NPC2_DANRE
ID NPC2_DANRE Reviewed; 149 AA.
AC Q9DGJ3;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=NPC intracellular cholesterol transporter 2 {ECO:0000250|UniProtKB:P61916};
DE AltName: Full=16.5 kDa secretory protein;
DE AltName: Full=Epididymal secretory protein E1;
DE AltName: Full=Niemann Pick type C2 protein homolog;
DE Flags: Precursor;
GN Name=npc2;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Tanguay R.L.;
RT "Danio rerio 16.5 kDa secretory protein.";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Intracellular cholesterol transporter which acts in concert
CC with NPC1 and plays an important role in the egress of cholesterol from
CC the lysosomal compartment. Unesterified cholesterol that has been
CC released from LDLs in the lumen of the late endosomes/lysosomes is
CC transferred by NPC2 to the cholesterol-binding pocket in the N-terminal
CC domain of NPC1. May bind and mobilize cholesterol that is associated
CC with membranes. NPC2 binds cholesterol with a 1:1 stoichiometry. Can
CC bind a variety of sterols, including lathosterol, desmosterol and the
CC plant sterols stigmasterol and beta-sitosterol.
CC {ECO:0000250|UniProtKB:P61916}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholesterol(in) = cholesterol(out); Xref=Rhea:RHEA:39747,
CC ChEBI:CHEBI:16113; Evidence={ECO:0000250|UniProtKB:P79345};
CC -!- SUBUNIT: Interacts with NPC1 (via the second lumenal domain) in a
CC cholestrol-dependent manner. {ECO:0000250|UniProtKB:P61916}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P61916}.
CC Endoplasmic reticulum {ECO:0000250|UniProtKB:P61916}. Lysosome
CC {ECO:0000250|UniProtKB:P61916}. Note=Interaction with cell-surface M6PR
CC mediates endocytosis and targeting to lysosomes.
CC {ECO:0000250|UniProtKB:P61916}.
CC -!- DOMAIN: Binds cholesterol in a hydrophobic pocket; there are no
CC hydrogen bonds between the sterol and the protein.
CC {ECO:0000250|UniProtKB:P79345}.
CC -!- SIMILARITY: Belongs to the NPC2 family. {ECO:0000305}.
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DR EMBL; AF291663; AAF99719.1; -; mRNA.
DR EMBL; BC045895; AAH45895.1; -; mRNA.
DR RefSeq; NP_775331.1; NM_173224.1.
DR AlphaFoldDB; Q9DGJ3; -.
DR SMR; Q9DGJ3; -.
DR STRING; 7955.ENSDARP00000050398; -.
DR PaxDb; Q9DGJ3; -.
DR Ensembl; ENSDART00000050399; ENSDARP00000050398; ENSDARG00000090912.
DR Ensembl; ENSDART00000132754; ENSDARP00000113663; ENSDARG00000090912.
DR GeneID; 282673; -.
DR KEGG; dre:282673; -.
DR CTD; 282673; -.
DR ZFIN; ZDB-GENE-021206-13; npc2.1.
DR eggNOG; KOG4063; Eukaryota.
DR GeneTree; ENSGT00390000006223; -.
DR HOGENOM; CLU_109192_1_0_1; -.
DR InParanoid; Q9DGJ3; -.
DR OMA; PNADACQ; -.
DR OrthoDB; 1612792at2759; -.
DR PhylomeDB; Q9DGJ3; -.
DR TreeFam; TF317963; -.
DR Reactome; R-DRE-6798695; Neutrophil degranulation.
DR Reactome; R-DRE-8964038; LDL clearance.
DR PRO; PR:Q9DGJ3; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 17.
DR Bgee; ENSDARG00000090912; Expressed in early embryo and 28 other tissues.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0015485; F:cholesterol binding; IBA:GO_Central.
DR GO; GO:0032934; F:sterol binding; IBA:GO_Central.
DR GO; GO:0033344; P:cholesterol efflux; IBA:GO_Central.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0032367; P:intracellular cholesterol transport; IBA:GO_Central.
DR GO; GO:0015918; P:sterol transport; IBA:GO_Central.
DR CDD; cd00916; Npc2_like; 1.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR003172; ML_dom.
DR InterPro; IPR033916; ML_Npc2-like.
DR InterPro; IPR039670; NPC2-like.
DR PANTHER; PTHR11306; PTHR11306; 1.
DR Pfam; PF02221; E1_DerP2_DerF2; 1.
DR SMART; SM00737; ML; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
PE 2: Evidence at transcript level;
KW Cholesterol metabolism; Disulfide bond; Endoplasmic reticulum;
KW Glycoprotein; Lipid metabolism; Lipid transport; Lysosome;
KW Reference proteome; Secreted; Signal; Steroid metabolism;
KW Sterol metabolism; Transport.
FT SIGNAL 1..19
FT /evidence="ECO:0000250"
FT CHAIN 20..149
FT /note="NPC intracellular cholesterol transporter 2"
FT /id="PRO_0000019859"
FT CARBOHYD 58
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 27..140
FT /evidence="ECO:0000250|UniProtKB:P61916"
FT DISULFID 42..47
FT /evidence="ECO:0000250|UniProtKB:P61916"
FT DISULFID 93..99
FT /evidence="ECO:0000250|UniProtKB:P61916"
SQ SEQUENCE 149 AA; 16306 MW; 53B47D72537C4060 CRC64;
MDYRVLGVVL LSFLAYTCAD PVKFVDCGSV DGKVVQVDIK PCSQQPCKLH KGQSYTVNVT
FSSGVESQTS KAVVHGVLAG VPVPFPIPID DGCKSGIQCP IVPQKPYNYV TELPVKTEYP
AIKVVVEWEL RDDSSKDLFC IKFPVQIVN
