Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

N-acylethanolamine-hydrolyzing acid amidase

Gene

NAAA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Degrades bioactive fatty acid amides to their corresponding acids, with the following preference: N-palmitoylethanolamine > N-myristoylethanolamine > N-lauroylethanolamine = N-stearoylethanolamine > N-arachidonoylethanolamine > N-oleoylethanolamine. Also exhibits weak hydrolytic activity against the ceramides N-lauroylsphingosine and N-palmitoylsphingosine.1 Publication

Enzyme regulationi

Stimulated by DTT and Nonidet P-40.1 Publication

Kineticsi

  1. KM=97 µM for N-palmitoylethanolamine1 Publication

    pH dependencei

    Optimum pH is 4.5 with N-palmitoylethanolamine as substrate.1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei126Nucleophile1 Publication1

    GO - Molecular functioni

    • hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds Source: MGI
    • transcription factor binding Source: UniProtKB

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase

    Enzyme and pathway databases

    BioCyciZFISH:ENSG00000138744-MONOMER.
    BRENDAi3.5.1.4. 2681.
    ReactomeiR-HSA-112310. Neurotransmitter Release Cycle.

    Protein family/group databases

    MEROPSiC89.002.

    Chemistry databases

    SwissLipidsiSLP:000001125.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    N-acylethanolamine-hydrolyzing acid amidase (EC:3.5.1.-)
    Alternative name(s):
    Acid ceramidase-like protein
    N-acylsphingosine amidohydrolase-like
    Short name:
    ASAH-like protein
    Cleaved into the following 2 chains:
    Gene namesi
    Name:NAAA
    Synonyms:ASAHL, PLT
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 4

    Organism-specific databases

    HGNCiHGNC:736. NAAA.

    Subcellular locationi

    GO - Cellular componenti

    • cytoplasm Source: MGI
    • extracellular exosome Source: UniProtKB
    • lysosomal lumen Source: Reactome
    • presynapse Source: GOC
    Complete GO annotation...

    Keywords - Cellular componenti

    Lysosome

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi27163.
    OpenTargetsiENSG00000138744.
    PharmGKBiPA162396672.

    Chemistry databases

    ChEMBLiCHEMBL4349.
    GuidetoPHARMACOLOGYi1402.

    Polymorphism and mutation databases

    BioMutaiNAAA.
    DMDMi116241258.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Signal peptidei1 – 281 PublicationAdd BLAST28
    ChainiPRO_000000231829 – 359N-acylethanolamine-hydrolyzing acid amidaseAdd BLAST331
    ChainiPRO_000041965029 – 125N-acylethanolamine-hydrolyzing acid amidase subunit alphaAdd BLAST97
    ChainiPRO_0000419651126 – 349N-acylethanolamine-hydrolyzing acid amidase subunit betaAdd BLAST224

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Glycosylationi37N-linked (GlcNAc...)2 Publications1
    Glycosylationi107N-linked (GlcNAc...)1 Publication1
    Glycosylationi309N-linked (GlcNAc...)1 Publication1
    Glycosylationi333N-linked (GlcNAc...)1 Publication1

    Post-translational modificationi

    N-glycosylated. Tunicamycin treatment causes a reduction in specific activity against N-palmitoylethanolamine.3 Publications
    Autoproteolytic cleavage in the acidic lumen of the lysosome activates the enzyme.1 Publication

    Keywords - PTMi

    Autocatalytic cleavage, Glycoprotein, Zymogen

    Proteomic databases

    EPDiQ02083.
    MaxQBiQ02083.
    PaxDbiQ02083.
    PeptideAtlasiQ02083.
    PRIDEiQ02083.

    Expressioni

    Tissue specificityi

    Expressed in numerous tissues, with highest levels in liver and kidney, followed by pancreas.1 Publication

    Gene expression databases

    BgeeiENSG00000138744.
    CleanExiHS_NAAA.
    ExpressionAtlasiQ02083. baseline and differential.
    GenevisibleiQ02083. HS.

    Organism-specific databases

    HPAiCAB026135.

    Interactioni

    Subunit structurei

    Heterodimer of an alpha and a beta subunit, non-covalently linked.1 Publication

    GO - Molecular functioni

    • transcription factor binding Source: UniProtKB

    Protein-protein interaction databases

    BioGridi118042. 54 interactors.
    STRINGi9606.ENSP00000286733.

    Chemistry databases

    BindingDBiQ02083.

    Structurei

    3D structure databases

    ProteinModelPortaliQ02083.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the acid ceramidase family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiENOG410IJHJ. Eukaryota.
    ENOG4111HJY. LUCA.
    GeneTreeiENSGT00530000063548.
    HOGENOMiHOG000007253.
    HOVERGENiHBG050586.
    InParanoidiQ02083.
    KOiK13720.
    OMAiRFLPQPF.
    OrthoDBiEOG091G0E3H.
    PhylomeDBiQ02083.
    TreeFamiTF313219.

    Family and domain databases

    InterProiIPR016699. Acid_ceramidase-like.
    IPR029130. Acid_ceramidase_N.
    IPR029132. CBAH/NAAA_C.
    [Graphical view]
    PfamiPF02275. CBAH. 1 hit.
    PF15508. NAAA-beta. 1 hit.
    [Graphical view]
    PIRSFiPIRSF017632. Acid_ceramidase-like. 1 hit.

    Sequences (3)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q02083-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MRTADREARP GLPSLLLLLL AGAGLSAASP PAAPRFNVSL DSVPELRWLP
    60 70 80 90 100
    VLRHYDLDLV RAAMAQVIGD RVPKWVHVLI GKVVLELERF LPQPFTGEIR
    110 120 130 140 150
    GMCDFMNLSL ADCLLVNLAY ESSVFCTSIV AQDSRGHIYH GRNLDYPFGN
    160 170 180 190 200
    VLRKLTVDVQ FLKNGQIAFT GTTFIGYVGL WTGQSPHKFT VSGDERDKGW
    210 220 230 240 250
    WWENAIAALF RRHIPVSWLI RATLSESENF EAAVGKLAKT PLIADVYYIV
    260 270 280 290 300
    GGTSPREGVV ITRNRDGPAD IWPLDPLNGA WFRVETNYDH WKPAPKEDDR
    310 320 330 340 350
    RTSAIKALNA TGQANLSLEA LFQILSVVPV YNNFTIYTTV MSAGSPDKYM

    TRIRNPSRK
    Length:359
    Mass (Da):40,066
    Last modified:October 17, 2006 - v3
    Checksum:iA8E214DB383B872A
    GO
    Isoform 2 (identifier: Q02083-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         324-359: Missing.

    Show »
    Length:323
    Mass (Da):35,963
    Checksum:i453B1D0E4B99AA90
    GO
    Isoform 3 (identifier: Q02083-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         198-199: KG → PE
         200-359: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:199
    Mass (Da):22,020
    Checksum:iC35E612CFC738971
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti147P → A in AAA60119 (PubMed:1446826).Curated1
    Sequence conflicti240T → S in AAA60119 (PubMed:1446826).Curated1
    Sequence conflicti250V → L in AAA60119 (PubMed:1446826).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_048336107N → K.Corresponds to variant rs34751328dbSNPEnsembl.1
    Natural variantiVAR_028428151V → I.Corresponds to variant rs4859571dbSNPEnsembl.1
    Natural variantiVAR_048337334F → L.Corresponds to variant rs6823734dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_000328198 – 199KG → PE in isoform 3. 1 Publication2
    Alternative sequenceiVSP_000329200 – 359Missing in isoform 3. 1 PublicationAdd BLAST160
    Alternative sequenceiVSP_000330324 – 359Missing in isoform 2. 1 PublicationAdd BLAST36

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB161353 mRNA. Translation: BAD88528.1.
    BC006388 mRNA. Translation: AAH06388.2.
    BC011854 mRNA. No translation available.
    M92449 mRNA. Translation: AAA60119.1.
    CCDSiCCDS43239.1. [Q02083-1]
    RefSeqiNP_001035861.1. NM_001042402.1. [Q02083-2]
    NP_055250.2. NM_014435.3. [Q02083-1]
    XP_005262977.1. XM_005262920.3. [Q02083-1]
    XP_005262982.1. XM_005262925.3. [Q02083-2]
    XP_016863517.1. XM_017008028.1. [Q02083-1]
    UniGeneiHs.437365.

    Genome annotation databases

    EnsembliENST00000286733; ENSP00000286733; ENSG00000138744. [Q02083-1]
    ENST00000507956; ENSP00000427641; ENSG00000138744. [Q02083-2]
    GeneIDi27163.
    KEGGihsa:27163.
    UCSCiuc003hjb.4. human. [Q02083-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB161353 mRNA. Translation: BAD88528.1.
    BC006388 mRNA. Translation: AAH06388.2.
    BC011854 mRNA. No translation available.
    M92449 mRNA. Translation: AAA60119.1.
    CCDSiCCDS43239.1. [Q02083-1]
    RefSeqiNP_001035861.1. NM_001042402.1. [Q02083-2]
    NP_055250.2. NM_014435.3. [Q02083-1]
    XP_005262977.1. XM_005262920.3. [Q02083-1]
    XP_005262982.1. XM_005262925.3. [Q02083-2]
    XP_016863517.1. XM_017008028.1. [Q02083-1]
    UniGeneiHs.437365.

    3D structure databases

    ProteinModelPortaliQ02083.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi118042. 54 interactors.
    STRINGi9606.ENSP00000286733.

    Chemistry databases

    BindingDBiQ02083.
    ChEMBLiCHEMBL4349.
    GuidetoPHARMACOLOGYi1402.
    SwissLipidsiSLP:000001125.

    Protein family/group databases

    MEROPSiC89.002.

    Polymorphism and mutation databases

    BioMutaiNAAA.
    DMDMi116241258.

    Proteomic databases

    EPDiQ02083.
    MaxQBiQ02083.
    PaxDbiQ02083.
    PeptideAtlasiQ02083.
    PRIDEiQ02083.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000286733; ENSP00000286733; ENSG00000138744. [Q02083-1]
    ENST00000507956; ENSP00000427641; ENSG00000138744. [Q02083-2]
    GeneIDi27163.
    KEGGihsa:27163.
    UCSCiuc003hjb.4. human. [Q02083-1]

    Organism-specific databases

    CTDi27163.
    DisGeNETi27163.
    GeneCardsiNAAA.
    HGNCiHGNC:736. NAAA.
    HPAiCAB026135.
    MIMi607469. gene.
    neXtProtiNX_Q02083.
    OpenTargetsiENSG00000138744.
    PharmGKBiPA162396672.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiENOG410IJHJ. Eukaryota.
    ENOG4111HJY. LUCA.
    GeneTreeiENSGT00530000063548.
    HOGENOMiHOG000007253.
    HOVERGENiHBG050586.
    InParanoidiQ02083.
    KOiK13720.
    OMAiRFLPQPF.
    OrthoDBiEOG091G0E3H.
    PhylomeDBiQ02083.
    TreeFamiTF313219.

    Enzyme and pathway databases

    BioCyciZFISH:ENSG00000138744-MONOMER.
    BRENDAi3.5.1.4. 2681.
    ReactomeiR-HSA-112310. Neurotransmitter Release Cycle.

    Miscellaneous databases

    ChiTaRSiNAAA. human.
    GeneWikiiASAHL.
    GenomeRNAii27163.
    PROiQ02083.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000138744.
    CleanExiHS_NAAA.
    ExpressionAtlasiQ02083. baseline and differential.
    GenevisibleiQ02083. HS.

    Family and domain databases

    InterProiIPR016699. Acid_ceramidase-like.
    IPR029130. Acid_ceramidase_N.
    IPR029132. CBAH/NAAA_C.
    [Graphical view]
    PfamiPF02275. CBAH. 1 hit.
    PF15508. NAAA-beta. 1 hit.
    [Graphical view]
    PIRSFiPIRSF017632. Acid_ceramidase-like. 1 hit.
    ProtoNetiSearch...

    Entry informationi

    Entry nameiNAAA_HUMAN
    AccessioniPrimary (citable) accession number: Q02083
    Secondary accession number(s): Q5KTF2, Q96EY2, Q9BRA8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: October 17, 2006
    Last modified: November 2, 2016
    This is version 146 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 4
      Human chromosome 4: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.