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-NOV-2015, entry version 120. DE RecName: Full=Rab-interacting lysosomal protein; GN Name=RILP; ORFNames=PP10141; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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 RT for transport to lysosomes."; RL EMBO J. 20:683-693(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT RP 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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., RA Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., RA Shu H., Chen X., Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., RA 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 RT 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 RT project: 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 RT 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 RT inducing 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 RT apparatus through Rab34 interaction with Rab-interacting lysosomal RT protein."; RL Mol. Biol. Cell 13:4317-4332(2002). RN [9] RP FUNCTION IN PHAGOSOME MIGRATION AND PHAGOLYSOSOMAL FUSION, 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 [10] RP FUNCTION IN LYSOSOMAL MORPHOLOGY AND DISTRIBUTION, INTERACTION WITH RP RAB7A 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 RT its regulation of lysosomal morphology and interaction with Rab7 and RT 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 RT proteins and modifies location of late endosomal compartments."; RL Cell. Mol. Life Sci. 69:2075-2089(2012). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-308, AND IDENTIFICATION RP 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., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [15] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 244-308 IN COMPLEX WITH RP RAB7A, SUBUNIT, AND MUTAGENESIS OF PHE-248; ILE-251; LEU-252; ARG-255; RP LEU-258; 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 CC to degradative compartments. Involved in the regulation of CC lysosomal morphology and distribution. Induces recruitment of CC dynein-dynactin motor complexes to Rab7A-containing late endosome CC and lysosome compartments. Promotes centripetal migration of CC phagosomes and the fusion of phagosomes with the late endosomes CC and lysosomes. {ECO:0000269|PubMed:11179213, CC ECO:0000269|PubMed:11696325, ECO:0000269|PubMed:12944476, CC ECO:0000269|PubMed:14668488}. CC -!- SUBUNIT: Homodimer. Each subunit can interact with either RAB7A or CC RAB34. Interacts with CLN3. {ECO:0000269|PubMed:11179213, CC ECO:0000269|PubMed:12475955, ECO:0000269|PubMed:14668488, CC ECO:0000269|PubMed:15933719, ECO:0000269|PubMed:15996637, CC ECO:0000269|PubMed:22261744}. CC -!- INTERACTION: CC P49754:VPS41; NbExp=4; IntAct=EBI-2856119, EBI-2130459; CC -!- SUBCELLULAR LOCATION: Endomembrane system. Late endosome membrane. CC Lysosome membrane. Cytoplasmic vesicle, phagosome membrane. CC Note=Associated with late endosomal, lysosomal and phagosomal CC membranes. The interaction with RAB7A is necessary for its CC recruitment to phagosomes. 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 CC gland, fetal liver, liver and lung. Poorly expressed in brain. CC {ECO:0000269|PubMed:11179213, ECO:0000269|PubMed:11520070, CC ECO:0000269|PubMed:14668488}. CC -!- SIMILARITY: Contains 1 RILP-like domain. {ECO:0000305}. 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 UniGene; Hs.534497; -. DR PDB; 1YHN; X-ray; 3.00 A; B=244-308. DR PDBsum; 1YHN; -. DR ProteinModelPortal; Q96NA2; -. DR SMR; Q96NA2; 244-308. DR BioGrid; 123679; 7. DR IntAct; Q96NA2; 9. DR STRING; 9606.ENSP00000301336; -. DR PhosphoSite; Q96NA2; -. DR BioMuta; RILP; -. DR DMDM; 74732524; -. DR MaxQB; Q96NA2; -. DR PaxDb; Q96NA2; -. DR PRIDE; Q96NA2; -. 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.3; human. [Q96NA2-1] DR CTD; 83547; -. DR GeneCards; RILP; -. DR HGNC; HGNC:30266; RILP. DR HPA; HPA052041; -. DR MIM; 607848; gene. DR neXtProt; NX_Q96NA2; -. DR PharmGKB; PA134915969; -. DR eggNOG; ENOG410IH32; Eukaryota. DR eggNOG; ENOG4111FK2; LUCA. DR GeneTree; ENSGT00530000063269; -. DR HOGENOM; HOG000007529; -. DR HOVERGEN; HBG082629; -. DR InParanoid; Q96NA2; -. DR KO; K13883; -. DR OMA; RFMKMNE; -. DR PhylomeDB; Q96NA2; -. DR TreeFam; TF313489; -. DR Reactome; R-HSA-2132295; MHC class II antigen presentation. DR EvolutionaryTrace; Q96NA2; -. DR GeneWiki; RILP_(gene); -. DR GenomeRNAi; 83547; -. DR NextBio; 72481; -. DR PRO; PR:Q96NA2; -. DR Proteomes; UP000005640; Chromosome 17. DR Bgee; Q96NA2; -. DR CleanEx; HS_RILP; -. DR ExpressionAtlas; Q96NA2; baseline and differential. DR Genevisible; Q96NA2; HS. 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; NAS:UniProtKB. DR GO; GO:0005764; C:lysosome; IDA:BHF-UCL. DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl. DR GO; GO:0030670; C:phagocytic vesicle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0043234; C:protein complex; IEA:Ensembl. DR GO; GO:0017137; F:Rab GTPase binding; TAS:UniProtKB. 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; IPR021563; RILP. DR Pfam; PF09744; Jnk-SapK_ap_N; 1. DR Pfam; PF11461; RILP; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Coiled coil; Complete proteome; KW Cytoplasmic vesicle; Endosome; Lysosome; Membrane; Phosphoprotein; KW Polymorphism; Protein transport; Reference proteome; Transport. FT CHAIN 1 401 Rab-interacting lysosomal protein. FT /FTId=PRO_0000097339. FT DOMAIN 236 270 RILP-like. FT REGION 272 333 Necessary for the interaction with RAB7A FT and RAB34, lysosomal distribution and FT morphology. FT COILED 75 181 {ECO:0000255}. FT MOD_RES 308 308 Phosphothreonine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 314 314 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 315 315 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT VAR_SEQ 1 210 Missing (in isoform 2). FT {ECO:0000303|PubMed:15498874}. FT /FTId=VSP_016043. FT VAR_SEQ 211 213 WAT -> MGA (in isoform 2). FT {ECO:0000303|PubMed:15498874}. FT /FTId=VSP_016044. FT VARIANT 81 81 A -> T (in dbSNP:rs9909321). FT {ECO:0000269|PubMed:14702039}. FT /FTId=VAR_051321. FT VARIANT 281 281 R -> Q (in dbSNP:rs34982553). FT /FTId=VAR_034417. FT MUTAGEN 248 248 F->A: Strongly reduces dimerization and FT localization to late endosomal/lysosomal FT compartments. FT {ECO:0000269|PubMed:15933719}. FT MUTAGEN 251 251 I->A: Abolishes dimerization, interaction FT with RAB7A and localization to late FT endosomal/lysosomal compartments. FT {ECO:0000269|PubMed:15933719}. FT MUTAGEN 252 252 L->A: Abolishes interaction with RAB7A FT and localization to late FT endosomal/lysosomal compartments. FT {ECO:0000269|PubMed:15933719}. FT MUTAGEN 255 255 R->A: Abolishes dimerization, interaction FT with RAB7A and localization to late FT endosomal/lysosomal compartments. FT {ECO:0000269|PubMed:15933719}. FT MUTAGEN 258 258 L->A: Reduces dimerization, interaction FT with RAB7A and localization to late FT endosomal/lysosomal compartments. FT {ECO:0000269|PubMed:15933719}. FT MUTAGEN 304 304 K->A: Abolishes interaction with RAB7A FT and localization to late FT endosomal/lysosomal compartments. FT {ECO:0000269|PubMed:15933719}. FT MUTAGEN 305 305 M->A: Abolishes interaction with RAB7A FT and localization to late FT endosomal/lysosomal compartments. FT {ECO:0000269|PubMed:15933719}. FT MUTAGEN 306 306 L->A: Abolishes interaction with RAB7A FT and localization to late FT endosomal/lysosomal compartments. FT {ECO:0000269|PubMed:15933719}. FT CONFLICT 284 284 G -> S (in Ref. 1; CAC33443). FT {ECO:0000305}. FT HELIX 248 276 {ECO:0000244|PDB:1YHN}. FT HELIX 284 306 {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 //