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Protein

Epididymal secretory protein E1

Gene

NPC2

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Cholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism

Chemistry

SwissLipidsiSLP:000000474.

Names & Taxonomyi

Protein namesi
Recommended name:
Epididymal secretory protein E1
Alternative name(s):
EPV20
Niemann Pick type C2 protein homolog
Gene namesi
Name:NPC2
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 10

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Lysosome, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1919Add
BLAST
Chaini20 – 149130Epididymal secretory protein E1PRO_0000019852Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi27 ↔ 1401 Publication
Disulfide bondi42 ↔ 471 Publication
Glycosylationi58 – 581N-linked (GlcNAc...)Sequence analysis
Disulfide bondi93 ↔ 991 Publication
Modified residuei116 – 1161N6-acetyllysineBy similarity

Keywords - PTMi

Acetylation, Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP79345.
PRIDEiP79345.

Expressioni

Tissue specificityi

Expressed in kidney, spleen, liver and mammary gland, but not in testis.

Interactioni

Subunit structurei

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 similarity1 Publication

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000029271.

Structurei

Secondary structure

1
149
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi25 – 273Combined sources
Beta strandi31 – 4111Combined sources
Beta strandi43 – 508Combined sources
Beta strandi54 – 6512Combined sources
Beta strandi71 – 788Combined sources
Beta strandi81 – 844Combined sources
Helixi92 – 943Combined sources
Beta strandi99 – 1013Combined sources
Beta strandi106 – 1149Combined sources
Beta strandi121 – 13111Combined sources
Beta strandi137 – 14812Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1NEPX-ray1.70A20-149[»]
2HKAX-ray1.81A/B/C20-149[»]
ProteinModelPortaliP79345.
SMRiP79345. Positions 20-149.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP79345.

Family & Domainsi

Sequence similaritiesi

Belongs to the NPC2 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG4063. Eukaryota.
ENOG4111Q8S. LUCA.
GeneTreeiENSGT00390000006223.
HOGENOMiHOG000007181.
HOVERGENiHBG018181.
InParanoidiP79345.
KOiK13443.
OMAiLVVEWEL.
OrthoDBiEOG7SBNQN.
TreeFamiTF317963.

Family and domain databases

Gene3Di2.60.40.770. 1 hit.
InterProiIPR014756. Ig_E-set.
IPR003172. ML_dom.
[Graphical view]
PfamiPF02221. E1_DerP2_DerF2. 1 hit.
[Graphical view]
SMARTiSM00737. ML. 1 hit.
[Graphical view]
SUPFAMiSSF81296. SSF81296. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P79345-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRFLTVAFLF LALSASALAE PVKFKDCGSW VGVIKEVNVS PCPTQPCKLH
60 70 80 90 100
RGQSYSVNVT FTSNTQSQSS KAVVHGIVMG IPVPFPIPES DGCKSGIRCP
110 120 130 140
IEKDKTYNYV NKLPVKNEYP SIKVVVEWEL TDDKNQRFFC WQIPIEVEA
Length:149
Mass (Da):16,640
Last modified:May 1, 1997 - v1
Checksum:i91156DC7E805B655
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X85799 mRNA. Translation: CAA59794.1.
BT021533 mRNA. Translation: AAX46380.1.
BC102504 mRNA. Translation: AAI02505.1.
RefSeqiNP_776343.1. NM_173918.2.
UniGeneiBt.23268.

Genome annotation databases

EnsembliENSBTAT00000029271; ENSBTAP00000029271; ENSBTAG00000021955.
GeneIDi280815.
KEGGibta:280815.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X85799 mRNA. Translation: CAA59794.1.
BT021533 mRNA. Translation: AAX46380.1.
BC102504 mRNA. Translation: AAI02505.1.
RefSeqiNP_776343.1. NM_173918.2.
UniGeneiBt.23268.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1NEPX-ray1.70A20-149[»]
2HKAX-ray1.81A/B/C20-149[»]
ProteinModelPortaliP79345.
SMRiP79345. Positions 20-149.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000029271.

Chemistry

SwissLipidsiSLP:000000474.

Proteomic databases

PaxDbiP79345.
PRIDEiP79345.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000029271; ENSBTAP00000029271; ENSBTAG00000021955.
GeneIDi280815.
KEGGibta:280815.

Organism-specific databases

CTDi10577.

Phylogenomic databases

eggNOGiKOG4063. Eukaryota.
ENOG4111Q8S. LUCA.
GeneTreeiENSGT00390000006223.
HOGENOMiHOG000007181.
HOVERGENiHBG018181.
InParanoidiP79345.
KOiK13443.
OMAiLVVEWEL.
OrthoDBiEOG7SBNQN.
TreeFamiTF317963.

Miscellaneous databases

EvolutionaryTraceiP79345.

Family and domain databases

Gene3Di2.60.40.770. 1 hit.
InterProiIPR014756. Ig_E-set.
IPR003172. ML_dom.
[Graphical view]
PfamiPF02221. E1_DerP2_DerF2. 1 hit.
[Graphical view]
SMARTiSM00737. ML. 1 hit.
[Graphical view]
SUPFAMiSSF81296. SSF81296. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Primary structure of EPV20, a secretory glycoprotein containing a previously uncharacterized type of domain."
    Larsen L.B., Ravn P., Boisen A., Berglund L., Petersen T.E.
    Eur. J. Biochem. 243:437-441(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, DISULFIDE BONDS.
    Tissue: Mammary gland.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  3. NIH - Mammalian Gene Collection (MGC) project
    Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Crossbred X Angus.
    Tissue: Ileum.
  4. "Regulation of sterol transport between membranes and NPC2."
    Xu Z., Farver W., Kodukula S., Storch J.
    Biochemistry 47:11134-11143(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  5. "Niemann-Pick type C 1 function requires lumenal domain residues that mediate cholesterol-dependent NPC2 binding."
    Deffieu M.S., Pfeffer S.R.
    Proc. Natl. Acad. Sci. U.S.A. 108:18932-18936(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NPC1.
  6. "Structure of a cholesterol-binding protein deficient in Niemann-Pick type C2 disease."
    Friedland N., Liou H.L., Lobel P., Stock A.M.
    Proc. Natl. Acad. Sci. U.S.A. 100:2512-2517(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS).

Entry informationi

Entry nameiNPC2_BOVIN
AccessioniPrimary (citable) accession number: P79345
Secondary accession number(s): Q3T091, Q58DR4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: May 1, 1997
Last modified: June 8, 2016
This is version 112 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.