UniProt ID | NPC1_HUMAN | |
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UniProt AC | O15118 | |
Protein Name | NPC intracellular cholesterol transporter 1 {ECO:0000312|HGNC:HGNC:7897} | |
Gene Name | NPC1 {ECO:0000312|HGNC:HGNC:7897} | |
Organism | Homo sapiens (Human). | |
Sequence Length | 1278 | |
Subcellular Localization |
Late endosome membrane Multi-pass membrane protein . Lysosome membrane Multi-pass membrane protein . |
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Protein 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.; (Microbial infection) Acts as an endosomal entry receptor for ebolavirus.. | |
Protein Sequence | MTARGLALGLLLLLLCPAQVFSQSCVWYGECGIAYGDKRYNCEYSGPPKPLPKDGYDLVQELCPGFFFGNVSLCCDVRQLQTLKDNLQLPLQFLSRCPSCFYNLLNLFCELTCSPRQSQFLNVTATEDYVDPVTNQTKTNVKELQYYVGQSFANAMYNACRDVEAPSSNDKALGLLCGKDADACNATNWIEYMFNKDNGQAPFTITPVFSDFPVHGMEPMNNATKGCDESVDEVTAPCSCQDCSIVCGPKPQPPPPPAPWTILGLDAMYVIMWITYMAFLLVFFGAFFAVWCYRKRYFVSEYTPIDSNIAFSVNASDKGEASCCDPVSAAFEGCLRRLFTRWGSFCVRNPGCVIFFSLVFITACSSGLVFVRVTTNPVDLWSAPSSQARLEKEYFDQHFGPFFRTEQLIIRAPLTDKHIYQPYPSGADVPFGPPLDIQILHQVLDLQIAIENITASYDNETVTLQDICLAPLSPYNTNCTILSVLNYFQNSHSVLDHKKGDDFFVYADYHTHFLYCVRAPASLNDTSLLHDPCLGTFGGPVFPWLVLGGYDDQNYNNATALVITFPVNNYYNDTEKLQRAQAWEKEFINFVKNYKNPNLTISFTAERSIEDELNRESDSDVFTVVISYAIMFLYISLALGHMKSCRRLLVDSKVSLGIAGILIVLSSVACSLGVFSYIGLPLTLIVIEVIPFLVLAVGVDNIFILVQAYQRDERLQGETLDQQLGRVLGEVAPSMFLSSFSETVAFFLGALSVMPAVHTFSLFAGLAVFIDFLLQITCFVSLLGLDIKRQEKNRLDIFCCVRGAEDGTSVQASESCLFRFFKNSYSPLLLKDWMRPIVIAIFVGVLSFSIAVLNKVDIGLDQSLSMPDDSYMVDYFKSISQYLHAGPPVYFVLEEGHDYTSSKGQNMVCGGMGCNNDSLVQQIFNAAQLDNYTRIGFAPSSWIDDYFDWVKPQSSCCRVDNITDQFCNASVVDPACVRCRPLTPEGKQRPQGGDFMRFLPMFLSDNPNPKCGKGGHAAYSSAVNILLGHGTRVGATYFMTYHTVLQTSADFIDALKKARLIASNVTETMGINGSAYRVFPYSVFYVFYEQYLTIIDDTIFNLGVSLGAIFLVTMVLLGCELWSAVIMCATIAMVLVNMFGVMWLWGISLNAVSLVNLVMSCGISVEFCSHITRAFTVSMKGSRVERAEEALAHMGSSVFSGITLTKFGGIVVLAFAKSQIFQIFYFRMYLAMVLLGATHGLIFLPVLLSYIGPSVNKAKSCATEERYKGTERERLLNF | |
Overview of Protein Modification Sites with Functional and Structural Information | ||
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* ASA = Accessible Surface Area
Locations | Modification | Substrate Peptides & Secondary Structure |
ASA (%) | Reference | Orthologous Protein Cluster |
---|---|---|---|---|---|
49 | Ubiquitination | CEYSGPPKPLPKDGY CCCCCCCCCCCCCCH | 63.42 | 29967540 | |
70 | N-linked_Glycosylation | CPGFFFGNVSLCCDV CCCCCCCCEEEECCH | 18.30 | 10821832 | |
84 | Ubiquitination | VRQLQTLKDNLQLPL HHHHHHHHHHCHHCH | 48.21 | 21906983 | |
95 | Phosphorylation | QLPLQFLSRCPSCFY HHCHHHHHCCCHHHH | 32.88 | 21712546 | |
122 | N-linked_Glycosylation | PRQSQFLNVTATEDY CCHHHCCCEEECCCC | 30.31 | 10821832 | |
135 | N-linked_Glycosylation | DYVDPVTNQTKTNVK CCCCCCCCCCCCCHH | 48.00 | 27238017 | |
142 | Ubiquitination | NQTKTNVKELQYYVG CCCCCCHHHHHHHHH | 55.57 | - | |
158 | N-linked_Glycosylation | SFANAMYNACRDVEA HHHHHHHHHHHCCCC | 21.34 | 19563754 | |
171 | Ubiquitination | EAPSSNDKALGLLCG CCCCCCCCCHHHHHC | 50.16 | 29967540 | |
185 | N-linked_Glycosylation | GKDADACNATNWIEY CCCHHHCCCCHHHHH | 52.07 | 10821832 | |
222 | N-linked_Glycosylation | HGMEPMNNATKGCDE CCCCCCCCCCCCCCC | 42.61 | 19563754 | |
254 | Ubiquitination | CGPKPQPPPPPAPWT ECCCCCCCCCCCCCC | 49.10 | 22817900 | |
297 | Phosphorylation | VWCYRKRYFVSEYTP HHHHHHHHEEEECCC | 16.03 | 29888752 | |
300 | Phosphorylation | YRKRYFVSEYTPIDS HHHHHEEEECCCCCC | 18.26 | 29888752 | |
302 | Phosphorylation | KRYFVSEYTPIDSNI HHHEEEECCCCCCCE | 15.43 | 29888752 | |
303 | Phosphorylation | RYFVSEYTPIDSNIA HHEEEECCCCCCCEE | 15.09 | 29888752 | |
307 | Phosphorylation | SEYTPIDSNIAFSVN EECCCCCCCEEEEEE | 30.75 | 29888752 | |
312 | Phosphorylation | IDSNIAFSVNASDKG CCCCEEEEEECCCCC | 12.87 | 29888752 | |
316 | Phosphorylation | IAFSVNASDKGEASC EEEEEECCCCCCCCC | 34.35 | 29888752 | |
382 | Phosphorylation | TNPVDLWSAPSSQAR CCCCCCCCCCCHHHH | 37.28 | 25599653 | |
385 | Phosphorylation | VDLWSAPSSQARLEK CCCCCCCCHHHHHHH | 34.50 | - | |
386 | Phosphorylation | DLWSAPSSQARLEKE CCCCCCCHHHHHHHH | 27.14 | - | |
392 | Ubiquitination | SSQARLEKEYFDQHF CHHHHHHHHHHHHHC | 63.41 | 21906983 | |
394 | Phosphorylation | QARLEKEYFDQHFGP HHHHHHHHHHHHCCC | 24.43 | - | |
409 | Ubiquitination | FFRTEQLIIRAPLTD CCCCCEEEEECCCCC | 1.68 | 22817900 | |
447 | Ubiquitination | LHQVLDLQIAIENIT HHHHHHHHHHHEEEC | 23.80 | 21963094 | |
452 | N-linked_Glycosylation | DLQIAIENITASYDN HHHHHHEEECEECCC | 30.69 | 28784760 | |
459 | N-linked_Glycosylation | NITASYDNETVTLQD EECEECCCCCEEEEE | 38.31 | 28784760 | |
478 | N-linked_Glycosylation | PLSPYNTNCTILSVL CCCCCCCCCCHHHHH | 19.80 | 28784760 | |
504 | Ubiquitination | HKKGDDFFVYADYHT CCCCCCEEEEEECCC | 5.44 | - | |
524 | N-linked_Glycosylation | VRAPASLNDTSLLHD EECCCCCCCCCCCCC | 48.28 | 26846330 | |
557 | N-linked_Glycosylation | YDDQNYNNATALVIT CCCCCCCCCEEEEEE | 28.45 | 28784760 | |
564 | Phosphorylation | NATALVITFPVNNYY CCEEEEEEEECCCCC | 17.88 | 28787133 | |
570 | Phosphorylation | ITFPVNNYYNDTEKL EEEECCCCCCCHHHH | 9.84 | 28787133 | |
571 | Phosphorylation | TFPVNNYYNDTEKLQ EEECCCCCCCHHHHH | 14.53 | 28787133 | |
572 | N-linked_Glycosylation | FPVNNYYNDTEKLQR EECCCCCCCHHHHHH | 39.09 | 26846330 | |
574 | Phosphorylation | VNNYYNDTEKLQRAQ CCCCCCCHHHHHHHH | 31.23 | 28787133 | |
585 | Ubiquitination | QRAQAWEKEFINFVK HHHHHHHHHHHHHHH | 47.42 | 21906983 | |
598 | N-linked_Glycosylation | VKNYKNPNLTISFTA HHHCCCCCEEEEEEE | 60.24 | 28784760 | |
602 | Ubiquitination | KNPNLTISFTAERSI CCCCEEEEEEECCCH | 16.00 | 21963094 | |
684 | Ubiquitination | YIGLPLTLIVIEVIP HCCCCHHHHHHHHHH | 3.76 | 22817900 | |
692 | Ubiquitination | IVIEVIPFLVLAVGV HHHHHHHHHHHHHCC | 5.18 | - | |
799 | S-palmitoylation | KNRLDIFCCVRGAED HCCCEEEEEEECCCC | 1.83 | 29575903 | |
800 | S-palmitoylation | NRLDIFCCVRGAEDG CCCEEEEEEECCCCC | 1.30 | 29575903 | |
822 | Ubiquitination | SCLFRFFKNSYSPLL HHHHHHHHCCCCCHH | 42.12 | 21906983 | |
826 | Phosphorylation | RFFKNSYSPLLLKDW HHHHCCCCCHHHHHC | 14.64 | - | |
839 | Ubiquitination | DWMRPIVIAIFVGVL HCHHHHHHHHHHHHH | 2.23 | 22817900 | |
862 | Ubiquitination | KVDIGLDQSLSMPDD CCCCCCCCCCCCCCC | 51.84 | 21890473 | |
903 | Acetylation | GHDYTSSKGQNMVCG CCCCCCCCCCCEECC | 65.37 | 30590875 | |
916 | N-linked_Glycosylation | CGGMGCNNDSLVQQI CCCCCCCCHHHHHHH | 44.30 | 28784760 | |
931 | N-linked_Glycosylation | FNAAQLDNYTRIGFA HHHHHCCCCCEEECC | 48.98 | 28784760 | |
961 | N-linked_Glycosylation | SSCCRVDNITDQFCN CCCCCCCCCCHHCCC | 35.88 | 28784760 | |
963 | Phosphorylation | CCRVDNITDQFCNAS CCCCCCCCHHCCCCC | 29.97 | 30576142 | |
968 | N-linked_Glycosylation | NITDQFCNASVVDPA CCCHHCCCCCCCCHH | 36.22 | 28784760 | |
987 | Ubiquitination | RPLTPEGKQRPQGGD EECCCCCCCCCCCCC | 41.28 | 29967540 | |
1010 | Ubiquitination | LSDNPNPKCGKGGHA HCCCCCCCCCCCHHH | 63.36 | - | |
1042 | Ubiquitination | ATYFMTYHTVLQTSA CEEEECHHHHHHCCH | 10.59 | 27667366 | |
1064 | N-linked_Glycosylation | KARLIASNVTETMGI HHHHHHCCCCCCCCC | 35.39 | 28784760 | |
1072 | N-linked_Glycosylation | VTETMGINGSAYRVF CCCCCCCCCCCEECC | 32.41 | UniProtKB CARBOHYD | |
1180 | Ubiquitination | RAFTVSMKGSRVERA HCEEEEECCCHHHHH | 46.35 | 32142685 | |
1182 | Phosphorylation | FTVSMKGSRVERAEE EEEEECCCHHHHHHH | 27.86 | 28985074 | |
1196 | Phosphorylation | EALAHMGSSVFSGIT HHHHHCCCCCCCCCE | 18.76 | 28985074 | |
1197 | Phosphorylation | ALAHMGSSVFSGITL HHHHCCCCCCCCCEE | 22.81 | 28985074 | |
1197 | Ubiquitination | ALAHMGSSVFSGITL HHHHCCCCCCCCCEE | 22.81 | 27667366 | |
1259 | Ubiquitination | GPSVNKAKSCATEER CCCCCCHHCCCCCHH | 47.91 | 33845483 | |
1270 | Phosphorylation | TEERYKGTERERLLN CCHHHCCCHHHHHHC | 27.93 | 20068231 |
Modified Location | Modified Residue | Modification | Type of Upstream Proteins | Gene Name of Upstream Proteins | UniProt AC of Upstream Proteins | Sources |
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Oops, there are no upstream regulatory protein records of NPC1_HUMAN !! |
Modified Location | Modified Residue | Modification | Function | Reference | ||
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Oops, there are no descriptions of PTM sites of NPC1_HUMAN !! |
* Distance = the distance between SAP position and PTM sites.
Modified Location | Modification | Variant Position (Distance <= 10) |
Residue Change | SAP | Related Disease | Reference |
---|---|---|---|---|---|---|
Oops, there are no SNP-PTM records of NPC1_HUMAN !! |
Interacting Protein | Gene Name | Interaction Type | PPI Reference | Domain-Domain Interactions |
---|---|---|---|---|
RT28_HUMAN | MRPS28 | physical | 22939629 | |
TMOD3_HUMAN | TMOD3 | physical | 22939629 |
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N-linked Glycosylation | |
Reference | PubMed |
"Glycoproteomics analysis of human liver tissue by combination ofmultiple 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). Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-135 AND ASN-524, AND MASSSPECTROMETRY. |