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Epididymal secretory protein E1 (Epididymal secretory protein 14.6) (ESP14.6) (Niemann Pick type C2 protein homolog)

 NPC2_MACFA              Reviewed;         151 AA.
P61918; Q15668; Q29413; Q4R3F4;
07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
07-JUN-2004, sequence version 1.
16-JAN-2019, entry version 62.
RecName: Full=NPC intracellular cholesterol transporter 2 {ECO:0000250|UniProtKB:P61916};
AltName: Full=Epididymal secretory protein 14.6 {ECO:0000303|PubMed:7875608};
Short=ESP14.6 {ECO:0000303|PubMed:7875608};
AltName: Full=Epididymal secretory protein E1;
AltName: Full=Niemann Pick type C2 protein homolog;
Flags: Precursor;
Name=NPC2 {ECO:0000250|UniProtKB:P61916}; ORFNames=QtsA-17309;
Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Cercopithecidae; Cercopithecinae; Macaca.
PubMed=7875608; DOI=10.1016/0378-1119(94)00739-F;
Perry A.C.F., Jones R., Hall L.;
"The monkey ESP14.6 mRNA, a novel transcript expressed at high levels
in the epididymis.";
Gene 153:291-292(1995).
International consortium for macaque cDNA sequencing and analysis;
"DNA sequences of macaque genes expressed in brain or testis and its
evolutionary implications.";
Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
-!- FUNCTION: Intracellular cholesterol transporter which acts in
concert with NPC1 and plays an important role in the egress of
cholesterol from the lysosomal compartment. Unesterified
cholesterol that has been released from LDLs in the lumen of the
late endosomes/lysosomes is transferred by NPC2 to the
cholesterol-binding pocket in the N-terminal domain of NPC1. May
bind and mobilize cholesterol that is associated with membranes.
NPC2 binds cholesterol with a 1:1 stoichiometry. Can bind a
variety of sterols, including lathosterol, desmosterol and the
plant sterols stigmasterol and beta-sitosterol (By similarity).
The secreted form of NCP2 regulates biliary cholesterol secretion
via stimulation of ABCG5/ABCG8-mediated cholesterol transport (By
similarity). {ECO:0000250|UniProtKB:P61916,
-!- SUBUNIT: Interacts with NPC1 (via the second lumenal domain) in a
cholestrol-dependent manner. Interacts with NUS1/NgBR, the
interaction stabilizes NCP2 and regulates cholesterol trafficking.
Interacts with DHDDS. Interacts with NEDD4L (via C2 domain).
Interacts with NPC1L1. {ECO:0000250|UniProtKB:P61916}.
-!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P61916}.
Endoplasmic reticulum {ECO:0000250|UniProtKB:P61916}. Lysosome
{ECO:0000250|UniProtKB:P61916}. Note=Interaction with cell-surface
M6PR mediates endocytosis and targeting to lysosomes.
-!- TISSUE SPECIFICITY: Detected in epididymis.
-!- DOMAIN: Binds cholesterol in a hydrophobic pocket; there are no
hydrogen bonds between the sterol and the protein.
-!- SIMILARITY: Belongs to the NPC2 family. {ECO:0000305}.
Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
Distributed under the Creative Commons Attribution (CC BY 4.0) License
EMBL; X78134; CAA55013.1; -; mRNA.
EMBL; AB179312; BAE02363.1; -; mRNA.
PIR; I53929; I53929.
RefSeq; XP_005561827.1; XM_005561770.2.
UniGene; Mfa.6332; -.
ProteinModelPortal; P61918; -.
SMR; P61918; -.
Ensembl; ENSMFAT00000034352; ENSMFAP00000021665; ENSMFAG00000035734.
GeneID; 101865784; -.
KEGG; mcf:101865784; -.
CTD; 10577; -.
GeneTree; ENSGT00390000006223; -.
HOVERGEN; HBG018181; -.
KO; K13443; -.
OrthoDB; 1612792at2759; -.
GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
GO; GO:0015485; F:cholesterol binding; ISS:UniProtKB.
GO; GO:0033344; P:cholesterol efflux; ISS:UniProtKB.
GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
GO; GO:0030301; P:cholesterol transport; ISS:UniProtKB.
GO; GO:0032367; P:intracellular cholesterol transport; ISS:UniProtKB.
CDD; cd00916; Npc2_like; 1.
InterPro; IPR014756; Ig_E-set.
InterPro; IPR003172; ML_dom.
InterPro; IPR033916; ML_Npc2-like.
InterPro; IPR039670; NPC2-like.
PANTHER; PTHR11306; PTHR11306; 1.
Pfam; PF02221; E1_DerP2_DerF2; 1.
SMART; SM00737; ML; 1.
SUPFAM; SSF81296; SSF81296; 1.
2: Evidence at transcript level;
Acetylation; Cholesterol metabolism; Disulfide bond;
Endoplasmic reticulum; Glycoprotein; Lipid metabolism;
Lipid transport; Lysosome; Secreted; Signal; Steroid metabolism;
Sterol metabolism; Transport.
SIGNAL 1 19 {ECO:0000255}.
CHAIN 20 151 NPC intracellular cholesterol transporter
MOD_RES 116 116 N6-acetyllysine.
CARBOHYD 58 58 N-linked (GlcNAc...) asparagine.
CARBOHYD 135 135 N-linked (GlcNAc...) asparagine.
DISULFID 27 140 {ECO:0000250|UniProtKB:P61916}.
DISULFID 42 47 {ECO:0000250|UniProtKB:P61916}.
DISULFID 93 99 {ECO:0000250|UniProtKB:P61916}.
SEQUENCE 151 AA; 16570 MW; B141B611805DC910 CRC64;

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