ID RB39B_HUMAN Reviewed; 213 AA. AC Q96DA2; Q5JT79; Q8NEX3; DT 10-JAN-2003, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 02-SEP-2026, entry version 191. DE RecName: Full=Ras-related protein Rab-39B; DE EC=3.6.5.2 {ECO:0000250|UniProtKB:P62820}; GN Name=RAB39B {ECO:0000312|HGNC:HGNC:16499}; 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=Fetal brain; RX PubMed=12438742; DOI=10.1159/000064047; RA Cheng H., Ma Y., Ni X., Jiang M., Guo L., Ying K., Xie Y., Mao Y.; RT "Isolation and characterization of a human novel RAB (RAB39B) gene."; RL Cytogenet. Genome Res. 97:72-75(2002). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Pancreas; 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 [5] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INVOLVEMENT IN XLID72. RX PubMed=20159109; DOI=10.1016/j.ajhg.2010.01.011; RA Giannandrea M., Bianchi V., Mignogna M.L., Sirri A., Carrabino S., RA D'Elia E., Vecellio M., Russo S., Cogliati F., Larizza L., Ropers H.H., RA Tzschach A., Kalscheuer V., Oehl-Jaschkowitz B., Skinner C., Schwartz C.E., RA Gecz J., Van Esch H., Raynaud M., Chelly J., de Brouwer A.P., Toniolo D., RA D'Adamo P.; RT "Mutations in the small GTPase gene RAB39B are responsible for X-linked RT mental retardation associated with autism, epilepsy, and macrocephaly."; RL Am. J. Hum. Genet. 86:185-195(2010). RN [6] RP SUBCELLULAR LOCATION. RX PubMed=24349490; DOI=10.1371/journal.pone.0083324; RA Seto S., Sugaya K., Tsujimura K., Nagata T., Horii T., Koide Y.; RT "Rab39a interacts with phosphatidylinositol 3-kinase and negatively RT regulates autophagy induced by lipopolysaccharide stimulation in RT macrophages."; RL PLoS ONE 8:E83324-E83324(2013). RN [7] RP INTERACTION WITH PICK1. RX PubMed=25784538; DOI=10.1038/ncomms7504; RA Mignogna M.L., Giannandrea M., Gurgone A., Fanelli F., Raimondi F., RA Mapelli L., Bassani S., Fang H., Van Anken E., Alessio M., Passafaro M., RA Gatti S., Esteban J.A., Huganir R., D'Adamo P.; RT "The intellectual disability protein RAB39B selectively regulates GluA2 RT trafficking to determine synaptic AMPAR composition."; RL Nat. Commun. 6:6504-6504(2015). RN [8] RP INVOLVEMENT IN WSMN, VARIANT WSMN LYS-168, AND CHARACTERIZATION OF VARIANT RP WSMN LYS-168. RX PubMed=25434005; DOI=10.1016/j.ajhg.2014.10.015; RA Wilson G.R., Sim J.C., McLean C., Giannandrea M., Galea C.A., Riseley J.R., RA Stephenson S.E., Fitzpatrick E., Haas S.A., Pope K., Hogan K.J., RA Gregg R.G., Bromhead C.J., Wargowski D.S., Lawrence C.H., James P.A., RA Churchyard A., Gao Y., Phelan D.G., Gillies G., Salce N., Stanford L., RA Marsh A.P., Mignogna M.L., Hayflick S.J., Leventer R.J., Delatycki M.B., RA Mellick G.D., Kalscheuer V.M., D'Adamo P., Bahlo M., Amor D.J., RA Lockhart P.J.; RT "Mutations in RAB39B cause X-linked intellectual disability and early-onset RT Parkinson disease with alpha-synuclein pathology."; RL Am. J. Hum. Genet. 95:729-735(2014). RN [9] RP FUNCTION, MUTAGENESIS OF SER-22 AND GLN-68, AND ACTIVITY REGULATION. RX PubMed=27103069; DOI=10.15252/embj.201593350; RA Sellier C., Campanari M.L., Julie Corbier C., Gaucherot A., RA Kolb-Cheynel I., Oulad-Abdelghani M., Ruffenach F., Page A., Ciura S., RA Kabashi E., Charlet-Berguerand N.; RT "Loss of C9ORF72 impairs autophagy and synergizes with polyQ Ataxin-2 to RT induce motor neuron dysfunction and cell death."; RL EMBO J. 35:1276-1297(2016). RN [10] RP DISCUSSION ON INVOLVEMENT IN WSMN. RX PubMed=27459931; DOI=10.1016/j.neurobiolaging.2016.03.021; RA Hodges K., Brewer S.S., Labbe C., Soto-Ortolaza A.I., Walton R.L., RA Strongosky A.J., Uitti R.J., van Gerpen J.A., Ertekin-Taner N., RA Kantarci K., Lowe V.J., Parisi J.E., Savica R., Graff-Radford J., RA Jones D.T., Knopman D.S., Petersen R.C., Murray M.E., Graff-Radford N.R., RA Ferman T.J., Dickson D.W., Wszolek Z.K., Boeve B.F., Ross O.A., RA Lorenzo-Betancor O.; RT "RAB39B gene mutations are not a common cause of Parkinson's disease or RT dementia with Lewy bodies."; RL Neurobiol. Aging 45:107-108(2016). RN [11] RP DISCUSSION ON INVOLVEMENT IN WSMN. RX PubMed=26739247; DOI=10.1016/j.parkreldis.2015.12.014; RA Loechte T., Brueggemann N., Vollstedt E.J., Krause P., Domingo A., RA Rosales R., Lee L.V., Hopfner F., Westenberger A., Kuehn A., Klein C., RA Lohmann K.; RT "RAB39B mutations are a rare finding in Parkinson disease patients."; RL Parkinsonism Relat. Disord. 23:116-117(2016). RN [12] RP FUNCTION, INTERACTION WITH 9ORF72; VPS39 AND VPS41, AND SUBCELLULAR RP LOCATION. RX PubMed=37821429; DOI=10.1038/s41467-023-42003-0; RA Zhang S., Tong M., Zheng D., Huang H., Li L., Ungermann C., Pan Y., Luo H., RA Lei M., Tang Z., Fu W., Chen S., Liu X., Zhong Q.; RT "C9orf72-catalyzed GTP loading of Rab39A enables HOPS-mediated membrane RT tethering and fusion in mammalian autophagy."; RL Nat. Commun. 14:6360-6360(2023). RN [13] {ECO:0007744|PDB:6S5F} RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 1-207 IN COMPLEX WITH MG(2+) AND RP GTP ANALOG, COFACTOR, AND DOMAIN. RA Diaz-Saez L., Jung S., Huber K., von Delft F., Arrowsmith C.H., Edwards A., RA Bountra C.; RT "Structure of the human RAB39B in complex with GMPPNP."; RL Submitted (JUL-2019) to the PDB data bank. RN [14] RP VARIANT WSMN ARG-192, AND SUBCELLULAR LOCATION. RX PubMed=26399558; DOI=10.1186/s13024-015-0045-4; RA Mata I.F., Jang Y., Kim C.H., Hanna D.S., Dorschner M.O., Samii A., RA Agarwal P., Roberts J.W., Klepitskaya O., Shprecher D.R., Chung K.A., RA Factor S.A., Espay A.J., Revilla F.J., Higgins D.S., Litvan I., RA Leverenz J.B., Yearout D., Inca-Martinez M., Martinez E., Thompson T.R., RA Cholerton B.A., Hu S.C., Edwards K.L., Kim K.S., Zabetian C.P.; RT "The RAB39B p.G192R mutation causes X-linked dominant Parkinson's RT disease."; RL Mol. Neurodegener. 10:50-50(2015). RN [15] RP VARIANT WSMN 186-TRP--CYS-213 DEL. RX PubMed=27066548; DOI=10.1212/nxg.0000000000000009; RG French Parkinson's Disease Genetics Study Group (PDG) and the International Parkinson's Disease Genomics Consortium (IPDGC); RA Lesage S., Bras J., Cormier-Dequaire F., Condroyer C., Nicolas A., RA Darwent L., Guerreiro R., Majounie E., Federoff M., Heutink P., Wood N.W., RA Gasser T., Hardy J., Tison F., Singleton A., Brice A.; RT "Loss-of-function mutations in RAB39B are associated with typical early- RT onset Parkinson disease."; RL Neurol. Genet. 1:E9-E9(2015). CC -!- FUNCTION: The small GTPases Rab are key regulators of intracellular CC membrane trafficking, from the formation of transport vesicles to their CC fusion with membranes. Rabs cycle between an inactive GDP-bound form CC and an active GTP-bound form that is able to recruit to membranes CC different sets of downstream effectors directly responsible for vesicle CC formation, movement, tethering and fusion (PubMed:27103069). RAB39B is CC involved in autophagy and may function in autophagosome formation CC (PubMed:27103069, PubMed:37821429). Binds downstream effector PICK1 to CC ensure selectively GRIA2 exit from the endoplasmic reticulum to the CC Golgi and to regulate AMPAR composition at the post-synapses and thus CC synaptic transmission (By similarity). May regulate the homeostasis of CC SNCA/alpha-synuclein (By similarity). {ECO:0000250|UniProtKB:Q8BHC1, CC ECO:0000269|PubMed:27103069, ECO:0000269|PubMed:37821429}. CC -!- CATALYTIC ACTIVITY: CC Reaction=GTP + H2O = GDP + phosphate + H(+); 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:0000250|UniProtKB:P62820}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670; CC Evidence={ECO:0000250|UniProtKB:P62820}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|Ref.13}; CC -!- ACTIVITY REGULATION: Regulated by guanine nucleotide exchange factors CC (GEFs) including C9orf72-SMCR8 complex, which promote the exchange of CC bound GDP for free GTP (PubMed:27103069). Regulated by GTPase CC activating proteins (GAPs) which increase the GTP hydrolysis activity CC (Probable). Inhibited by GDP dissociation inhibitors (GDIs) (Probable). CC {ECO:0000269|PubMed:27103069, ECO:0000305}. CC -!- SUBUNIT: Interacts (GDP-bound) with C9orf72; C9orf72 in complex with CC SMCR8 acts as a GEF for RAB39B (PubMed:37821429). Interacts (in GTP- CC bound form) with PICK1 (via PDZ domain); a PICK1 homodimer may allow CC simultaneous association of RAB39B and GRIA2 to PICK1 which is involved CC in GRIA2 trafficking (PubMed:25784538). Interacts with isoform c of CC RASSF1; the interaction is strong (By similarity). Interacts with CC isoform a of RASSF1; the interaction is weak (By similarity). Interacts CC with the DLG4/PSD-95 (By similarity). Interacts (GTP-bound) with HOPS CC complex components VPS39 and VPS41 (PubMed:37821429). CC {ECO:0000250|UniProtKB:Q8BHC1, ECO:0000269|PubMed:25784538, CC ECO:0000269|PubMed:37821429}. CC -!- INTERACTION: CC Q96DA2; Q08379: GOLGA2; NbExp=4; IntAct=EBI-9089467, EBI-618309; CC Q96DA2; Q96T51: RUFY1; NbExp=4; IntAct=EBI-9089467, EBI-3941207; CC Q96DA2; O14972: VPS26C; NbExp=3; IntAct=EBI-9089467, EBI-7207091; CC Q96DA2; Q8IUH5: ZDHHC17; NbExp=3; IntAct=EBI-9089467, EBI-524753; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Lipid-anchor CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Cytoplasmic vesicle CC membrane {ECO:0000269|PubMed:26399558}; Lipid-anchor {ECO:0000305}; CC Cytoplasmic side {ECO:0000305}. Golgi apparatus CC {ECO:0000269|PubMed:20159109, ECO:0000269|PubMed:24349490}. Cytoplasmic CC vesicle, autophagosome membrane {ECO:0000269|PubMed:37821429}. CC Autolysosome membrane {ECO:0000269|PubMed:37821429}. Note=Partial CC colocalization with markers that cycle from the cell surface to the CC trans-Golgi network. Colocalized with STX17 in autolysosomes in CC autophagy-induced conditions, although less compared with RAB39A CC (PubMed:37821429). {ECO:0000250|UniProtKB:Q8BHC1, CC ECO:0000269|PubMed:37821429}. CC -!- TISSUE SPECIFICITY: Highly expressed in the brain. CC {ECO:0000269|PubMed:20159109}. CC -!- DOMAIN: Switch I, switch II and the interswitch regions are CC characteristic of Rab GTPases and mediate the interactions with Rab CC downstream effectors. The switch regions undergo conformational changes CC upon nucleotide binding which drive interaction with specific sets of CC effector proteins, with most effectors only binding to GTP-bound Rab. CC {ECO:0000269|Ref.13}. CC -!- DISEASE: Intellectual developmental disorder, X-linked 72 (XLID72) CC [MIM:300271]: A disorder characterized by significantly below average CC general intellectual functioning associated with impairments in CC adaptive behavior and manifested during the developmental period. CC Intellectual deficiency is the only primary symptom of non-syndromic X- CC linked forms, while syndromic forms present with associated physical, CC neurological and/or psychiatric manifestations. XLID72 patients can CC manifest autism spectrum disorder, seizures and macrocephaly as CC additional features. {ECO:0000269|PubMed:20159109}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- DISEASE: Waisman syndrome (WSMN) [MIM:311510]: A neurologic disorder CC characterized by delayed psychomotor development, intellectual CC disability, and early-onset Parkinson disease. CC {ECO:0000269|PubMed:25434005, ECO:0000269|PubMed:26399558, CC ECO:0000269|PubMed:27066548}. Note=The disease is caused by variants CC affecting the gene represented in this entry. Its association with CC Parkinson disease is however unclear (PubMed:26739247, CC PubMed:27459931). According to a number of studies, variations CC affecting this gene are not a frequent cause of Parkinson disease, CC suggesting that RAB39B does not play a major role in Parkinson disease CC etiology (PubMed:26739247, PubMed:27459931). CC {ECO:0000269|PubMed:26739247, ECO:0000269|PubMed:27459931}. CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family. CC {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; AY052478; AAL12244.1; -; mRNA. DR EMBL; AL834460; CAD39120.1; -; mRNA. DR EMBL; AL356738; CAI41468.1; -; Genomic_DNA. DR EMBL; BC009714; AAH09714.1; -; mRNA. DR CCDS; CCDS14766.1; -. DR RefSeq; NP_741995.1; NM_171998.4. DR PDB; 6S5F; X-ray; 1.70 A; A=1-207. DR AlphaFoldDB; Q96DA2; -. DR SMR; Q96DA2; -. DR BioGRID; 125507; 57. DR FunCoup; Q96DA2; 1325. DR IntAct; Q96DA2; 57. DR MINT; Q96DA2; -. DR NDEx; IQUERY-CP-RAB39B; 1 NDEx IQuery Curated Pathway. DR STRING; 9606.ENSP00000358466; -. DR GlyGen; Q96DA2; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q96DA2; -. DR PhosphoSitePlus; Q96DA2; -. DR BioMuta; RAB39B; -. DR DMDM; 27734447; -. DR jPOST; Q96DA2; -. DR MassIVE; Q96DA2; -. DR PaxDb; 9606-ENSP00000358466; -. DR PeptideAtlas; Q96DA2; -. DR ProteomicsDB; 76264; -. DR Pumba; Q96DA2; -. DR Antibodypedia; 350; 190 antibodies from 29 providers. DR DNASU; 116442; -. DR Ensembl; ENST00000369454.4; ENSP00000358466.3; ENSG00000155961.5. DR GeneID; 116442; -. DR KEGG; hsa:116442; -. DR MANE-Select; ENST00000369454.4; ENSP00000358466.3; NM_171998.4; NP_741995.1. DR UCSC; uc004fne.5; human. DR AGR; HGNC:16499; -. DR ClinPGx; PA34131; -. DR CTD; 116442; -. DR DisGeNET; 116442; -. DR GeneCards; RAB39B; -. DR GeneReviews; RAB39B; -. DR HGNC; HGNC:16499; RAB39B. DR HPA; ENSG00000155961; Tissue enhanced (brain, retina). DR MalaCards; RAB39B; -. DR MIM; 300271; phenotype. DR MIM; 300774; gene. DR MIM; 311510; phenotype. DR OpenTargets; ENSG00000155961; -. DR Orphanet; 2379; Early-onset parkinsonism-intellectual disability syndrome. DR Orphanet; 777; X-linked non-syndromic intellectual disability. DR VEuPathDB; HostDB:ENSG00000155961; -. DR eggNOG; KOG0091; Eukaryota. DR GeneTree; ENSGT00940000158132; -. DR HOGENOM; CLU_041217_23_1_1; -. DR InParanoid; Q96DA2; -. DR OMA; XSITRAY; -. DR OrthoDB; 9989112at2759; -. DR PAN-GO; Q96DA2; 4 GO annotations based on evolutionary models. DR PhylomeDB; Q96DA2; -. DR PathwayCommons; Q96DA2; -. DR Reactome; R-HSA-8873719; RAB geranylgeranylation. DR Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs. DR SignaLink; Q96DA2; -. DR SIGNOR; Q96DA2; -. DR Agora; ENSG00000155961; -. DR BioGRID-ORCS; 116442; 12 hits in 769 CRISPR screens. DR GeneWiki; RAB39B; -. DR GenomeRNAi; 116442; -. DR Pharos; Q96DA2; Tbio. DR PRO; PR:Q96DA2; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; Q96DA2; protein. DR Bgee; ENSG00000155961; Expressed in endothelial cell and 123 other cell types or tissues. DR GO; GO:0120281; C:autolysosome membrane; EXP:UniProtKB. DR GO; GO:0000421; C:autophagosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0030659; C:cytoplasmic vesicle membrane; EXP:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0043005; C:neuron projection; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0031982; C:vesicle; IDA:UniProtKB. DR GO; GO:0003925; F:G protein activity; IEA:UniProtKB-EC. DR GO; GO:0005525; F:GTP binding; IEA:InterPro. DR GO; GO:0003924; F:GTPase activity; ISS:UniProtKB. DR GO; GO:0031489; F:myosin V binding; IPI:UniProtKB. DR GO; GO:0032482; P:Rab protein signal transduction; IEA:InterPro. DR GO; GO:0010506; P:regulation of autophagy; IMP:UniProtKB. DR GO; GO:0050808; P:synapse organization; ISS:UniProtKB. DR GO; GO:0016192; P:vesicle-mediated transport; ISS:UniProtKB. DR CDD; cd04111; Rab39; 1. DR FunFam; 3.40.50.300:FF:000358; RAB39B, member RAS oncogene family; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR041818; Rab39. DR InterPro; IPR050209; Rab_GTPases_membrane_traffic. DR InterPro; IPR005225; Small_GTP-bd. DR InterPro; IPR001806; Small_GTPase. DR NCBIfam; TIGR00231; small_GTP; 1. DR PANTHER; PTHR47979; DRAB11-RELATED; 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. DR PDBsum; 6S5F; -. PE 1: Evidence at protein level; KW 3D-structure; Autism spectrum disorder; Autophagy; Cell membrane; KW Cytoplasmic vesicle; Disease variant; Golgi apparatus; GTP-binding; KW Hydrolase; Intellectual disability; Lipoprotein; Lysosome; Magnesium; KW Membrane; Metal-binding; Methylation; Nucleotide-binding; KW Parkinson disease; Phosphoprotein; Prenylation; Protein transport; KW Proteomics identification; Reference proteome; Transport. FT CHAIN 1..213 FT /note="Ras-related protein Rab-39B" FT /id="PRO_0000121255" FT REGION 35..43 FT /note="Switch-I" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00753" FT REGION 67..83 FT /note="Switch-II" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00753" FT BINDING 17 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000305|Ref.13, ECO:0007744|PDB:6S5F" FT BINDING 20 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000305|Ref.13, ECO:0007744|PDB:6S5F" FT BINDING 21 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000305|Ref.13, ECO:0007744|PDB:6S5F" FT BINDING 22 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000305|Ref.13, ECO:0007744|PDB:6S5F" FT BINDING 22 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|Ref.13, ECO:0007744|PDB:6S5F" FT BINDING 23 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000305|Ref.13, ECO:0007744|PDB:6S5F" FT BINDING 37 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000305|Ref.13, ECO:0007744|PDB:6S5F" FT BINDING 40 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000305|Ref.13, ECO:0007744|PDB:6S5F" FT BINDING 40 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|Ref.13, ECO:0007744|PDB:6S5F" FT BINDING 64 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P62820, FT ECO:0000269|Ref.13" FT BINDING 67 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000305|Ref.13, ECO:0007744|PDB:6S5F" FT BINDING 123 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000305|Ref.13, ECO:0007744|PDB:6S5F" FT BINDING 124 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000305|Ref.13, ECO:0007744|PDB:6S5F" FT BINDING 126 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000305|Ref.13, ECO:0007744|PDB:6S5F" FT BINDING 154 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000305|Ref.13, ECO:0007744|PDB:6S5F" FT BINDING 155 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000305|Ref.13, ECO:0007744|PDB:6S5F" FT MOD_RES 201 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8BHC1" FT MOD_RES 213 FT /note="Cysteine methyl ester" FT /evidence="ECO:0000250|UniProtKB:P20336" FT LIPID 211 FT /note="S-geranylgeranyl cysteine" FT /evidence="ECO:0000250|UniProtKB:P20336" FT LIPID 213 FT /note="S-geranylgeranyl cysteine" FT /evidence="ECO:0000250|UniProtKB:P20336" FT VARIANT 168 FT /note="T -> K (in WSMN; loss of function mutation; FT expression of the mutation in neuroblastoma cells results FT in low levels of the mutant protein; dbSNP:rs587777874)" FT /evidence="ECO:0000269|PubMed:25434005" FT /id="VAR_073264" FT VARIANT 186..213 FT /note="Missing (in WSMN)" FT /evidence="ECO:0000269|PubMed:27066548" FT /id="VAR_078514" FT VARIANT 192 FT /note="G -> R (in WSMN; impaired localization to FT cytoplasmic vesicles; dbSNP:rs864309527)" FT /evidence="ECO:0000269|PubMed:26399558" FT /id="VAR_078515" FT MUTAGEN 22 FT /note="S->N: Dominant negative mutant." FT /evidence="ECO:0000269|PubMed:27103069" FT MUTAGEN 68 FT /note="Q->L: Constitutively active mutant locked in the FT active GTP-bound form." FT /evidence="ECO:0000269|PubMed:27103069" FT CONFLICT 57 FT /note="R -> T (in Ref. 1; AAL12244)" FT /evidence="ECO:0000305" FT STRAND 6..14 FT /evidence="ECO:0007829|PDB:6S5F" FT HELIX 21..30 FT /evidence="ECO:0007829|PDB:6S5F" FT HELIX 38..40 FT /evidence="ECO:0007829|PDB:6S5F" FT STRAND 42..53 FT /evidence="ECO:0007829|PDB:6S5F" FT STRAND 56..65 FT /evidence="ECO:0007829|PDB:6S5F" FT HELIX 69..71 FT /evidence="ECO:0007829|PDB:6S5F" FT HELIX 72..76 FT /evidence="ECO:0007829|PDB:6S5F" FT STRAND 83..90 FT /evidence="ECO:0007829|PDB:6S5F" FT HELIX 94..98 FT /evidence="ECO:0007829|PDB:6S5F" FT HELIX 100..107 FT /evidence="ECO:0007829|PDB:6S5F" FT STRAND 112..114 FT /evidence="ECO:0007829|PDB:6S5F" FT STRAND 117..123 FT /evidence="ECO:0007829|PDB:6S5F" FT HELIX 128..130 FT /evidence="ECO:0007829|PDB:6S5F" FT HELIX 135..144 FT /evidence="ECO:0007829|PDB:6S5F" FT STRAND 149..153 FT /evidence="ECO:0007829|PDB:6S5F" FT TURN 154..157 FT /evidence="ECO:0007829|PDB:6S5F" FT HELIX 160..176 FT /evidence="ECO:0007829|PDB:6S5F" FT STRAND 188..190 FT /evidence="ECO:0007829|PDB:6S5F" SQ SEQUENCE 213 AA; 24622 MW; 2B2C5B35C61FA88E CRC64; MEAIWLYQFR LIVIGDSTVG KSCLIRRFTE GRFAQVSDPT VGVDFFSRLV EIEPGKRIKL QIWDTAGQER FRSITRAYYR NSVGGLLLFD ITNRRSFQNV HEWLEETKVH VQPYQIVFVL VGHKCDLDTQ RQVTRHEAEK LAAAYGMKYI ETSARDAINV EKAFTDLTRD IYELVKRGEI TIQEGWEGVK SGFVPNVVHS SEEVVKSERR CLC //