Target Information
| Target General Information | Top | |||||
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| Target ID |
T49327
(Former ID: TTDI02222)
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| Target Name |
ATP-binding cassette transporter A4 (ABCA4)
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| Synonyms |
Stargardt disease protein; RmP; Retinal-specific ATP-binding cassette transporter; RIM protein; RIM ABC transporter; ATP-binding cassette sub-family A member 4; ABCA4
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| Gene Name |
ABCA4
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Inherited retinal dystrophy [ICD-11: 9B70] | |||||
| Function |
In the visualcycle, acts as an inward-directed retinoid flipase, retinoid substrates imported by ABCA4 from the extracellular or intradiscal (rod) membrane surfaces to the cytoplasmic membrane surface are all-trans-retinaldehyde (ATR) and N-retinyl-phosphatidyl-ethanolamine (NR-PE). Once transported to the cytoplasmic surface, ATR is reduced to vitamin A by trans- retinol dehydrogenase (tRDH) and then transferred to the retinal pigment epithelium (RPE) where it is converted to 11-cis-retinal. May play a role in photoresponse, removing ATR/NR-PE from the extracellular photoreceptor surfaces during bleach recovery.
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| BioChemical Class |
ABC transporter
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| UniProt ID | ||||||
| EC Number |
EC 7.6.2.1
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| Sequence |
MGFVRQIQLLLWKNWTLRKRQKIRFVVELVWPLSLFLVLIWLRNANPLYSHHECHFPNKA
MPSAGMLPWLQGIFCNVNNPCFQSPTPGESPGIVSNYNNSILARVYRDFQELLMNAPESQ HLGRIWTELHILSQFMDTLRTHPERIAGRGIRIRDILKDEETLTLFLIKNIGLSDSVVYL LINSQVRPEQFAHGVPDLALKDIACSEALLERFIIFSQRRGAKTVRYALCSLSQGTLQWI EDTLYANVDFFKLFRVLPTLLDSRSQGINLRSWGGILSDMSPRIQEFIHRPSMQDLLWVT RPLMQNGGPETFTKLMGILSDLLCGYPEGGGSRVLSFNWYEDNNYKAFLGIDSTRKDPIY SYDRRTTSFCNALIQSLESNPLTKIAWRAAKPLLMGKILYTPDSPAARRILKNANSTFEE LEHVRKLVKAWEEVGPQIWYFFDNSTQMNMIRDTLGNPTVKDFLNRQLGEEGITAEAILN FLYKGPRESQADDMANFDWRDIFNITDRTLRLVNQYLECLVLDKFESYNDETQLTQRALS LLEENMFWAGVVFPDMYPWTSSLPPHVKYKIRMDIDVVEKTNKIKDRYWDSGPRADPVED FRYIWGGFAYLQDMVEQGITRSQVQAEAPVGIYLQQMPYPCFVDDSFMIILNRCFPIFMV LAWIYSVSMTVKSIVLEKELRLKETLKNQGVSNAVIWCTWFLDSFSIMSMSIFLLTIFIM HGRILHYSDPFILFLFLLAFSTATIMLCFLLSTFFSKASLAAACSGVIYFTLYLPHILCF AWQDRMTAELKKAVSLLSPVAFGFGTEYLVRFEEQGLGLQWSNIGNSPTEGDEFSFLLSM QMMLLDAAVYGLLAWYLDQVFPGDYGTPLPWYFLLQESYWLGGEGCSTREERALEKTEPL TEETEDPEHPEGIHDSFFEREHPGWVPGVCVKNLVKIFEPCGRPAVDRLNITFYENQITA FLGHNGAGKTTTLSILTGLLPPTSGTVLVGGRDIETSLDAVRQSLGMCPQHNILFHHLTV AEHMLFYAQLKGKSQEEAQLEMEAMLEDTGLHHKRNEEAQDLSGGMQRKLSVAIAFVGDA KVVILDEPTSGVDPYSRRSIWDLLLKYRSGRTIIMSTHHMDEADLLGDRIAIIAQGRLYC SGTPLFLKNCFGTGLYLTLVRKMKNIQSQRKGSEGTCSCSSKGFSTTCPAHVDDLTPEQV LDGDVNELMDVVLHHVPEAKLVECIGQELIFLLPNKNFKHRAYASLFRELEETLADLGLS SFGISDTPLEEIFLKVTEDSDSGPLFAGGAQQKRENVNPRHPCLGPREKAGQTPQDSNVC SPGAPAAHPEGQPPPEPECPGPQLNTGTQLVLQHVQALLVKRFQHTIRSHKDFLAQIVLP ATFVFLALMLSIVIPPFGEYPALTLHPWIYGQQYTFFSMDEPGSEQFTVLADVLLNKPGF GNRCLKEGWLPEYPCGNSTPWKTPSVSPNITQLFQKQKWTQVNPSPSCRCSTREKLTMLP ECPEGAGGLPPPQRTQRSTEILQDLTDRNISDFLVKTYPALIRSSLKSKFWVNEQRYGGI SIGGKLPVVPITGEALVGFLSDLGRIMNVSGGPITREASKEIPDFLKHLETEDNIKVWFN NKGWHALVSFLNVAHNAILRASLPKDRSPEEYGITVISQPLNLTKEQLSEITVLTTSVDA VVAICVIFSMSFVPASFVLYLIQERVNKSKHLQFISGVSPTTYWVTNFLWDIMNYSVSAG LVVGIFIGFQKKAYTSPENLPALVALLLLYGWAVIPMMYPASFLFDVPSTAYVALSCANL FIGINSSAITFILELFENNRTLLRFNAVLRKLLIVFPHFCLGRGLIDLALSQAVTDVYAR FGEEHSANPFHWDLIGKNLFAMVVEGVVYFLLTLLVQRHFFLSQWIAEPTKEPIVDEDDD VAEERQRIITGGNKTDILRLHELTKIYPGTSSPAVDRLCVGVRPGECFGLLGVNGAGKTT TFKMLTGDTTVTSGDATVAGKSILTNISEVHQNMGYCPQFDAIDELLTGREHLYLYARLR GVPAEEIEKVANWSIKSLGLTVYADCLAGTYSGGNKRKLSTAIALIGCPPLVLLDEPTTG MDPQARRMLWNVIVSIIREGRAVVLTSHSMEECEALCTRLAIMVKGAFRCMGTIQHLKSK FGDGYIVTMKIKSPKDDLLPDLNPVEQFFQGNFPGSVQRERHYNMLQFQVSSSSLARIFQ LLLSHKDSLLIEEYSVTQTTLDQVFVNFAKQQTESHDLPLHPRAAGASRQAQD Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | StarGen | Drug Info | Phase 1/2 | Retinitis pigmentosa | [2] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | StarGen | Drug Info | [1] | |||
| 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 | Structure of ATP-bound human ABCA4 | PDB:7LKZ | ||||
| Method | Electron microscopy | Resolution | 3.27 Å | Mutation | Yes | [3] |
| PDB Sequence |
FVRQIQLLLW
12 KNWTLRKRQK22 IRFVVELVWP32 LSLFLVLIWL42 RNANPLYSHH52 ECHFPNKAMP 62 SAGMLPWLQG72 IFCNVNNPCF82 QSPTPGESPG92 IVSNYNNSIL102 ARVYRDFQEL 112 LMNAPESQHL122 GRIWTELHIL132 SQFMDWGGIL277 SDMSPRIQEF287 IHRPSMQDLL 297 WVTRPLGPET311 FTKLMGILSD321 LLCGYPEGGG331 WYEDNNYKAF348 LGYDRRTTSF 369 CNALIQSLES379 NPLTKIAWRA389 AKPLLMGKIL399 YTPDSPAARR409 ILKNANSTFE 419 ELEHVRKLVK429 AWEEVGPQIW439 YFFDNSTQMN449 MIRDTLGNPT459 VKDFLNRQLD 498 WRDIFNITDR508 TLRLVNQYLE518 CLVLDKFESY528 NDETQLTQRA538 LSLLEENMFW 548 AGVVFPDMYP558 WTSSLPPHVK568 YKIRMDIDVV578 EKTNKIKDRY588 WDSGPRADPV 598 EDFRYIWGGF608 AYLQDMVEQG618 ITRSQVQAEA628 PVGIYLQQMP638 YPCFVDDSFM 648 IILNRCFPIF658 MVLAWIYSVS668 MTVKSIVLEK678 ELRLKETLKN688 QGVSNAVIWC 698 TWFLDSFSIM708 SMSIFLLTIF718 IMHGRILHYS728 DPFILFLFLL738 AFSTATIMLC 748 FLLSTFFSKA758 SLAAACSGVI768 YFTLYLPHIL778 CFAWQDRMTA788 ELKKAVSLLS 798 PVAFGFGTEY808 LVRFEEQGLG818 LQWSNIGNSP828 TEGDEFSFLL838 SMQMMLLDAA 848 VYGLLAWYLD858 QVFPGDYGTP868 LPWYFLLQES878 YWLHDSFFER920 EHPGWVPGVC 930 VKNLVKIFEP940 CGRPAVDRLN950 ITFYENQITA960 FLGHNGAGKT970 TTLSILTGLL 980 PPTSGTVLVG990 GRDIETSLDA1000 VRQSLGMCPQ1010 HNILFHHLTV1020 AEHMLFYAQL 1030 KGKSQEEAQL1040 EMEAMLEDTG1050 LHHKRNEEAQ1060 DLSGGMQRKL1070 SVAIAFVGDA 1080 KVVILDQPTS1090 GVDPYSRRSI1100 WDLLLKYRSG1110 RTIIMSTHHM1120 DEADLLGDRI 1130 AIIAQGRLYC1140 SGTPLFLKNC1150 FGTGLYLTLV1160 RKMKQVLDGD1204 VNELMDVVLH 1214 HVPEAKLVEC1224 IGQELIFLLP1234 NKNFKHRAYA1244 SLFRELEETL1254 ADLGLSSFGI 1264 SDTPLEEIFL1274 KVTEDSPQLN1345 TGTQLVLQHV1355 QALLVKRFQH1365 TIRSHKDFLA 1375 QIVLPATFVF1385 LALMLSIVIP1395 PFGEYPALTL1405 HPWIYGQQYT1415 FFSMDEPGSE 1425 QFTVLADVLL1435 NKPGFGNRCL1445 KEGWLPEYPC1455 GNSTPWKTPS1465 VSPNITQLFQ 1475 KQKWTQVNPS1485 PSCRCSTREK1495 LTMLPECPEG1505 AGGLPPPQRT1515 QRSTEILQDL 1525 TDRNISDFLV1535 KTYPALIRSS1545 LKSKFWVNEQ1555 RYGGISIGGK1565 LPVVPITGEA 1575 LVGFLSDLGR1585 IMNVSGGPIT1595 REASKEIPDF1605 LKHLETEDNI1615 KVWFNNKGWH 1625 ALVSFLNVAH1635 NAILRASLPK1645 DRSPEEYGIT1655 VISQPLNLTK1665 EQLSEITVLT 1675 TSVDAVVAIC1685 VIFSMSFVPA1695 SFVLYLIQER1705 VNKSKHLQFI1715 SGVSPTTYWV 1725 TNFLWDIMNY1735 SVSAGLVVGI1745 FIGFQKKAYT1755 SPENLPALVA1765 LLLLYGWAVI 1775 PMMYPASFLF1785 DVPSTAYVAL1795 SCANLFIGIN1805 SSAITFILEL1815 FENNRTLLRF 1825 NAVLRKLLIV1835 FPHFCLGRGL1845 IDLALSQAVT1855 DVYARFGEEH1865 SANPFHWDLI 1875 GKNLFAMVVE1885 GVVYFLLTLL1895 VQRHFFLDED1918 DDVAEERQRI1928 ITGGNKTDIL 1938 RLHELTKIYP1948 GTSSPAVDRL1958 CVGVRPGECF1968 GLLGVNGAGK1978 TTTFKMLTGD 1988 TTVTSGDATV1998 AGKSILTNIS2008 EVHQNMGYCP2018 QFDAIDELLT2028 GREHLYLYAR 2038 LRGVPAEEIE2048 KVANWSIKSL2058 GLTVYADCLA2068 GTYSGGNKRK2078 LSTAIALIGC 2088 PPLVLLDQPT2098 TGMDPQARRM2108 LWNVIVSIIR2118 EGRAVVLTSH2128 SMEECEALCT 2138 RLAIMVKGAF2148 RCMGTIQHLK2158 SKFGDGYIVT2168 MKIKSLLPDL2182 NPVEQFFQGN 2192 FPGSVQRERH2202 YNMLQFQVSS2212 SSLARIFQLL2222 LSHKDSLLIE2232 EYSVTQTTLD 2242 QVFVNFAKQQ2252
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PHE938
3.328
ARG943
4.590
ALA945
3.425
GLY963
4.904
HIS964
4.173
ASN965
3.151
GLY966
3.226
ALA967
4.051
GLY968
3.247
LYS969
2.961
THR970
3.123
THR971
3.515
GLN1010
3.165
LYS1054
2.854
GLU1057
3.752
ASP1061
3.284
LEU1062
4.878
SER1063
3.396
GLY1064
3.218
GLY1065
3.292
MET1066
4.701
GLN1087
4.137
GLY1091
4.529
HIS1118
3.131
TYR1947
3.565
THR1950
4.527
ALA1954
4.060
VAL1973
4.509
ASN1974
2.674
GLY1975
3.069
ALA1976
4.114
GLY1977
3.385
LYS1978
2.887
THR1979
3.156
THR1980
2.931
GLN2019
3.828
TYR2063
4.068
GLY2069
4.768
THR2070
2.696
TYR2071
4.416
SER2072
3.280
GLY2073
2.709
GLY2074
2.947
ASN2075
4.989
GLN2096
3.665
GLY2100
4.158
HIS2128
3.820
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Cholesterol | Ligand Info | |||||
| Structure Description | Structure of ATP-free human ABCA4 | PDB:7LKP | ||||
| Method | Electron microscopy | Resolution | 3.27 Å | Mutation | No | [3] |
| PDB Sequence |
FVRQIQLLLW
12 KNWTLRKRQK22 IRFVVELVWP32 LSLFLVLIWL42 RNANPLYSHH52 ECHFPNKAMP 62 SAGMLPWLQG72 IFCNVNNPCF82 QSPTPGESPG92 IVSNYNNSIL102 ARVYRDFQEL 112 LMNAPESQHL122 GRIWTELHIL132 SQFMDSWGGI276 LSDMSPRIQE286 FIHRPSMQDL 296 LWVTRPLMQN306 GGPETFTKLM316 GILSDLLCGY326 PEGGGSRVLS336 FNWYEDNNYK 346 AFLGIDSTRK356 DPIYSYDRRT366 TSFCNALIQS376 LESNPLTKIA386 WRAAKPLLMG 396 KILYTPDSPA406 ARRILKNANS416 TFEELEHVRK426 LVKAWEEVGP436 QIWYFFDNST 446 QMNMIRDTLG456 NPTVKDFLNR466 QLITAEAILN486 FLYKGPRESQ496 FDWRDIFNIT 506 DRTLRLVNQY516 LECLVLDKFE526 SYNDETQLTQ536 RALSLLEENM546 FWAGVVFPDM 556 YPWTSSLPPH566 VKYKIRMDID576 VVEKTNKIKD586 RYWDSGPRAD596 PVEDFRYIWG 606 GFAYLQDMVE616 QGITRSQVQA626 EAPVGIYLQQ636 MPYPCFVDDS646 FMIILNRCFP 656 IFMVLAWIYS666 VSMTVKSIVL676 EKELRLKETL686 KNQGVSNAVI696 WCTWFLDSFS 706 IMSMSIFLLT716 IFIMHGRILH726 YSDPFILFLF736 LLAFSTATIM746 LCFLLSTFFS 756 KASLAAACSG766 VIYFTLYLPH776 ILCFAWQDRM786 TAELKKAVSL796 LSPVAFGFGT 806 EYLVRFEEQG816 LGLQWSNIGN826 SPTEGDEFSF836 LLSMQMMLLD846 AAVYGLLAWY 856 LDQVFPGDYG866 TPLPWYFSFF918 EREHPGWVPG928 VCVKNLVKID947 RLNITFYENQ 957 ITAFLGHNGA967 GKTTTLSILT977 GLLPPTSGTV987 LVGGRDIETS997 LDAVRQSLGM 1007 CPQHNILFHH1017 LTVAEHMLFY1027 AQLKGKSQEE1037 AQLEMEAMLE1047 DTGLHHKRNE 1057 EAQDLSGGMQ1067 RKLSVAIAFV1077 GDAKVVILDE1087 PTSGVDPYSR1097 RSIWDLLLKY 1107 RSGRTIIMST1117 HHMDEADLLG1127 DRIAIIAQGR1137 LYCSGTPLFL1147 KNCFGTGLYL 1157 TLVRKLDGDV1205 NELMDVVLHH1215 VPEAKLVECI1225 GQELIFLLPN1235 KNFKHRAYAS 1245 LFRELEETLA1255 DLGLSSFGIS1265 DTPLEEIFLK1275 VTPGPQLNTG1347 TQLVLQHVQA 1357 LLVKRFQHTI1367 RSHKDFLAQI1377 VLPATFVFLA1387 LMLSIVIPPF1397 GEYPALTLHP 1407 WIYGQQYTFF1417 SMDEPGSEQF1427 TVLADVLLNK1437 PGFGNRCLKE1447 GWLPEYPCGN 1457 STPWKTPSVS1467 PNITQLFQKQ1477 KWTQVNPSPS1487 CRCSTREKLT1497 MLPECPEGAG 1507 GLPPPQRTQR1517 STEILQDLTD1527 RNISDFLVKT1537 YPALIRSSLK1547 SKFWVNEQRY 1557 GGISIGGKLP1567 VVPITGEALV1577 GFLSDLGRIM1587 NVSGGPITRE1597 ASKEIPDFLK 1607 HLETEDNIKV1617 WFNNKGWHAL1627 VSFLNVAHNA1637 ILRASLPKDR1647 SPEEYGITVI 1657 SQPLNLTKEQ1667 LSEITVLTTS1677 VDAVVAICVI1687 FSMSFVPASF1697 VLYLIQERVN 1707 KSKHLQFISG1717 VSPTTYWVTN1727 FLWDIMNYSV1737 SAGLVVGIFI1747 GFQKKAYTSP 1757 ENLPALVALL1767 LLYGWAVIPM1777 MYPASFLFDV1787 PSTAYVALSC1797 ANLFIGINSS 1807 AITFILELFE1817 NNRTLLRFNA1827 VLRKLLIVFP1837 HFCLGRGLID1847 LALSQAVTDV 1857 YARFGEEHSA1867 NPFHWDLIGK1877 NLFAMVVEGV1887 VYFLLTLLVQ1897 RHFKEPIVDE 1917 DDDVAEERQR1927 IITGGNKTDI1937 LRLHELTKIY1947 PGTSSPAVDR1957 LCVGVRPGEC 1967 FGLLGVNGAG1977 KTTTFKMLTG1987 DTTVTSGDAT1997 VAGKSILTNI2007 SEVHQNMGYC 2017 PQFDAIDELL2027 TGREHLYLYA2037 RLRGVPAEEI2047 EKVANWSIKS2057 LGLTVYADCL 2067 AGTYSGGNKR2077 KLSTAIALIG2087 CPPLVLLDEP2097 TTGMDPQARR2107 MLWNVIVSII 2117 REGRAVVLTS2127 HSMEECEALC2137 TRLAIMVKGA2147 FRCMGTIQHL2157 KSKFGDGYIV 2167 TMKIKLLPDL2182 NPVEQFFQGN2192 FPGSVQRERH2202 YNMLQFQVSS2212 SSLARIFQLL 2222 LSHKDSLLIE2232 EYSVTQTTLD2242 QVFVNFAKQQ2252 T
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LEU11
3.387
TRP12
2.927
TRP15
2.320
THR16
4.645
LYS19
4.244
ILE23
3.997
VAL27
4.076
TRP31
3.955
LEU661
4.412
ILE664
2.869
TYR665
4.676
LEU702
3.569
SER706
3.199
LEU760
3.994
ALA763
3.676
CYS764
4.740
VAL767
3.614
LEU1359
4.572
VAL1360
3.945
PHE1363
2.241
THR1366
3.994
ILE1367
3.381
SER1369
3.419
HIS1370
3.118
LYS1371
2.764
PHE1373
2.454
GLN1376
4.804
ILE1377
4.375
PHE1688
4.164
PHE1692
4.430
LEU1699
2.646
TRP1730
3.882
MET1733
3.250
ASN1734
3.706
VAL1737
4.248
PRO1780
3.828
PHE1783
3.800
LEU1784
3.165
PRO1788
3.882
SER1789
2.625
THR1790
3.604
TYR1792
2.561
VAL1793
1.978
ALA1794
4.829
SER1796
1.914
CYS1797
3.715
LEU1892
3.989
VAL1896
3.558
PHE1900
3.613
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| 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 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).
Human Similarity Proteins
Human Pathway Affiliation
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There is no similarity protein (E value < 0.005) for this target
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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 | ||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | ABC transporters | |||||
| Reactome | [+] 3 Reactome Pathways | + | ||||
| 1 | Retinoid cycle disease events | |||||
| 2 | The canonical retinoid cycle in rods (twilight vision) | |||||
| 3 | ABC-family proteins mediated transport | |||||
| WikiPathways | [+] 2 WikiPathways | + | ||||
| 1 | Visual phototransduction | |||||
| 2 | ABC-family proteins mediated transport | |||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Clinical pipeline report, company report or official report of Oxford BioMedica. | |||||
| REF 2 | ClinicalTrials.gov (NCT01736592) A Study to Determine the Long Term Safety, Tolerability and Biological Activity of StarGen in Patients With Stargardt's Macular Degeneration. U.S. National Institutesof Health. | |||||
| REF 3 | Molecular structures of the eukaryotic retinal importer ABCA4. Elife. 2021 Feb 19;10:e63524. | |||||
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