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Protein

N-acylethanolamine-hydrolyzing acid amidase

Gene

NAAA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Activity 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

    Keywordsi

    Molecular functionHydrolase

    Enzyme and pathway databases

    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

    EuPathDBiHostDB:ENSG00000138744.14
    HGNCiHGNC:736 NAAA
    MIMi607469 gene
    neXtProtiNX_Q02083

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    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...) asparagine2 Publications1
    Glycosylationi107N-linked (GlcNAc...) asparagine1 Publication1
    Glycosylationi309N-linked (GlcNAc...) asparagine1 Publication1
    Glycosylationi333N-linked (GlcNAc...) asparagine1 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
    ProteomicsDBi58044
    58045 [Q02083-2]
    58046 [Q02083-3]

    PTM databases

    iPTMnetiQ02083

    Expressioni

    Tissue specificityi

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

    Gene expression databases

    BgeeiENSG00000138744 Expressed in 218 organ(s), highest expression level in leukocyte
    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

    Protein-protein interaction databases

    BioGridi118042, 59 interactors
    STRINGi9606.ENSP00000286733

    Chemistry databases

    BindingDBiQ02083

    Structurei

    3D structure databases

    ProteinModelPortaliQ02083
    SMRiQ02083
    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
    OMAiYESTAFC
    OrthoDBiEOG091G0E3H
    PhylomeDBiQ02083
    TreeFamiTF313219

    Family and domain databases

    InterProiView protein in InterPro
    IPR016699 Acid_ceramidase-like
    IPR029130 Acid_ceramidase_N
    IPR029132 CBAH/NAAA_C
    PfamiView protein in Pfam
    PF02275 CBAH, 1 hit
    PF15508 NAAA-beta, 1 hit
    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

    This entry has 3 described isoforms and 4 potential isoforms that are computationally mapped.iShow all

    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

    Computationally mapped potential isoform sequencesi

    There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    D6R9S9D6R9S9_HUMAN
    N-acylethanolamine-hydrolyzing acid...
    NAAA
    167Annotation score:
    B4DVL2B4DVL2_HUMAN
    N-acylethanolamine-hydrolyzing acid...
    NAAA
    252Annotation score:
    R4GNC0R4GNC0_HUMAN
    N-acylethanolamine-hydrolyzing acid...
    NAAA
    222Annotation score:
    H0Y988H0Y988_HUMAN
    N-acylethanolamine-hydrolyzing acid...
    NAAA
    139Annotation score:

    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 dbSNP:rs34751328Ensembl.1
    Natural variantiVAR_028428151V → I. Corresponds to variant dbSNP:rs4859571Ensembl.1
    Natural variantiVAR_048337334F → L. Corresponds to variant dbSNP:rs6823734Ensembl.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]
    CCDS87233.1 [Q02083-2]
    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

    Similar proteinsi

    Entry informationi

    Entry nameiNAAA_HUMAN
    AccessioniPrimary (citable) accession number: Q02083
    Secondary accession number(s): Q5KTF2, Q96EY2, Q9BRA8
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: October 17, 2006
    Last modified: September 12, 2018
    This is version 156 of the entry and version 3 of the sequence. See 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
    UniProt is an ELIXIR core data resource
    Main funding by: National Institutes of Health

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