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Epididymal secretory protein E1 (16 kDa secretory protein) (Niemann Pick type C2 protein homolog)

 NPC2_PIG                Reviewed;         149 AA.
O97763;
20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
01-MAY-1999, sequence version 1.
23-MAY-2018, entry version 94.
RecName: Full=NPC intracellular cholesterol transporter 2 {ECO:0000250|UniProtKB:P61916};
AltName: Full=16 kDa secretory protein;
AltName: Full=Epididymal secretory protein E1;
AltName: Full=Niemann Pick type C2 protein homolog;
Flags: Precursor;
Name=NPC2 {ECO:0000250|UniProtKB:P61916};
Sus scrofa (Pig).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Laurasiatheria; Cetartiodactyla; Suina; Suidae;
Sus.
NCBI_TaxID=9823;
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 20-39.
TISSUE=Epididymis;
PubMed=10366780; DOI=10.1016/S1388-1981(99)00070-0;
Okamura N., Kiuchi S., Tamba M., Kashima T., Hiramoto S., Baba T.,
Dacheux F., Dacheux J.-L., Sugita Y., Jin Y.-Z.;
"A porcine homolog of the major secretory protein of human epididymis,
HE1, specifically binds cholesterol.";
Biochim. Biophys. Acta 1438:377-387(1999).
-!- FUNCTION: Intracellular cholesterol transporter which acts in
concert with NPC1 and plays an important role in the egress of
cholesterol from the endosomal/lysosomal compartment. Both NPC1
and NPC2 function as the cellular 'tag team duo' (TTD) to catalyze
the mobilization of cholesterol within the multivesicular
environment of the late endosome (LE) to effect egress through the
limiting bilayer of the LE. NPC2 binds unesterified cholesterol
that has been released from LDLs in the lumen of the late
endosomes/lysosomes and transfers it to the cholesterol-binding
pocket of the N-terminal domain of NPC1. Cholesterol binds to NPC1
with the hydroxyl group buried in the binding pocket and is
exported from the limiting membrane of late endosomes/ lysosomes
to the ER and plasma membrane by an unknown mechanism. The
secreted form of NCP2 regulates biliary cholesterol secretion via
stimulation of ABCG5/ABCG8-mediated cholesterol transport (By
similarity). May be involved in the regulation of the lipid
composition of sperm membranes during the maturation in the
epididymis. Binds cholesterol in a 1:1 ratio. {ECO:0000250}.
-!- SUBUNIT: Interacts with NUS1/NgBR, the interaction stabilizes NCP2
and regulates cholesterol trafficking. Interacts with DHDDS (By
similarity). Interacts with NEDD4L (via C2 domain) (By
similarity). Interacts with NPC1L1 (By similarity). Interacts with
NPC1 (via the second lumenal domain) in a cholestrol-dependent
manner (By similarity). {ECO:0000250}.
-!- SUBCELLULAR LOCATION: Secreted. Endoplasmic reticulum
{ECO:0000250}. Lysosome {ECO:0000250}.
-!- TISSUE SPECIFICITY: Found in the fluid from the distal caput to
cauda epididymis, not detected in the rete testis and the proximal
and middle caput epididymal fluids.
-!- PTM: N-glycosylated. Found in the epididymal fluid as a 19 kDa
glycoprotein that is processed during its passage through the
epididymis into a 16 kDa protein.
-!- SIMILARITY: Belongs to the NPC2 family. {ECO:0000305}.
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EMBL; U62253; AAD00096.1; -; mRNA.
RefSeq; NP_999371.1; NM_214206.1.
UniGene; Ssc.16778; -.
ProteinModelPortal; O97763; -.
SMR; O97763; -.
STRING; 9823.ENSSSCP00000002564; -.
PaxDb; O97763; -.
PeptideAtlas; O97763; -.
PRIDE; O97763; -.
Ensembl; ENSSSCT00000002630; ENSSSCP00000002564; ENSSSCG00000002366.
GeneID; 397410; -.
KEGG; ssc:397410; -.
CTD; 10577; -.
eggNOG; KOG4063; Eukaryota.
eggNOG; ENOG4111Q8S; LUCA.
GeneTree; ENSGT00390000006223; -.
HOGENOM; HOG000007181; -.
HOVERGEN; HBG018181; -.
InParanoid; O97763; -.
KO; K13443; -.
OMA; CKSGISC; -.
OrthoDB; EOG091G0W4T; -.
TreeFam; TF317963; -.
Reactome; R-SSC-6798695; Neutrophil degranulation.
Reactome; R-SSC-8964038; LDL clearance.
Proteomes; UP000008227; Chromosome 7.
Bgee; ENSSSCG00000002366; -.
Genevisible; O97763; SS.
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:0017127; F:cholesterol transporter activity; IEA:Ensembl.
GO; GO:0019899; F:enzyme binding; IEA:Ensembl.
GO; GO:0033344; P:cholesterol efflux; ISS:UniProtKB.
GO; GO:0042632; P:cholesterol homeostasis; IEA:Ensembl.
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.
GO; GO:0009615; P:response to virus; IEA:Ensembl.
CDD; cd00916; Npc2_like; 1.
InterPro; IPR014756; Ig_E-set.
InterPro; IPR003172; ML_dom.
InterPro; IPR033916; ML_Npc2-like.
Pfam; PF02221; E1_DerP2_DerF2; 1.
SMART; SM00737; ML; 1.
SUPFAM; SSF81296; SSF81296; 1.
1: Evidence at protein level;
Acetylation; Cholesterol metabolism; Complete proteome;
Direct protein sequencing; Disulfide bond; Endoplasmic reticulum;
Glycoprotein; Lipid metabolism; Lysosome; Reference proteome;
Secreted; Signal; Steroid metabolism; Sterol metabolism.
SIGNAL 1 19 {ECO:0000269|PubMed:10366780}.
CHAIN 20 149 NPC intracellular cholesterol transporter
2.
/FTId=PRO_0000019858.
MOD_RES 116 116 N6-acetyllysine.
{ECO:0000250|UniProtKB:Q9Z0J0}.
CARBOHYD 58 58 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
DISULFID 27 140 {ECO:0000250}.
DISULFID 42 47 {ECO:0000250}.
DISULFID 93 99 {ECO:0000250}.
SEQUENCE 149 AA; 16288 MW; 78F0920057CA0102 CRC64;
MHFLAAAFLL LTLSASALAE PVHFRDCGSG VGVIKEVNVN PCPTQPCQLH KGQSYSVNVT
FTSNTQSKGS KAVVHGIVMG VPIPFPIPDP DGCKSGINCP IQKDQTYSYL NKLPVKAEYP
SIKLVVEWKL QDDNDQCLFC WQIPVQIES


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