RAB7A_HUMAN
ID RAB7A_HUMAN Reviewed; 207 AA.
AC P51149; A8K3V6; Q9NWJ0; Q9UPB0;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 226.
DE RecName: Full=Ras-related protein Rab-7a {ECO:0000305};
DE EC=3.6.5.2 {ECO:0000269|PubMed:20028791};
GN Name=RAB7A {ECO:0000312|HGNC:HGNC:9788}; Synonyms=RAB7;
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].
RC TISSUE=Placenta;
RX PubMed=8954989; DOI=10.1006/bbrc.1996.1897;
RA Vitelli R., Chiariello M., Lattero D., Bruni C.B., Bucci C.;
RT "Molecular cloning and expression analysis of the human Rab7 GTP-ase
RT complementary deoxyribonucleic acid.";
RL Biochem. Biophys. Res. Commun. 229:887-890(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9126495; DOI=10.1006/geno.1997.4644;
RA Davies J.P., Cotter P.D., Ioannou Y.A.;
RT "Cloning and mapping of human Rab7 and Rab9 cDNA sequences and
RT identification of a Rab9 pseudogene.";
RL Genomics 41:131-134(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RA Kim J.Y., Park Y.B.;
RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [8]
RP FUNCTION IN LATE ENDOCYTOSIS, AND INTERACTION WITH RILP.
RX PubMed=11179213; DOI=10.1093/emboj/20.4.683;
RA Cantalupo G., Alifano P., Roberti V., Bruni C.B., Bucci C.;
RT "Rab-interacting lysosomal protein (RILP): the Rab7 effector required for
RT transport to lysosomes.";
RL EMBO J. 20:683-693(2001).
RN [9]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Melanoma;
RX PubMed=12643545; DOI=10.1021/pr025562r;
RA Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K., Valencia J.,
RA Muller J., Vieira W.D., Watabe H., Shabanowitz J., Hearing V.J., Hunt D.F.,
RA Appella E.;
RT "Proteomic analysis of early melanosomes: identification of novel
RT melanosomal proteins.";
RL J. Proteome Res. 2:69-79(2003).
RN [10]
RP FUNCTION IN PHAGOSOMAL BIOGENESIS, MUTAGENESIS OF THR-22 AND GLN-67, AND
RP SUBCELLULAR LOCATION.
RX PubMed=12944476; DOI=10.1128/mcb.23.18.6494-6506.2003;
RA Harrison R.E., Bucci C., Vieira O.V., Schroer T.A., Grinstein S.;
RT "Phagosomes fuse with late endosomes and/or lysosomes by extension of
RT membrane protrusions along microtubules: role of Rab7 and RILP.";
RL Mol. Cell. Biol. 23:6494-6506(2003).
RN [11]
RP FUNCTION, INTERACTION WITH PIK3C3/VPS34-PIK3R4 COMPLEX, AND SUBCELLULAR
RP LOCATION.
RX PubMed=14617358; DOI=10.1034/j.1600-0854.2003.00133.x;
RA Stein M.P., Feng Y., Cooper K.L., Welford A.M., Wandinger-Ness A.;
RT "Human VPS34 and p150 are Rab7 interacting partners.";
RL Traffic 4:754-771(2003).
RN [12]
RP INTERACTION WITH PSMA7.
RX PubMed=14998988; DOI=10.1074/jbc.m401022200;
RA Dong J., Chen W., Welford A., Wandinger-Ness A.;
RT "The proteasome alpha-subunit XAPC7 interacts specifically with Rab7 and
RT late endosomes.";
RL J. Biol. Chem. 279:21334-21342(2004).
RN [13]
RP INTERACTION WITH RILP.
RX PubMed=14668488; DOI=10.1091/mbc.e03-06-0413;
RA Wang T., Wong K.K., Hong W.;
RT "A unique region of RILP distinguishes it from its related proteins in its
RT regulation of lysosomal morphology and interaction with Rab7 and Rab34.";
RL Mol. Biol. Cell 15:815-826(2004).
RN [14]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH OSBPL1A.
RX PubMed=16176980; DOI=10.1091/mbc.e05-03-0189;
RA Johansson M., Lehto M., Tanhuanpaeae K., Cover T.L., Olkkonen V.M.;
RT "The oxysterol-binding protein homologue ORP1L interacts with Rab7 and
RT alters functional properties of late endocytic compartments.";
RL Mol. Biol. Cell 16:5480-5492(2005).
RN [15]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J.,
RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S.,
RA Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [16]
RP INTERACTION WITH RNF115.
RX PubMed=16925951; DOI=10.1593/neo.06469;
RA Burger A., Amemiya Y., Kitching R., Seth A.K.;
RT "Novel RING E3 ubiquitin ligases in breast cancer.";
RL Neoplasia 8:689-695(2006).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-72, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [18]
RP REVIEW ON FUNCTION.
RX PubMed=19392663; DOI=10.1042/bsr20090032;
RA Zhang M., Chen L., Wang S., Wang T.;
RT "Rab7: roles in membrane trafficking and disease.";
RL Biosci. Rep. 29:193-209(2009).
RN [19]
RP LACK OF INTERACTION WITH HPS4 AND THE BLOC-3 COMPLEX.
RX PubMed=20048159; DOI=10.1074/jbc.m109.069088;
RA Kloer D.P., Rojas R., Ivan V., Moriyama K., van Vlijmen T., Murthy N.,
RA Ghirlando R., van der Sluijs P., Hurley J.H., Bonifacino J.S.;
RT "Assembly of the biogenesis of lysosome-related organelles complex-3 (BLOC-
RT 3) and its interaction with Rab9.";
RL J. Biol. Chem. 285:7794-7804(2010).
RN [20]
RP INTERACTION WITH FYCO1.
RX PubMed=20100911; DOI=10.1083/jcb.200907015;
RA Pankiv S., Alemu E.A., Brech A., Bruun J.A., Lamark T., Overvatn A.,
RA Bjorkoy G., Johansen T.;
RT "FYCO1 is a Rab7 effector that binds to LC3 and PI3P to mediate microtubule
RT plus end-directed vesicle transport.";
RL J. Cell Biol. 188:253-269(2010).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-72, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [23]
RP REVIEW ON FUNCTION.
RX PubMed=20851765; DOI=10.1016/j.cellsig.2010.09.012;
RA Wang T., Ming Z., Xiaochun W., Hong W.;
RT "Rab7: role of its protein interaction cascades in endo-lysosomal
RT traffic.";
RL Cell. Signal. 23:516-521(2011).
RN [24]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21255211; DOI=10.1111/j.1600-0854.2011.01165.x;
RA Seto S., Tsujimura K., Koide Y.;
RT "Rab GTPases regulating phagosome maturation are differentially recruited
RT to mycobacterial phagosomes.";
RL Traffic 12:407-420(2011).
RN [25]
RP INTERACTION WITH CLN3.
RX PubMed=22261744; DOI=10.1007/s00018-011-0913-1;
RA Uusi-Rauva K., Kyttala A., van der Kant R., Vesa J., Tanhuanpaa K.,
RA Neefjes J., Olkkonen V.M., Jalanko A.;
RT "Neuronal ceroid lipofuscinosis protein CLN3 interacts with motor proteins
RT and modifies location of late endosomal compartments.";
RL Cell. Mol. Life Sci. 69:2075-2089(2012).
RN [26]
RP INTERACTION WITH CLN5 AND RILP, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP THR-22 AND GLN-67.
RX PubMed=22431521; DOI=10.1128/mcb.06726-11;
RA Mamo A., Jules F., Dumaresq-Doiron K., Costantino S., Lefrancois S.;
RT "The role of ceroid lipofuscinosis neuronal protein 5 (CLN5) in endosomal
RT sorting.";
RL Mol. Cell. Biol. 32:1855-1866(2012).
RN [27]
RP FUNCTION.
RX PubMed=22660413; DOI=10.1038/ncb2502;
RA Baietti M.F., Zhang Z., Mortier E., Melchior A., Degeest G., Geeraerts A.,
RA Ivarsson Y., Depoortere F., Coomans C., Vermeiren E., Zimmermann P.,
RA David G.;
RT "Syndecan-syntenin-ALIX regulates the biogenesis of exosomes.";
RL Nat. Cell Biol. 14:677-685(2012).
RN [28]
RP INTERACTION WITH PRPH, CHARACTERIZATION OF VARIANTS CMT2B PHE-129; ASN-157;
RP THR-161 AND MET-162, AND MUTAGENESIS OF THR-22 AND GLN-67.
RX PubMed=23179371; DOI=10.1007/s00401-012-1063-8;
RA Cogli L., Progida C., Thomas C.L., Spencer-Dene B., Donno C., Schiavo G.,
RA Bucci C.;
RT "Charcot-Marie-Tooth type 2B disease-causing RAB7A mutant proteins show
RT altered interaction with the neuronal intermediate filament peripherin.";
RL Acta Neuropathol. 125:257-272(2013).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-72, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [30]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [31]
RP INTERACTION WITH RUFY4.
RX PubMed=26416964; DOI=10.1083/jcb.201501059;
RA Terawaki S., Camosseto V., Prete F., Wenger T., Papadopoulos A.,
RA Rondeau C., Combes A., Rodriguez Rodrigues C., Vu Manh T.P., Fallet M.,
RA English L., Santamaria R., Soares A.R., Weil T., Hammad H., Desjardins M.,
RA Gorvel J.P., Santos M.A., Gatti E., Pierre P.;
RT "RUN and FYVE domain-containing protein 4 enhances autophagy and lysosome
RT tethering in response to Interleukin-4.";
RL J. Cell Biol. 210:1133-1152(2015).
RN [32]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [33]
RP INTERACTION WITH PLEKHM1.
RX PubMed=28325809; DOI=10.1083/jcb.201607085;
RA Marwaha R., Arya S.B., Jagga D., Kaur H., Tuli A., Sharma M.;
RT "The Rab7 effector PLEKHM1 binds Arl8b to promote cargo traffic to
RT lysosomes.";
RL J. Cell Biol. 216:1051-1070(2017).
RN [34]
RP INTERACTION WITH VPS13A, AND MUTAGENESIS OF THR-22 AND GLN-67.
RX PubMed=30709847; DOI=10.1242/dmm.036681;
RA Munoz-Braceras S., Tornero-Ecija A.R., Vincent O., Escalante R.;
RT "VPS13A is closely associated with mitochondria and is required for
RT efficient lysosomal degradation.";
RL Dis. Model. Mech. 12:0-0(2019).
RN [35]
RP FUNCTION.
RX PubMed=33147445; DOI=10.1016/j.cell.2020.10.030;
RA Daniloski Z., Jordan T.X., Wessels H.H., Hoagland D.A., Kasela S.,
RA Legut M., Maniatis S., Mimitou E.P., Lu L., Geller E., Danziger O.,
RA Rosenberg B.R., Phatnani H., Smibert P., Lappalainen T., tenOever B.R.,
RA Sanjana N.E.;
RT "Identification of Required Host Factors for SARS-CoV-2 Infection in Human
RT Cells.";
RL Cell 0:0-0(2020).
RN [36]
RP INTERACTION WITH MON1A-CCZ1B COMPLEX AND RIMOC1, AND SUBCELLULAR LOCATION.
RX PubMed=34432599; DOI=10.1080/15548627.2021.1960116;
RA Yan B.R., Li T., Coyaud E., Laurent E.M.N., St-Germain J., Zhou Y.,
RA Kim P.K., Raught B., Brumell J.H.;
RT "C5orf51 is a component of the MON1-CCZ1 complex and controls RAB7A
RT localization and stability during mitophagy.";
RL Autophagy 18:829-840(2022).
RN [37]
RP MUTAGENESIS OF THR-22 AND GLN-67.
RX PubMed=34159616; DOI=10.15252/embj.2021107821;
RA Koch J., Uckeley Z.M., Doldan P., Stanifer M., Boulant S., Lozach P.Y.;
RT "TMPRSS2 expression dictates the entry route used by SARS-CoV-2 to infect
RT host cells.";
RL EMBO J. 40:1-20(2021).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH GTP AND RILP, AND
RP MUTAGENESIS OF LEU-8; LYS-10; VAL-180; LEU-182 AND TYR-183.
RX PubMed=15933719; DOI=10.1038/sj.emboj.7600643;
RA Wu M., Wang T., Loh E., Hong W., Song H.;
RT "Structural basis for recruitment of RILP by small GTPase Rab7.";
RL EMBO J. 24:1491-1501(2005).
RN [39]
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF VARIANT CMT2B PHE-129 IN COMPLEX
RP WITH GTP, CHARACTERIZATION OF VARIANTS CMT2B PHE-129 AND MET-162, FUNCTION,
RP SUBUNIT, SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY.
RX PubMed=20028791; DOI=10.1093/hmg/ddp567;
RA McCray B.A., Skordalakes E., Taylor J.P.;
RT "Disease mutations in Rab7 result in unregulated nucleotide exchange and
RT inappropriate activation.";
RL Hum. Mol. Genet. 19:1033-1047(2010).
RN [40]
RP VARIANTS CMT2B PHE-129 AND MET-162, AND TISSUE SPECIFICITY.
RX PubMed=12545426; DOI=10.1086/367847;
RA Verhoeven K., De Jonghe P., Coen K., Verpoorten N., Auer-Grumbach M.,
RA Kwon J.M., FitzPatrick D., Schmedding E., De Vriendt E., Jacobs A.,
RA Van Gerwen V., Wagner K., Hartung H.-P., Timmerman V.;
RT "Mutations in the small GTP-ase late endosomal protein RAB7 cause Charcot-
RT Marie-Tooth type 2B neuropathy.";
RL Am. J. Hum. Genet. 72:722-727(2003).
RN [41]
RP VARIANT CMT2B THR-161.
RX PubMed=15455439; DOI=10.1002/ana.20281;
RA Houlden H., King R.H.M., Muddle J.R., Warner T.T., Reilly M.M.,
RA Orrell R.W., Ginsberg L.;
RT "A novel RAB7 mutation associated with ulcero-mutilating neuropathy.";
RL Ann. Neurol. 56:586-590(2004).
RN [42]
RP VARIANT CMT2B ASN-157.
RX PubMed=17060578; DOI=10.1212/01.wnl.0000240068.21499.f5;
RA Meggouh F., Bienfait H.M.E., Weterman M.A.J., de Visser M., Baas F.;
RT "Charcot-Marie-Tooth disease due to a de novo mutation of the RAB7 gene.";
RL Neurology 67:1476-1478(2006).
RN [43]
RP CHARACTERIZATION OF VARIANTS CMT2B PHE-129; ASN-157; THR-161 AND MET-162.
RX PubMed=21151572; DOI=10.1371/journal.pone.0015351;
RA Basuray S., Mukherjee S., Romero E., Wilson M.C., Wandinger-Ness A.;
RT "Rab7 mutants associated with Charcot-Marie-Tooth disease exhibit enhanced
RT NGF-stimulated signaling.";
RL PLoS ONE 5:E15351-E15351(2010).
CC -!- FUNCTION: Small GTPase which cycles between active GTP-bound and
CC inactive GDP-bound states. In its active state, binds to a variety of
CC effector proteins playing a key role in the regulation of endo-
CC lysosomal trafficking. Governs early-to-late endosomal maturation,
CC microtubule minus-end as well as plus-end directed endosomal migration
CC and positioning, and endosome-lysosome transport through different
CC protein-protein interaction cascades. Plays a central role, not only in
CC endosomal traffic, but also in many other cellular and physiological
CC events, such as growth-factor-mediated cell signaling, nutrient-
CC transportor mediated nutrient uptake, neurotrophin transport in the
CC axons of neurons and lipid metabolism. Also involved in regulation of
CC some specialized endosomal membrane trafficking, such as maturation of
CC melanosomes, pathogen-induced phagosomes (or vacuoles) and
CC autophagosomes. Plays a role in the maturation and acidification of
CC phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis.
CC Plays a role in the fusion of phagosomes with lysosomes. Plays
CC important roles in microbial pathogen infection and survival, as well
CC as in participating in the life cycle of viruses. Microbial pathogens
CC possess survival strategies governed by RAB7A, sometimes by employing
CC RAB7A function (e.g. Salmonella) and sometimes by excluding RAB7A
CC function (e.g. Mycobacterium). In concert with RAC1, plays a role in
CC regulating the formation of RBs (ruffled borders) in osteoclasts.
CC Controls the endosomal trafficking and neurite outgrowth signaling of
CC NTRK1/TRKA (PubMed:11179213, PubMed:12944476, PubMed:14617358,
CC PubMed:20028791, PubMed:21255211). Regulates the endocytic trafficking
CC of the EGF-EGFR complex by regulating its lysosomal degradation.
CC Involved in the ADRB2-stimulated lipolysis through lipophagy, a
CC cytosolic lipase-independent autophagic pathway (By similarity).
CC Required for the exosomal release of SDCBP, CD63 and syndecan
CC (PubMed:22660413). Required for vesicular trafficking and cell surface
CC expression of ACE2 (PubMed:33147445). May play a role in PRPH neuronal
CC intermediate filament assembly (By similarity).
CC {ECO:0000250|UniProtKB:P51150, ECO:0000269|PubMed:11179213,
CC ECO:0000269|PubMed:12944476, ECO:0000269|PubMed:14617358,
CC ECO:0000269|PubMed:20028791, ECO:0000269|PubMed:22660413,
CC ECO:0000269|PubMed:33147445}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.2;
CC Evidence={ECO:0000269|PubMed:20028791};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC Evidence={ECO:0000269|PubMed:20028791};
CC -!- SUBUNIT: The GTP-bound form interacts with RAC1 (By similarity).
CC Interacts with NTRK1/TRKA (By similarity). Interacts with C9orf72 (By
CC similarity). Interacts with CHM, the substrate-binding subunit of the
CC Rab geranylgeranyltransferase complex (By similarity). Interacts with
CC RILP (PubMed:11179213, PubMed:14668488, PubMed:15933719,
CC PubMed:20028791, PubMed:22431521). Interacts with PSMA7
CC (PubMed:14998988). Interacts with RNF115 (PubMed:16925951). Interacts
CC with FYCO1 (PubMed:20100911). Interacts with the PIK3C3/VPS34-PIK3R4
CC complex (PubMed:14617358). The GTP-bound form interacts with OSBPL1A
CC (PubMed:16176980). Interacts with CLN3 (PubMed:22261744). Does not
CC interact with HPS4 and the BLOC-3 complex (heterodimer of HPS1 and
CC HPS4) (PubMed:20048159). Interacts with CLN5 (PubMed:22431521).
CC Interacts with PLEKHM1 (via N- and C-terminus) (PubMed:28325809).
CC Interacts with RUFY4 (PubMed:26416964). Interacts with PRPH; the
CC interaction is direct (PubMed:23179371). Interacts with VPS13A
CC (PubMed:30709847). The GDP-bound form interacts with RIMOC1
CC (PubMed:34432599). Interacts with the MON1A-CCZ1B complex and this
CC interaction is enhanced in the presence of RIMOC1 (PubMed:34432599).
CC {ECO:0000250|UniProtKB:P09527, ECO:0000250|UniProtKB:P51150,
CC ECO:0000269|PubMed:11179213, ECO:0000269|PubMed:14617358,
CC ECO:0000269|PubMed:14668488, ECO:0000269|PubMed:14998988,
CC ECO:0000269|PubMed:15933719, ECO:0000269|PubMed:16176980,
CC ECO:0000269|PubMed:16925951, ECO:0000269|PubMed:20028791,
CC ECO:0000269|PubMed:20048159, ECO:0000269|PubMed:20100911,
CC ECO:0000269|PubMed:22261744, ECO:0000269|PubMed:22431521,
CC ECO:0000269|PubMed:23179371, ECO:0000269|PubMed:26416964,
CC ECO:0000269|PubMed:28325809, ECO:0000269|PubMed:30709847,
CC ECO:0000269|PubMed:34432599}.
CC -!- INTERACTION:
CC P51149; Q8WXF7: ATL1; NbExp=3; IntAct=EBI-1056089, EBI-2410266;
CC P51149; Q9UNS2: COPS3; NbExp=3; IntAct=EBI-1056089, EBI-350590;
CC P51149; Q02535: ID3; NbExp=3; IntAct=EBI-1056089, EBI-1387094;
CC P51149; Q9BXW6: OSBPL1A; NbExp=5; IntAct=EBI-1056089, EBI-765918;
CC P51149; Q6ZR37: PLEKHG7; NbExp=3; IntAct=EBI-1056089, EBI-12891828;
CC P51149; Q96NA2: RILP; NbExp=8; IntAct=EBI-1056089, EBI-2856119;
CC P51149; Q9UNE7: STUB1; NbExp=3; IntAct=EBI-1056089, EBI-357085;
CC P51149; Q96JC1: VPS39; NbExp=2; IntAct=EBI-1056089, EBI-1050197;
CC P51149; Q9GZS3: WDR61; NbExp=3; IntAct=EBI-1056089, EBI-358545;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, phagosome membrane
CC {ECO:0000269|PubMed:12944476, ECO:0000269|PubMed:21255211}; Peripheral
CC membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Late
CC endosome membrane {ECO:0000269|PubMed:12944476,
CC ECO:0000269|PubMed:14617358, ECO:0000269|PubMed:16176980,
CC ECO:0000269|PubMed:20028791, ECO:0000269|PubMed:28325809}; Peripheral
CC membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}.
CC Lysosome membrane {ECO:0000269|PubMed:12944476,
CC ECO:0000269|PubMed:20028791}; Peripheral membrane protein
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Melanosome membrane
CC {ECO:0000269|PubMed:12643545, ECO:0000269|PubMed:17081065}; Peripheral
CC membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}.
CC Cytoplasmic vesicle, autophagosome membrane
CC {ECO:0000269|PubMed:20028791}; Peripheral membrane protein
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Lipid droplet
CC {ECO:0000250|UniProtKB:P51150}. Endosome membrane
CC {ECO:0000269|PubMed:22431521}; Peripheral membrane protein
CC {ECO:0000305}. Cytoplasmic vesicle {ECO:0000250|UniProtKB:P51150}.
CC Mitochondrion membrane {ECO:0000305|PubMed:34432599}; Peripheral
CC membrane protein {ECO:0000305}. Note=Colocalizes with OSBPL1A at the
CC late endosome (PubMed:16176980). Found in the ruffled border (a late
CC endosomal-like compartment in the plasma membrane) of bone-resorbing
CC osteoclasts. Recruited to phagosomes containing S.aureus or
CC Mycobacterium (PubMed:21255211). Lipid droplet localization is
CC increased upon ADRB2 stimulation (By similarity). Recruited to damaged
CC mitochondria during mitophagy in a RIMOC1-dependent manner
CC (PubMed:34432599). {ECO:0000250|UniProtKB:P51150,
CC ECO:0000269|PubMed:16176980, ECO:0000269|PubMed:21255211,
CC ECO:0000269|PubMed:34432599}.
CC -!- TISSUE SPECIFICITY: Widely expressed; high expression found in skeletal
CC muscle. {ECO:0000269|PubMed:12545426}.
CC -!- DISEASE: Charcot-Marie-Tooth disease 2B (CMT2B) [MIM:600882]: A
CC dominant axonal form of Charcot-Marie-Tooth disease, a disorder of the
CC peripheral nervous system, characterized by progressive weakness and
CC atrophy, initially of the peroneal muscles and later of the distal
CC muscles of the arms. Charcot-Marie-Tooth disease is classified in two
CC main groups on the basis of electrophysiologic properties and
CC histopathology: primary peripheral demyelinating neuropathies
CC (designated CMT1 when they are dominantly inherited) and primary
CC peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group
CC are characterized by signs of axonal degeneration in the absence of
CC obvious myelin alterations, normal or slightly reduced nerve conduction
CC velocities, and progressive distal muscle weakness and atrophy.
CC {ECO:0000269|PubMed:12545426, ECO:0000269|PubMed:15455439,
CC ECO:0000269|PubMed:17060578, ECO:0000269|PubMed:20028791,
CC ECO:0000269|PubMed:21151572, ECO:0000269|PubMed:23179371}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA91390.1; Type=Erroneous translation; Note=Wrong choice of frame.; Evidence={ECO:0000305};
CC Sequence=BAF83410.1; Type=Erroneous translation; Note=Wrong choice of frame.; Evidence={ECO:0000305};
CC Sequence=EAW79303.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Inherited peripheral neuropathies mutation db;
CC URL="https://uantwerpen.vib.be/CMTMutations";
CC -!- WEB RESOURCE: Name=Leiden Muscular Dystrophy pages RAB7A, member RAS
CC oncogene family (RAB7A); Note=Leiden Open Variation Database (LOVD);
CC URL="https://databases.lovd.nl/shared/genes/RAB7A";
CC ---------------------------------------------------------------------------
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DR EMBL; X93499; CAA63763.1; -; mRNA.
DR EMBL; U44104; AAA86640.1; -; mRNA.
DR EMBL; AF050175; AAD02565.1; -; Genomic_DNA.
DR EMBL; AF498942; AAM21090.1; -; mRNA.
DR EMBL; AK000826; BAA91390.1; ALT_SEQ; mRNA.
DR EMBL; AK290721; BAF83410.1; ALT_SEQ; mRNA.
DR EMBL; BC008721; AAH08721.2; -; mRNA.
DR EMBL; CH471052; EAW79303.1; ALT_SEQ; Genomic_DNA.
DR CCDS; CCDS3052.1; -.
DR PIR; JC5268; JC5268.
DR RefSeq; NP_004628.4; NM_004637.5.
DR PDB; 1T91; X-ray; 1.90 A; A/B/C/D=1-207.
DR PDB; 1YHN; X-ray; 3.00 A; A=1-207.
DR PDB; 3LAW; X-ray; 2.80 A; A/B/C/D/E=1-207.
DR PDB; 6IYB; X-ray; 2.09 A; A/C=2-195.
DR PDB; 6WCW; X-ray; 2.80 A; B=2-182.
DR PDB; 7F6J; X-ray; 2.10 A; A/B=2-195.
DR PDBsum; 1T91; -.
DR PDBsum; 1YHN; -.
DR PDBsum; 3LAW; -.
DR PDBsum; 6IYB; -.
DR PDBsum; 6WCW; -.
DR PDBsum; 7F6J; -.
DR AlphaFoldDB; P51149; -.
DR SMR; P51149; -.
DR BioGRID; 113624; 388.
DR DIP; DIP-39879N; -.
DR IntAct; P51149; 156.
DR MINT; P51149; -.
DR STRING; 9606.ENSP00000265062; -.
DR ChEMBL; CHEMBL4105784; -.
DR DrugBank; DB04315; Guanosine-5'-Diphosphate.
DR TCDB; 9.A.3.1.1; the sorting nexin27 (snx27)-retromer assembly apparatus (retromeraa) family.
DR GlyGen; P51149; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P51149; -.
DR PhosphoSitePlus; P51149; -.
DR SwissPalm; P51149; -.
DR BioMuta; RAB7A; -.
DR DMDM; 1709999; -.
DR EPD; P51149; -.
DR jPOST; P51149; -.
DR MassIVE; P51149; -.
DR MaxQB; P51149; -.
DR PaxDb; P51149; -.
DR PeptideAtlas; P51149; -.
DR PRIDE; P51149; -.
DR ProteomicsDB; 56284; -.
DR TopDownProteomics; P51149; -.
DR Antibodypedia; 1885; 366 antibodies from 40 providers.
DR DNASU; 7879; -.
DR Ensembl; ENST00000265062.8; ENSP00000265062.3; ENSG00000075785.14.
DR Ensembl; ENST00000674589.1; ENSP00000502088.1; ENSG00000075785.14.
DR Ensembl; ENST00000675342.1; ENSP00000502486.1; ENSG00000075785.14.
DR Ensembl; ENST00000675497.1; ENSP00000502000.1; ENSG00000075785.14.
DR Ensembl; ENST00000676214.1; ENSP00000501618.1; ENSG00000075785.14.
DR GeneID; 7879; -.
DR KEGG; hsa:7879; -.
DR MANE-Select; ENST00000265062.8; ENSP00000265062.3; NM_004637.6; NP_004628.4.
DR UCSC; uc003eks.2; human.
DR CTD; 7879; -.
DR DisGeNET; 7879; -.
DR GeneCards; RAB7A; -.
DR GeneReviews; RAB7A; -.
DR HGNC; HGNC:9788; RAB7A.
DR HPA; ENSG00000075785; Low tissue specificity.
DR MalaCards; RAB7A; -.
DR MIM; 600882; phenotype.
DR MIM; 602298; gene.
DR neXtProt; NX_P51149; -.
DR OpenTargets; ENSG00000075785; -.
DR Orphanet; 99936; Autosomal dominant Charcot-Marie-Tooth disease type 2B.
DR PharmGKB; PA162400619; -.
DR VEuPathDB; HostDB:ENSG00000075785; -.
DR eggNOG; KOG0394; Eukaryota.
DR GeneTree; ENSGT00940000155864; -.
DR InParanoid; P51149; -.
DR OMA; KAMQHET; -.
DR OrthoDB; 1172019at2759; -.
DR PhylomeDB; P51149; -.
DR TreeFam; TF105605; -.
DR PathwayCommons; P51149; -.
DR Reactome; R-HSA-2132295; MHC class II antigen presentation.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-8854214; TBC/RABGAPs.
DR Reactome; R-HSA-8873719; RAB geranylgeranylation.
DR Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013404; RAC2 GTPase cycle.
DR Reactome; R-HSA-9013405; RHOD GTPase cycle.
DR Reactome; R-HSA-9013406; RHOQ GTPase cycle.
DR Reactome; R-HSA-9013407; RHOH GTPase cycle.
DR Reactome; R-HSA-9013408; RHOG GTPase cycle.
DR Reactome; R-HSA-9013409; RHOJ GTPase cycle.
DR Reactome; R-HSA-9013423; RAC3 GTPase cycle.
DR Reactome; R-HSA-9035034; RHOF GTPase cycle.
DR Reactome; R-HSA-9636383; Prevention of phagosomal-lysosomal fusion.
DR Reactome; R-HSA-9636569; Suppression of autophagy.
DR SignaLink; P51149; -.
DR SIGNOR; P51149; -.
DR BioGRID-ORCS; 7879; 285 hits in 1095 CRISPR screens.
DR ChiTaRS; RAB7A; human.
DR EvolutionaryTrace; P51149; -.
DR GeneWiki; RAB7A; -.
DR GenomeRNAi; 7879; -.
DR Pharos; P51149; Tchem.
DR PRO; PR:P51149; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P51149; protein.
DR Bgee; ENSG00000075785; Expressed in stromal cell of endometrium and 205 other tissues.
DR ExpressionAtlas; P51149; baseline and differential.
DR Genevisible; P51149; HS.
DR GO; GO:0097208; C:alveolar lamellar body; IEA:Ensembl.
DR GO; GO:0098993; C:anchored component of synaptic vesicle membrane; IEA:Ensembl.
DR GO; GO:0000421; C:autophagosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0032419; C:extrinsic component of lysosome membrane; ISS:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; ISS:GO_Central.
DR GO; GO:0005811; C:lipid droplet; ISS:GO_Central.
DR GO; GO:0005765; C:lysosomal membrane; TAS:Reactome.
DR GO; GO:0005764; C:lysosome; IDA:HPA.
DR GO; GO:0033162; C:melanosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0045335; C:phagocytic vesicle; IDA:UniProtKB.
DR GO; GO:0030670; C:phagocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0034045; C:phagophore assembly site membrane; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0030667; C:secretory granule membrane; TAS:Reactome.
DR GO; GO:0003925; F:G protein activity; IEA:UniProtKB-EC.
DR GO; GO:0019003; F:GDP binding; IDA:BHF-UCL.
DR GO; GO:0005525; F:GTP binding; IDA:BHF-UCL.
DR GO; GO:0003924; F:GTPase activity; IDA:BHF-UCL.
DR GO; GO:1905394; F:retromer complex binding; IMP:ParkinsonsUK-UCL.
DR GO; GO:0031267; F:small GTPase binding; IEA:Ensembl.
DR GO; GO:0000045; P:autophagosome assembly; IMP:GO_Central.
DR GO; GO:0045453; P:bone resorption; IEA:Ensembl.
DR GO; GO:0045022; P:early endosome to late endosome transport; IMP:UniProtKB.
DR GO; GO:0006897; P:endocytosis; TAS:ProtInc.
DR GO; GO:0008333; P:endosome to lysosome transport; IMP:BHF-UCL.
DR GO; GO:0099638; P:endosome to plasma membrane protein transport; IMP:UniProtKB.
DR GO; GO:0007174; P:epidermal growth factor catabolic process; IMP:BHF-UCL.
DR GO; GO:0051650; P:establishment of vesicle localization; IEA:Ensembl.
DR GO; GO:0046907; P:intracellular transport; IMP:ParkinsonsUK-UCL.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0061724; P:lipophagy; ISS:GO_Central.
DR GO; GO:1903542; P:negative regulation of exosomal secretion; IMP:ParkinsonsUK-UCL.
DR GO; GO:1905366; P:negative regulation of intralumenal vesicle formation; TAS:ParkinsonsUK-UCL.
DR GO; GO:0090383; P:phagosome acidification; IMP:UniProtKB.
DR GO; GO:0090382; P:phagosome maturation; TAS:UniProtKB.
DR GO; GO:0090385; P:phagosome-lysosome fusion; IMP:UniProtKB.
DR GO; GO:1903543; P:positive regulation of exosomal secretion; IMP:UniProtKB.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IMP:CACAO.
DR GO; GO:0048524; P:positive regulation of viral process; IMP:CACAO.
DR GO; GO:0006622; P:protein targeting to lysosome; IMP:BHF-UCL.
DR GO; GO:0022615; P:protein to membrane docking; IDA:UniProtKB.
DR GO; GO:0015031; P:protein transport; TAS:UniProtKB.
DR GO; GO:0009617; P:response to bacterium; IMP:ParkinsonsUK-UCL.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; IMP:UniProtKB.
DR GO; GO:0019076; P:viral release from host cell; IMP:CACAO.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR Pfam; PF00071; Ras; 1.
DR SMART; SM00174; RHO; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51419; RAB; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Autophagy; Charcot-Marie-Tooth disease;
KW Cytoplasmic vesicle; Disease variant; Endosome; GTP-binding;
KW Host-virus interaction; Hydrolase; Lipid degradation; Lipid droplet;
KW Lipid metabolism; Lipoprotein; Lysosome; Membrane; Methylation;
KW Mitochondrion; Neurodegeneration; Neuropathy; Nucleotide-binding;
KW Phosphoprotein; Prenylation; Protein transport; Reference proteome;
KW Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:25944712"
FT CHAIN 2..207
FT /note="Ras-related protein Rab-7a"
FT /id="PRO_0000121121"
FT MOTIF 37..45
FT /note="Effector region"
FT /evidence="ECO:0000250"
FT BINDING 15..22
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:15933719,
FT ECO:0000269|PubMed:20028791"
FT BINDING 34..40
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:15933719,
FT ECO:0000269|PubMed:20028791"
FT BINDING 63..67
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:15933719,
FT ECO:0000269|PubMed:20028791"
FT BINDING 125..128
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:15933719,
FT ECO:0000269|PubMed:20028791"
FT BINDING 156..157
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:15933719,
FT ECO:0000269|PubMed:20028791"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0007744|PubMed:25944712"
FT MOD_RES 72
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 207
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250"
FT LIPID 205
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 207
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT VARIANT 32
FT /note="K -> E (in dbSNP:rs11549759)"
FT /id="VAR_037886"
FT VARIANT 129
FT /note="L -> F (in CMT2B; increases GTP hydrolysis;
FT decreases affinity for GTP and GDP; does not affect
FT interaction with NTRK1; results in higher levels of NTRK1
FT and MAPK1/MAPK3 phosphorylation after NGF stimulation
FT consistent with enhanced MAPK signaling; increases
FT interaction with PRPH; dbSNP:rs121909078)"
FT /evidence="ECO:0000269|PubMed:12545426,
FT ECO:0000269|PubMed:20028791, ECO:0000269|PubMed:21151572,
FT ECO:0000269|PubMed:23179371"
FT /id="VAR_018722"
FT VARIANT 157
FT /note="K -> N (in CMT2B; does not affect interaction with
FT NTRK1; results in higher levels of NTRK1 and MAPK1/MAPK3
FT phosphorylation after NGF stimulation consistent with
FT enhanced MAPK signaling; increases interaction with PRPH;
FT dbSNP:rs121909081)"
FT /evidence="ECO:0000269|PubMed:17060578,
FT ECO:0000269|PubMed:21151572, ECO:0000269|PubMed:23179371"
FT /id="VAR_037887"
FT VARIANT 161
FT /note="N -> T (in CMT2B; does not affect interaction with
FT NTRK1; results in higher levels of NTRK1 and MAPK1/MAPK3
FT phosphorylation after NGF stimulation consistent with
FT enhanced MAPK signaling; increases interaction with PRPH;
FT dbSNP:rs121909080)"
FT /evidence="ECO:0000269|PubMed:15455439,
FT ECO:0000269|PubMed:21151572, ECO:0000269|PubMed:23179371"
FT /id="VAR_037888"
FT VARIANT 162
FT /note="V -> M (in CMT2B; increases GTP hydrolysis;
FT decreases affinity for GTP and GDP; does not affect
FT interaction with NTRK1; results in higher levels of NTRK1
FT and MAPK1/MAPK3 phosphorylation after NGF stimulation
FT consistent with enhanced MAPK signaling; increases
FT interaction with PRPH; dbSNP:rs121909079)"
FT /evidence="ECO:0000269|PubMed:12545426,
FT ECO:0000269|PubMed:20028791, ECO:0000269|PubMed:21151572,
FT ECO:0000269|PubMed:23179371"
FT /id="VAR_018723"
FT MUTAGEN 8
FT /note="L->A: Abolishes interaction with RILP and reduces
FT its localization to late endosomal/lysosomal compartments."
FT /evidence="ECO:0000269|PubMed:15933719"
FT MUTAGEN 10
FT /note="K->A: Abolishes interaction with RILP and
FT localization to late endosomal/lysosomal compartments."
FT /evidence="ECO:0000269|PubMed:15933719"
FT MUTAGEN 22
FT /note="T->N: Abolishes localization on late endosomes,
FT lysosomes and phagosomes and reduces phagosomal fusions.
FT Abolishes association of RILP with the phagosomes. No loss
FT of interaction with CLN5. No loss of interaction with PRPH.
FT Reduced interaction with VPS13A. Inhibits SARS-CoV-2
FT infection."
FT /evidence="ECO:0000269|PubMed:12944476,
FT ECO:0000269|PubMed:22431521, ECO:0000269|PubMed:23179371,
FT ECO:0000269|PubMed:30709847, ECO:0000269|PubMed:34159616"
FT MUTAGEN 67
FT /note="Q->L: Does not abolish localization on late
FT endosomes, lysosomes and phagosomes and does not reduce
FT phagosomal fusions. No loss of interaction with CLN5 and
FT VPS13A. Increases interaction with PRPH. Inhibits SARS-CoV-
FT 2 infection."
FT /evidence="ECO:0000269|PubMed:12944476,
FT ECO:0000269|PubMed:22431521, ECO:0000269|PubMed:23179371,
FT ECO:0000269|PubMed:30709847, ECO:0000269|PubMed:34159616"
FT MUTAGEN 180
FT /note="V->A: Abolishes interaction with RILP and
FT localization to late endosomal/lysosomal compartments."
FT /evidence="ECO:0000269|PubMed:15933719"
FT MUTAGEN 182
FT /note="L->A: Does not abolish interaction with RILP and
FT localization to late endosomal/lysosomal compartments. Does
FT not abolish interaction with RILP and localization to late
FT endosomal/lysosomal compartments; when associated with A-
FT 183."
FT /evidence="ECO:0000269|PubMed:15933719"
FT MUTAGEN 183
FT /note="Y->A: Does not abolish interaction with RILP and
FT localization to late endosomal/lysosomal compartments. Does
FT not abolish interaction with RILP and localization to late
FT endosomal/lysosomal compartments; when associated with A-
FT 182."
FT /evidence="ECO:0000269|PubMed:15933719"
FT CONFLICT 47
FT /note="T -> I (in Ref. 3; AAD02565)"
FT /evidence="ECO:0000305"
FT CONFLICT 108
FT /note="I -> V (in Ref. 2; AAA86640)"
FT /evidence="ECO:0000305"
FT CONFLICT 127
FT /note="I -> V (in Ref. 2; AAA86640)"
FT /evidence="ECO:0000305"
FT CONFLICT 180
FT /note="V -> E (in Ref. 3; AAD02565)"
FT /evidence="ECO:0000305"
FT STRAND 8..14
FT /evidence="ECO:0007829|PDB:1T91"
FT HELIX 21..30
FT /evidence="ECO:0007829|PDB:1T91"
FT STRAND 42..54
FT /evidence="ECO:0007829|PDB:1T91"
FT STRAND 56..64
FT /evidence="ECO:0007829|PDB:1T91"
FT HELIX 68..70
FT /evidence="ECO:0007829|PDB:1T91"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:6IYB"
FT STRAND 82..89
FT /evidence="ECO:0007829|PDB:1T91"
FT HELIX 93..97
FT /evidence="ECO:0007829|PDB:1T91"
FT HELIX 99..110
FT /evidence="ECO:0007829|PDB:1T91"
FT HELIX 115..117
FT /evidence="ECO:0007829|PDB:1T91"
FT STRAND 120..125
FT /evidence="ECO:0007829|PDB:1T91"
FT STRAND 129..131
FT /evidence="ECO:0007829|PDB:6IYB"
FT HELIX 136..145
FT /evidence="ECO:0007829|PDB:1T91"
FT STRAND 151..153
FT /evidence="ECO:0007829|PDB:1T91"
FT TURN 156..159
FT /evidence="ECO:0007829|PDB:1T91"
FT HELIX 162..181
FT /evidence="ECO:0007829|PDB:1T91"
SQ SEQUENCE 207 AA; 23490 MW; A2AF33B16A672971 CRC64;
MTSRKKVLLK VIILGDSGVG KTSLMNQYVN KKFSNQYKAT IGADFLTKEV MVDDRLVTMQ
IWDTAGQERF QSLGVAFYRG ADCCVLVFDV TAPNTFKTLD SWRDEFLIQA SPRDPENFPF
VVLGNKIDLE NRQVATKRAQ AWCYSKNNIP YFETSAKEAI NVEQAFQTIA RNALKQETEV
ELYNEFPEPI KLDKNDRAKA SAESCSC
