P61916 (NPC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Epididymal secretory protein E1

Alternative name(s):
Human epididymis-specific protein 1
Short name=He1
Niemann-Pick disease type C2 protein

Gene names

Name:	NPC2
Synonyms:	HE1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	151 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May be involved in the regulation of the lipid composition of sperm membranes during the maturation in the epididymis By similarity.
Subcellular location	Secreted Potential.
Tissue specificity	Epididymis.
Induction	Down-regulated in response to enterovirus 71 (EV71) infection. Ref.4
Involvement in disease	Defects in NPC2 are the cause of Niemann-Pick disease type C2 (NPDC2) [MIM:607625]. A lysosomal storage disorder that affects the viscera and the central nervous system. It is due to defective intracellular processing and transport of low-density lipoprotein derived cholesterol. It causes accumulation of cholesterol in lysosomes, with delayed induction of cholesterol homeostatic reactions. Niemann-Pick disease type C2 has a highly variable clinical phenotype. Clinical features include variable hepatosplenomegaly and severe progressive neurological dysfunction such as ataxia, dystonia and dementia. The age of onset can vary from infancy to late adulthood. Ref.3 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11
Sequence similarities	Belongs to the NPC2 family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation Niemann-Pick disease
Domain	Signal
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cholesterol efflux Inferred from direct assay. Source: BHF-UCL cholesterol homeostasis Inferred from direct assay. Source: UniProtKB glycolipid transport Traceable author statement. Source: HGNC intracellular cholesterol transport Inferred from direct assay. Source: HGNC phospholipid transport Traceable author statement. Source: HGNC regulation of isoprenoid metabolic process Traceable author statement. Source: UniProtKB response to virus Inferred from expression pattern Ref.4. Source: UniProtKB
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell lysosome Inferred from direct assay Ref.3. Source: HGNC
Molecular function	cholesterol binding Inferred from direct assay. Source: HGNC enzyme binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19	Potential
	Chain	20 – 151	132	Epididymal secretory protein E1		PRO_0000019854
Amino acid modifications
	Glycosylation	58	1	N-linked (GlcNAc...) Potential
	Glycosylation	135	1	N-linked (GlcNAc...) Ref.5
	Disulfide bond	27 ↔ 140		By similarity
	Disulfide bond	42 ↔ 47		By similarity
	Disulfide bond	93 ↔ 99		By similarity
Natural variations
	Natural variant	30	1	V → M in NPDC2. Ref.9		VAR_043303
	Natural variant	39	1	V → M in NPDC2; results in the synthesis of functional recombinant proteins correctly targeted to lysosomes. Ref.8		VAR_015848
	Natural variant	47	1	C → F in NPDC2; leads to the synthesis of misfolded recombinant proteins that colocalized with an endoplasmic reticulum marker; normally secreted but unable to correct cholesterol storage in NPC2-deficient cells. Ref.9 Ref.10		VAR_043304
	Natural variant	67	1	S → P in NPDC2; leads to the synthesis of misfolded recombinant proteins that colocalized with an endoplasmic reticulum marker; normally secreted but unable to correct cholesterol storage in NPC2-deficient cells. Ref.7 Ref.10 Corresponds to variant rs11694 [ dbSNP | Ensembl ].		VAR_015849
	Natural variant	86	1	P → L. Corresponds to variant rs4688 [ dbSNP | Ensembl ].		VAR_011899
	Natural variant	93	1	C → F in NPDC2; leads to the synthesis of misfolded recombinant proteins that colocalized with an endoplasmic reticulum marker; normally secreted but unable to correct cholesterol storage in NPC2-deficient cells. Ref.9 Ref.10		VAR_043305
	Natural variant	99	1	C → R in NPDC2; leads to the synthesis of misfolded recombinant proteins that colocalized with an endoplasmic reticulum marker; normally secreted but unable to correct cholesterol storage in NPC2-deficient cells. Ref.10		VAR_043306
	Natural variant	120	1	P → S in NPDC2. Ref.11		VAR_043307

Sequences

	Sequence		Length	Mass (Da)
	P61916 [UniParc]. Last modified June 7, 2004. Version 1. Checksum: B141B611805DC910	FASTA	151	16,570
	10 20 30 40 50 60 MRFLAATFLL LALSTAAQAE PVQFKDCGSV DGVIKEVNVS PCPTQPCQLS KGQSYSVNVT 70 80 90 100 110 120 FTSNIQSKSS KAVVHGILMG VPVPFPIPEP DGCKSGINCP IQKDKTYSYL NKLPVKSEYP 130 140 150 SIKLVVEWQL QDDKNQSLFC WEIPVQIVSH L

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Region-specific variation of gene expression in the human epididymis as revealed by in situ hybridization with tissue-specific cDNAs." Krull N., Ivell R., Osterhoff C., Kirchhoff C. Mol. Reprod. Dev. 34:16-24(1993) [PubMed: 8418812] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Epididymis.
[2]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Ovary.
[3]	"Identification of HE1 as the second gene of Niemann-Pick C disease." Naureckiene S., Sleat D.E., Lackland H., Fensom A., Vanier M.T., Wattiaux R., Jadot M., Lobel P. Science 290:2298-2301(2000) [PubMed: 11125141] [Abstract] Cited for: INVOLVEMENT IN NPDC2.
[4]	"Transcriptomic and proteomic analyses of rhabdomyosarcoma cells reveal differential cellular gene expression in response to enterovirus 71 infection." Leong W.F., Chow V.T. Cell. Microbiol. 8:565-580(2006) [PubMed: 16548883] [Abstract] Cited for: INDUCTION, MASS SPECTROMETRY.
[5]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-135, MASS SPECTROMETRY. Tissue: Liver.
[6]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]	"Niemann-Pick disease type C: spectrum of HE1 mutations and genotype/phenotype correlations in the NPC2 group." Millat G., Chikh K., Naureckiene S., Sleat D.E., Fensom A.H., Higaki K., Elleder M., Lobel P., Vanier M.T. Am. J. Hum. Genet. 69:1013-1021(2001) [PubMed: 11567215] [Abstract] Cited for: VARIANT NPDC2 PRO-67.
[8]	"Frontal lobe atrophy due to a mutation in the cholesterol binding protein HE1/NPC2." Klunemann H.H., Elleder M., Kaminski W.E., Snow K., Peyser J.M., O'Brien J.F., Munoz D., Schmitz G., Klein H.E., Pendlebury W.W. Ann. Neurol. 52:743-749(2002) [PubMed: 12447927] [Abstract] Cited for: VARIANT NPDC2 MET-39.
[9]	"Identification of 58 novel mutations in Niemann-Pick disease type C: correlation with biochemical phenotype and importance of PTC1-like domains in NPC1." Park W.D., O'Brien J.F., Lundquist P.A., Kraft D.L., Vockley C.W., Karnes P.S., Patterson M.C., Snow K. Hum. Mutat. 22:313-325(2003) [PubMed: 12955717] [Abstract] Cited for: VARIANTS NPDC2 MET-30; PHE-47 AND PHE-93.
[10]	"Niemann-Pick type C disease: subcellular location and functional characterization of NPC2 proteins with naturally occurring missense mutations." Chikh K., Rodriguez C., Vey S., Vanier M.T., Millat G. Hum. Mutat. 26:20-28(2005) [PubMed: 15937921] [Abstract] Cited for: VARIANT NPDC2 ARG-99, CHARACTERIZATION OF VARIANTS NPDC2 METH-39; PHE-47; PRO-67; PHE-93 AND ARG-99.
[11]	"Niemann-Pick C disease: use of denaturing high performance liquid chromatography for the detection of NPC1 and NPC2 genetic variations and impact on management of patients and families." Millat G., Baielo N., Molinero S., Rodriguez C., Chikh K., Vanier M.T. Mol. Genet. Metab. 86:220-232(2005) [PubMed: 16126423] [Abstract] Cited for: VARIANT NPDC2 SER-120.
+	Additional computationally mapped references.

Web resources

Niemann-Pick type C disease gene variation database

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	X67698 mRNA. Translation: CAA47928.1. BC002532 mRNA. Translation: AAH02532.1.
IPI	IPI00940960.
PIR	I38365.
RefSeq	NP_006423.1. NM_006432.3.
UniGene	Hs.433222.
3D structure databases
ProteinModelPortal	P61916.
SMR	P61916. Positions 20-147.
ModBase	Search...
Protein-protein interaction databases
IntAct	P61916. 1 interaction.
STRING	P61916.
Protein family/group databases
TCDB	2.A.6.6.1. resistance-nodulation-cell division (RND) superfamily.
Polymorphism databases
DMDM	48429027.
Proteomic databases
PeptideAtlas	P61916.
PRIDE	P61916.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000238633; ENSP00000238633; ENSG00000119655.
GeneID	10577.
KEGG	hsa:10577.
UCSC	uc001xpy.1. human.
Organism-specific databases
CTD	10577.
GeneCards	GC14M074943.
H-InvDB	HIX0011812.
HGNC	HGNC:14537. NPC2.
HPA	HPA000835.
MIM	601015. gene. 607625. phenotype.
neXtProt	NX_P61916.
Orphanet	216986. Niemann-Pick disease type C, adult neurologic onset. 216981. Niemann-Pick disease type C, juvenile neurologic onset. 216978. Niemann-Pick disease type C, late infantile neurologic onset. 216975. Niemann-Pick disease type C, severe early infantile neurologic onset. 216972. Niemann-Pick disease type C, severe perinatal.
PharmGKB	PA31700.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG13566.
HOVERGEN	HBG018181.
InParanoid	P61916.
OrthoDB	EOG4BZN42.
PhylomeDB	P61916.
Gene expression databases
ArrayExpress	P61916.
Bgee	P61916.
CleanEx	HS_NPC2.
Genevestigator	P61916.
GermOnline	ENSG00000119655. Homo sapiens.
Family and domain databases
InterPro	IPR014756. Ig_E-set. IPR003172. MD-2_lipid-recog. [Graphical view]
Gene3D	G3DSA:2.60.40.770. MD-2_lipid-recog. 1 hit.
KO	K13443.
Pfam	PF02221. E1_DerP2_DerF2. 1 hit. [Graphical view]
SMART	SM00737. ML. 1 hit. [Graphical view]
SUPFAM	SSF81296. Ig_E-set. 1 hit.
ProtoNet	Search...
Other
NextBio	40145.
PMAP-CutDB	P61916.
SOURCE	Search...

Entry information

Entry name

NPC2_HUMAN

Accession

Primary (citable) accession number: P61916
Secondary accession number(s): Q15668, Q29413

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 7, 2004
Last sequence update:	June 7, 2004
Last modified:	January 25, 2012
This is version 82 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.