NPC2_PANTR
ID NPC2_PANTR Reviewed; 151 AA.
AC P61917; Q15668; Q29413;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2004, sequence version 1.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=NPC intracellular cholesterol transporter 2 {ECO:0000250|UniProtKB:P61916};
DE AltName: Full=EPI-1 {ECO:0000303|PubMed:8924506};
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 Pan troglodytes (Chimpanzee).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pan.
OX NCBI_TaxID=9598;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 20-38, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND GLYCOSYLATION.
RC TISSUE=Epididymis;
RX PubMed=8924506; DOI=10.1095/biolreprod54.4.857;
RA Froehlich O., Young L.G.;
RT "Molecular cloning and characterization of EPI-1, the major protein in
RT chimpanzee (Pan troglodytes) cauda epididymal fluid.";
RL Biol. Reprod. 54:857-864(1996).
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:0000269|PubMed:8924506}.
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 cauda epididymal fluid and seminal
CC fluid (at protein level). Detected in distal half of caput
CC epididymidis. {ECO:0000269|PubMed:8924506}.
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; U25748; AAA67077.1; -; mRNA.
DR RefSeq; NP_001009075.1; NM_001009075.1.
DR RefSeq; XP_009426323.1; XM_009428048.2.
DR AlphaFoldDB; P61917; -.
DR SMR; P61917; -.
DR STRING; 9598.ENSPTRP00000011092; -.
DR PaxDb; P61917; -.
DR GeneID; 450192; -.
DR KEGG; ptr:450192; -.
DR CTD; 10577; -.
DR eggNOG; KOG4063; Eukaryota.
DR HOGENOM; CLU_109192_1_0_1; -.
DR InParanoid; P61917; -.
DR OrthoDB; 1612792at2759; -.
DR TreeFam; TF317963; -.
DR Proteomes; UP000002277; Unplaced.
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; ISS: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:8924506"
FT CHAIN 20..151
FT /note="NPC intracellular cholesterol transporter 2"
FT /id="PRO_0000019857"
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
