Reviewed, UniProtKB/Swiss-Prot O15118 (NPC1_HUMAN)

Names and origin

Protein names

Recommended name:
    Niemann-Pick C1 protein

Gene names

Name:

NPC1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	1278 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	Involved in the intracellular trafficking of cholesterol. May play a role in vesicular trafficking in glia, a process that may be crucial for maintaining the structural and functional integrity of nerve terminals.
Subcellular location	Late endosome membrane; Multi-pass membrane protein. Lysosome membrane; Multi-pass membrane protein.
Domain	A cysteine-rich N-terminal domain and a C-terminal domain containing a di-leucine motif necessary for lysosomal targeting are critical for mobilization of cholesterol from lysosomes.
Post-translational modification	Glycosylated. Ref.6
Involvement in disease	Defects in NPC1 are the cause of Niemann-Pick disease type C1 (NPC1) [MIM:257220]. NPC1 is an autosomal recessive lipid storage disorder, which affects particularly the brain, liver and spleen, and which is characterized by lysosomal accumulation of low density lipoprotein derived cholesterol. 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.1 Ref.3 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Defects in NPC1 are the cause of Niemann-Pick disease type D (NPD) [MIM:257220]; also known as Niemann-Pick disease without sphingomyelinase deficiency or Niemann-Pick disease Nova Scotian type. Because of evidence from biochemical changes, lack of complementation, and linkage mapping to the same chromosome site, NPD and NPC1 are considered to be allelic disorders.
Sequence similarities	Belongs to the patched family. Contains 1 SSD (sterol-sensing) domain.

Ontologies

Keywords
Cellular component	Endosome Lysosome Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal Transmembrane
PTM	Glycoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	bile acid metabolic process Inferred from sequence or structural similarity. Source: UniProtKB cholesterol homeostasis Inferred from direct assay. Source: UniProtKB lysosomal transport Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	endoplasmic reticulum Ref.18 Inferred from direct assay. Source: UniProtKB endosome Inferred from electronic annotation. Source: UniProtKB-KW integral to plasma membrane Inferred from direct assay. Source: UniProtKB lysosome Ref.5 Traceable author statement. Source: ProtInc nuclear envelope Ref.18 Inferred from direct assay. Source: UniProtKB perinuclear region of cytoplasm Ref.18 Inferred from direct assay. Source: UniProtKB
Molecular function	hedgehog receptor activity Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: UniProtKB sterol transporter activity Ref.5 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 22	22	Potential
	Chain	23 – 1278	1256	Niemann-Pick C1 protein		PRO_0000023261
Regions
	Transmembrane	270 – 290	21	Potential
	Transmembrane	351 – 371	21	Potential
	Transmembrane	622 – 642	21	Potential
	Transmembrane	655 – 675	21	Potential
	Transmembrane	678 – 698	21	Potential
	Transmembrane	760 – 780	21	Potential
	Transmembrane	833 – 853	21	Potential
	Transmembrane	1099 – 1119	21	Potential
	Transmembrane	1125 – 1145	21	Potential
	Transmembrane	1196 – 1216	21	Potential
	Transmembrane	1228 – 1248	21	Potential
	Domain	620 – 785	166	SSD
	Motif	1275 – 1278	4	Di-leucine motif
	Compositional bias	249 – 259	11	Poly-Pro
Amino acid modifications
	Glycosylation	70	1	N-linked (GlcNAc...) Potential
	Glycosylation	122	1	N-linked (GlcNAc...) Potential
	Glycosylation	135	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	185	1	N-linked (GlcNAc...) Potential
	Glycosylation	222	1	N-linked (GlcNAc...) Potential
	Glycosylation	452	1	N-linked (GlcNAc...) Potential
	Glycosylation	459	1	N-linked (GlcNAc...) Potential
	Glycosylation	478	1	N-linked (GlcNAc...) Potential
	Glycosylation	524	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	916	1	N-linked (GlcNAc...) Potential
	Glycosylation	1064	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	63	1	C → R in NPC1. Ref.14		VAR_043172
	Natural variant	74	1	C → Y in NPC1. Ref.19		VAR_043173
	Natural variant	92	1	Q → R in NPC1. Ref.12 Ref.15		VAR_043174
	Natural variant	113	1	C → R in NPC1; partially mislocalized from late endocytic organelles diffusely to the cell periphery; localizes to the endoplasmic reticulum Rab7-negative endosomes and the cell surface; does not clears the lysosomal cholesterol accumulation in NPC1-deficient cells. Ref.18		VAR_043175
	Natural variant	137	1	T → M in NPC1. Ref.12 Ref.20		VAR_043176
	Natural variant	151	1	S → G: dbSNP rs17855819. Ref.4		VAR_043177
	Natural variant	166	1	P → S in NPC1. Ref.19 Ref.22		VAR_043178
	Natural variant	177	1	C → G in NPC1; late infantile form. Ref.11		VAR_008815
	Natural variant	177	1	C → Y in NPC1. Ref.15 Ref.20 Ref.22		VAR_015561
	Natural variant	215	1	H → R Common polymorphism in Japanese. dbSNP rs1805081. Ref.3 Ref.10 Ref.15 Ref.17 Ref.19 Ref.20 Ref.21		VAR_008816
	Natural variant	222	1	N → S in NPC1. Ref.19		VAR_043179
	Natural variant	231	1	V → G in NPC1. Ref.16		VAR_043180
	Natural variant	237	1	P → S in NPC1; late infantile form. Ref.11 Ref.12 Ref.13 Ref.16 Ref.19		VAR_008817
	Natural variant	242	1	D → H in NPC1. Ref.13		VAR_043181
	Natural variant	242	1	D → N in NPC1. Ref.12		VAR_043182
	Natural variant	247	1	C → Y in NPC1. Ref.19		VAR_043183
	Natural variant	248	1	G → V in NPC1. Ref.12		VAR_043184
	Natural variant	272	1	M → R in NPC1. Ref.13		VAR_043185
	Natural variant	273	1	W → S Colocalizes with the wild-type protein with Rab7-positive late endosomes; clears the lysosomal cholesterol accumulation in NPC1-deficient cells. Ref.18		VAR_043186
	Natural variant	333	1	G → D		VAR_008818
	Natural variant	372	1	R → W in NPC1. Ref.20		VAR_043187
	Natural variant	378	1	V → A in NPC1. Ref.13		VAR_015562
	Natural variant	380	1	L → F in NPC1. Ref.19		VAR_043188
	Natural variant	381	1	W → C		VAR_043189
	Natural variant	388	1	A → P in NPC1. Ref.19		VAR_043190
	Natural variant	389	1	R → C in NPC1. Ref.19		VAR_043191
	Natural variant	401	1	P → T in NPC1. Ref.12		VAR_043192
	Natural variant	404	1	R → P in NPC1. Ref.22		VAR_043193
	Natural variant	404	1	R → Q in NPC1. Ref.12 Ref.13 Ref.14		VAR_043194
	Natural variant	404	1	R → W in NPC1. Ref.19		VAR_043195
	Natural variant	433	1	P → L in NPC1. Ref.19		VAR_043196
	Natural variant	434	1	P → L in NPC1. Ref.20		VAR_043197
	Natural variant	434	1	P → S		VAR_043198
	Natural variant	451	1	E → K in NPC1. Ref.17		VAR_043199
	Natural variant	472	1	L → P		VAR_008819
	Natural variant	473	1	S → P in NPC1; late infantile form. Ref.11		VAR_008820
	Natural variant	474	1	P → L in NPC1. Ref.17 Ref.20		VAR_043200
	Natural variant	479	1	C → Y in NPC1. Ref.20		VAR_043201
	Natural variant	509	1	Y → S in NPC1. Ref.19		VAR_043202
	Natural variant	510	1	H → P in NPC1; late infantile form. Ref.11		VAR_008821
	Natural variant	511	1	T → M: dbSNP rs13381670. Ref.22		VAR_043203
	Natural variant	512	1	H → R in NPC1. Ref.3		VAR_043204
	Natural variant	518	1	R → Q in NPC1; late infantile form; Common in Japanese. Ref.11 Ref.13		VAR_008822
	Natural variant	518	1	R → W in NPC1. Ref.15		VAR_043205
	Natural variant	521	1	A → S in NPC1. Ref.19		VAR_043206
	Natural variant	537	1	F → L in NPC1. Ref.22		VAR_043207
	Natural variant	543	1	P → L in NPC1. Ref.19 Ref.22		VAR_043208
	Natural variant	574	1	T → K in NPC1.		VAR_043209
	Natural variant	576	1	K → R in NPC1. Ref.20		VAR_043210
	Natural variant	605	1	A → V in NPC1. Ref.13		VAR_043211
	Natural variant	612	1	E → D in NPC1. Ref.12		VAR_043212
	Natural variant	615	1	R → C in NPC1. Ref.19		VAR_043213
	Natural variant	615	1	R → L in NPC1. Ref.22		VAR_043214
	Natural variant	631	1	M → R in NPC1. Ref.13 Ref.22		VAR_043215
	Natural variant	640	1	G → R in NPC1. Ref.19		VAR_043216
	Natural variant	642	1	M → I: dbSNP rs1788799. Ref.1 Ref.3 Ref.15 Ref.16 Ref.17 Ref.20 Ref.21 Ref.4		VAR_008823
	Natural variant	652	1	S → W in NPC1. Ref.12		VAR_043217
	Natural variant	660	1	G → S in NPC1. Ref.19		VAR_043218
	Natural variant	664	1	V → M in NPC1. Ref.19 Ref.20		VAR_043219
	Natural variant	666	1	S → N in NPC1. Ref.23		VAR_043220
	Natural variant	670	1	C → W in NPC1. Ref.3		VAR_043221
	Natural variant	673	1	G → V in NPC1. Ref.19		VAR_043222
	Natural variant	684	1	L → F in NPC1. Ref.19		VAR_043223
	Natural variant	691	1	P → L in NPC1. Ref.19		VAR_043224
	Natural variant	695	1	L → V in NPC1. Ref.19		VAR_043225
	Natural variant	700	1	D → N in NPC1. Ref.19		VAR_043226
	Natural variant	703	1	F → S in NPC1. Ref.11		VAR_043227
	Natural variant	724	1	L → P in NPC1. Ref.13		VAR_043228
	Natural variant	727	1	V → F in NPC1. Ref.20		VAR_043229
	Natural variant	734	1	S → I in NPC1. Ref.19		VAR_043230
	Natural variant	742	1	E → K in NPC1. Ref.19		VAR_043231
	Natural variant	745	1	A → E in NPC1. Ref.19		VAR_043232
	Natural variant	754	1	M → K in NPC1. Ref.20		VAR_043233
	Natural variant	757	1	V → A		VAR_008824
	Natural variant	763	1	F → L in NPC1. Ref.22		VAR_043234
	Natural variant	767	1	A → V in NPC1. Ref.19		VAR_043235
	Natural variant	775	1	Q → P in NPC1. Ref.13 Ref.20		VAR_043236
	Natural variant	789	1	R → C in NPC1. Ref.12		VAR_043237
	Natural variant	789	1	R → G in NPC1. Ref.19		VAR_043238
	Natural variant	825	1	Y → C in NPC1. Ref.3 Ref.12 Ref.13 Ref.22		VAR_043239
	Natural variant	849	1	S → I in NPC1. Ref.3		VAR_043240
	Natural variant	858	1	I → V Common polymorphism in Japanese. dbSNP rs1805082. Ref.3 Ref.10 Ref.15 Ref.17 Ref.20 Ref.21		VAR_008825
	Natural variant	862	1	Q → L in NPC1. Ref.22		VAR_043241
	Natural variant	865	1	S → L in NPC1. Ref.20 Ref.22		VAR_043242
	Natural variant	871	1	Y → C in NPC1. Ref.22		VAR_043243
	Natural variant	873	1	V → A		VAR_043244
	Natural variant	874	1	D → V in NPC1. Ref.3 Ref.12 Ref.13 Ref.16		VAR_043245
	Natural variant	888	1	P → S in NPC1. Ref.12		VAR_043246
	Natural variant	889	1	V → M in NPC1; adult form. Ref.11		VAR_008826
	Natural variant	890	1	Y → C in NPC1. Ref.17		VAR_043247
	Natural variant	899	1	Y → D in NPC1. Ref.17		VAR_043248
	Natural variant	910	1	G → S in NPC1. Ref.17		VAR_043249
	Natural variant	917	1	D → Y in NPC1. Ref.22		VAR_043250
	Natural variant	926	1	A → T in NPC1. Ref.20		VAR_043251
	Natural variant	927	1	A → V in NPC1. Ref.14		VAR_043252
	Natural variant	928	1	Q → P in NPC1. dbSNP rs28940897.		VAR_008827
	Natural variant	929	1	L → P in NPC1. Ref.12		VAR_043253
	Natural variant	934	1	R → Q in NPC1. Ref.8 Ref.13 Ref.22		VAR_008828
	Natural variant	940	1	S → L in NPC1. Ref.8 Ref.12 Ref.22		VAR_008829
	Natural variant	942	1	W → C in NPC1. Ref.15 Ref.20		VAR_043254
	Natural variant	943	1	I → M in NPC1. Ref.13		VAR_043255
	Natural variant	944	1	D → N in NPC1. Ref.12 Ref.13 Ref.20		VAR_043256
	Natural variant	945	1	D → N in NPC1. Ref.19		VAR_043257
	Natural variant	948	1	D → H in NPC1. Ref.20		VAR_043258
	Natural variant	948	1	D → N in NPC1. Ref.8 Ref.12 Ref.16		VAR_008830
	Natural variant	948	1	D → Y in NPC1. Ref.3		VAR_043259
	Natural variant	950	1	V → M in NPC1; adult form. Ref.13 Ref.22		VAR_015563
	Natural variant	954	1	S → L in NPC1. Ref.3 Ref.8 Ref.11		VAR_008831
	Natural variant	956	1	C → Y in NPC1; late infantile form. Ref.11		VAR_008832
	Natural variant	958	1	R → L in NPC1. Ref.3		VAR_043260
	Natural variant	958	1	R → Q in NPC1. Ref.12		VAR_015564
	Natural variant	959	1	V → E in NPC1. Ref.20		VAR_043261
	Natural variant	961 – 966	6	NITDQF → S in NPC1. Ref.23		VAR_043262
	Natural variant	961	1	N → S in NPC1. dbSNP rs34084984. Ref.23		VAR_043263
	Natural variant	968	1	N → S in NPC1. Ref.21 Ref.22		VAR_043264
	Natural variant	971	1	V → G		VAR_043265
	Natural variant	976	1	C → R in NPC1. Ref.12		VAR_043266
	Natural variant	978	1	R → C in NPC1. dbSNP rs28942108. Ref.12 Ref.15		VAR_015565
	Natural variant	986	1	G → S in NPC1. Ref.13		VAR_043267
	Natural variant	992	1	G → A in NPC1. Ref.22		VAR_043268
	Natural variant	992	1	G → R in NPC1. Ref.13 Ref.22		VAR_015566
	Natural variant	992	1	G → W in NPD and NPC1. Ref.8 Ref.14 Ref.17 Ref.22 Ref.7		VAR_008833
	Natural variant	996	1	M → R in NPC1. Ref.11		VAR_043269
	Natural variant	1004	1	S → L in NPC1. Ref.12		VAR_043270
	Natural variant	1007	1	P → A in NPC1. Ref.3 Ref.8 Ref.12 Ref.13 Ref.15 Ref.17 Ref.20 Ref.22		VAR_008834
	Natural variant	1012	1	G → D in NPC1. Ref.14		VAR_043271
	Natural variant	1015	1	G → V in NPC1. Ref.21		VAR_043272
	Natural variant	1016	1	H → R in NPC1. Ref.19		VAR_043273
	Natural variant	1023	1	V → G in NPC1. Ref.12		VAR_043274
	Natural variant	1034	1	G → R in NPC1. Ref.21		VAR_043275
	Natural variant	1035	1	A → V in NPC1. Ref.15 Ref.20		VAR_015567
	Natural variant	1036	1	T → K in NPC1. Ref.20		VAR_043276
	Natural variant	1036	1	T → M in NPC1. Ref.22		VAR_008835
	Natural variant	1049	1	A → V		VAR_043277
	Natural variant	1054	1	A → T in NPC1. Ref.13		VAR_043278
	Natural variant	1059	1	R → Q in NPC1. Ref.19		VAR_043279
	Natural variant	1061	1	I → T in NPC1; late infantile form. Ref.3 Ref.8 Ref.9 Ref.11 Ref.12 Ref.13 Ref.15 Ref.17 Ref.20 Ref.22		VAR_008836
	Natural variant	1062	1	A → V in NPC1. Ref.22		VAR_043280
	Natural variant	1066	1	T → N in NPC1. Ref.20		VAR_043281
	Natural variant	1087	1	F → L in NPC1. Ref.19		VAR_043282
	Natural variant	1088	1	Y → C in NPC1; juvenile form. dbSNP rs28942106. Ref.11		VAR_008837
	Natural variant	1089	1	E → K in NPC1. Ref.12		VAR_043283
	Natural variant	1094	1	I → T in NPC1. Ref.16		VAR_043284
	Natural variant	1097	1	D → N in NPC1. Ref.22		VAR_043285
	Natural variant	1137	1	N → I in NPC1. Ref.19		VAR_043286
	Natural variant	1140	1	G → V in NPC1. Ref.19		VAR_043287
	Natural variant	1142	1	M → T in NPC1. Ref.12 Ref.13		VAR_043288
	Natural variant	1150	1	N → K in NPC1. Ref.12		VAR_043289
	Natural variant	1156	1	N → I in NPC1. dbSNP rs28942105. Ref.20		VAR_043290
	Natural variant	1156	1	N → S in NPC1. Ref.12 Ref.14 Ref.17 Ref.20		VAR_008838
	Natural variant	1165	1	V → M in NPC1. Ref.12		VAR_043291
	Natural variant	1167	1	F → L in NPC1.		VAR_008839
	Natural variant	1168	1	C → Y in NPC1. Ref.13		VAR_043292
	Natural variant	1174	1	A → V in NPC1. Ref.22		VAR_043293
	Natural variant	1186	1	R → H in NPC1. Ref.12 Ref.13 Ref.22		VAR_008840
	Natural variant	1189	1	E → G in NPC1. Ref.12		VAR_043294
	Natural variant	1205	1	T → K in NPC1. Ref.19		VAR_043295
	Natural variant	1205	1	T → R in NPC1. Ref.11		VAR_043296
	Natural variant	1212	1	V → L in NPC1. Ref.21		VAR_043297
	Natural variant	1213	1	L → F in NPC1; juvenile form. Ref.11		VAR_008841
	Natural variant	1213	1	L → V in NPC1. Ref.8		VAR_008842
	Natural variant	1216	1	A → V in NPC1. Ref.22		VAR_043298
	Natural variant	1220	1	I → T		VAR_008843
	Natural variant	1224	1	F → L in NPC1. Ref.20		VAR_043299
	Natural variant	1236	1	G → E in NPC1. Ref.11		VAR_043300
	Natural variant	1240	1	G → R in NPC1. Ref.22		VAR_043301
	Natural variant	1249	1	S → G in NPC1. Ref.19		VAR_043302
	Natural variant	1266	1	R → Q Common polymorphism in Japanese. dbSNP rs1805084. Ref.10 Ref.19 Ref.20 Ref.21		VAR_008844
Experimental info
	Mutagenesis	63	1	C → S: Loss of function.
	Mutagenesis	97	1	C → S: Loss of function.

Sequences

	Sequence		Length	Mass (Da)
	O15118-1 [UniParc]. Last modified May 10, 2005. Version 2. Checksum: DA1523E09822E5C7	FASTA	1,278	142,167
	10 20 30 40 50 60 MTARGLALGL LLLLLCPAQV FSQSCVWYGE CGIAYGDKRY NCEYSGPPKP LPKDGYDLVQ 70 80 90 100 110 120 ELCPGFFFGN VSLCCDVRQL QTLKDNLQLP LQFLSRCPSC FYNLLNLFCE LTCSPRQSQF 130 140 150 160 170 180 LNVTATEDYV DPVTNQTKTN VKELQYYVGQ SFANAMYNAC RDVEAPSSND KALGLLCGKD 190 200 210 220 230 240 ADACNATNWI EYMFNKDNGQ APFTITPVFS DFPVHGMEPM NNATKGCDES VDEVTAPCSC 250 260 270 280 290 300 QDCSIVCGPK PQPPPPPAPW TILGLDAMYV IMWITYMAFL LVFFGAFFAV WCYRKRYFVS 310 320 330 340 350 360 EYTPIDSNIA FSVNASDKGE ASCCDPVSAA FEGCLRRLFT RWGSFCVRNP GCVIFFSLVF 370 380 390 400 410 420 ITACSSGLVF VRVTTNPVDL WSAPSSQARL EKEYFDQHFG PFFRTEQLII RAPLTDKHIY 430 440 450 460 470 480 QPYPSGADVP FGPPLDIQIL HQVLDLQIAI ENITASYDNE TVTLQDICLA PLSPYNTNCT 490 500 510 520 530 540 ILSVLNYFQN SHSVLDHKKG DDFFVYADYH THFLYCVRAP ASLNDTSLLH DPCLGTFGGP 550 560 570 580 590 600 VFPWLVLGGY DDQNYNNATA LVITFPVNNY YNDTEKLQRA QAWEKEFINF VKNYKNPNLT 610 620 630 640 650 660 ISFTAERSIE DELNRESDSD VFTVVISYAI MFLYISLALG HMKSCRRLLV DSKVSLGIAG 670 680 690 700 710 720 ILIVLSSVAC SLGVFSYIGL PLTLIVIEVI PFLVLAVGVD NIFILVQAYQ RDERLQGETL 730 740 750 760 770 780 DQQLGRVLGE VAPSMFLSSF SETVAFFLGA LSVMPAVHTF SLFAGLAVFI DFLLQITCFV 790 800 810 820 830 840 SLLGLDIKRQ EKNRLDIFCC VRGAEDGTSV QASESCLFRF FKNSYSPLLL KDWMRPIVIA 850 860 870 880 890 900 IFVGVLSFSI AVLNKVDIGL DQSLSMPDDS YMVDYFKSIS QYLHAGPPVY FVLEEGHDYT 910 920 930 940 950 960 SSKGQNMVCG GMGCNNDSLV QQIFNAAQLD NYTRIGFAPS SWIDDYFDWV KPQSSCCRVD 970 980 990 1000 1010 1020 NITDQFCNAS VVDPACVRCR PLTPEGKQRP QGGDFMRFLP MFLSDNPNPK CGKGGHAAYS 1030 1040 1050 1060 1070 1080 SAVNILLGHG TRVGATYFMT YHTVLQTSAD FIDALKKARL IASNVTETMG INGSAYRVFP 1090 1100 1110 1120 1130 1140 YSVFYVFYEQ YLTIIDDTIF NLGVSLGAIF LVTMVLLGCE LWSAVIMCAT IAMVLVNMFG 1150 1160 1170 1180 1190 1200 VMWLWGISLN AVSLVNLVMS CGISVEFCSH ITRAFTVSMK GSRVERAEEA LAHMGSSVFS 1210 1220 1230 1240 1250 1260 GITLTKFGGI VVLAFAKSQI FQIFYFRMYL AMVLLGATHG LIFLPVLLSY IGPSVNKAKS 1270 CATEERYKGT ERERLLNF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis." Carstea E.D., Morris J.A., Coleman K.G., Loftus S.K., Zhang D., Cummings C., Gu J., Rosenfeld M.A., Pavan W.J., Krizman D.B., Nagle J., Polymeropoulos M.H., Sturley S.L., Ioannou Y.A., Higgins M.E., Comly M., Cooney A., Brown A. , Kaneski C.R., Blanchette-Mackie E.J., Dwyer N.K., Neufeld E.B., Chang T.-Y., Liscum L., Strauss J.F. III, Ohno K., Zeigler M., Carmi R., Sokol J., Markie D., O'Neill R.R., van Diggelen O.P., Elleder M., Patterson M.C., Brady R.O., Vanier M.T., Pentchev P.G., Tagle D.A. Science 277:228-231(1997) [PubMed: 9211849] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ILE-642, VARIANTS NPC1.
[2]	"The genomic organization and polymorphism analysis of the human Niemann-Pick C1 gene." Morris J.A., Zhang D., Coleman K.G., Nagle J., Pentchev P.G., Carstea E.D. Biochem. Biophys. Res. Commun. 261:493-498(1999) [PubMed: 10425213] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS.
[3]	"NPC1: complete genomic sequence, mutation analysis, and characterization of haplotypes." Bauer P., Knoblich R., Bauer C., Finckh U., Hufen A., Kropp J., Braun S., Kustermann-Kuhn B., Schmidt D., Harzer K., Rolfs A. Hum. Mutat. 19:30-38(2002) [PubMed: 11754101] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS NPC1 ARG-512; TRP-670; CYS-825; ILE-849; VAL-874; TYR-948; LEU-954; LEU-958; ALA-1007 AND THR-1061, VARIANTS ARG-215; ILE-642; VAL-858; GLY-971 AND VAL-1049.
[4]	"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], VARIANTS GLY-151 AND ILE-642. Tissue: Placenta.
[5]	"Niemann-Pick C1 protein: obligatory roles for N-terminal domains and lysosomal targeting in cholesterol mobilization." Watari H., Blanchette-Mackie E.J., Dwyer N.K., Glick J.M., Patel S., Neufeld E.B., Brady R.O., Pentchev P.G., Strauss J.F. III Proc. Natl. Acad. Sci. U.S.A. 96:805-810(1999) [PubMed: 9927649] [Abstract] Cited for: CHARACTERIZATION.
[6]	"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 AND ASN-524, MASS SPECTROMETRY. Tissue: Liver.
[7]	"The Nova Scotia (type D) form of Niemann-Pick disease is caused by a G3097-->T transversion in NPC1." Greer W.L., Riddell D.C., Gillan T.L., Girouard G.S., Sparrow S.M., Byers D.M., Dobson M.J., Neumann P.E. Am. J. Hum. Genet. 63:52-54(1998) [PubMed: 9634529] [Abstract] Cited for: VARIANT NPD TRP-992.
[8]	"Mutations in NPC1 highlight a conserved NPC1-specific cysteine-rich domain." Greer W.L., Dobson M.J., Girouard G.S., Byers D.M., Riddell D.C., Neumann P.E. Am. J. Hum. Genet. 65:1252-1260(1999) [PubMed: 10521290] [Abstract] Cited for: VARIANTS NPC1 GLN-934; LEU-940; ASN-948; LEU-954; TRP-992; ALA-1007; THR-1061 AND VAL-1213.
[9]	"Niemann-Pick C1 disease: the I1061T substitution is a frequent mutant allele in patients of Western European descent and correlates with a classic juvenile phenotype." Millat G., Marcais C., Rafi M.A., Yamamoto T., Morris J.A., Pentchev P.G., Ohno K., Wenger D.A., Vanier M.T. Am. J. Hum. Genet. 65:1321-1329(1999) [PubMed: 10521297] [Abstract] Cited for: VARIANT NPC1 THR-1061.
[10]	"NPC1 gene mutations in Japanese patients with Niemann-Pick disease type C." Yamamoto T., Nanba E., Ninomiya H., Higaki K., Taniguchi M., Zhang H., Akaboshi S., Watanabe Y., Takeshima T., Inui K., Okada S., Tanaka A., Sakuragawa N., Millat G., Vanier M.T., Morris J.A., Pentchev P.G., Ohno K. Hum. Genet. 105:10-16(1999) [PubMed: 10480349] [Abstract] Cited for: VARIANTS NPC1, VARIANTS ARG-215; VAL-858 AND GLN-1266.
[11]	"Genotype-phenotype relationship of Niemann-Pick disease type C: a possible correlation between clinical onset and levels of NPC1 protein in isolated skin fibroblasts." Yamamoto T., Ninomiya H., Matsumoto M., Ohta Y., Nanba E., Tsutsumi Y., Yamakawa K., Millat G., Vanier M.T., Pentchev P.G., Ohno K. J. Med. Genet. 37:707-712(2000) [PubMed: 11182931] [Abstract] Cited for: VARIANTS NPC1 GLY-177; SER-237; PRO-473; PRO-510; GLN-518; SER-703; MET-889; LEU-954; TYR-956; ARG-996; THR-1061; CYS-1088; ARG-1205; PHE-1213 AND GLU-1236, VARIANT ALA-873.
[12]	"Niemann-Pick C variant detection by altered sphingolipid trafficking and correlation with mutations within a specific domain of NPC1." Sun X., Marks D.L., Park W.D., Wheatley C.L., Puri V., O'Brien J.F., Kraft D.L., Lundquist P.A., Patterson M.C., Pagano R.E., Snow K. Am. J. Hum. Genet. 68:1361-1372(2001) [PubMed: 11349231] [Abstract] Cited for: VARIANTS NPC1 ARG-92; MET-137; SER-237; ASN-242; VAL-248; THR-401; GLN-404; ASP-612; TRP-652; CYS-789; CYS-825; VAL-874; SER-888; PRO-929; LEU-940; ASN-944; ASN-948; GLN-958; ARG-976; CYS-978; LEU-1004; ALA-1007; GLY-1023; THR-1061; LYS-1089; THR-1142; LYS-1150; SER-1156; MET-1165; HIS-1186 AND GLY-1189.
[13]	"Niemann-Pick C1 disease: correlations between NPC1 mutations, levels of NPC1 protein, and phenotypes emphasize the functional significance of the putative sterol-sensing domain and of the cysteine-rich luminal loop." Millat G., Marcais C., Tomasetto C., Chikh K., Fensom A.H., Harzer K., Wenger D.A., Ohno K., Vanier M.T. Am. J. Hum. Genet. 68:1373-1385(2001) [PubMed: 11333381] [Abstract] Cited for: VARIANTS NPC1 SER-237; HIS-242; ARG-272; ALA-378; GLN-404; GLN-518; VAL-605; ARG-631; PRO-724; PRO-775; CYS-825; VAL-874; GLN-934; MET-943; ASN-944; MET-950; SER-986; ARG-992; ALA-1007; THR-1054; THR-1061; THR-1142; TYR-1168 AND HIS-1186.
[14]	"Clinical-biochemical correlation in molecularly characterized patients with Niemann-Pick type C." Meiner V., Shpitzen S., Mandel H., Klar A., Ben-Neriah Z., Zlotogora J., Sagi M., Lossos A., Bargal R., Sury V., Carmi R., Leitersdorf E., Zeigler M. Genet. Med. 3:343-348(2001) [PubMed: 11545687] [Abstract] Cited for: VARIANTS NPC1 ARG-63; GLN-404; VAL-927; TRP-992; ASP-1012 AND SER-1156.
[15]	"Niemann-Pick type C disease: NPC1 mutations associated with severe and mild cellular cholesterol trafficking alterations." Ribeiro I., Marcao A., Amaral O., Sa Miranda M.C., Vanier M.T., Millat G. Hum. Genet. 109:24-32(2001) [PubMed: 11479732] [Abstract] Cited for: VARIANTS NPC1 ARG-92; TYR-177; TRP-518; CYS-942; CYS-978; ALA-1007 VAL-1035 AND THR-1061, VARIANTS ARG-215; ILE-642 AND VAL-858.
[16]	"Identification of novel mutations in the NPC1 gene in German patients with Niemann-Pick C disease." Kaminski W.E., Kluenemann H.H., Ibach B., Aslanidis C., Klein H.E., Schmitz G. J. Inherit. Metab. Dis. 25:385-389(2002) [PubMed: 12408188] [Abstract] Cited for: VARIANTS NPC1 GLY-231; SER-237; VAL-874 ASN-948 AND THR-1094, VARIANTS CYS-381 AND ILE-642.
[17]	"Niemann-Pick type C disease: mutations of NPC1 gene and evidence of abnormal expression of some mutant alleles in fibroblasts." Tarugi P., Ballarini G., Bembi B., Battisti C., Palmeri S., Panzani F., Di Leo E., Martini C., Federico A., Calandra S. J. Lipid Res. 43:1908-1919(2002) [PubMed: 12401890] [Abstract] Cited for: VARIANTS NPC1 LYS-451; LEU-474; CYS-890; ASP-899; SER-910; TRP-992; ALA-1007; THR-1061 AND SER-1156, VARIANTS ARG-215; ILE-642 AND VAL-858.
[18]	"Defective endocytic trafficking of NPC1 and NPC2 underlying infantile Niemann-Pick type C disease." Blom T.S., Linder M.D., Snow K., Pihko H., Hess M.W., Jokitalo E., Veckman V., Syvaenen A.-C., Ikonen E. Hum. Mol. Genet. 12:257-272(2003) [PubMed: 12554680] [Abstract] Cited for: VARIANT NPC1 ARG-113, VARIANT SER-273, CHARACTERIZATION OF VARIANT NPC1 ARG-113, CHARACTERIZATION OF VARIANT SER-273.
[19]	"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 NPC1 TYR-74; SER-166; SER-222; TYR-247; PHE-380; PRO-388; CYS-389; TRP-404; LEU-433; SER-509; SER-521; LEU-543; CYS-615; ARG-640; SER-660; MET-664; VAL-673; PHE-684; LEU-691; VAL-695; ASN-700; ILE-734; LYS-742; GLU-745; VAL-767; GLY-789; ASN-945; ARG-1016; GLN-1059; LEU-1087; ILE-1137; VAL-1140; LYS-1205 AND GLY-1249, VARIANTS ARG-215; SER-237; SER-434 AND GLN-1266.
[20]	"Identification of 25 new mutations in 40 unrelated Spanish Niemann-Pick type C patients: genotype-phenotype correlations." Fernandez-Valero E.M., Ballart A., Iturriaga C., Lluch M., Macias J., Vanier M.T., Pineda M., Coll M.J. Clin. Genet. 68:245-254(2005) [PubMed: 16098014] [Abstract] Cited for: VARIANTS NPC1 MET-137; TYR-177; TRP-372; LEU-434; LEU-474; TYR-479; ARG-576; MET-664; PHE-727; LYS-754; PRO-775; LEU-865; THR-926; CYS-942; ASN-944; HIS-948; GLU-959; 961-ASN--PHE-966 DELINS SER; ALA-1007; VAL-1035; LYS-1036; THR-1061; ASN-1066; ILE-1156; SER-1156 AND LEU-1224, VARIANTS ARG-215; ILE-642; VAL-858 AND GLN-1266.
[21]	"Six novel NPC1 mutations in Chinese patients with Niemann-Pick disease type C." Yang C.-C., Su Y.-N., Chiou P.-C., Fietz M.J., Yu C.-L., Hwu W.-L., Lee M.-J. J. Neurol. Neurosurg. Psych. 76:592-595(2005) [PubMed: 15774455] [Abstract] Cited for: VARIANTS NPC1 SER-968; VAL-1015; ARG-1034 AND LEU-1212, VARIANTS ARG-215; ILE-642; VAL-858 AND GLN-1266.
[22]	"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: VARIANTS NPC1 SER-166; TYR-177; PRO-404; LEU-537; LEU-543; LEU-615; ARG-631; LEU-763; CYS-825; LEU-862; LEU-865; CYS-871; TYR-917; GLN-934; LEU-940; MET-950; SER-968; ALA-992; ARG-992; TRP-992; ALA-1007; MET-1036; THR-1061; VAL-1062; ASN-1097; VAL-1174; HIS-1186; VAL-1216 AND ARG-1240, VARIANT MET-511.
[23]	"Subclinical course of adult visceral Niemann-Pick type C1 disease. A rare or underdiagnosed disorder?" Dvorakova L., Sikora J., Hrebicek M., Hulkova H., Bouckova M., Stolnaja L., Elleder M. J. Inherit. Metab. Dis. 29:591-591(2006) [PubMed: 16802107] [Abstract] Cited for: VARIANTS NPC1 ASN-666 AND SER-961.
+	Additional computationally mapped references.

Web resources

Niemann-Pick type C disease gene variation database

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF002020 mRNA. Translation: AAB63982.1.
AF157379 , AF157365, AF157366, AF157367, AF157368, AF157369, AF157370, AF157371, AF157372, AF157373, AF157374, AF157375, AF157376, AF157377, AF157378 Genomic DNA. Translation: AAD48006.1.
AF338230 Genomic DNA. Translation: AAK25791.1.
AF123046, AF123045 Genomic DNA. Translation: AAF28875.1.
BC063302 mRNA. Translation: AAH63302.1.

IPI

IPI00005107.

RefSeq

NP_000262.2.

UniGene

Hs.464779
Hs.529006

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3GKH	X-ray	1.81	A	23-252	[»]
3GKI	X-ray	1.80	A	23-252	[»]
3GKJ	X-ray	1.60	A	23-252	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

O15118.

Protein family/group databases

TCDB

2.A.6.6.1. resistance-nodulation-cell division (RND) superfamily.

Proteomic databases

PeptideAtlas

O15118.

PRIDE

O15118.

Genome annotation databases

Ensembl

ENST00000269228; ENSP00000269228; ENSG00000141458; Homo sapiens. [Genome view]
ENST00000412552; ENSP00000408606; ENSG00000141458; Homo sapiens. [Genome view]

GeneID

4864.

KEGG

hsa:4864.

NMPDR

fig|9606.3.peg.14865.

UCSC

uc002kum.2. human.

Organism-specific databases

CTD

4864.

GeneCards

GC18M019365.

HGNC

HGNC:7897. NPC1.

HPA

HPA026618.

MIM

257220. phenotype.
607623. gene.

Orphanet

646. Niemann-Pick disease, type C.

PharmGKB

PA26398.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

O15118.

OMA

VGATYFM.

Gene expression databases

ArrayExpress

O15118.

Bgee

O15118.

CleanEx

HS_NPC1.

Genevestigator

O15118.

GermOnline

ENSG00000141458. Homo sapiens.

Family and domain databases

InterPro

IPR004765. NP_C_type.
IPR003392. Patched.
IPR000731. SSD_5TM.
[Graphical view]

Pfam

PF02460. Patched. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00917. 2A060601. 1 hit.

PROSITE

PS50156. SSD. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

18738.

SOURCE

Search...

Entry information

Entry name

NPC1_HUMAN

Accession

Primary (citable) accession number: O15118
Secondary accession number(s): Q9P130

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	May 10, 2005
Last modified:	November 3, 2009
This is version 96 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.