NPC2_PIG
ID NPC2_PIG Reviewed; 149 AA.
AC O97763;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=NPC intracellular cholesterol transporter 2 {ECO:0000250|UniProtKB:P61916};
DE AltName: Full=16 kDa secretory protein {ECO:0000303|PubMed:10366780};
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};
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 20-39, TISSUE SPECIFICITY,
RP SUBCELLULAR LOCATION, GLYCOSYLATION, AND FUNCTION.
RC TISSUE=Epididymis;
RX PubMed=10366780; DOI=10.1016/s1388-1981(99)00070-0;
RA Okamura N., Kiuchi S., Tamba M., Kashima T., Hiramoto S., Baba T.,
RA Dacheux F., Dacheux J.-L., Sugita Y., Jin Y.-Z.;
RT "A porcine homolog of the major secretory protein of human epididymis, HE1,
RT specifically binds cholesterol.";
RL Biochim. Biophys. Acta 1438:377-387(1999).
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 (By similarity). NPC2 binds cholesterol with a 1:1
CC stoichiometry (PubMed:10366780). Can bind a variety of sterols,
CC including lathosterol, desmosterol and the plant sterols stigmasterol
CC and beta-sitosterol (By similarity). The secreted form of NCP2
CC regulates biliary cholesterol secretion via stimulation of ABCG5/ABCG8-
CC mediated cholesterol transport (By similarity).
CC {ECO:0000250|UniProtKB:P61916, ECO:0000250|UniProtKB:Q9Z0J0,
CC ECO:0000269|PubMed:10366780}.
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:0000269|PubMed:10366780}.
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: Found in the fluid from the distal caput to cauda
CC epididymis, not detected in the rete testis and the proximal and middle
CC caput epididymal fluids (at protein level).
CC {ECO:0000269|PubMed:10366780}.
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 -!- PTM: N-glycosylated. Found in the epididymal fluid as a 19 kDa
CC glycoprotein that is processed during its passage through the
CC epididymis into a 16 kDa protein. {ECO:0000269|PubMed:10366780}.
CC -!- SIMILARITY: Belongs to the NPC2 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U62253; AAD00096.1; -; mRNA.
DR RefSeq; NP_999371.1; NM_214206.1.
DR AlphaFoldDB; O97763; -.
DR SMR; O97763; -.
DR STRING; 9823.ENSSSCP00000002564; -.
DR PaxDb; O97763; -.
DR PeptideAtlas; O97763; -.
DR PRIDE; O97763; -.
DR Ensembl; ENSSSCT00000002630; ENSSSCP00000002564; ENSSSCG00000002366.
DR Ensembl; ENSSSCT00005064187; ENSSSCP00005039655; ENSSSCG00005040002.
DR Ensembl; ENSSSCT00015107137; ENSSSCP00015045201; ENSSSCG00015079034.
DR Ensembl; ENSSSCT00025015410; ENSSSCP00025006069; ENSSSCG00025011176.
DR Ensembl; ENSSSCT00030043905; ENSSSCP00030019816; ENSSSCG00030031683.
DR Ensembl; ENSSSCT00035014997; ENSSSCP00035005118; ENSSSCG00035011913.
DR Ensembl; ENSSSCT00040079466; ENSSSCP00040034313; ENSSSCG00040057371.
DR Ensembl; ENSSSCT00045058199; ENSSSCP00045040685; ENSSSCG00045034006.
DR Ensembl; ENSSSCT00050094206; ENSSSCP00050040623; ENSSSCG00050069000.
DR Ensembl; ENSSSCT00055001194; ENSSSCP00055000871; ENSSSCG00055000690.
DR Ensembl; ENSSSCT00060009877; ENSSSCP00060003610; ENSSSCG00060007744.
DR Ensembl; ENSSSCT00065033318; ENSSSCP00065013770; ENSSSCG00065024849.
DR Ensembl; ENSSSCT00070018316; ENSSSCP00070015212; ENSSSCG00070009444.
DR GeneID; 397410; -.
DR KEGG; ssc:397410; -.
DR CTD; 10577; -.
DR VGNC; VGNC:90843; NPC2.
DR eggNOG; KOG4063; Eukaryota.
DR GeneTree; ENSGT00390000006223; -.
DR HOGENOM; CLU_109192_1_0_1; -.
DR InParanoid; O97763; -.
DR OMA; NLFCWEI; -.
DR OrthoDB; 1612792at2759; -.
DR TreeFam; TF317963; -.
DR Reactome; R-SSC-6798695; Neutrophil degranulation.
DR Reactome; R-SSC-8964038; LDL clearance.
DR Proteomes; UP000008227; Chromosome 7.
DR Proteomes; UP000314985; Chromosome 7.
DR Bgee; ENSSSCG00000002366; Expressed in epididymis and 44 other tissues.
DR ExpressionAtlas; O97763; baseline and differential.
DR Genevisible; O97763; SS.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0015485; F:cholesterol binding; IDA:UniProtKB.
DR GO; GO:0032934; F:sterol binding; IBA:GO_Central.
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 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 1: Evidence at protein level;
KW Acetylation; Cholesterol metabolism; Direct protein sequencing;
KW Disulfide bond; Endoplasmic reticulum; Glycoprotein; Lipid metabolism;
KW Lipid transport; Lysosome; Reference proteome; Secreted; Signal;
KW Steroid metabolism; Sterol metabolism; Transport.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:10366780"
FT CHAIN 20..149
FT /note="NPC intracellular cholesterol transporter 2"
FT /id="PRO_0000019858"
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 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; 16288 MW; 78F0920057CA0102 CRC64;
MHFLAAAFLL LTLSASALAE PVHFRDCGSG VGVIKEVNVN PCPTQPCQLH KGQSYSVNVT
FTSNTQSKGS KAVVHGIVMG VPIPFPIPDP DGCKSGINCP IQKDQTYSYL NKLPVKAEYP
SIKLVVEWKL QDDNDQCLFC WQIPVQIES
