ID PRRT2_MOUSE Reviewed; 346 AA. AC E9PUL5; DT 22-FEB-2012, integrated into UniProtKB/Swiss-Prot. DT 05-APR-2011, sequence version 1. DT 24-JAN-2024, entry version 77. DE RecName: Full=Proline-rich transmembrane protein 2; DE AltName: Full=Dispanin subfamily B member 3; DE Short=DSPB3; GN Name=Prrt2; 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 [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [2] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-28; THR-74; THR-78; SER-98; RP SER-102; SER-254 AND SER-255, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, and Liver; 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). RN [3] RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=22101681; DOI=10.1038/ng.1008; RA Chen W.J., Lin Y., Xiong Z.Q., Wei W., Ni W., Tan G.H., Guo S.L., He J., RA Chen Y.F., Zhang Q.J., Li H.F., Lin Y., Murong S.X., Xu J., Wang N., RA Wu Z.Y.; RT "Exome sequencing identifies truncating mutations in PRRT2 that cause RT paroxysmal kinesigenic dyskinesia."; RL Nat. Genet. 43:1252-1255(2011). RN [4] RP TISSUE SPECIFICITY. RX PubMed=22243967; DOI=10.1016/j.ajhg.2011.12.003; RA Heron S.E., Grinton B.E., Kivity S., Afawi Z., Zuberi S.M., Hughes J.N., RA Pridmore C., Hodgson B.L., Iona X., Sadleir L.G., Pelekanos J., RA Herlenius E., Goldberg-Stern H., Bassan H., Haan E., Korczyn A.D., RA Gardner A.E., Corbett M.A., Gecz J., Thomas P.Q., Mulley J.C., RA Berkovic S.F., Scheffer I.E., Dibbens L.M.; RT "PRRT2 mutations cause benign familial infantile epilepsy and infantile RT convulsions with choreoathetosis syndrome."; RL Am. J. Hum. Genet. 90:152-160(2012). RN [5] RP TISSUE SPECIFICITY, AND INTERACTION WITH SNAP25. RX PubMed=22832103; DOI=10.1016/j.celrep.2011.11.001; RA Lee H.Y., Huang Y., Bruneau N., Roll P., Roberson E.D., Hermann M., RA Quinn E., Maas J., Edwards R., Ashizawa T., Baykan B., Bhatia K., RA Bressman S., Bruno M.K., Brunt E.R., Caraballo R., Echenne B., Fejerman N., RA Frucht S., Gurnett C.A., Hirsch E., Houlden H., Jankovic J., Lee W.L., RA Lynch D.R., Mohammed S., Mueller U., Nespeca M.P., Renner D., Rochette J., RA Rudolf G., Saiki S., Soong B.W., Swoboda K.J., Tucker S., Wood N., RA Hanna M., Bowcock A.M., Szepetowski P., Fu Y.H., Ptacek L.J.; RT "Mutations in the gene PRRT2 cause paroxysmal kinesigenic dyskinesia with RT infantile convulsions."; RL Cell Rep. 1:2-12(2012). RN [6] RP IDENTIFICATION IN AMPAR COMPLEX, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RX PubMed=22632720; DOI=10.1016/j.neuron.2012.03.034; RA Schwenk J., Harmel N., Brechet A., Zolles G., Berkefeld H., Muller C.S., RA Bildl W., Baehrens D., Huber B., Kulik A., Klocker N., Schulte U., RA Fakler B.; RT "High-resolution proteomics unravel architecture and molecular diversity of RT native AMPA receptor complexes."; RL Neuron 74:621-633(2012). RN [7] RP GENE FAMILY. RX PubMed=22363774; DOI=10.1371/journal.pone.0031961; RA Sallman Almen M., Bringeland N., Fredriksson R., Schioth H.B.; RT "The dispanins: a novel gene family of ancient origin that contains 14 RT human members."; RL PLoS ONE 7:E31961-E31961(2012). RN [8] RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-246, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain; RX PubMed=24129315; DOI=10.1074/mcp.o113.027870; RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M., RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V., RA Bedford M.T., Comb M.J.; RT "Immunoaffinity enrichment and mass spectrometry analysis of protein RT methylation."; RL Mol. Cell. Proteomics 13:372-387(2014). RN [9] RP INTERACTION WITH GRIA1, AND TISSUE SPECIFICITY. RX PubMed=25915028; DOI=10.3390/ijms16059134; RA Li M., Niu F., Zhu X., Wu X., Shen N., Peng X., Liu Y.; RT "PRRT2 Mutant Leads to Dysfunction of Glutamate Signaling."; RL Int. J. Mol. Sci. 16:9134-9151(2015). RN [10] RP FUNCTION, INTERACTION WITH SNAP25; SYT1 AND SYT2, SUBCELLULAR LOCATION, RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=27052163; DOI=10.1016/j.celrep.2016.03.005; RA Valente P., Castroflorio E., Rossi P., Fadda M., Sterlini B., RA Cervigni R.I., Prestigio C., Giovedi S., Onofri F., Mura E., RA Guarnieri F.C., Marte A., Orlando M., Zara F., Fassio A., Valtorta F., RA Baldelli P., Corradi A., Benfenati F.; RT "PRRT2 Is a Key Component of the Ca(2+)-Dependent Neurotransmitter Release RT Machinery."; RL Cell Rep. 15:117-131(2016). RN [11] RP INTERACTION WITH ITSN1, SUBCELLULAR LOCATION, AND TOPOLOGY. RX PubMed=26797119; DOI=10.1074/jbc.m115.683888; RA Rossi P., Sterlini B., Castroflorio E., Marte A., Onofri F., Valtorta F., RA Maragliano L., Corradi A., Benfenati F.; RT "A Novel Topology of Proline-rich Transmembrane Protein 2 (PRRT2): hints RT for an intracellular function at the synapse."; RL J. Biol. Chem. 291:6111-6123(2016). RN [12] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=27172900; DOI=10.18632/oncotarget.9258; RA Liu Y.T., Nian F.S., Chou W.J., Tai C.Y., Kwan S.Y., Chen C., Kuo P.W., RA Lin P.H., Chen C.Y., Huang C.W., Lee Y.C., Soong B.W., Tsai J.W.; RT "PRRT2 mutations lead to neuronal dysfunction and neurodevelopmental RT defects."; RL Oncotarget 7:39184-39196(2016). RN [13] RP TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE. RX PubMed=28007585; DOI=10.1016/j.nbd.2016.12.018; RA Michetti C., Castroflorio E., Marchionni I., Forte N., Sterlini B., RA Binda F., Fruscione F., Baldelli P., Valtorta F., Zara F., Corradi A., RA Benfenati F.; RT "The PRRT2 knockout mouse recapitulates the neurological diseases RT associated with PRRT2 mutations."; RL Neurobiol. Dis. 99:66-83(2017). RN [14] RP FUNCTION, INTERACTION WITH SNAP25 AND STX1A, SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE. RX PubMed=29056747; DOI=10.1038/cr.2017.128; RA Tan G.H., Liu Y.Y., Wang L., Li K., Zhang Z.Q., Li H.F., Yang Z.F., Li Y., RA Li D., Wu M.Y., Yu C.L., Long J.J., Chen R.C., Li L.X., Yin L.P., Liu J.W., RA Cheng X.W., Shen Q., Shu Y.S., Sakimura K., Liao L.J., Wu Z.Y., Xiong Z.Q.; RT "PRRT2 deficiency induces paroxysmal kinesigenic dyskinesia by regulating RT synaptic transmission in cerebellum."; RL Cell Res. 28:90-110(2018). CC -!- FUNCTION: As a component of the outer core of AMPAR complex, may be CC involved in synaptic transmission in the central nervous system. In CC hippocampal neurons, in presynaptic terminals, plays an important role CC in the final steps of neurotransmitter release, possibly by regulating CC Ca(2+)-sensing (PubMed:27052163). In the cerebellum, may inhibit SNARE CC complex formation and down-regulate short-term facilitation CC (PubMed:29056747). {ECO:0000269|PubMed:27052163, CC ECO:0000269|PubMed:29056747}. CC -!- SUBUNIT: Component of the outer core of AMPAR complex (PubMed:22632720, CC PubMed:25915028). AMPAR complex consists of an inner core made of 4 CC pore-forming GluA/GRIA proteins (GRIA1, GRIA2, GRIA3 and GRIA4) and 4 CC major auxiliary subunits arranged in a twofold symmetry. One of the two CC pairs of distinct binding sites is occupied either by CNIH2, CNIH3 or CC CACNG2, CACNG3. The other harbors CACNG2, CACNG3, CACNG4, CACNG8 or CC GSG1L. This inner core of AMPAR complex is complemented by outer core CC constituents binding directly to the GluA/GRIA proteins at sites CC distinct from the interaction sites of the inner core constituents. CC Outer core constituents include at least PRRT1, PRRT2, CKAMP44/SHISA9, CC FRRS1L and NRN1. The proteins of the inner and outer core serve as a CC platform for other, more peripherally associated AMPAR constituents. CC Alone or in combination, these auxiliary subunits control the gating CC and pharmacology of the AMPAR complex and profoundly impact their CC biogenesis and protein processing (PubMed:22632720). Interacts with CC intersectin 1/ITSN1 (PubMed:26797119). Interacts with SNARE complex CC components, including SNAP25, STX1A, SYT1 and SYT2; this interaction CC may inhibit SNARE complex formation (PubMed:22832103, PubMed:27052163, CC PubMed:29056747). {ECO:0000269|PubMed:22632720, CC ECO:0000269|PubMed:22832103, ECO:0000269|PubMed:25915028, CC ECO:0000269|PubMed:26797119, ECO:0000269|PubMed:27052163, CC ECO:0000269|PubMed:29056747}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26797119, CC ECO:0000269|PubMed:27172900}; Single-pass membrane protein CC {ECO:0000305|PubMed:26797119}. Presynaptic cell membrane CC {ECO:0000269|PubMed:27052163, ECO:0000269|PubMed:29056747}; Single-pass CC membrane protein {ECO:0000305|PubMed:26797119}. Synapse CC {ECO:0000269|PubMed:27052163, ECO:0000269|PubMed:29056747, CC ECO:0000305|PubMed:22632720}. Cell projection, axon CC {ECO:0000269|PubMed:29056747}. Cytoplasmic vesicle, secretory vesicle, CC synaptic vesicle membrane {ECO:0000250|UniProtKB:D3ZFB6}. Postsynaptic CC density membrane {ECO:0000250|UniProtKB:D3ZFB6}. Cell projection, CC dendritic spine {ECO:0000250|UniProtKB:D3ZFB6}. CC -!- TISSUE SPECIFICITY: Neuron-specific expression throughout the brain, CC with the highest levels in the cerebellum, basal ganglia, hippocampus, CC substantia nigra, and neocortex (at protein level) (PubMed:22101681, CC PubMed:22243967, PubMed:22832103, PubMed:22632720, PubMed:25915028, CC PubMed:27052163, PubMed:27172900, PubMed:28007585, PubMed:29056747). CC Highly expressed also in spinal cord (at protein level) CC (PubMed:22101681, PubMed:22832103). Detected at very low levels in the CC heart, lung, kidney and skin (PubMed:22101681). CC {ECO:0000269|PubMed:22101681, ECO:0000269|PubMed:22243967, CC ECO:0000269|PubMed:22632720, ECO:0000269|PubMed:22832103, CC ECO:0000269|PubMed:25915028, ECO:0000269|PubMed:27052163, CC ECO:0000269|PubMed:27172900, ECO:0000269|PubMed:28007585, CC ECO:0000269|PubMed:29056747}. CC -!- DEVELOPMENTAL STAGE: At the mRNA level, expressed at low levels in the CC developing brain before 16 dpc. Expression markedly increases during CC early postnatal stages with a peak at P14. At this stage, expressed CC throughout the brain, with high levels in the cerebral cortex (cortical CC layers), hippocampus and cerebellum (granule cells and Purkinje cell CC layers). Progressively declines to relatively low levels in adulthood. CC At the protein level, first detected at very low levels at 17.5 dpc. CC Expression increases at early postnatal stages in the cerebral cortex, CC hippocampus and cerebellum. Expression increases to reach a plateau CC around P14, a period of intense synapse formation and rearrangement, CC and starts to slightly decrease around P90 (at protein level) CC (PubMed:27052163, PubMed:29056747). {ECO:0000269|PubMed:22101681, CC ECO:0000269|PubMed:27052163, ECO:0000269|PubMed:29056747}. CC -!- DISRUPTION PHENOTYPE: Mutant mice are normal at birth, but display CC paroxysmal movements at the onset of locomotion that persist in the CC adulthood. Adult animals present abnormal motor behaviors characterized CC by wild running and jumping in response to audiogenic stimuli that are CC ineffective in wild-type mice and an increased sensitivity to the CC convulsive effects of pentylentetrazol. Although the overall brain CC structure is not affected by the knockout, the thickness of the CC neocortex in young adult is significantly reduced in medial and caudal CC regions compared to their wild-type littermates. No significant CC differences are observed in the thickness of the CA1, CA3 and DG CC regions of the hippocampus, as well as for the molecular and granule CC layers of the cerebellum (PubMed:28007585). Mice with a conditional CC knockout in the central nervous system develop normally, but showed CC poor performance in motor coordination functions (PubMed:29056747). CC {ECO:0000269|PubMed:28007585, ECO:0000269|PubMed:29056747}. CC -!- SIMILARITY: Belongs to the CD225/Dispanin family. {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; AC122863; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS52405.1; -. DR RefSeq; NP_001096033.1; NM_001102563.1. DR AlphaFoldDB; E9PUL5; -. DR BioGRID; 213173; 209. DR IntAct; E9PUL5; 1. DR MINT; E9PUL5; -. DR STRING; 10090.ENSMUSP00000124520; -. DR GlyGen; E9PUL5; 4 sites, 1 O-linked glycan (4 sites). DR iPTMnet; E9PUL5; -. DR PhosphoSitePlus; E9PUL5; -. DR SwissPalm; E9PUL5; -. DR MaxQB; E9PUL5; -. DR PaxDb; 10090-ENSMUSP00000124520; -. DR PeptideAtlas; E9PUL5; -. DR ProteomicsDB; 291802; -. DR Ensembl; ENSMUST00000159916.5; ENSMUSP00000124520.2; ENSMUSG00000045114.11. DR GeneID; 69017; -. DR KEGG; mmu:69017; -. DR UCSC; uc009jty.1; mouse. DR AGR; MGI:1916267; -. DR CTD; 112476; -. DR MGI; MGI:1916267; Prrt2. DR VEuPathDB; HostDB:ENSMUSG00000045114; -. DR eggNOG; ENOG502S2U1; Eukaryota. DR GeneTree; ENSGT00940000161103; -. DR HOGENOM; CLU_070349_0_0_1; -. DR InParanoid; E9PUL5; -. DR OMA; DPQPDCQ; -. DR OrthoDB; 4641723at2759; -. DR PhylomeDB; E9PUL5; -. DR TreeFam; TF331357; -. DR BioGRID-ORCS; 69017; 4 hits in 79 CRISPR screens. DR ChiTaRS; Prrt2; mouse. DR PRO; PR:E9PUL5; -. DR Proteomes; UP000000589; Chromosome 7. DR RNAct; E9PUL5; Protein. DR Bgee; ENSMUSG00000045114; Expressed in cerebellar cortex and 58 other cell types or tissues. DR ExpressionAtlas; E9PUL5; baseline and differential. DR GO; GO:0043679; C:axon terminus; IDA:UniProtKB. DR GO; GO:0043197; C:dendritic spine; IEA:UniProtKB-SubCell. DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO. DR GO; GO:0016020; C:membrane; IDA:MGI. DR GO; GO:0043005; C:neuron projection; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; IDA:MGI. DR GO; GO:0098839; C:postsynaptic density membrane; IEA:UniProtKB-SubCell. DR GO; GO:0098793; C:presynapse; IDA:UniProtKB. DR GO; GO:0042734; C:presynaptic membrane; IDA:UniProtKB. DR GO; GO:0008021; C:synaptic vesicle; IDA:UniProtKB. DR GO; GO:0030672; C:synaptic vesicle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0031982; C:vesicle; IDA:UniProtKB. DR GO; GO:0017124; F:SH3 domain binding; ISO:MGI. DR GO; GO:0017075; F:syntaxin-1 binding; IDA:UniProtKB. DR GO; GO:1905513; P:negative regulation of short-term synaptic potentiation; IMP:UniProtKB. DR GO; GO:0035544; P:negative regulation of SNARE complex assembly; IMP:UniProtKB. DR GO; GO:0050884; P:neuromuscular process controlling posture; ISO:MGI. DR GO; GO:0150037; P:regulation of calcium-dependent activation of synaptic vesicle fusion; IDA:SynGO. DR GO; GO:0031629; P:synaptic vesicle fusion to presynaptic active zone membrane; IMP:UniProtKB. DR InterPro; IPR007593; CD225/Dispanin_fam. DR PANTHER; PTHR14948; NG5; 1. DR PANTHER; PTHR14948:SF20; PROLINE-RICH TRANSMEMBRANE PROTEIN 2; 1. DR Pfam; PF04505; CD225; 1. DR Genevisible; E9PUL5; MM. PE 1: Evidence at protein level; KW Cell membrane; Cell projection; Cytoplasmic vesicle; Membrane; Methylation; KW Phosphoprotein; Postsynaptic cell membrane; Reference proteome; Synapse; KW Transmembrane; Transmembrane helix. FT CHAIN 1..346 FT /note="Proline-rich transmembrane protein 2" FT /id="PRO_0000415735" FT TOPO_DOM 1..274 FT /note="Cytoplasmic" FT /evidence="ECO:0000255, ECO:0000305|PubMed:26797119" FT INTRAMEM 275..295 FT /note="Helical" FT /evidence="ECO:0000255, ECO:0000305|PubMed:26797119" FT TOPO_DOM 296..323 FT /note="Cytoplasmic" FT /evidence="ECO:0000255, ECO:0000305|PubMed:26797119" FT TRANSMEM 324..344 FT /note="Helical" FT /evidence="ECO:0000255, ECO:0000305|PubMed:26797119" FT TOPO_DOM 345..346 FT /note="Extracellular" FT /evidence="ECO:0000255, ECO:0000305|PubMed:26797119" FT REGION 1..222 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 235..267 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1..15 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 74..107 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 123..150 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 151..167 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 168..187 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 203..217 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 28 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 74 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 78 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 98 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 102 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 244 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:D3ZFB6" FT MOD_RES 246 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 254 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 255 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" SQ SEQUENCE 346 AA; 35924 MW; E7C3AF4159F4995F CRC64; MAASSSQVSE MKGVEDSSKT QTEGPRHSEE GLGPVQVVAE IPDQPEALQP GPGITAAPVD SGPKAELAPE TTETPVETPE TVQATDLSLN PEEGSKASPS PSPSEARQEP ASKPDVNRET AAEEGSEPQS TAPPEPTSEP AFQINTQSDP QPTSQPPPKP PLQAEPPTQE DPTTEVLTES TGEKQENGAV VPLQAGDGEE GPAPQPHSPP STKTPPANGA PPRVLQKLVE EDRIGRAHGG HPGSPRGSLS RHPSSQLAGP GVEGGEGTQK PRDYIILAIL SCFCPMWPVN IVAFAYAVMS RNSLQQGDVD GAQRLGRVAK LLSIVALVGG VLIIIASCVI NLGVYK //