDVKNLF 209
NAAA-beta pfam15508
beta subunit of N-acylethanolamine-hydrolyzing acid amidase; NAAA-beta is a family of ...
32-91 3.03e-12

beta subunit of N-acylethanolamine-hydrolyzing acid amidase; NAAA-beta is a family of vertebral sequences that form the beta subunit of vertebral N-acylethanolamine-hydrolyzing acid amidase, a member of the choloylglycine hydrolase acid ceramidase family. The alpha subunit is represented by family CBAH, pfam02275.


Pssm-ID: 464754  Cd Length: 63  Bit Score: 60.72  E-value: 3.03e-12
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 530377543   32 AAPRFNVSLDSVPELRWLPVLRHYD--LDLVRAAMAQVIGDRVPKWVHVLIGKVVLELERFL 91
Cdd:pfam15508   2 PVPWYVINLDLPPEERWTQVAKDYKpeIKSLIPALKDLLKSLVPGKLVPLVDKLAADLLRYL 63
C45_proenzyme NF040521
C45 family autoproteolytic acyltransferase/hydolase; Members of this family include hydrolases ...
59-266 3.27e-11

C45 family autoproteolytic acyltransferase/hydolase; Members of this family include hydrolases and N-acyltransferases, and belong to the Ntn (N-terminal nucleophile) hydrolase family. Members have an invariant Cys residue (Cys-103 in XP_002569112.1) required both for autoproteolytic processing into alpha and beta chains and for activity. The family is described by MEROPs as a cysteine protease, family C45, because of its autoproteolytic activity. Characterized members include TAN from Drosophila, which removes beta-alanine from both carcinine and N-beta-alanyl dopamine, and isopenicillin-N N-acyltransferase from various fungi. The latter has been heavily studied because of its role in penicillin biosynthesis.


Pssm-ID: 468523 [Multi-domain]  Cd Length: 312  Bit Score: 63.08  E-value: 3.27e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377543  59 LVRAAMAQVIGDRVPKWVHV-------LIGKVVLELERFLPQpFTGEIRGMCDFMNLSLADCLLVNLAYE---SSVFCTS 128
Cdd:NF040521  14 LLKELIRDLYLALLRAWGLVswrelrdFAKEFLAALEAFAPE-LWEELEGIADGLGLPFEDVLALNARTEilaAPDGCST 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377543 129 IVAQDSRGHIYHGRNLDYPFGnvLRKLTVDVQFLKNGQIAFtgtTFIGYVGLWTGQS----PHKFTVSGDERDKGWWWEN 204
Cdd:NF040521  93 FAVLGEDGEPILARNYDWHPE--LYDGCLLLTIRPDGGPRY---ASIGYAGLLPGRTdgmnEAGLAVTLNFLDGRKLPGV 167
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 530377543 205 AiaalfrrhIPVSWLIRATLSESENFEAAVGKLAKTPLIADVYYIVGG---------TSPREGVVITRNRD 266
Cdd:NF040521 168 G--------VPVHLLARAILENCKTVDEAIALLKEIPRASSFNLTLADasgraasveASPDRVVVVRPEDG 230
CBAH pfam02275
Linear amide C-N hydrolases, choloylglycine hydrolase family; This family includes several ...
126-316 7.46e-09

Linear amide C-N hydrolases, choloylglycine hydrolase family; This family includes several hydrolases which cleave carbon-nitrogen bonds, other than peptide bonds, in linear amides. These include choloylglycine hydrolase (conjugated bile acid hydrolase, CBAH) EC:3.5.1.24, penicillin acylase EC:3.5.1.11 and acid ceramidase EC:3.5.1.23. This domain forms the alpha-subunit for members from vertebral species, see family NAAA-beta, pfam15508.


Pssm-ID: 396726  Cd Length: 316  Bit Score: 55.98  E-value: 7.46e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377543  126 CTSIVAQDSRGHIYHGRNLDYPFGN----VLRKLTVDVQFLKNGQIAFTGTTFIGyVGLWTGQSPhKFTVSGDERDKGww 201
Cdd:pfam02275   1 CTSITLETKKGNLLFGRNMDFGISYgeevIITPRNYKLVFEKLGNMLVTKYAVIG-MGTDVGSYP-LFYDGLNEKGLG-- 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377543  202 wenaIAALF--------------RRHIPVSWLIRATLSESENFEAAVGKLAKTPLIADVYYIVGGTSPR---------EG 258
Cdd:pfam02275  77 ----IAGLYfpgyafyskgpkkdKVNIQPGELILWVLGNFTSVEEVKELLTKLNIVNEALDILGGKAPLhwiisdasgES 152
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 530377543  259 VVItRNRDGPADIWPLDPL----NGAWFRVETNYDHWK-------PAPKEDDRRTSAIKalNATGQANL 316
Cdd:pfam02275 153 IVI-EPRKEGLKVYDNEVGvmtnSPTFDWHLTNLNNYTglrpnqpQNFFMGDLDLTPFG--QGTGGLGL 218
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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