ABCB9_HUMAN
ID ABCB9_HUMAN Reviewed; 766 AA.
AC Q9NP78; B4E2J0; Q5W9G7; Q769F3; Q769F4; Q96AB1; Q9P208;
DT 02-AUG-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=ABC-type oligopeptide transporter ABCB9;
DE EC=7.4.2.6 {ECO:0000269|PubMed:15863492, ECO:0000269|PubMed:17977821, ECO:0000269|PubMed:18434309, ECO:0000269|PubMed:22641697};
DE AltName: Full=ATP-binding cassette sub-family B member 9;
DE AltName: Full=ATP-binding cassette transporter 9;
DE Short=ABC transporter 9 protein;
DE Short=hABCB9;
DE AltName: Full=TAP-like protein {ECO:0000303|PubMed:11011155};
DE Short=TAPL {ECO:0000303|PubMed:11011155};
GN Name=ABCB9 {ECO:0000312|HGNC:HGNC:50};
GN Synonyms=KIAA1520 {ECO:0000303|PubMed:10819331};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INDUCTION.
RC TISSUE=Embryonic kidney;
RX PubMed=11011155; DOI=10.1093/oxfordjournals.jbchem.a022805;
RA Kobayashi A., Kasano M., Maeda T., Hori S., Motojima K., Suzuki M.,
RA Fujiwara T., Takahashi E., Yabe T., Tanaka K., Kasahara M., Yamaguchi Y.,
RA Maeda M.;
RT "A half-type ABC transporter TAPL is highly conserved between rodent and
RT man, and the human gene is not responsive to interferon-gamma in contrast
RT to TAP1 and TAP2.";
RL J. Biochem. 128:711-718(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Lymphoblast;
RX PubMed=10748049; DOI=10.1074/jbc.m001819200;
RA Zhang F., Zhang W., Liu L., Fisher C.L., Hui D., Childs S.,
RA Dorovini-Zis K., Ling V.;
RT "Characterization of ABCB9, an ATP binding cassette protein associated with
RT lysosomes.";
RL J. Biol. Chem. 275:23287-23294(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4 AND 5).
RC TISSUE=Cervix carcinoma, and Embryonic kidney;
RX PubMed=13679046; DOI=10.1016/j.bbrc.2003.08.081;
RA Kobayashi A., Hori S., Suita N., Maeda M.;
RT "Gene organization of human transporter associated with antigen processing-
RT like (TAPL, ABCB9): analysis of alternative splicing variants and promoter
RT activity.";
RL Biochem. Biophys. Res. Commun. 309:815-822(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15491607; DOI=10.1016/j.jmb.2004.09.028;
RA Homma K., Kikuno R.F., Nagase T., Ohara O., Nishikawa K.;
RT "Alternative splice variants encoding unstable protein domains exist in the
RT human brain.";
RL J. Mol. Biol. 343:1207-1220(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10819331; DOI=10.1093/dnares/7.2.143;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:143-150(2000).
RN [6]
RP SEQUENCE REVISION.
RA Ohara O., Nagase T., Kikuno R.;
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP SUBCELLULAR LOCATION, AND DOMAIN.
RX PubMed=15577206; DOI=10.1248/bpb.27.1916;
RA Kobayashi A., Maeda T., Maeda M.;
RT "Membrane localization of transporter associated with antigen processing
RT (TAP)-like (ABCB9) visualized in vivo with a fluorescence protein-fusion
RT technique.";
RL Biol. Pharm. Bull. 27:1916-1922(2004).
RN [11]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND CATALYTIC ACTIVITY.
RX PubMed=15863492; DOI=10.1074/jbc.m503231200;
RA Wolters J.C., Abele R., Tampe R.;
RT "Selective and ATP-dependent translocation of peptides by the homodimeric
RT ATP binding cassette transporter TAP-like (ABCB9).";
RL J. Biol. Chem. 280:23631-23636(2005).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND CATALYTIC ACTIVITY.
RX PubMed=17977821; DOI=10.1074/jbc.m708139200;
RA Demirel O., Waibler Z., Kalinke U., Grunebach F., Appel S., Brossart P.,
RA Hasilik A., Tampe R., Abele R.;
RT "Identification of a lysosomal peptide transport system induced during
RT dendritic cell development.";
RL J. Biol. Chem. 282:37836-37843(2007).
RN [13]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Placenta;
RX PubMed=17897319; DOI=10.1111/j.1600-0854.2007.00643.x;
RA Schroeder B., Wrocklage C., Pan C., Jaeger R., Koesters B., Schaefer H.,
RA Elsaesser H.-P., Mann M., Hasilik A.;
RT "Integral and associated lysosomal membrane proteins.";
RL Traffic 8:1676-1686(2007).
RN [14]
RP SUBCELLULAR LOCATION, DOMAIN, AND SUBUNIT.
RX PubMed=18952056; DOI=10.1016/j.bbrc.2008.10.078;
RA Kamakura A., Fujimoto Y., Motohashi Y., Ohashi K., Ohashi-Kobayashi A.,
RA Maeda M.;
RT "Functional dissection of transmembrane domains of human TAP-like
RT (ABCB9).";
RL Biochem. Biophys. Res. Commun. 377:847-851(2008).
RN [15]
RP SUBCELLULAR LOCATION, AND DOMAIN.
RX PubMed=18175933; DOI=10.1248/bpb.31.1;
RA Ohara T., Ohashi-Kobayashi A., Maeda M.;
RT "Biochemical characterization of transporter associated with antigen
RT processing (TAP)-like (ABCB9) expressed in insect cells.";
RL Biol. Pharm. Bull. 31:1-5(2008).
RN [16]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=18434309; DOI=10.1074/jbc.m801794200;
RA Zhao C., Haase W., Tampe R., Abele R.;
RT "Peptide specificity and lipid activation of the lysosomal transport
RT complex ABCB9 (TAPL).";
RL J. Biol. Chem. 283:17083-17091(2008).
RN [17]
RP SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF 136-LYS-LYS-137.
RX PubMed=20377823; DOI=10.1111/j.1600-0854.2009.01021.x;
RA Demirel O., Bangert I., Tampe R., Abele R.;
RT "Tuning the cellular trafficking of the lysosomal peptide transporter TAPL
RT by its N-terminal domain.";
RL Traffic 11:383-393(2010).
RN [18]
RP SUBCELLULAR LOCATION.
RX PubMed=21212514; DOI=10.1248/bpb.34.36;
RA Fujimoto Y., Kamakura A., Motohashi Y., Ohashi-Kobayashi A., Maeda M.;
RT "Transporter associated with antigen processing-like (ABCB9) stably
RT expressed in Chinese hamster ovary-K1 cells is sorted to the microdomains
RT of lysosomal membranes.";
RL Biol. Pharm. Bull. 34:36-40(2011).
RN [19]
RP SUBCELLULAR LOCATION, INTERACTION WITH LAMP1 AND LAMP2 (ISOFORM LAMP-2B),
RP FUNCTION, CATALYTIC ACTIVITY, AND DOMAIN.
RX PubMed=22641697; DOI=10.1242/jcs.087346;
RA Demirel O., Jan I., Wolters D., Blanz J., Saftig P., Tampe R., Abele R.;
RT "The lysosomal polypeptide transporter TAPL is stabilized by interaction
RT with LAMP-1 and LAMP-2.";
RL J. Cell Sci. 125:4230-4240(2012).
RN [20]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY
RP REGULATION.
RX PubMed=25646430; DOI=10.1073/pnas.1418100112;
RA Zollmann T., Moiset G., Tumulka F., Tampe R., Poolman B., Abele R.;
RT "Single liposome analysis of peptide translocation by the ABC transporter
RT TAPL.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:2046-2051(2015).
RN [21]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT.
RX PubMed=30353140; DOI=10.1038/s41598-018-33841-w;
RA Bock C., Loehr F., Tumulka F., Reichel K., Wuerz J., Hummer G.,
RA Schaefer L., Tampe R., Joseph B., Bernhard F., Doetsch V., Abele R.;
RT "Structural and functional insights into the interaction and targeting hub
RT TMD0 of the polypeptide transporter TAPL.";
RL Sci. Rep. 8:15662-15662(2018).
RN [22]
RP SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-17; ASP-45; ASP-49; ARG-57 AND
RP LYS-100, INTERACTION WITH YIF1B, DOMAIN, SITE, FUNCTION, AND CATALYTIC
RP ACTIVITY.
RX PubMed=30877195; DOI=10.1074/jbc.ra118.007071;
RA Graab P., Bock C., Weiss K., Hirth A., Koller N., Braner M., Jung J.,
RA Loehr F., Tampe R., Behrends C., Abele R.;
RT "Lysosomal targeting of the ABC transporter TAPL is determined by membrane-
RT localized charged residues.";
RL J. Biol. Chem. 294:7308-7323(2019).
RN [23]
RP MUTAGENESIS OF LYS-545 AND HIS-699, CATALYTIC ACTIVITY, FUNCTION,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY REGULATION.
RX PubMed=31417173; DOI=10.1038/s41598-019-48343-6;
RA Bock C., Zollmann T., Lindt K.A., Tampe R., Abele R.;
RT "Peptide translocation by the lysosomal ABC transporter TAPL is regulated
RT by coupling efficiency and activation energy.";
RL Sci. Rep. 9:11884-11884(2019).
RN [24]
RP VARIANT MET-121.
RX PubMed=11829140; DOI=10.1007/s10038-002-8653-6;
RA Saito S., Iida A., Sekine A., Miura Y., Ogawa C., Kawauchi S., Higuchi S.,
RA Nakamura Y.;
RT "Three hundred twenty-six genetic variations in genes encoding nine members
RT of ATP-binding cassette, subfamily B (ABCB/MDR/TAP), in the Japanese
RT population.";
RL J. Hum. Genet. 47:38-50(2002).
CC -!- FUNCTION: ATP-dependent low-affinity peptide transporter which
CC translocates a broad spectrum of peptides from the cytosol to the
CC lysosomal lumen for degradation (PubMed:15863492, PubMed:17977821,
CC PubMed:18434309, PubMed:22641697, PubMed:25646430, PubMed:30877195,
CC PubMed:31417173, PubMed:30353140). Displays a broad peptide length
CC specificity from 6-mer up to at least 59-mer peptides with an optimum
CC of 23-mers (PubMed:15863492, PubMed:25646430). Binds and transports
CC smaller and larger peptides with the same affinity (PubMed:31417173).
CC Favors positively charged, aromatic or hydrophobic residues in the
CC N- and C-terminal positions whereas negatively charged residues as well
CC as asparagine and methionine are not favored (PubMed:15863492,
CC PubMed:17977821, PubMed:18434309). {ECO:0000269|PubMed:15863492,
CC ECO:0000269|PubMed:17977821, ECO:0000269|PubMed:18434309,
CC ECO:0000269|PubMed:22641697, ECO:0000269|PubMed:25646430,
CC ECO:0000269|PubMed:30353140, ECO:0000269|PubMed:30877195,
CC ECO:0000269|PubMed:31417173}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a [oligopeptide](in) + ATP + H2O = a [oligopeptide](out) + ADP
CC + H(+) + phosphate; Xref=Rhea:RHEA:14429, Rhea:RHEA-COMP:10531,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:83228, ChEBI:CHEBI:456216; EC=7.4.2.6;
CC Evidence={ECO:0000269|PubMed:15863492, ECO:0000269|PubMed:17977821,
CC ECO:0000269|PubMed:18434309, ECO:0000269|PubMed:22641697,
CC ECO:0000269|PubMed:30353140, ECO:0000269|PubMed:30877195,
CC ECO:0000269|PubMed:31417173};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14430;
CC Evidence={ECO:0000269|PubMed:15863492, ECO:0000269|PubMed:17977821,
CC ECO:0000269|PubMed:18434309, ECO:0000269|PubMed:22641697,
CC ECO:0000269|PubMed:30353140, ECO:0000269|PubMed:30877195,
CC ECO:0000269|PubMed:31417173};
CC -!- ACTIVITY REGULATION: Transport activity is limited by threshold levels
CC of luminal peptide (PubMed:25646430). ATP hydrolysis is reduced in the
CC presence of the spatial challenging 18-mer peptide by 50% and the
CC branched 16-mer peptide by 75% (PubMed:31417173). Transport rate of the
CC longer peptides is strongly reduced (PubMed:31417173).
CC {ECO:0000269|PubMed:25646430, ECO:0000269|PubMed:31417173}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.8 uM for a 9-mer oligopeptide {ECO:0000269|PubMed:15863492};
CC KM=2.8 uM for a 9-mer oligopeptide (with a macroscopic filter assay)
CC {ECO:0000269|PubMed:25646430};
CC KM=0.9 uM for a 9-mer oligopeptide (with a dual-color
CC fluorescenceburst analysis (DCFBA)) {ECO:0000269|PubMed:25646430};
CC KM=15 uM for a 9-mer oligopeptide {ECO:0000269|PubMed:31417173};
CC KM=8 uM for a branched 16-mer oligopeptide
CC {ECO:0000269|PubMed:31417173};
CC KM=7 uM for a spatial challenging 18-mer oligopeptide
CC {ECO:0000269|PubMed:31417173};
CC KM=4.4 uM for a 9-mer oligopeptide (in presence of mM GTP)
CC {ECO:0000269|PubMed:31417173};
CC KM=97 uM for ATP {ECO:0000269|PubMed:31417173};
CC KM=87 uM for GTP {ECO:0000269|PubMed:31417173};
CC pH dependence:
CC Optimum pH is 7.0. {ECO:0000269|PubMed:15863492};
CC Temperature dependence:
CC Optimum temperature is 37 degrees Celsius.
CC {ECO:0000269|PubMed:15863492};
CC -!- SUBUNIT: Homodimer (PubMed:15863492, PubMed:30353140). Interacts (via
CC TMD0 region) with LAMP1; this interaction strongly stabilizes ABCB9 and
CC protects ABCB9 against lysosomal degradation (PubMed:22641697).
CC Interacts (via TMD0 region) with LAMP2 (isoform LAMP-2B)
CC (PubMed:22641697). Interacts (via TMD0) with YIF1B; this interaction
CC allows (but is not essential) the ER-to-Golgi trafficking and strongly
CC depends on a salt bridge within TMD0 (PubMed:30877195).
CC {ECO:0000269|PubMed:15863492, ECO:0000269|PubMed:22641697,
CC ECO:0000269|PubMed:30353140, ECO:0000269|PubMed:30877195}.
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:10748049,
CC ECO:0000269|PubMed:15577206, ECO:0000269|PubMed:17897319,
CC ECO:0000269|PubMed:17977821, ECO:0000269|PubMed:18175933,
CC ECO:0000269|PubMed:18952056, ECO:0000269|PubMed:20377823,
CC ECO:0000269|PubMed:21212514, ECO:0000269|PubMed:22641697,
CC ECO:0000269|PubMed:30877195}; Multi-pass membrane protein
CC {ECO:0000255|PROSITE-ProRule:PRU00441, ECO:0000269|PubMed:10748049,
CC ECO:0000269|PubMed:15577206, ECO:0000269|PubMed:17897319,
CC ECO:0000269|PubMed:17977821, ECO:0000269|PubMed:18175933,
CC ECO:0000269|PubMed:18952056, ECO:0000269|PubMed:20377823,
CC ECO:0000269|PubMed:21212514}. Note=May be located in membrane rafts.
CC Takes an intracellular route from the endoplasmic reticulum (ER), via
CC Golgi and early endosomes to late endosomal and lysosomal compartments
CC (PubMed:30877195). {ECO:0000269|PubMed:30877195}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1; Synonyms=12A, c1-l;
CC IsoId=Q9NP78-1; Sequence=Displayed;
CC Name=2; Synonyms=c1-s;
CC IsoId=Q9NP78-2; Sequence=VSP_000027;
CC Name=3;
CC IsoId=Q9NP78-3; Sequence=VSP_000029, VSP_000030;
CC Name=4; Synonyms=12B;
CC IsoId=Q9NP78-5; Sequence=VSP_041884, VSP_041886;
CC Name=5; Synonyms=12C;
CC IsoId=Q9NP78-6; Sequence=VSP_041885;
CC Name=6;
CC IsoId=Q9NP78-7; Sequence=VSP_044884;
CC -!- TISSUE SPECIFICITY: Highly expressed in testis, and at moderate levels
CC in brain, spinal cord, and thyroid. Not expressed in monocytes but
CC strongly expressed during differentiation of monocytes to dendritic
CC cells and macrophages. {ECO:0000269|PubMed:10748049,
CC ECO:0000269|PubMed:17977821}.
CC -!- INDUCTION: Not induced by interferon-gamma.
CC {ECO:0000269|PubMed:11011155}.
CC -!- DOMAIN: Divided into an N-terminal domain (TMD0) comprising four
CC transmembrane helices and the following core domain (coreABCB9)
CC (PubMed:18952056). TMD0 is required for lysosomal localization and
CC LAMP1, LAMP2 and YIF1B interaction (PubMed:15577206, PubMed:18175933,
CC PubMed:20377823, PubMed:22641697, PubMed:30877195). The core domain is
CC required for homodimerization and peptide transport activity
CC (PubMed:18952056, PubMed:20377823). {ECO:0000269|PubMed:15577206,
CC ECO:0000269|PubMed:18175933, ECO:0000269|PubMed:18952056,
CC ECO:0000269|PubMed:20377823, ECO:0000269|PubMed:22641697,
CC ECO:0000269|PubMed:30877195}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCB family.
CC MHC peptide exporter (TC 3.A.1.209) subfamily. {ECO:0000305}.
CC -!- CAUTION: Has also been detected in the endoplasmic reticulum but
CC appears to be a lysosomal protein in vivo.
CC {ECO:0000305|PubMed:11011155}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA96044.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAD66830.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=ABCMdb; Note=Database for mutations in ABC proteins;
CC URL="http://abcm2.hegelab.org/search";
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DR EMBL; AB045381; BAA97989.2; -; mRNA.
DR EMBL; AF216494; AAF89993.1; -; mRNA.
DR EMBL; AB112582; BAC98409.1; -; mRNA.
DR EMBL; AB112583; BAC98410.1; -; mRNA.
DR EMBL; AB177852; BAD66830.1; ALT_INIT; mRNA.
DR EMBL; AB040953; BAA96044.2; ALT_INIT; mRNA.
DR EMBL; AK304295; BAG65152.1; -; mRNA.
DR EMBL; AC026362; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC027290; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC017348; AAH17348.1; -; mRNA.
DR CCDS; CCDS58286.1; -. [Q9NP78-7]
DR CCDS; CCDS58287.1; -. [Q9NP78-6]
DR CCDS; CCDS58288.1; -. [Q9NP78-5]
DR CCDS; CCDS9241.1; -. [Q9NP78-1]
DR RefSeq; NP_001229942.1; NM_001243013.1. [Q9NP78-7]
DR RefSeq; NP_001229943.1; NM_001243014.1. [Q9NP78-6]
DR RefSeq; NP_062570.1; NM_019624.3. [Q9NP78-2]
DR RefSeq; NP_062571.1; NM_019625.3. [Q9NP78-1]
DR RefSeq; NP_982269.2; NM_203444.3. [Q9NP78-5]
DR RefSeq; XP_011536397.1; XM_011538095.2. [Q9NP78-1]
DR RefSeq; XP_011536398.1; XM_011538096.2. [Q9NP78-1]
DR RefSeq; XP_016874592.1; XM_017019103.1. [Q9NP78-1]
DR AlphaFoldDB; Q9NP78; -.
DR SMR; Q9NP78; -.
DR BioGRID; 117021; 39.
DR IntAct; Q9NP78; 9.
DR STRING; 9606.ENSP00000440288; -.
DR ChEMBL; CHEMBL1293189; -.
DR TCDB; 3.A.1.209.2; the atp-binding cassette (abc) superfamily.
DR iPTMnet; Q9NP78; -.
DR PhosphoSitePlus; Q9NP78; -.
DR BioMuta; ABCB9; -.
DR DMDM; 22095458; -.
DR EPD; Q9NP78; -.
DR MassIVE; Q9NP78; -.
DR PaxDb; Q9NP78; -.
DR PeptideAtlas; Q9NP78; -.
DR PRIDE; Q9NP78; -.
DR ProteomicsDB; 5823; -.
DR ProteomicsDB; 81917; -. [Q9NP78-1]
DR ProteomicsDB; 81918; -. [Q9NP78-2]
DR ProteomicsDB; 81919; -. [Q9NP78-3]
DR ProteomicsDB; 81920; -. [Q9NP78-5]
DR ProteomicsDB; 81921; -. [Q9NP78-6]
DR Antibodypedia; 31719; 249 antibodies from 30 providers.
DR DNASU; 23457; -.
DR Ensembl; ENST00000280560.13; ENSP00000280560.8; ENSG00000150967.19. [Q9NP78-1]
DR Ensembl; ENST00000344275.11; ENSP00000456813.1; ENSG00000150967.19. [Q9NP78-6]
DR Ensembl; ENST00000346530.9; ENSP00000280559.7; ENSG00000150967.19. [Q9NP78-2]
DR Ensembl; ENST00000392439.7; ENSP00000376234.3; ENSG00000150967.19. [Q9NP78-1]
DR Ensembl; ENST00000442833.6; ENSP00000456375.1; ENSG00000150967.19. [Q9NP78-5]
DR Ensembl; ENST00000540285.5; ENSP00000441734.1; ENSG00000150967.19. [Q9NP78-7]
DR Ensembl; ENST00000542678.5; ENSP00000440288.1; ENSG00000150967.19. [Q9NP78-1]
DR GeneID; 23457; -.
DR KEGG; hsa:23457; -.
DR MANE-Select; ENST00000280560.13; ENSP00000280560.8; NM_019625.4; NP_062571.1.
DR UCSC; uc001udm.5; human. [Q9NP78-1]
DR CTD; 23457; -.
DR DisGeNET; 23457; -.
DR GeneCards; ABCB9; -.
DR HGNC; HGNC:50; ABCB9.
DR HPA; ENSG00000150967; Tissue enhanced (brain, testis).
DR MIM; 605453; gene.
DR neXtProt; NX_Q9NP78; -.
DR OpenTargets; ENSG00000150967; -.
DR PharmGKB; PA24391; -.
DR VEuPathDB; HostDB:ENSG00000150967; -.
DR eggNOG; KOG0058; Eukaryota.
DR GeneTree; ENSGT00940000155431; -.
DR InParanoid; Q9NP78; -.
DR PhylomeDB; Q9NP78; -.
DR TreeFam; TF105197; -.
DR BRENDA; 7.4.2.5; 2681.
DR PathwayCommons; Q9NP78; -.
DR Reactome; R-HSA-382556; ABC-family proteins mediated transport.
DR SABIO-RK; Q9NP78; -.
DR SignaLink; Q9NP78; -.
DR BioGRID-ORCS; 23457; 14 hits in 1081 CRISPR screens.
DR ChiTaRS; ABCB9; human.
DR GeneWiki; ABCB9; -.
DR GenomeRNAi; 23457; -.
DR Pharos; Q9NP78; Tbio.
DR PRO; PR:Q9NP78; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9NP78; protein.
DR Bgee; ENSG00000150967; Expressed in buccal mucosa cell and 169 other tissues.
DR ExpressionAtlas; Q9NP78; baseline and differential.
DR Genevisible; Q9NP78; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:MGI.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0042824; C:MHC class I peptide loading complex; IBA:GO_Central.
DR GO; GO:0015421; F:ABC-type oligopeptide transporter activity; IDA:UniProtKB.
DR GO; GO:0015433; F:ABC-type peptide antigen transporter activity; IBA:GO_Central.
DR GO; GO:0015440; F:ABC-type peptide transporter activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0046978; F:TAP1 binding; IBA:GO_Central.
DR GO; GO:0022857; F:transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0019885; P:antigen processing and presentation of endogenous peptide antigen via MHC class I; IBA:GO_Central.
DR GO; GO:0006518; P:peptide metabolic process; IDA:UniProtKB.
DR GO; GO:0015833; P:peptide transport; IDA:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR Gene3D; 1.20.1560.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR011527; ABC1_TM_dom.
DR InterPro; IPR036640; ABC1_TM_sf.
DR InterPro; IPR003439; ABC_transporter-like_ATP-bd.
DR InterPro; IPR017871; ABC_transporter-like_CS.
DR InterPro; IPR030254; ABCB9.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR039421; Type_1_exporter.
DR PANTHER; PTHR24221; PTHR24221; 1.
DR PANTHER; PTHR24221:SF242; PTHR24221:SF242; 1.
DR Pfam; PF00664; ABC_membrane; 1.
DR Pfam; PF00005; ABC_tran; 1.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF90123; SSF90123; 1.
DR PROSITE; PS50929; ABC_TM1F; 1.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Lysosome; Membrane; Nucleotide-binding;
KW Peptide transport; Protein transport; Reference proteome; Translocase;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..766
FT /note="ABC-type oligopeptide transporter ABCB9"
FT /id="PRO_0000000252"
FT TRANSMEM 7..27
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 47..67
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 84..104
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 116..136
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 185..205
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 225..245
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 319..339
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 416..436
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 188..471
FT /note="ABC transmembrane type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 504..740
FT /note="ABC transporter"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT BINDING 539..546
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT SITE 17
FT /note="Intramolecular salt bridge with Arg-57. Essential
FT for the release from the ER"
FT /evidence="ECO:0000269|PubMed:30877195"
FT SITE 45
FT /note="Important for the second trafficking step from the
FT Golgi to the endosomal and lysosomal compartments"
FT /evidence="ECO:0000269|PubMed:30877195"
FT SITE 49
FT /note="Important for the second trafficking step from the
FT Golgi to the endosomal and lysosomal compartments"
FT /evidence="ECO:0000269|PubMed:30877195"
FT SITE 57
FT /note="Intramolecular salt bridge with Asp-17. Essential
FT for the release from the ER"
FT /evidence="ECO:0000269|PubMed:30877195"
FT VAR_SEQ 418..460
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10748049"
FT /id="VSP_000027"
FT VAR_SEQ 461..523
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000305"
FT /id="VSP_044884"
FT VAR_SEQ 582..596
FT /note="ISLVSQEPVLFARSI -> VCARAWATLLRPFCI (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_000029"
FT VAR_SEQ 597..766
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_000030"
FT VAR_SEQ 681..683
FT /note="IQQ -> CAG (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:13679046"
FT /id="VSP_041884"
FT VAR_SEQ 682..766
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:13679046"
FT /id="VSP_041885"
FT VAR_SEQ 684..766
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:13679046"
FT /id="VSP_041886"
FT VARIANT 121
FT /note="V -> M (in dbSNP:rs3803002)"
FT /evidence="ECO:0000269|PubMed:11829140"
FT /id="VAR_013701"
FT MUTAGEN 17
FT /note="D->N: Loss of lysosomal localization. Does not
FT affect interaction between coreABCB9 and TMD0 domains. Does
FT not affect dimerization. Does not affect peptide transport
FT activity. Decreases interaction with YIF1B."
FT /evidence="ECO:0000269|PubMed:30877195"
FT MUTAGEN 17
FT /note="D->R: Loss of lysosomal localization. Does not
FT affect lysosomal localization; when associated with D-57.
FT Does not affect interaction between coreABCB9 and TMD0
FT domains. Does not affect interaction between coreABCB9 and
FT TMD0 domains; when associated with D-57. Does not affect
FT interaction between coreABCB9 and TMD0 domains; when
FT associated with D-100."
FT /evidence="ECO:0000269|PubMed:30877195"
FT MUTAGEN 45
FT /note="D->K: Loss of lysosomal localization; when
FT assosiated with K-49. Loss of lysosomal localization; when
FT assosiated with K-49 and D-100. Does not affect peptide
FT transport activity; when assosiated with K-49 and D-100."
FT /evidence="ECO:0000269|PubMed:30877195"
FT MUTAGEN 45
FT /note="D->N: Decreases lysosomal localization; when
FT associated with N-49."
FT /evidence="ECO:0000269|PubMed:30877195"
FT MUTAGEN 49
FT /note="D->K: Loss of lysosomal localization; when
FT assosiated with K-45. Loss of lysosomal localization; when
FT assosiated with K-45 and D-100. Does not affect peptide
FT transport activity; when assosiated with K-45 and D-100."
FT /evidence="ECO:0000269|PubMed:30877195"
FT MUTAGEN 49
FT /note="D->N: Decreases lysosomal localization; when
FT associated with N-45."
FT /evidence="ECO:0000269|PubMed:30877195"
FT MUTAGEN 57
FT /note="R->A: Decreases lysosomal localization. Loss of
FT lysosomal localization; when associated with A-100."
FT /evidence="ECO:0000269|PubMed:30877195"
FT MUTAGEN 57
FT /note="R->D: Loss of lysosomal localization. Does not
FT affect lysosomal localization; when associated with R-17.
FT Does not affect interaction between coreABCB9 and TMD0
FT domains. Does not affect interaction between coreABCB9 and
FT TMD0 domains; when associated with R-17."
FT /evidence="ECO:0000269|PubMed:30877195"
FT MUTAGEN 100
FT /note="K->A: Decreases lysosomal localization. Loss of
FT lysosomal localization; when associated with A-57."
FT /evidence="ECO:0000269|PubMed:30877195"
FT MUTAGEN 100
FT /note="K->D: Decreases lysosomal localization. Loss of
FT lysosomal localization; when assosiated with R-17. Loss of
FT lysosomal localization; when assosiated with K-45 and K-49.
FT Does not affect peptide transport activity; when assosiated
FT with K-45 and K-49. Does not affect interaction between
FT coreABCB9 and TMD0 domains. Does not affect interaction
FT between coreABCB9 and TMD0 domains; when associated with R-
FT 17."
FT /evidence="ECO:0000269|PubMed:30877195"
FT MUTAGEN 136..137
FT /note="LL->AA: No effect on lysosomal localization."
FT /evidence="ECO:0000269|PubMed:20377823"
FT MUTAGEN 545
FT /note="K->A: Loss of peptide transport activity; whena
FT ssociated with A-699."
FT /evidence="ECO:0000269|PubMed:31417173"
FT MUTAGEN 699
FT /note="H->A: Loss of peptide transport activity; whena
FT ssociated with A-545."
FT /evidence="ECO:0000269|PubMed:31417173"
SQ SEQUENCE 766 AA; 84475 MW; C83FA62C929EC792 CRC64;
MRLWKAVVVT LAFMSVDICV TTAIYVFSHL DRSLLEDIRH FNIFDSVLDL WAACLYRSCL
LLGATIGVAK NSALGPRRLR ASWLVITLVC LFVGIYAMVK LLLFSEVRRP IRDPWFWALF
VWTYISLGAS FLLWWLLSTV RPGTQALEPG AATEAEGFPG SGRPPPEQAS GATLQKLLSY
TKPDVAFLVA ASFFLIVAAL GETFLPYYTG RAIDGIVIQK SMDQFSTAVV IVCLLAIGSS
FAAGIRGGIF TLIFARLNIR LRNCLFRSLV SQETSFFDEN RTGDLISRLT SDTTMVSDLV
SQNINVFLRN TVKVTGVVVF MFSLSWQLSL VTFMGFPIIM MVSNIYGKYY KRLSKEVQNA
LARASNTAEE TISAMKTVRS FANEEEEAEV YLRKLQQVYK LNRKEAAAYM YYVWGSGLTL
LVVQVSILYY GGHLVISGQM TSGNLIAFII YEFVLGDCME SVGSVYSGLM QGVGAAEKVF
EFIDRQPTMV HDGSLAPDHL EGRVDFENVT FTYRTRPHTQ VLQNVSFSLS PGKVTALVGP
SGSGKSSCVN ILENFYPLEG GRVLLDGKPI SAYDHKYLHR VISLVSQEPV LFARSITDNI
SYGLPTVPFE MVVEAAQKAN AHGFIMELQD GYSTETGEKG AQLSGGQKQR VAMARALVRN
PPVLILDEAT SALDAESEYL IQQAIHGNLQ KHTVLIIAHR LSTVEHAHLI VVLDKGRVVQ
QGTHQQLLAQ GGLYAKLVQR QMLGLQPAAD FTAGHNEPVA NGSHKA
