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Protein

Epididymal secretory protein E1

Gene

Npc2

Organism
Mus musculus (Mouse)
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

  • cholesterol binding Source: UniProtKB
  • enzyme binding Source: MGI

GO - Biological processi

  • cholesterol efflux Source: UniProtKB
  • cholesterol homeostasis Source: HGNC
  • cholesterol metabolic process Source: UniProtKB-KW
  • cholesterol transport Source: UniProtKB
  • intracellular cholesterol transport Source: HGNC
  • intracellular sterol transport Source: HGNC
  • response to virus Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Cholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism

Chemistry

SwissLipidsiSLP:000000473.

Names & Taxonomyi

Protein namesi
Recommended name:
Epididymal secretory protein E1
Short name:
mE1
Alternative name(s):
Niemann Pick type C2 protein homolog
Gene namesi
Name:Npc2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:1915213. Npc2.

Subcellular locationi

GO - Cellular componenti

  • endoplasmic reticulum Source: UniProtKB-SubCell
  • extracellular exosome Source: MGI
  • lysosome Source: HGNC
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Lysosome, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1919Sequence analysisAdd
BLAST
Chaini20 – 149130Epididymal secretory protein E1PRO_0000019856Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi27 ↔ 140By similarity
Disulfide bondi42 ↔ 47By similarity
Glycosylationi58 – 581N-linked (GlcNAc...)Sequence analysis
Glycosylationi69 – 691N-linked (GlcNAc...)Sequence analysis
Disulfide bondi93 ↔ 99By similarity
Modified residuei116 – 1161N6-acetyllysineCombined sources

Post-translational modificationi

N-glycosylated.

Keywords - PTMi

Acetylation, Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ9Z0J0.
MaxQBiQ9Z0J0.
PaxDbiQ9Z0J0.
PRIDEiQ9Z0J0.

PTM databases

iPTMnetiQ9Z0J0.
PhosphoSiteiQ9Z0J0.
SwissPalmiQ9Z0J0.

Expressioni

Tissue specificityi

Highly expressed in epididymis.

Gene expression databases

BgeeiQ9Z0J0.
CleanExiMM_NPC2.
GenevisibleiQ9Z0J0. MM.

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 similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ9Z0J0. 1 interaction.
MINTiMINT-4104065.
STRINGi10090.ENSMUSP00000021668.

Structurei

3D structure databases

ProteinModelPortaliQ9Z0J0.
SMRiQ9Z0J0. Positions 20-149.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the NPC2 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG4063. Eukaryota.
ENOG4111Q8S. LUCA.
GeneTreeiENSGT00390000006223.
HOGENOMiHOG000007181.
HOVERGENiHBG018181.
InParanoidiQ9Z0J0.
KOiK13443.
OMAiLVVEWEL.
OrthoDBiEOG7SBNQN.
PhylomeDBiQ9Z0J0.
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.

Q9Z0J0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRFLAATILL LALVAASQAE PLHFKDCGSK VGVIKEVNVS PCPTDPCQLH
60 70 80 90 100
KGQSYSVNIT FTSGTQSQNS TALVHGILEG IRVPFPIPEP DGCKSGINCP
110 120 130 140
IQKDKVYSYL NKLPVKNEYP SIKLVVEWKL EDDKKNNLFC WEIPVQITS
Length:149
Mass (Da):16,442
Last modified:May 1, 1999 - v1
Checksum:i6BDE56CF69791805
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB021289 mRNA. Translation: BAA35183.1.
AK008603 mRNA. Translation: BAB25771.1.
AK009127 mRNA. Translation: BAB26090.1.
AK151067 mRNA. Translation: BAE30083.1.
AK151133 mRNA. Translation: BAE30141.1.
AK153020 mRNA. Translation: BAE31654.1.
AK153203 mRNA. Translation: BAE31803.1.
AK158624 mRNA. Translation: BAE34585.1.
AK165263 mRNA. Translation: BAE38111.1.
AK167869 mRNA. Translation: BAE39885.1.
AK170327 mRNA. Translation: BAE41721.1.
BC003471 mRNA. Translation: AAH03471.1.
BC007190 mRNA. Translation: AAH07190.1.
CCDSiCCDS26050.1.
RefSeqiNP_075898.1. NM_023409.4.
UniGeneiMm.282556.

Genome annotation databases

EnsembliENSMUST00000021668; ENSMUSP00000021668; ENSMUSG00000021242.
GeneIDi67963.
KEGGimmu:67963.
UCSCiuc007oft.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB021289 mRNA. Translation: BAA35183.1.
AK008603 mRNA. Translation: BAB25771.1.
AK009127 mRNA. Translation: BAB26090.1.
AK151067 mRNA. Translation: BAE30083.1.
AK151133 mRNA. Translation: BAE30141.1.
AK153020 mRNA. Translation: BAE31654.1.
AK153203 mRNA. Translation: BAE31803.1.
AK158624 mRNA. Translation: BAE34585.1.
AK165263 mRNA. Translation: BAE38111.1.
AK167869 mRNA. Translation: BAE39885.1.
AK170327 mRNA. Translation: BAE41721.1.
BC003471 mRNA. Translation: AAH03471.1.
BC007190 mRNA. Translation: AAH07190.1.
CCDSiCCDS26050.1.
RefSeqiNP_075898.1. NM_023409.4.
UniGeneiMm.282556.

3D structure databases

ProteinModelPortaliQ9Z0J0.
SMRiQ9Z0J0. Positions 20-149.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9Z0J0. 1 interaction.
MINTiMINT-4104065.
STRINGi10090.ENSMUSP00000021668.

Chemistry

SwissLipidsiSLP:000000473.

PTM databases

iPTMnetiQ9Z0J0.
PhosphoSiteiQ9Z0J0.
SwissPalmiQ9Z0J0.

Proteomic databases

EPDiQ9Z0J0.
MaxQBiQ9Z0J0.
PaxDbiQ9Z0J0.
PRIDEiQ9Z0J0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000021668; ENSMUSP00000021668; ENSMUSG00000021242.
GeneIDi67963.
KEGGimmu:67963.
UCSCiuc007oft.1. mouse.

Organism-specific databases

CTDi10577.
MGIiMGI:1915213. Npc2.

Phylogenomic databases

eggNOGiKOG4063. Eukaryota.
ENOG4111Q8S. LUCA.
GeneTreeiENSGT00390000006223.
HOGENOMiHOG000007181.
HOVERGENiHBG018181.
InParanoidiQ9Z0J0.
KOiK13443.
OMAiLVVEWEL.
OrthoDBiEOG7SBNQN.
PhylomeDBiQ9Z0J0.
TreeFamiTF317963.

Miscellaneous databases

ChiTaRSiNpc2. mouse.
NextBioi326080.
PROiQ9Z0J0.
SOURCEiSearch...

Gene expression databases

BgeeiQ9Z0J0.
CleanExiMM_NPC2.
GenevisibleiQ9Z0J0. MM.

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, genomic organization and expression of the major secretory protein of murine epididymis, ME1."
    Nakamura Y., Takayama N., Minamitani T., Ikuta T., Ariga H., Matsumoto K.
    Gene 251:55-62(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Embryo.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: BALB/cJ, C57BL/6J and NOD.
    Tissue: Bone marrow, Small intestine, Spleen, Tongue and Visual cortex.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N.
    Tissue: Mammary gland.
  4. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Brown adipose tissue, Kidney, Liver, Lung, Pancreas, Spleen and Testis.
  5. "NPC2 regulates biliary cholesterol secretion via stimulation of ABCG5/G8-mediated cholesterol transport."
    Yamanashi Y., Takada T., Yoshikado T., Shoda J., Suzuki H.
    Gastroenterology 140:1664-1674(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "Niemann-Pick C2 (NPC2) and intracellular cholesterol trafficking."
    Storch J., Xu Z.
    Biochim. Biophys. Acta 1791:671-678(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.
  7. "Function of the Niemann-Pick type C proteins and their bypass by cyclodextrin."
    Vance J.E., Peake K.B.
    Curr. Opin. Lipidol. 22:204-209(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.
  8. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
    Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
    Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-116, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Embryonic fibroblast.

Entry informationi

Entry nameiNPC2_MOUSE
AccessioniPrimary (citable) accession number: Q9Z0J0
Secondary accession number(s): Q3UB23
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: May 1, 1999
Last modified: March 16, 2016
This is version 122 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

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  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.