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NPC2_MACFA
ID   NPC2_MACFA              Reviewed;         151 AA.
AC   P61918; Q15668; Q29413; Q4R3F4;
DT   07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT   07-JUN-2004, sequence version 1.
DT   03-AUG-2022, entry version 75.
DE   RecName: Full=NPC intracellular cholesterol transporter 2 {ECO:0000250|UniProtKB:P61916};
DE   AltName: Full=Epididymal secretory protein 14.6 {ECO:0000303|PubMed:7875608};
DE            Short=ESP14.6 {ECO:0000303|PubMed:7875608};
DE   AltName: Full=Epididymal secretory protein E1;
DE   AltName: Full=Niemann Pick type C2 protein homolog;
DE   Flags: Precursor;
GN   Name=NPC2 {ECO:0000250|UniProtKB:P61916}; ORFNames=QtsA-17309;
OS   Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC   Cercopithecidae; Cercopithecinae; Macaca.
OX   NCBI_TaxID=9541;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Epididymis;
RX   PubMed=7875608; DOI=10.1016/0378-1119(94)00739-f;
RA   Perry A.C.F., Jones R., Hall L.;
RT   "The monkey ESP14.6 mRNA, a novel transcript expressed at high levels in
RT   the epididymis.";
RL   Gene 153:291-292(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Testis;
RG   International consortium for macaque cDNA sequencing and analysis;
RT   "DNA sequences of macaque genes expressed in brain or testis and its
RT   evolutionary implications.";
RL   Submitted (JUN-2005) 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 (By similarity). The
CC       secreted form of NCP2 regulates biliary cholesterol secretion via
CC       stimulation of ABCG5/ABCG8-mediated cholesterol transport (By
CC       similarity). {ECO:0000250|UniProtKB:P61916,
CC       ECO:0000250|UniProtKB:Q9Z0J0}.
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. Interacts with NUS1/NgBR, the interaction
CC       stabilizes NCP2 and regulates cholesterol trafficking. Interacts with
CC       DHDDS. Interacts with NEDD4L (via C2 domain). Interacts with NPC1L1.
CC       {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   -!- TISSUE SPECIFICITY: Detected in epididymis.
CC       {ECO:0000269|PubMed:7875608}.
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; X78134; CAA55013.1; -; mRNA.
DR   EMBL; AB179312; BAE02363.1; -; mRNA.
DR   PIR; I53929; I53929.
DR   RefSeq; XP_005561827.1; XM_005561770.2.
DR   AlphaFoldDB; P61918; -.
DR   SMR; P61918; -.
DR   STRING; 9541.XP_005561826.1; -.
DR   Ensembl; ENSMFAT00000034352; ENSMFAP00000021665; ENSMFAG00000035734.
DR   GeneID; 101865784; -.
DR   KEGG; mcf:101865784; -.
DR   CTD; 10577; -.
DR   VEuPathDB; HostDB:ENSMFAG00000035734; -.
DR   eggNOG; KOG4063; Eukaryota.
DR   GeneTree; ENSGT00390000006223; -.
DR   OMA; NLFCWEI; -.
DR   OrthoDB; 1612792at2759; -.
DR   Proteomes; UP000233100; Chromosome 7.
DR   Bgee; ENSMFAG00000035734; Expressed in lung and 13 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; ISS:UniProtKB.
DR   GO; GO:0033344; P:cholesterol efflux; ISS:UniProtKB.
DR   GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0030301; P:cholesterol transport; ISS:UniProtKB.
DR   GO; GO:0032367; P:intracellular cholesterol transport; ISS:UniProtKB.
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   Acetylation; 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:0000255"
FT   CHAIN           20..151
FT                   /note="NPC intracellular cholesterol transporter 2"
FT                   /id="PRO_0000019855"
FT   MOD_RES         116
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Z0J0"
FT   CARBOHYD        58
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        135
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   151 AA;  16570 MW;  B141B611805DC910 CRC64;
     MRFLAATFLL LALSTAAQAE PVQFKDCGSV DGVIKEVNVS PCPTQPCQLS KGQSYSVNVT
     FTSNIQSKSS KAVVHGILMG VPVPFPIPEP DGCKSGINCP IQKDKTYSYL NKLPVKSEYP
     SIKLVVEWQL QDDKNQSLFC WEIPVQIVSH L
 
 
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