ID RILP_HUMAN Reviewed; 401 AA. AC Q96NA2; B2RBQ8; Q71RE6; Q9BSL3; Q9BYS3; DT 08-NOV-2005, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 11-DEC-2019, entry version 152. DE RecName: Full=Rab-interacting lysosomal protein; GN Name=RILP; ORFNames=PP10141; 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), FUNCTION IN LATE ENDOCYTOSIS, RP INTERACTION WITH RAB7A, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RC TISSUE=Cervix carcinoma; 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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT THR-81. RC TISSUE=Kidney, and Thalamus; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RX PubMed=15498874; DOI=10.1073/pnas.0404089101; RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X., RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.; RT "Large-scale cDNA transfection screening for genes related to cancer RT development and progression."; RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Skeletal muscle; RA Frigimelica E., Lanfranchi G.; RT "Study of 100 skeletal muscle full length mRNA (Telethon project B41)."; RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain, Lung, Testis, and Uterus; 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 [6] RP TISSUE SPECIFICITY. RX PubMed=11520070; DOI=10.1006/bbrc.2001.5466; RA Bucci C., De Gregorio L., Bruni C.B.; RT "Expression analysis and chromosomal assignment of PRA1 and RILP genes."; RL Biochem. Biophys. Res. Commun. 286:815-819(2001). RN [7] RP FUNCTION IN DYNEIN-DYNACTIN COMPLEX RECRUITMENT. RX PubMed=11696325; DOI=10.1016/s0960-9822(01)00531-0; RA Jordens I., Fernandez-Borja M., Marsman M., Dusseljee S., Janssen L., RA Calafat J., Janssen H., Wubbolts R., Neefjes J.; RT "The Rab7 effector protein RILP controls lysosomal transport by inducing RT the recruitment of dynein-dynactin motors."; RL Curr. Biol. 11:1680-1685(2001). RN [8] RP INTERACTION WITH RAB34. RX PubMed=12475955; DOI=10.1091/mbc.e02-05-0280; RA Wang T., Hong W.; RT "Interorganellar regulation of lysosome positioning by the Golgi apparatus RT through Rab34 interaction with Rab-interacting lysosomal protein."; RL Mol. Biol. Cell 13:4317-4332(2002). RN [9] RP FUNCTION IN PHAGOSOME MIGRATION AND PHAGOLYSOSOMAL FUSION, AND SUBCELLULAR RP 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 [10] RP FUNCTION IN LYSOSOMAL MORPHOLOGY AND DISTRIBUTION, INTERACTION WITH RAB7A RP AND RAB34, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. 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 [11] RP SUBUNIT. RX PubMed=15996637; DOI=10.1016/j.bbrc.2005.06.067; RA Colucci A.M.R., Campana M.C., Bellopede M., Bucci C.; RT "The Rab-interacting lysosomal protein, a Rab7 and Rab34 effector, is RT capable of self-interaction."; RL Biochem. Biophys. Res. Commun. 334:128-133(2005). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-314 AND SER-315, AND RP IDENTIFICATION BY 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 [13] 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 [14] RP INTERACTION WITH RAB7A. 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 [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-308, AND IDENTIFICATION BY RP 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 [16] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 244-308 IN COMPLEX WITH RAB7A, RP SUBUNIT, AND MUTAGENESIS OF PHE-248; ILE-251; LEU-252; ARG-255; LEU-258; RP LYS-304; MET-305 AND LEU-306. 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). CC -!- FUNCTION: Rab effector playing a role in late endocytic transport to CC degradative compartments. Involved in the regulation of lysosomal CC morphology and distribution. Induces recruitment of dynein-dynactin CC motor complexes to Rab7A-containing late endosome and lysosome CC compartments. Promotes centripetal migration of phagosomes and the CC fusion of phagosomes with the late endosomes and lysosomes. CC {ECO:0000269|PubMed:11179213, ECO:0000269|PubMed:11696325, CC ECO:0000269|PubMed:12944476, ECO:0000269|PubMed:14668488}. CC -!- SUBUNIT: Homodimer (PubMed:15996637, PubMed:15933719). Interacts with CC RAB7A (PubMed:11179213, PubMed:14668488, PubMed:22431521). Interacts CC with RAB34 (PubMed:14668488, PubMed:12475955). Identified in a complex CC with MREG and DCTN1; interacts directly with MREG (By similarity). CC Interacts with CLN3 (PubMed:22261744). {ECO:0000250|UniProtKB:Q5ND29, CC ECO:0000269|PubMed:11179213, ECO:0000269|PubMed:12475955, CC ECO:0000269|PubMed:14668488, ECO:0000269|PubMed:15933719, CC ECO:0000269|PubMed:15996637, ECO:0000269|PubMed:22261744, CC ECO:0000269|PubMed:22431521}. CC -!- INTERACTION: CC P51149:RAB7A; NbExp=2; IntAct=EBI-2856119, EBI-1056089; CC P49754:VPS41; NbExp=4; IntAct=EBI-2856119, EBI-2130459; CC -!- SUBCELLULAR LOCATION: Late endosome membrane CC {ECO:0000269|PubMed:11179213, ECO:0000269|PubMed:12944476}. Lysosome CC membrane {ECO:0000269|PubMed:11179213, ECO:0000269|PubMed:12944476, CC ECO:0000269|PubMed:14668488}. Cytoplasmic vesicle, phagosome membrane CC {ECO:0000269|PubMed:12944476}. Note=Associated with late endosomal, CC lysosomal and phagosomal membranes. The interaction with RAB7A is CC necessary for its recruitment to phagosomes. CC {ECO:0000269|PubMed:12944476}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q96NA2-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96NA2-2; Sequence=VSP_016043, VSP_016044; CC -!- TISSUE SPECIFICITY: Ubiquitous. Strongly expressed in fetal heart, CC heart, stomach, spleen, adrenal gland, thyroid gland, salivary gland, CC fetal liver, liver and lung. Poorly expressed in brain. CC {ECO:0000269|PubMed:11179213, ECO:0000269|PubMed:11520070, CC ECO:0000269|PubMed:14668488}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AJ404317; CAC33443.1; -; mRNA. DR EMBL; AK055755; BAB71003.1; -; mRNA. DR EMBL; AK314767; BAG37305.1; -; mRNA. DR EMBL; AF370391; AAQ15227.1; -; mRNA. DR EMBL; AJ278711; CAC82174.1; -; mRNA. DR EMBL; BC004961; AAH04961.1; -; mRNA. DR EMBL; BC031621; AAH31621.1; -; mRNA. DR CCDS; CCDS11009.1; -. [Q96NA2-1] DR RefSeq; NP_113618.2; NM_031430.2. [Q96NA2-1] DR PDB; 1YHN; X-ray; 3.00 A; B=244-308. DR PDBsum; 1YHN; -. DR SMR; Q96NA2; -. DR BioGrid; 123679; 12. DR DIP; DIP-29458N; -. DR IntAct; Q96NA2; 11. DR STRING; 9606.ENSP00000301336; -. DR iPTMnet; Q96NA2; -. DR PhosphoSitePlus; Q96NA2; -. DR BioMuta; RILP; -. DR DMDM; 74732524; -. DR EPD; Q96NA2; -. DR jPOST; Q96NA2; -. DR MassIVE; Q96NA2; -. DR MaxQB; Q96NA2; -. DR PaxDb; Q96NA2; -. DR PeptideAtlas; Q96NA2; -. DR PRIDE; Q96NA2; -. DR ProteomicsDB; 77494; -. [Q96NA2-1] DR ProteomicsDB; 77495; -. [Q96NA2-2] DR DNASU; 83547; -. DR Ensembl; ENST00000301336; ENSP00000301336; ENSG00000167705. [Q96NA2-1] DR Ensembl; ENST00000622136; ENSP00000481849; ENSG00000274145. [Q96NA2-1] DR GeneID; 83547; -. DR KEGG; hsa:83547; -. DR UCSC; uc002ftd.4; human. [Q96NA2-1] DR CTD; 83547; -. DR DisGeNET; 83547; -. DR EuPathDB; HostDB:ENSG00000167705.11; -. DR GeneCards; RILP; -. DR HGNC; HGNC:30266; RILP. DR MIM; 607848; gene. DR neXtProt; NX_Q96NA2; -. DR OpenTargets; ENSG00000167705; -. DR PharmGKB; PA134915969; -. DR eggNOG; ENOG410IH32; Eukaryota. DR eggNOG; ENOG4111FK2; LUCA. DR GeneTree; ENSGT00940000161117; -. DR HOGENOM; HOG000007529; -. DR InParanoid; Q96NA2; -. DR KO; K13883; -. DR OMA; ALHEHLC; -. DR OrthoDB; 890179at2759; -. DR PhylomeDB; Q96NA2; -. DR TreeFam; TF313489; -. DR Reactome; R-HSA-2132295; MHC class II antigen presentation. DR ChiTaRS; RILP; human. DR EvolutionaryTrace; Q96NA2; -. DR GeneWiki; RILP_(gene); -. DR GenomeRNAi; 83547; -. DR Pharos; Q96NA2; Tbio. DR PRO; PR:Q96NA2; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q96NA2; protein. DR Bgee; ENSG00000167705; Expressed in 196 organ(s), highest expression level in apex of heart. DR ExpressionAtlas; Q96NA2; baseline and differential. DR Genevisible; Q96NA2; HS. DR GO; GO:0005829; C:cytosol; IEA:GOC. DR GO; GO:0005770; C:late endosome; IDA:UniProtKB. DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005765; C:lysosomal membrane; TAS:Reactome. DR GO; GO:0005764; C:lysosome; IDA:BHF-UCL. DR GO; GO:0030670; C:phagocytic vesicle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl. DR GO; GO:0051959; F:dynein light intermediate chain binding; IPI:FlyBase. DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro. DR GO; GO:0017137; F:Rab GTPase binding; IPI:BHF-UCL. DR GO; GO:0031267; F:small GTPase binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; TAS:Reactome. DR GO; GO:0045022; P:early endosome to late endosome transport; IMP:UniProtKB. DR GO; GO:0008333; P:endosome to lysosome transport; IMP:BHF-UCL. DR GO; GO:0032509; P:endosome transport via multivesicular body sorting pathway; IDA:UniProtKB. DR GO; GO:0070676; P:intralumenal vesicle formation; IMP:UniProtKB. DR GO; GO:0042177; P:negative regulation of protein catabolic process; IDA:UniProtKB. DR GO; GO:0045732; P:positive regulation of protein catabolic process; IMP:UniProtKB. DR GO; GO:0015031; P:protein transport; NAS:UniProtKB. DR GO; GO:0010796; P:regulation of multivesicular body size; IDA:UniProtKB. DR InterPro; IPR019143; JNK/Rab-associated_protein-1_N. DR InterPro; IPR034743; RH1. DR InterPro; IPR034744; RH2. DR InterPro; IPR021563; RILP_dimer. DR Pfam; PF09744; Jnk-SapK_ap_N; 1. DR Pfam; PF11461; RILP; 1. DR PROSITE; PS51776; RH1; 1. DR PROSITE; PS51777; RH2; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Coiled coil; Cytoplasmic vesicle; KW Endosome; Lysosome; Membrane; Phosphoprotein; Polymorphism; KW Protein transport; Reference proteome; Transport. FT CHAIN 1..401 FT /note="Rab-interacting lysosomal protein" FT /id="PRO_0000097339" FT DOMAIN 11..101 FT /note="RH1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01112" FT DOMAIN 240..316 FT /note="RH2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01113" FT REGION 272..333 FT /note="Necessary for interaction with RAB7A and RAB34, FT lysosomal distribution and morphology" FT COILED 75..181 FT /evidence="ECO:0000255" FT MOD_RES 308 FT /note="Phosphothreonine" FT /evidence="ECO:0000244|PubMed:24275569" FT MOD_RES 314 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:18669648" FT MOD_RES 315 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:18669648" FT VAR_SEQ 1..210 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15498874" FT /id="VSP_016043" FT VAR_SEQ 211..213 FT /note="WAT -> MGA (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15498874" FT /id="VSP_016044" FT VARIANT 81 FT /note="A -> T (in dbSNP:rs9909321)" FT /evidence="ECO:0000269|PubMed:14702039" FT /id="VAR_051321" FT VARIANT 281 FT /note="R -> Q (in dbSNP:rs34982553)" FT /id="VAR_034417" FT MUTAGEN 248 FT /note="F->A: Strongly reduces dimerization and localization FT to late endosomal/lysosomal compartments." FT /evidence="ECO:0000269|PubMed:15933719" FT MUTAGEN 251 FT /note="I->A: Abolishes dimerization, interaction with RAB7A FT and localization to late endosomal/lysosomal compartments." FT /evidence="ECO:0000269|PubMed:15933719" FT MUTAGEN 252 FT /note="L->A: Abolishes interaction with RAB7A and FT localization to late endosomal/lysosomal compartments." FT /evidence="ECO:0000269|PubMed:15933719" FT MUTAGEN 255 FT /note="R->A: Abolishes dimerization, interaction with RAB7A FT and localization to late endosomal/lysosomal compartments." FT /evidence="ECO:0000269|PubMed:15933719" FT MUTAGEN 258 FT /note="L->A: Reduces dimerization, interaction with RAB7A FT and localization to late endosomal/lysosomal compartments." FT /evidence="ECO:0000269|PubMed:15933719" FT MUTAGEN 304 FT /note="K->A: Abolishes interaction with RAB7A and FT localization to late endosomal/lysosomal compartments." FT /evidence="ECO:0000269|PubMed:15933719" FT MUTAGEN 305 FT /note="M->A: Abolishes interaction with RAB7A and FT localization to late endosomal/lysosomal compartments." FT /evidence="ECO:0000269|PubMed:15933719" FT MUTAGEN 306 FT /note="L->A: Abolishes interaction with RAB7A and FT localization to late endosomal/lysosomal compartments." FT /evidence="ECO:0000269|PubMed:15933719" FT CONFLICT 284 FT /note="G -> S (in Ref. 1; CAC33443)" FT /evidence="ECO:0000305" FT HELIX 248..276 FT /evidence="ECO:0000244|PDB:1YHN" FT HELIX 284..306 FT /evidence="ECO:0000244|PDB:1YHN" SQ SEQUENCE 401 AA; 44200 MW; 1057A1DAC2FFED94 CRC64; MEPRRAAPGV PGWGSREAAG SASAAELVYH LAGALGTELQ DLARRFGPEA AAGLVPLVVR ALELLEQAAV GPAPDSLQVS AQPAEQELRR LREENERLRR ELRAGPQEER ALLRQLKEVT DRQRDELRAH NRDLRQRGQE TEALQEQLQR LLLVNAELRH KLAAMQTQLR AAQDRERERQ QPGEAATPQA KERARGQAGR PGHQHGQEPE WATAGAGAPG NPEDPAEAAQ QLGRPSEAGQ CRFSREEFEQ ILQERNELKA KVFLLKEELA YFQRELLTDH RVPGLLLEAM KVAVRKQRKK IKAKMLGTPE EAESSEDEAG PWILLSDDKG DHPPPPESKI QSFFGLWYRG KAESSEDETS SPAPSKLGGE EEAQPQSPAP DPPCSALHEH LCLGASAAPE A //