ID   NEUR1_PONAB             Reviewed;         415 AA.
AC   Q5RAF4; Q5RA14; Q5RF22;
DT   11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT   21-DEC-2004, sequence version 1.
DT   22-FEB-2023, entry version 88.
DE   RecName: Full=Sialidase-1;
DE            EC=3.2.1.18;
DE   AltName: Full=Acetylneuraminyl hydrolase;
DE   AltName: Full=Lysosomal sialidase;
DE   AltName: Full=N-acetyl-alpha-neuraminidase 1;
DE   Flags: Precursor;
GN   Name=NEU1;
OS   Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Brain cortex, Heart, and Kidney;
RG   The German cDNA consortium;
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Catalyzes the removal of sialic acid (N-acetylneuraminic
CC       acid) moieties from glycoproteins and glycolipids. To be active, it is
CC       strictly dependent on its presence in the multienzyme complex. Appears
CC       to have a preference for alpha 2-3 and alpha 2-6 sialyl linkage (By
CC       similarity). {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Hydrolysis of alpha-(2->3)-, alpha-(2->6)-, alpha-
CC         (2->8)- glycosidic linkages of terminal sialic acid residues in
CC         oligosaccharides, glycoproteins, glycolipids, colominic acid and
CC         synthetic substrates.; EC=3.2.1.18;
CC   -!- SUBUNIT: Interacts with cathepsin A (protective protein), beta-
CC       galactosidase and N-acetylgalactosamine-6-sulfate sulfatase in a
CC       multienzyme complex. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000250}; Peripheral
CC       membrane protein {ECO:0000250}; Lumenal side {ECO:0000250}. Lysosome
CC       lumen {ECO:0000250}. Cell membrane {ECO:0000250}. Cytoplasmic vesicle
CC       {ECO:0000250}. Note=Localized not only on the inner side of the
CC       lysosomal membrane and in the lysosomal lumen, but also on the plasma
CC       membrane and in intracellular vesicles. {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q5RAF4-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q5RAF4-2; Sequence=VSP_028119;
CC   -!- DOMAIN: A C-terminal internalization signal (YGTL) appears to allow the
CC       targeting of plasma membrane proteins to endosomes.
CC   -!- PTM: N-glycosylated. {ECO:0000250}.
CC   -!- PTM: Phosphorylation of tyrosine within the internalization signal
CC       results in inhibition of sialidase internalization and blockage on the
CC       plasma membrane. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the glycosyl hydrolase 33 family. {ECO:0000305}.
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DR   EMBL; CR857339; CAH89635.1; -; mRNA.
DR   EMBL; CR859063; CAH91256.1; -; mRNA.
DR   EMBL; CR859212; CAH91396.1; -; mRNA.
DR   RefSeq; NP_001125743.1; NM_001132271.1. [Q5RAF4-1]
DR   RefSeq; NP_001128939.1; NM_001135467.1.
DR   AlphaFoldDB; Q5RAF4; -.
DR   SMR; Q5RAF4; -.
DR   CAZy; GH33; Glycoside Hydrolase Family 33.
DR   GlyCosmos; Q5RAF4; 3 sites, No reported glycans.
DR   GeneID; 100172668; -.
DR   KEGG; pon:100172668; -.
DR   CTD; 4758; -.
DR   InParanoid; Q5RAF4; -.
DR   OrthoDB; 2900690at2759; -.
DR   Proteomes; UP000001595; Unplaced.
DR   GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR   GO; GO:0043202; C:lysosomal lumen; IEA:UniProtKB-SubCell.
DR   GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0052794; F:exo-alpha-(2->3)-sialidase activity; IEA:UniProtKB-EC.
DR   GO; GO:0052795; F:exo-alpha-(2->6)-sialidase activity; IEA:UniProtKB-EC.
DR   GO; GO:0052796; F:exo-alpha-(2->8)-sialidase activity; IEA:UniProtKB-EC.
DR   GO; GO:0004308; F:exo-alpha-sialidase activity; ISS:UniProtKB.
DR   GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0009313; P:oligosaccharide catabolic process; ISS:UniProtKB.
DR   CDD; cd15482; Sialidase_non-viral; 1.
DR   Gene3D; 2.120.10.10; -; 1.
DR   InterPro; IPR011040; Sialidase.
DR   InterPro; IPR026856; Sialidase_fam.
DR   InterPro; IPR036278; Sialidase_sf.
DR   PANTHER; PTHR10628; SIALIDASE; 1.
DR   PANTHER; PTHR10628:SF25; SIALIDASE-1; 1.
DR   Pfam; PF13088; BNR_2; 1.
DR   SUPFAM; SSF50939; Sialidases; 1.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Carbohydrate metabolism; Cell membrane;
KW   Cytoplasmic vesicle; Glycoprotein; Glycosidase; Hydrolase;
KW   Lipid degradation; Lipid metabolism; Lysosome; Membrane; Phosphoprotein;
KW   Reference proteome; Repeat; Signal.
FT   SIGNAL          1..47
FT                   /evidence="ECO:0000250"
FT   CHAIN           48..415
FT                   /note="Sialidase-1"
FT                   /id="PRO_0000304728"
FT   REPEAT          112..123
FT                   /note="BNR 1"
FT   REPEAT          172..183
FT                   /note="BNR 2"
FT   REPEAT          231..242
FT                   /note="BNR 3"
FT   REPEAT          347..358
FT                   /note="BNR 4"
FT   MOTIF           77..80
FT                   /note="FRIP motif"
FT   MOTIF           412..415
FT                   /note="Internalization signal"
FT   ACT_SITE        103
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        370
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        394
FT                   /evidence="ECO:0000255"
FT   BINDING         78
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         97
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         264
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         280
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         341
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        186
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        343
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        352
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         267..414
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.1"
FT                   /id="VSP_028119"
FT   CONFLICT        5
FT                   /note="R -> Q (in Ref. 1; CAH89635/CAH91396)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        12
FT                   /note="D -> G (in Ref. 1; CAH89635/CAH91396)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        29
FT                   /note="W -> R (in Ref. 1; CAH89635/CAH91396)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        57
FT                   /note="L -> P (in Ref. 1; CAH91396)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        256
FT                   /note="Q -> H (in Ref. 1; CAH89635/CAH91396)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        344
FT                   /note="L -> P (in Ref. 1; CAH89635)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        406
FT                   /note="V -> M (in Ref. 1; CAH89635)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   415 AA;  45467 MW;  360E60A256DEA07F CRC64;
     MTGERPSTAL PDRRWGPRIL GFWGGCRVWV FAAIFLLLSL AASWSKAEND FGLVQPLVTM
     EQLLWVSGRQ IGSVDTFRIP LITATPRGTL LAFAEARKMS SSDEGAKFIA LRRSMDQGST
     WSPTAFIVND GDVPDGLNLG AVVSDVETGV VFLFYSLCAH KAGCQVASTM LVWSKDDGVS
     WSTPRNLSLD IGTEVFAPGP GSGIQKQREP RKGRLIVCGH GTLERDGVFC LLSDDHGASW
     RYGSGVSGIP YGQPKQENDF NPDECQPYEL PDGSVVINAR NQNNYHCHCR IVLRSYDACD
     TLRPRDVTFD PELVDPVVAA GAVVTSSGIV FFSNPAHPEF RVNLTLRWSF SNGTSWRKET
     VQLWPGPSGY SSLATLEGSM DGEEQAPQLY VLYEKGRNHY TESISVAKIS VYGTL
//