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   24-JUL-2024, entry version 237.
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   UBIQUITINATION AT LYS-191 AND LYS-194, AND DEUBIQUITINATION BY USP32.
RX   PubMed=36476874; DOI=10.1016/j.celrep.2022.111653;
RA   Hertel A., Alves L.M., Dutz H., Tascher G., Bonn F., Kaulich M., Dikic I.,
RA   Eimer S., Steinberg F., Bremm A.;
RT   "USP32-regulated LAMTOR1 ubiquitination impacts mTORC1 activation and
RT   autophagy induction.";
RL   Cell Rep. 41:111653-111653(2022).
RN   [39]
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   [40]
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   [41]
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   [42]
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   [43]
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   [44]
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       Interacts with VPS39 and VPS41 (By similarity).
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; Q9Y4G2: PLEKHM1; NbExp=11; IntAct=EBI-1056089, EBI-473814;
CC       P51149; Q96NA2: RILP; NbExp=10; IntAct=EBI-1056089, EBI-2856119;
CC       P51149; Q9GZS3: SKIC8; NbExp=3; IntAct=EBI-1056089, EBI-358545;
CC       P51149; Q9UNE7: STUB1; NbExp=3; IntAct=EBI-1056089, EBI-357085;
CC       P51149; Q96JC1: VPS39; NbExp=2; IntAct=EBI-1056089, EBI-1050197;
CC       P51149; Q5ZU30: setA; Xeno; NbExp=2; IntAct=EBI-1056089, EBI-40253342;
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   -!- PTM: Deubiquitination at Lys-191 and Lys-194 by USP32.
CC       {ECO:0000269|PubMed:36476874}.
CC   -!- DISEASE: Charcot-Marie-Tooth disease, axonal, 2B (CMT2B) [MIM:600882]:
CC       A dominant axonal form of Charcot-Marie-Tooth disease, a disorder of
CC       the peripheral nervous system, characterized by progressive weakness
CC       and 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";
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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; 895.
DR   DIP; DIP-39879N; -.
DR   IntAct; P51149; 173.
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   jPOST; P51149; -.
DR   MassIVE; P51149; -.
DR   PaxDb; 9606-ENSP00000265062; -.
DR   PeptideAtlas; P51149; -.
DR   PRIDE; P51149; -.
DR   ProteomicsDB; 56284; -.
DR   Pumba; P51149; -.
DR   TopDownProteomics; P51149; -.
DR   Antibodypedia; 1885; 370 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   AGR; HGNC:9788; -.
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; 586759at2759; -.
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; 299 hits in 1189 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 207 other cell types or tissues.
DR   ExpressionAtlas; P51149; baseline and differential.
DR   GO; GO:0097208; C:alveolar lamellar body; IEA:Ensembl.
DR   GO; GO:0000421; C:autophagosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005829; C:cytosol; ISS:GO_Central.
DR   GO; GO:0010008; C:endosome membrane; IDA:UniProtKB.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
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:MGI.
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:0030672; C:synaptic vesicle membrane; IEA:Ensembl.
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   CDD; cd01862; Rab7; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR005225; Small_GTP-bd_dom.
DR   InterPro; IPR001806; Small_GTPase.
DR   NCBIfam; TIGR00231; small_GTP; 1.
DR   PANTHER; PTHR47981; RAB FAMILY; 1.
DR   PANTHER; PTHR47981:SF13; RAS-RELATED PROTEIN RAB-7A; 1.
DR   Pfam; PF00071; Ras; 1.
DR   PRINTS; PR00449; RASTRNSFRMNG.
DR   SMART; SM00175; RAB; 1.
DR   SMART; SM00176; RAN; 1.
DR   SMART; SM00173; RAS; 1.
DR   SMART; SM00174; RHO; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 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; Isopeptide bond; Lipid degradation;
KW   Lipid droplet; Lipid metabolism; Lipoprotein; Lysosome; Membrane;
KW   Methylation; Mitochondrion; Neurodegeneration; Neuropathy;
KW   Nucleotide-binding; Phosphoprotein; Prenylation; Protein transport;
KW   Reference proteome; Transport; Ubl conjugation.
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   CROSSLNK        191
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000269|PubMed:36476874"
FT   CROSSLNK        194
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000269|PubMed:36476874"
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
//