PRAF3_MOUSE
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 03-AUG-2022, entry version 133.
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};
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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; 1.
DR IntAct; Q8R5J9; 2.
DR MINT; Q8R5J9; -.
DR STRING; 10090.ENSMUSP00000041503; -.
DR iPTMnet; Q8R5J9; -.
DR PhosphoSitePlus; Q8R5J9; -.
DR EPD; Q8R5J9; -.
DR jPOST; Q8R5J9; -.
DR MaxQB; Q8R5J9; -.
DR PaxDb; Q8R5J9; -.
DR PeptideAtlas; Q8R5J9; -.
DR PRIDE; Q8R5J9; -.
DR ProteomicsDB; 291549; -.
DR Antibodypedia; 3088; 227 antibodies from 30 providers.
DR DNASU; 65106; -.
DR Ensembl; ENSMUST00000044681; ENSMUSP00000041503; ENSMUSG00000035199.
DR GeneID; 65106; -.
DR KEGG; mmu:65106; -.
DR UCSC; uc009dar.1; mouse.
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; 1288023at2759; -.
DR PhylomeDB; Q8R5J9; -.
DR TreeFam; TF105479; -.
DR Reactome; R-MMU-210500; Glutamate Neurotransmitter Release Cycle.
DR BioGRID-ORCS; 65106; 2 hits in 72 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 259 other tissues.
DR Genevisible; Q8R5J9; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IPI:MGI.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IDA: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:0036475; P:neuron death in response to oxidative stress; IMP:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in 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; PTHR12859; 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
