Target Information
| Target General Information | Top | |||||
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| Target ID |
T47098
(Former ID: TTDI00233)
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| Target Name |
ATP-binding cassette transporter G1 (ABCG1)
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| Synonyms |
White protein homolog; WHT1; ATP-binding cassette transporter 8; ATP-binding cassette sub-family G member 1; ABC8
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| Gene Name |
ABCG1
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Catalyzes the efflux of phospholipids such as sphingomyelin, cholesterol and its oxygenated derivatives like 7beta-hydroxycholesterol and this transport is coupled to hydrlysis of ATP. The lipid efflux is ALB-dependent. Is an active component of the macrophage lipid export complex. Could also be involved in intracellular lipid transport processes. The role in cellular lipid homeostasis may not be limited to macrophages. Prevents cell death by transporting cytotoxic 7beta-hydroxycholesterol.
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| BioChemical Class |
ABC transporter
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| UniProt ID | ||||||
| Sequence |
MACLMAAFSVGTAMNASSYSAEMTEPKSVCVSVDEVVSSNMEATETDLLNGHLKKVDNNL
TEAQRFSSLPRRAAVNIEFRDLSYSVPEGPWWRKKGYKTLLKGISGKFNSGELVAIMGPS GAGKSTLMNILAGYRETGMKGAVLINGLPRDLRCFRKVSCYIMQDDMLLPHLTVQEAMMV SAHLKLQEKDEGRREMVKEILTALGLLSCANTRTGSLSGGQRKRLAIALELVNNPPVMFF DEPTSGLDSASCFQVVSLMKGLAQGGRSIICTIHQPSAKLFELFDQLYVLSQGQCVYRGK VCNLVPYLRDLGLNCPTYHNPADFVMEVASGEYGDQNSRLVRAVREGMCDSDHKRDLGGD AEVNPFLWHRPSEEVKQTKRLKGLRKDSSSMEGCHSFSASCLTQFCILFKRTFLSIMRDS VLTHLRITSHIGIGLLIGLLYLGIGNEAKKVLSNSGFLFFSMLFLMFAALMPTVLTFPLE MGVFLREHLNYWYSLKAYYLAKTMADVPFQIMFPVAYCSIVYWMTSQPSDAVRFVLFAAL GTMTSLVAQSLGLLIGAASTSLQVATFVGPVTAIPVLLFSGFFVSFDTIPTYLQWMSYIS YVRYGFEGVILSIYGLDREDLHCDIDETCHFQKSEAILRELDVENAKLYLDFIVLGIFFI SLRLIAYFVLRYKIRAER Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T69VYP | |||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Adenosine triphosphate | Ligand Info | |||||
| Structure Description | Cryo-EM structure of the human cholesterol transporter ABCG1 in complex with cholesterol | PDB:7FDV | ||||
| Method | Electron microscopy | Resolution | 3.26 Å | Mutation | No | [2] |
| PDB Sequence |
RAAVNIEFRD
81 LSYSVPGYKT99 LLKGISGKFN109 SGELVAIMGP119 SGAGKSTLMN129 ILAGYRETGM 139 KGAVLINGLP149 RDLRCFRKVS159 CYIMQDDMLL169 PHLTVQEAMM179 VSAHLKLQEK 189 DEGRREMVKE199 ILTALGLLSC209 ANTRTGSLSG219 GQRKRLAIAL229 ELVNNPPVMF 239 FDQPTSGLDS249 ASCFQVVSLM259 KGLAQGGRSI269 ICTIHQPSAK279 LFELFDQLYV 289 LSQGQCVYRG299 KVCNLVPYLR309 DLGLNCPTYH319 NPADFVMEVA329 SGEYCLTQFC 406 ILFKRTFLSI416 MRDSVLTHLR426 ITSHIGIGLL436 IGLLYLGIGN446 EAKKVLSNSG 456 FLFFSMLFLM466 FAALMPTVLT476 FPLEMGVFLR486 EHLNYWYSLK496 AYYLAKTMAD 506 VPFQIMFPVA516 YCSIVYWMTS526 QPSDAVRFVL536 FAALGTMTSL546 VAQSLGLLIG 556 AASTSLQVAT566 FVGPVTAIPV576 LLFSGFFVSF586 DTIPTYLQWM596 SYISYVRYGF 606 EGVILSIYGL616 DREDLHCDID626 ETCHFQKSEA636 ILRELDVENA646 KLYLDFIVLG 656 IFFISLRLIA666 YFVLRYKIR
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Cholesterol | Ligand Info | |||||
| Structure Description | The structure of human ABCG1 E242Q with cholesterol | PDB:7R8D | ||||
| Method | Electron microscopy | Resolution | 3.20 Å | Mutation | Yes | [3] |
| PDB Sequence |
RAAVNIEFRD
81 LSYSVLLKGI104 SGKFNSGELV114 AIMGPSGAGK124 STLMNILAGY134 RETGMKGAVL 144 INGLPRDLRC154 FRKVSCYIMQ164 DDMLLPHLTV174 QEAMMVSAHL184 KLQEKDEGRR 194 EMVKEILTAL204 GLLSCANTRT214 GSLSGGQRKR224 LAIALELVNN234 PPVMFFDQPT 244 SGLDSASCFQ254 VVSLMKGLAQ264 GGRSIICTIH274 QPSAKLFELF284 DQLYVLSQGQ 294 CVYRGKVCNL304 VPYLRDLGLN314 CPTYHNPADF324 VMEVASGEYG334 DQNSRLVRAV 344 REGFSASCLT391 QFCILFKRTF401 LSIMRDSVLT411 HLRITSHIGI421 GLLIGLLYLG 431 IGNEAKKVLS441 NSGFLFFSML451 FLMFAALMPT461 VLTFPLEMGV471 FLREHLNYWY 481 SLKAYYLAKT491 MADVPFQIMF501 PVAYCSIVYW511 MTSQPSDAVR521 FVLFAALGTM 531 TSLVAQSLGL541 LIGAASTSLQ551 VATFVGPVTA561 IPVLLFSGFF571 VSFDTIPTYL 581 QWMSYISYVR591 YGFEGVILSI601 YGLDREDLHC611 DIDETCHFQK621 SEAILRELDV 631 ENAKLYLDFI641 VLGIFFISLR651 LIAYFVLRYK661 IRAER
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| ABC transporters | hsa02010 | Affiliated Target |
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| Class: Environmental Information Processing => Membrane transport | Pathway Hierarchy | ||
| Degree | 2 | Degree centrality | 2.15E-04 | Betweenness centrality | 2.10E-09 |
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| Closeness centrality | 1.86E-01 | Radiality | 1.31E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.60E+01 | Topological coefficient | 7.50E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| References | Top | |||||
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| REF 1 | ABCG1 as a potential oncogene in lung cancer. Exp Ther Med. 2017 Jun;13(6):3189-3194. | |||||
| REF 2 | Structure and transport mechanism of the human cholesterol transporter ABCG1. Cell Rep. 2022 Jan 25;38(4):110298. | |||||
| REF 3 | Molecular basis of cholesterol efflux via ABCG subfamily transporters. Proc Natl Acad Sci U S A. 2021 Aug 24;118(34):e2110483118. | |||||
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