CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-000379
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Niemann-Pick C1 protein 
Protein Synonyms/Alias
  
Gene Name
 NPC1 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
49CEYSGPPKPLPKDGYubiquitination[1]
84VRQLQTLKDNLQLPLubiquitination[2, 3]
392SSQARLEKEYFDQHFubiquitination[1, 2]
585QRAQAWEKEFINFVKubiquitination[1, 2, 3, 4]
822SCLFRFFKNSYSPLLubiquitination[2]
1010LSDNPNPKCGKGGHAubiquitination[1]
1180RAFTVSMKGSRVERAubiquitination[1, 2, 4, 5, 6, 7]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [4] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [5] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [6] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [7] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789] 
Functional Description
 Intracellular cholesterol transporter which acts in concert with NPC2 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. Binds oxysterol with higher affinity than 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. 
Sequence Annotation
 DOMAIN 620 785 SSD.
 MOTIF 1275 1278 Di-leucine motif.
 CARBOHYD 70 70 N-linked (GlcNAc...) (Potential).
 CARBOHYD 122 122 N-linked (GlcNAc...) (Potential).
 CARBOHYD 135 135 N-linked (GlcNAc...).
 CARBOHYD 185 185 N-linked (GlcNAc...) (Potential).
 CARBOHYD 222 222 N-linked (GlcNAc...) (Potential).
 CARBOHYD 452 452 N-linked (GlcNAc...) (Potential).
 CARBOHYD 459 459 N-linked (GlcNAc...) (Potential).
 CARBOHYD 478 478 N-linked (GlcNAc...) (Potential).
 CARBOHYD 524 524 N-linked (GlcNAc...).
 CARBOHYD 961 961 N-linked (GlcNAc...) (Potential).
 CARBOHYD 968 968 N-linked (GlcNAc...) (Potential).
 CARBOHYD 1064 1064 N-linked (GlcNAc...) (Potential).
 CARBOHYD 1072 1072 N-linked (GlcNAc...) (Potential).  
Keyword
 3D-structure; Cholesterol metabolism; Complete proteome; Disease mutation; Endosome; Glycoprotein; Lipid metabolism; Lysosome; Membrane; Niemann-Pick disease; Polymorphism; Reference proteome; Signal; Steroid metabolism; Sterol metabolism; Transmembrane; Transmembrane helix. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1278 AA 
Protein Sequence
MTARGLALGL LLLLLCPAQV FSQSCVWYGE CGIAYGDKRY NCEYSGPPKP LPKDGYDLVQ 60
ELCPGFFFGN VSLCCDVRQL QTLKDNLQLP LQFLSRCPSC FYNLLNLFCE LTCSPRQSQF 120
LNVTATEDYV DPVTNQTKTN VKELQYYVGQ SFANAMYNAC RDVEAPSSND KALGLLCGKD 180
ADACNATNWI EYMFNKDNGQ APFTITPVFS DFPVHGMEPM NNATKGCDES VDEVTAPCSC 240
QDCSIVCGPK PQPPPPPAPW TILGLDAMYV IMWITYMAFL LVFFGAFFAV WCYRKRYFVS 300
EYTPIDSNIA FSVNASDKGE ASCCDPVSAA FEGCLRRLFT RWGSFCVRNP GCVIFFSLVF 360
ITACSSGLVF VRVTTNPVDL WSAPSSQARL EKEYFDQHFG PFFRTEQLII RAPLTDKHIY 420
QPYPSGADVP FGPPLDIQIL HQVLDLQIAI ENITASYDNE TVTLQDICLA PLSPYNTNCT 480
ILSVLNYFQN SHSVLDHKKG DDFFVYADYH THFLYCVRAP ASLNDTSLLH DPCLGTFGGP 540
VFPWLVLGGY DDQNYNNATA LVITFPVNNY YNDTEKLQRA QAWEKEFINF VKNYKNPNLT 600
ISFTAERSIE DELNRESDSD VFTVVISYAI MFLYISLALG HMKSCRRLLV DSKVSLGIAG 660
ILIVLSSVAC SLGVFSYIGL PLTLIVIEVI PFLVLAVGVD NIFILVQAYQ RDERLQGETL 720
DQQLGRVLGE VAPSMFLSSF SETVAFFLGA LSVMPAVHTF SLFAGLAVFI DFLLQITCFV 780
SLLGLDIKRQ EKNRLDIFCC VRGAEDGTSV QASESCLFRF FKNSYSPLLL KDWMRPIVIA 840
IFVGVLSFSI AVLNKVDIGL DQSLSMPDDS YMVDYFKSIS QYLHAGPPVY FVLEEGHDYT 900
SSKGQNMVCG GMGCNNDSLV QQIFNAAQLD NYTRIGFAPS SWIDDYFDWV KPQSSCCRVD 960
NITDQFCNAS VVDPACVRCR PLTPEGKQRP QGGDFMRFLP MFLSDNPNPK CGKGGHAAYS 1020
SAVNILLGHG TRVGATYFMT YHTVLQTSAD FIDALKKARL IASNVTETMG INGSAYRVFP 1080
YSVFYVFYEQ YLTIIDDTIF NLGVSLGAIF LVTMVLLGCE LWSAVIMCAT IAMVLVNMFG 1140
VMWLWGISLN AVSLVNLVMS CGISVEFCSH ITRAFTVSMK GSRVERAEEA LAHMGSSVFS 1200
GITLTKFGGI VVLAFAKSQI FQIFYFRMYL AMVLLGATHG LIFLPVLLSY IGPSVNKAKS 1260
CATEERYKGT ERERLLNF 1278 
Gene Ontology
 GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
 GO:0005576; C:extracellular region; ISS:UniProtKB.
 GO:0005794; C:Golgi apparatus; IEA:Compara.
 GO:0005887; C:integral to plasma membrane; IDA:UniProtKB.
 GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
 GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
 GO:0005764; C:lysosome; ISS:UniProtKB.
 GO:0045121; C:membrane raft; IEA:Compara.
 GO:0005635; C:nuclear envelope; IDA:UniProtKB.
 GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
 GO:0031982; C:vesicle; IEA:Compara.
 GO:0015485; F:cholesterol binding; IDA:UniProtKB.
 GO:0008158; F:hedgehog receptor activity; IEA:InterPro.
 GO:0015248; F:sterol transporter activity; TAS:ProtInc.
 GO:0004888; F:transmembrane signaling receptor activity; TAS:ProtInc.
 GO:0007628; P:adult walking behavior; IEA:Compara.
 GO:0006914; P:autophagy; IGI:MGI.
 GO:0008206; P:bile acid metabolic process; ISS:UniProtKB.
 GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; IEA:Compara.
 GO:0071383; P:cellular response to steroid hormone stimulus; IEA:Compara.
 GO:0033344; P:cholesterol efflux; IDA:BHF-UCL.
 GO:0042632; P:cholesterol homeostasis; IDA:UniProtKB.
 GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
 GO:0006897; P:endocytosis; IEA:Compara.
 GO:0007041; P:lysosomal transport; ISS:UniProtKB.
 GO:0016242; P:negative regulation of macroautophagy; IEA:Compara.
 GO:0006486; P:protein glycosylation; IDA:UniProtKB.
 GO:0042493; P:response to drug; IEA:Compara. 
Interpro
 IPR004765; NP_C_type.
 IPR003392; Patched.
 IPR000731; SSD. 
Pfam
 PF02460; Patched 
SMART
  
PROSITE
 PS50156; SSD 
PRINTS