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2.A.6.6.3
Yeast sterol transport system consisting of two proteins, NCR1 (YPL006w) and NPC2 (YDL046w), components of the Niemann-Pick Type C transporter. It drives sterol integration into the lysosomal membrane before redistributing them to other cellular membranes. Expression of yeast NP-C-related gene 1 (NCR1), the orthologue of the human NP-C gene 1 (NPC1) defective in the disease, in Chinese hamster ovary NPC1 mutant cells suppressed lipid accumulation (Malathi et al. 2004). Deletion of NCR1, encoding a transmembrane glycoprotein predominantly residing in the vacuole of normal yeast, gave no phenotype. However, a dominant mutation in the putative sterol-sensing domain of Ncr1p conferred temperature and polyene antibiotic sensitivity without changes in sterol metabolism. Instead, the mutant cells were resistant to inhibitors of sphingolipid biosynthesis and super sensitive to sphingosine and C2-ceramide. Plasma membrane sphingolipids accumulated and redistributed to the vacuole and other subcellular membranes of the mutant cells. Malathi et al. 2004 proposed that the primordial function of these proteins is to recycle sphingolipids, and that defects in this process in higher eukaryotes secondarily result in cholesterol accumulation. Winkler et al. 2019 presented a framework for sterol membrane integration. Sterols are transferred between hydrophobic pockets of vacuolar NPC2 and NCR1. NCR1 has its N-terminal domain (NTD) positioned to deliver a sterol to a tunnel connecting the NTD to the luminal membrane leaflet, 50 Å away. A sterol is caught inside this tunnel during transport, and a proton-relay network of charged residues in the transmembrane region is linked to this tunnel, supporting a proton-driven transport mechanism. Winkler et al. 2019 proposed a model for sterol integration that clarifies the role of these NPC proteins. . 

Accession Number:Q12200
Protein Name:NCR1 aka YPL006W aka LPA11W
Length:1170
Molecular Weight:132645.00
Species:Saccharomyces cerevisiae (Baker's yeast) [4932]
Number of TMSs:13
Location1 / Topology2 / Orientation3: Vacuole membrane1 / Multi-pass membrane protein2
Substrate

Cross database links:

RefSeq: NP_015319.1   
Entrez Gene ID: 856101   
Pfam: PF02460   
KEGG: sce:YPL006W   

Gene Ontology

GO:0000329 C:fungal-type vacuole membrane
GO:0016021 C:integral to membrane
GO:0008158 F:hedgehog receptor activity
GO:0005515 F:protein binding
GO:0046624 F:sphingolipid transporter activity
GO:0006869 P:lipid transport
GO:0006665 P:sphingolipid metabolic process

References (6)

[1] “The nucleotide sequence of Saccharomyces cerevisiae chromosome XVI.”  Bussey H.et.al.   9169875
[2] “Global analysis of protein localization in budding yeast.”  Huh W.-K.et.al.   14562095
[3] “Global analysis of protein expression in yeast.”  Ghaemmaghami S.et.al.   14562106
[4] “Mutagenesis of the putative sterol-sensing domain of yeast Niemann Pick C-related protein reveals a primordial role in subcellular sphingolipid distribution.”  Malathi K.et.al.   14970192
[5] “Ncr1p, the yeast ortholog of mammalian Niemann Pick C1 protein, is dispensable for endocytic transport.”  Zhang S.et.al.   15522102
[6] “A yeast model system for functional analysis of the Niemann-Pick type C protein 1 homolog, Ncr1p.”  Berger A.C.et.al.   16138904
Structure:
6R4L     

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MNVLWIIALV GQLMRLVQGT ATCAMYGNCG KKSVFGNELP CPVPRSFEPP VLSDETSKLL 
61:	VEVCGEEWKE VRYACCTKDQ VVALRDNLQK AQPLISSCPA CLKNFNNLFC HFTCAADQGR 
121:	FVNITKVEKS KEDKDIVAEL DVFMNSSWAS EFYDSCKNIK FSATNGYAMD LIGGGAKNYS 
181:	QFLKFLGDAK PMLGGSPFQI NYKYDLANEE KEWQEFNDEV YACDDAQYKC ACSDCQESCP 
241:	HLKPLKDGVC KVGPLPCFSL SVLIFYTICA LFAFMWYYLC KRKKNGAMIV DDDIVPESGS 
301:	LDESETNVFE SFNNETNFFN GKLANLFTKV GQFSVENPYK ILITTVFSIF VFSFIIFQYA 
361:	TLETDPINLW VSKNSEKFKE KEYFDDNFGP FYRTEQIFVV NETGPVLSYE TLHWWFDVEN 
421:	FITEELQSSE NIGYQDLCFR PTEDSTCVIE SFTQYFQGAL PNKDSWKREL QECGKFPVNC 
481:	LPTFQQPLKT NLLFSDDDIL NAHAFVVTLL LTNHTQSANR WEERLEEYLL DLKVPEGLRI 
541:	SFNTEISLEK ELNNNNDIST VAISYLMMFL YATWALRRKD GKTRLLLGIS GLLIVLASIV 
601:	CAAGFLTLFG LKSTLIIAEV IPFLILAIGI DNIFLITHEY DRNCEQKPEY SIDQKIISAI 
661:	GRMSPSILMS LLCQTGCFLI AAFVTMPAVH NFAIYSTVSV IFNGVLQLTA YVSILSLYEK 
721:	RSNYKQITGN EETKESFLKT FYFKMLTQKR LIIIIFSAWF FTSLVFLPEI QFGLDQTLAV 
781:	PQDSYLVDYF KDVYSFLNVG PPVYMVVKNL DLTKRQNQQK ICGKFTTCER DSLANVLEQE 
841:	RHRSTITEPL ANWLDDYFMF LNPQNDQCCR LKKGTDEVCP PSFPSRRCET CFQQGSWNYN 
901:	MSGFPEGKDF MEYLSIWINA PSDPCPLGGR APYSTALVYN ETSVSASVFR TAHHPLRSQK 
961:	DFIQAYSDGV RISSSFPELD MFAYSPFYIF FVQYQTLGPL TLKLIGSAII LIFFISSVFL 
1021:	QNIRSSFLLA LVVTMIIVDI GALMALLGIS LNAVSLVNLI ICVGLGVEFC VHIVRSFTVV 
1081:	PSETKKDANS RVLYSLNTIG ESVIKGITLT KFIGVCVLAF AQSKIFDVFY FRMWFTLIIV 
1141:	AALHALLFLP ALLSLFGGES YRDDSIEAED