ID PRAF3_MOUSE Reviewed; 188 AA. AC Q8R5J9; Q8C2Q1; Q9D838; Q9DB37; Q9WUG9; DT 04-JAN-2005, integrated into UniProtKB/Swiss-Prot. DT 04-JAN-2005, sequence version 2. DT 24-JAN-2024, entry version 141. DE RecName: Full=PRA1 family protein 3; DE AltName: Full=ADP-ribosylation factor-like protein 6-interacting protein 5; DE Short=ARL-6-interacting protein 5; DE Short=Aip-5; DE AltName: Full=Addicsin; DE AltName: Full=GTRAP3-18; DE AltName: Full=Glutamate transporter EAAC1-interacting protein; DE AltName: Full=Prenylated Rab acceptor protein 2; DE AltName: Full=Protein JWa; GN Name=Arl6ip5; Synonyms=Aip5, Jwa, Pra2, Praf3; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH SLC1A1, AND TISSUE RP SPECIFICITY. RC STRAIN=C57BL/6J; TISSUE=Brain; RX PubMed=12119102; DOI=10.1016/s0378-1119(02)00669-8; RA Butchbach M.E.R., Lai L., Lin C.-L.G.; RT "Molecular cloning, gene structure, expression profile and functional RT characterization of the mouse glutamate transporter (EAAT3) interacting RT protein GTRAP3-18."; RL Gene 292:81-90(2002). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, INDUCTION, AND TISSUE RP SPECIFICITY. RC TISSUE=Amygdala; RX PubMed=12438930; DOI=10.1097/00001756-200211150-00018; RA Ikemoto M.J., Inoue K., Akiduki S., Osugi T., Imamura T., Ishida N., RA Ohtomi M.; RT "Identification of addicsin/GTRAP3-18 as a chronic morphine-augumented gene RT in amygdala."; RL NeuroReport 13:2079-2084(2002). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=BALB/cJ; RA Xia W., Cao H.X., Zhou J.W.; RT "JWa and its biological evolution."; RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J, and NOD; RC TISSUE=Cerebellum, Head, Small intestine, and Thymus; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=FVB/N; TISSUE=Mammary tumor; 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 NUCLEOTIDE SEQUENCE [MRNA] OF 3-118, AND INTERACTION WITH ARL6. RX PubMed=10508919; DOI=10.1016/s0014-5793(99)01188-6; RA Ingley E., Williams J.H., Walker C.E., Tsai S., Colley S., Sayer M.S., RA Tilbrook P.A., Sarna M., Beaumont J.G., Klinken S.P.; RT "A novel ADP-ribosylation like factor (ARL-6), interacts with the protein- RT conducting channel SEC61beta subunit."; RL FEBS Lett. 459:69-74(1999). RN [7] RP PROTEIN SEQUENCE OF 10-27 AND 159-178, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC STRAIN=C57BL/6J; TISSUE=Brain; RA Lubec G., Kang S.U.; RL Submitted (APR-2007) to UniProtKB. RN [8] RP CHARACTERIZATION. RX PubMed=12562531; DOI=10.1046/j.1471-4159.2003.01588.x; RA Butchbach M.E.R., Guo H., Lin C.-L.G.; RT "Methyl-beta-cyclodextrin but not retinoic acid reduces EAAT3-mediated RT glutamate uptake and increases GTRAP3-18 expression."; RL J. Neurochem. 84:891-894(2003). RN [9] RP FUNCTION, SUBUNIT, INTERACTION WITH ARL6IP1 AND SLC1A1, TISSUE SPECIFICITY, RP AND MUTAGENESIS OF TYR-110 AND LEU-112. RX PubMed=18684713; DOI=10.1074/jbc.m801570200; RA Akiduki S., Ikemoto M.J.; RT "Modulation of the neural glutamate transporter EAAC1 by the addicsin- RT interacting protein ARL6IP1."; RL J. Biol. Chem. 283:31323-31332(2008). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, RC Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). CC -!- FUNCTION: Regulates intracellular concentrations of taurine and CC glutamate (By similarity). Negatively modulates SLC1A1/EAAC1 glutamate CC transport activity by decreasing its affinity for glutamate in a PKC CC activity-dependent manner (PubMed:12119102, PubMed:18684713). Plays a CC role in the retention of SLC1A1/EAAC1 in the endoplasmic reticulum (By CC similarity). {ECO:0000250|UniProtKB:Q9ES40, CC ECO:0000269|PubMed:12119102, ECO:0000269|PubMed:18684713}. CC -!- SUBUNIT: Homodimer. Heterodimer with ARL6IP1 (PubMed:18684713). Forms CC multimers. Interacts with ARL6 (PubMed:10508919). Interacts with CC prenylated RAB1A and RAB3A. Interacts with SLC1A1/EAAC1 CC (PubMed:18684713, PubMed:12119102). Interacts with RTN2 (via first CC transmembrane domain) (By similarity). Does not interact with VAMP1, CC VAMP2 or VAMP3 (By similarity). {ECO:0000250|UniProtKB:Q9ES40, CC ECO:0000269|PubMed:10508919, ECO:0000269|PubMed:12119102, CC ECO:0000269|PubMed:18684713}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:12438930}; Multi-pass membrane protein CC {ECO:0000255}. Cell membrane {ECO:0000250|UniProtKB:Q9ES40}; Multi-pass CC membrane protein {ECO:0000255}. Cytoplasm CC {ECO:0000269|PubMed:12438930}. Cytoplasm, cytoskeleton CC {ECO:0000269|PubMed:12438930}. Note=Also exists as a soluble form in CC the cytoplasm. Associated with microtubules. CC {ECO:0000269|PubMed:12438930}. CC -!- TISSUE SPECIFICITY: Expressed in the cerebral cortex, cerebellum, CC hippocampus, olfactory bulbs, medulla oblongate and limbic system (at CC protein level) (PubMed:18684713). Ubiquitous. CC {ECO:0000269|PubMed:12119102, ECO:0000269|PubMed:12438930, CC ECO:0000269|PubMed:18684713}. CC -!- INDUCTION: By methyl-beta-cyclodextrin. Up-regulated upon chronic CC morphine injection, in amygdala only, other brain regions remain CC unaffected. Induction by morphine may affect glutamate uptake in the CC amygdala, causing mice to develop morphine tolerance and dependence CC (PubMed:12438930). Was originally reported to be induced by retinoic CC acid (PubMed:12562531). {ECO:0000269|PubMed:12438930, CC ECO:0000305|PubMed:12562531}. CC -!- SIMILARITY: Belongs to the PRA1 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAD33050.1; Type=Erroneous translation; Note=Wrong choice of frame.; Evidence={ECO:0000305}; CC Sequence=AAD33050.1; Type=Frameshift; Evidence={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; AF421860; AAL77876.1; -; mRNA. DR EMBL; D87211; BAC24103.1; -; mRNA. DR EMBL; AF265214; AAL74056.1; -; mRNA. DR EMBL; AK005259; BAB23912.1; -; mRNA. DR EMBL; AK008519; BAB25717.1; -; mRNA. DR EMBL; AK088205; BAC40209.1; -; mRNA. DR EMBL; AK076519; BAC36376.1; -; mRNA. DR EMBL; BC003897; AAH03897.1; -; mRNA. DR EMBL; AF133912; AAD33050.1; ALT_SEQ; mRNA. DR CCDS; CCDS20384.1; -. DR RefSeq; NP_075368.1; NM_022992.2. DR AlphaFoldDB; Q8R5J9; -. DR SMR; Q8R5J9; -. DR BioGRID; 211132; 6. DR IntAct; Q8R5J9; 2. DR MINT; Q8R5J9; -. DR STRING; 10090.ENSMUSP00000041503; -. DR iPTMnet; Q8R5J9; -. DR PhosphoSitePlus; Q8R5J9; -. DR SwissPalm; Q8R5J9; -. DR EPD; Q8R5J9; -. DR jPOST; Q8R5J9; -. DR MaxQB; Q8R5J9; -. DR PaxDb; 10090-ENSMUSP00000041503; -. DR PeptideAtlas; Q8R5J9; -. DR ProteomicsDB; 291549; -. DR Pumba; Q8R5J9; -. DR Antibodypedia; 3088; 248 antibodies from 30 providers. DR DNASU; 65106; -. DR Ensembl; ENSMUST00000044681.7; ENSMUSP00000041503.7; ENSMUSG00000035199.7. DR GeneID; 65106; -. DR KEGG; mmu:65106; -. DR UCSC; uc009dar.1; mouse. DR AGR; MGI:1929501; -. DR CTD; 10550; -. DR MGI; MGI:1929501; Arl6ip5. DR VEuPathDB; HostDB:ENSMUSG00000035199; -. DR eggNOG; KOG4050; Eukaryota. DR GeneTree; ENSGT00390000008631; -. DR HOGENOM; CLU_097683_0_0_1; -. DR InParanoid; Q8R5J9; -. DR OMA; QMKKRYP; -. DR OrthoDB; 2879141at2759; -. DR PhylomeDB; Q8R5J9; -. DR TreeFam; TF105479; -. DR Reactome; R-MMU-210500; Glutamate Neurotransmitter Release Cycle. DR BioGRID-ORCS; 65106; 2 hits in 77 CRISPR screens. DR ChiTaRS; Arl6ip5; mouse. DR PRO; PR:Q8R5J9; -. DR Proteomes; UP000000589; Chromosome 6. DR RNAct; Q8R5J9; Protein. DR Bgee; ENSMUSG00000035199; Expressed in tarsal region and 263 other cell types or tissues. DR Genevisible; Q8R5J9; MM. DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; IPI:MGI. DR GO; GO:0099523; C:presynaptic cytosol; IDA:SynGO. DR GO; GO:0044325; F:transmembrane transporter binding; ISO:MGI. DR GO; GO:0071407; P:cellular response to organic cyclic compound; IDA:MGI. DR GO; GO:0034599; P:cellular response to oxidative stress; IMP:MGI. DR GO; GO:0006749; P:glutathione metabolic process; IMP:MGI. DR GO; GO:0008631; P:intrinsic apoptotic signaling pathway in response to oxidative stress; ISO:MGI. DR GO; GO:0098712; P:L-glutamate import across plasma membrane; IDA:MGI. DR GO; GO:0015813; P:L-glutamate transmembrane transport; IDA:MGI. DR GO; GO:0007611; P:learning or memory; IMP:MGI. DR GO; GO:0002037; P:negative regulation of L-glutamate import across plasma membrane; IDA:UniProtKB. DR GO; GO:0010917; P:negative regulation of mitochondrial membrane potential; ISO:MGI. DR GO; GO:0051051; P:negative regulation of transport; ISO:MGI. DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI. DR GO; GO:0032874; P:positive regulation of stress-activated MAPK cascade; ISO:MGI. DR GO; GO:0072659; P:protein localization to plasma membrane; IMP:MGI. DR GO; GO:0015031; P:protein transport; ISO:MGI. DR GO; GO:0051580; P:regulation of neurotransmitter uptake; ISO:MGI. DR InterPro; IPR004895; Prenylated_rab_accept_PRA1. DR PANTHER; PTHR12859:SF2; PRA1 FAMILY PROTEIN 3; 1. DR PANTHER; PTHR12859; PRA1 PROTEIN; 1. DR Pfam; PF03208; PRA1; 1. PE 1: Evidence at protein level; KW Acetylation; Cell membrane; Cytoplasm; Cytoskeleton; KW Direct protein sequencing; Endoplasmic reticulum; Membrane; KW Reference proteome; Transmembrane; Transmembrane helix. FT CHAIN 1..188 FT /note="PRA1 family protein 3" FT /id="PRO_0000220884" FT TOPO_DOM 1..39 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT TRANSMEM 40..60 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 64..84 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 85..92 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT TRANSMEM 93..113 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 115..135 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 136..188 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT REGION 103..117 FT /note="Required for homodimer formation and heterodimer FT formation with ARL6IP1" FT /evidence="ECO:0000269|PubMed:18684713" FT REGION 136..188 FT /note="Targeting to endoplasmic reticulum membrane" FT /evidence="ECO:0000250|UniProtKB:Q9ES40" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000250|UniProtKB:O75915" FT MUTAGEN 110 FT /note="Y->A: Significant decrease in interaction with FT ARL6IP1 and no influence on SLC1A1/EAAC1-mediated glutamate FT transport; when associated with A-112." FT /evidence="ECO:0000269|PubMed:18684713" FT MUTAGEN 112 FT /note="L->A: Significant decrease in interaction with FT ARL6IP1 and no influence on SLC1A1/EAAC1-mediated glutamate FT transport; when associated with A-110." FT /evidence="ECO:0000269|PubMed:18684713" FT CONFLICT 11 FT /note="W -> R (in Ref. 4; BAC40209)" FT /evidence="ECO:0000305" FT CONFLICT 14 FT /note="F -> S (in Ref. 4; BAC40209)" FT /evidence="ECO:0000305" FT CONFLICT 19 FT /note="Missing (in Ref. 6)" FT /evidence="ECO:0000305" FT CONFLICT 86 FT /note="Missing (in Ref. 6)" FT /evidence="ECO:0000305" FT CONFLICT 103 FT /note="M -> T (in Ref. 4; BAB25717)" FT /evidence="ECO:0000305" FT CONFLICT 117 FT /note="G -> R (in Ref. 6)" FT /evidence="ECO:0000305" FT CONFLICT 140 FT /note="R -> K (in Ref. 4; BAB25717)" FT /evidence="ECO:0000305" FT CONFLICT 163 FT /note="G -> V (in Ref. 1; AAL77876)" FT /evidence="ECO:0000305" FT CONFLICT 178 FT /note="K -> E (in Ref. 4; BAC40209)" FT /evidence="ECO:0000305" SQ SEQUENCE 188 AA; 21558 MW; 5A679FC5071319F0 CRC64; MDVNLAPLRA WDDFFPGSDR FARPDFRDIS KWNNRVVSNL LYYQTNYLVV AAMMISVVGF LSPFNMILGG VIVVLVFMGF VWAAHNKDIL RRMKKQYPTA FVMVVMLASY FLISMFGGVM VFVFGITLPL LLMFIHASLR LRNLKNKLEN KMEGIGLKKT PMGIILDALE QQEDNINKFA DYISKARE //