SHSA6_MOUSE
ID SHSA6_MOUSE Reviewed; 525 AA.
AC Q3UH99; A0A172Q417;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 99.
DE RecName: Full=Protein shisa-6 {ECO:0000305};
DE AltName: Full=Cystine-knot AMPAR modulating protein of 52 kDa {ECO:0000303|PubMed:26623514};
DE Short=CKAMP52 {ECO:0000303|PubMed:26623514};
DE AltName: Full=Shisa family member 6 {ECO:0000305};
DE Flags: Precursor;
GN Name=Shisa6 {ECO:0000303|PubMed:26623514, ECO:0000303|PubMed:26931375,
GN ECO:0000312|MGI:MGI:2685725}; Synonyms=Gm879 {ECO:0000312|MGI:MGI:2685725};
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] (ISOFORM 2), TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RC STRAIN=C57BL/6N;
RX PubMed=26623514; DOI=10.7554/elife.09693;
RA Farrow P., Khodosevich K., Sapir Y., Schulmann A., Aslam M., Stern-Bach Y.,
RA Monyer H., von Engelhardt J.;
RT "Auxiliary subunits of the CKAMP family differentially modulate AMPA
RT receptor properties.";
RL Elife 4:E09693-E09693(2015).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J;
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-434, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-416; SER-422; SER-434;
RP THR-458 AND THR-502, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Brain;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION, DOMAIN, MUTAGENESIS OF
RP 522-GLU--VAL-525, DISRUPTION PHENOTYPE, IDENTIFICATION IN AMPAR COMPLEX,
RP AND GLYCOSYLATION.
RX PubMed=26931375; DOI=10.1038/ncomms10682;
RA Klaassen R.V., Stroeder J., Coussen F., Hafner A.S., Petersen J.D.,
RA Renancio C., Schmitz L.J., Normand E., Lodder J.C., Rotaru D.C.,
RA Rao-Ruiz P., Spijker S., Mansvelder H.D., Choquet D., Smit A.B.;
RT "Shisa6 traps AMPA receptors at postsynaptic sites and prevents their
RT desensitization during synaptic activity.";
RL Nat. Commun. 7:10682-10682(2016).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN AMPAR COMPLEX.
RX PubMed=29199957; DOI=10.7554/elife.24192;
RA Schmitz L.J.M., Klaassen R.V., Ruiperez-Alonso M., Zamri A.E., Stroeder J.,
RA Rao-Ruiz P., Lodder J.C., van der Loo R.J., Mansvelder H.D., Smit A.B.,
RA Spijker S.;
RT "The AMPA receptor-associated protein Shisa7 regulates hippocampal synaptic
RT function and contextual memory.";
RL Elife 6:0-0(2017).
RN [7]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=28196692; DOI=10.1016/j.stemcr.2017.01.006;
RA Tokue M., Ikami K., Mizuno S., Takagi C., Miyagi A., Takada R., Noda C.,
RA Kitadate Y., Hara K., Mizuguchi H., Sato T., Taketo M.M., Sugiyama F.,
RA Ogawa T., Kobayashi S., Ueno N., Takahashi S., Takada S., Yoshida S.;
RT "SHISA6 Confers Resistance to Differentiation-Promoting Wnt/beta-Catenin
RT Signaling in Mouse Spermatogenic Stem Cells.";
RL Stem Cell Reports 8:561-575(2017).
CC -!- FUNCTION: Involved in maintenance of high-frequency synaptic
CC transmission at hippocampal CA3-CA1 synapses. Regulates AMPA-type
CC glutamate receptor (AMPAR) immobilization at postsynaptic density
CC keeping the channels in an activated state in the presence of glutamate
CC and preventing synaptic depression (PubMed:26931375). May play a role
CC in self-renewal and differentiation of spermatogonial stem cells by
CC inhibiting canonical Wnt signaling pathway (PubMed:28196692).
CC {ECO:0000269|PubMed:26931375, ECO:0000269|PubMed:28196692}.
CC -!- SUBUNIT: Component of the postsynaptic hippocampal AMPA-type glutamate
CC receptor (AMPAR) complex, at least composed of pore forming AMPAR
CC subunits GRIA1, GRIA2 and GRIA3 and AMPAR auxiliary proteins SHISA6 and
CC SHISA7 (PubMed:26931375, PubMed:29199957). Interacts (via PDZ-binding
CC motif) with DLG4/PSD-95 (via PDZ domain); the interaction is direct
CC (PubMed:26931375). {ECO:0000269|PubMed:26931375,
CC ECO:0000269|PubMed:29199957}.
CC -!- SUBCELLULAR LOCATION: Postsynaptic density membrane
CC {ECO:0000269|PubMed:26931375}; Single-pass type I membrane protein
CC {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q3UH99-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3UH99-2; Sequence=VSP_059384;
CC -!- TISSUE SPECIFICITY: Highly expressed in cerebellum and hippocampal
CC neurons: CA1 stratum oriens and stratum radiatum, CA3 stratum oriens
CC and stratum lucidum, and the dentate gyrus polymorphic layer
CC (PubMed:26931375). Expressed in other brain structures including
CC olfactory bulb, cortex, amygdala and midbrain (at protein level)
CC (PubMed:26623514, PubMed:26931375). Also expressed in a subset of
CC spermatogonial stem cells (PubMed:28196692). Also expressed in eye,
CC heart, kidney, lung, muscle and spleen. Isoform 2: Specifically
CC expressed in hippocampus (PubMed:26931375).
CC {ECO:0000269|PubMed:26623514, ECO:0000269|PubMed:26931375,
CC ECO:0000269|PubMed:28196692}.
CC -!- DEVELOPMENTAL STAGE: Barely detectable in the brain of embryonic day 17
CC (17 dpc). Expressed in hippocampus and septum from postnatal day 1 (P1)
CC and then in cerebellum and olfactory bulb from postnatal day 7 (P7).
CC {ECO:0000269|PubMed:26623514}.
CC -!- DOMAIN: The PDZ-binding motif interacts with PDZ-domain of scaffolding
CC protein DLG4. {ECO:0000269|PubMed:26931375}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:26931375}.
CC -!- DISRUPTION PHENOTYPE: Decreases decay times of miniature excitatory
CC postsynaptic currents (mEPSCs) and light-induced AMPA-type glutamate
CC receptor (AMPAR) currents in CA1 pyramidal cell.
CC {ECO:0000269|PubMed:26931375}.
CC -!- SIMILARITY: Belongs to the shisa family. {ECO:0000305}.
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DR EMBL; KU707904; AND76927.1; -; mRNA.
DR EMBL; AK147504; BAE27958.1; -; mRNA.
DR CCDS; CCDS24848.1; -. [Q3UH99-1]
DR RefSeq; NP_001030046.1; NM_001034874.3. [Q3UH99-1]
DR RefSeq; XP_006533682.1; XM_006533619.3. [Q3UH99-2]
DR AlphaFoldDB; Q3UH99; -.
DR SMR; Q3UH99; -.
DR BioGRID; 237606; 3.
DR IntAct; Q3UH99; 1.
DR MINT; Q3UH99; -.
DR STRING; 10090.ENSMUSP00000071025; -.
DR GlyGen; Q3UH99; 2 sites.
DR iPTMnet; Q3UH99; -.
DR PhosphoSitePlus; Q3UH99; -.
DR PaxDb; Q3UH99; -.
DR PeptideAtlas; Q3UH99; -.
DR PRIDE; Q3UH99; -.
DR ProteomicsDB; 257012; -. [Q3UH99-1]
DR Antibodypedia; 6361; 81 antibodies from 21 providers.
DR Ensembl; ENSMUST00000066679; ENSMUSP00000071025; ENSMUSG00000053930. [Q3UH99-1]
DR GeneID; 380702; -.
DR KEGG; mmu:380702; -.
DR UCSC; uc007jlm.2; mouse. [Q3UH99-1]
DR CTD; 388336; -.
DR MGI; MGI:2685725; Shisa6.
DR VEuPathDB; HostDB:ENSMUSG00000053930; -.
DR eggNOG; ENOG502QUEF; Eukaryota.
DR GeneTree; ENSGT00940000156854; -.
DR InParanoid; Q3UH99; -.
DR OMA; FECNNTN; -.
DR OrthoDB; 372505at2759; -.
DR PhylomeDB; Q3UH99; -.
DR TreeFam; TF330800; -.
DR BioGRID-ORCS; 380702; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Shisa6; mouse.
DR PRO; PR:Q3UH99; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q3UH99; protein.
DR Bgee; ENSMUSG00000053930; Expressed in CA1 field of hippocampus and 91 other tissues.
DR ExpressionAtlas; Q3UH99; baseline and differential.
DR GO; GO:0032281; C:AMPA glutamate receptor complex; IDA:MGI.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0098985; C:asymmetric, glutamatergic, excitatory synapse; IDA:UniProtKB.
DR GO; GO:0032591; C:dendritic spine membrane; IBA:GO_Central.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0099061; C:integral component of postsynaptic density membrane; IDA:SynGO.
DR GO; GO:0014069; C:postsynaptic density; IDA:UniProtKB.
DR GO; GO:0045211; C:postsynaptic membrane; IBA:GO_Central.
DR GO; GO:0035255; F:ionotropic glutamate receptor binding; IDA:UniProtKB.
DR GO; GO:0030165; F:PDZ domain binding; IPI:UniProtKB.
DR GO; GO:0098976; P:excitatory chemical synaptic transmission; IMP:UniProtKB.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0098970; P:postsynaptic neurotransmitter receptor diffusion trapping; IDA:SynGO.
DR GO; GO:1904717; P:regulation of AMPA glutamate receptor clustering; IMP:UniProtKB.
DR GO; GO:2000311; P:regulation of AMPA receptor activity; IBA:GO_Central.
DR GO; GO:0098962; P:regulation of postsynaptic neurotransmitter receptor activity; IDA:SynGO.
DR GO; GO:0048172; P:regulation of short-term neuronal synaptic plasticity; IBA:GO_Central.
DR GO; GO:0007283; P:spermatogenesis; IMP:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR026910; Shisa.
DR PANTHER; PTHR31774; PTHR31774; 2.
DR Pfam; PF13908; Shisa; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Glycoprotein; Membrane;
KW Phosphoprotein; Postsynaptic cell membrane; Reference proteome; Signal;
KW Synapse; Transmembrane; Transmembrane helix; Wnt signaling pathway.
FT SIGNAL 1..30
FT /evidence="ECO:0000255"
FT CHAIN 31..525
FT /note="Protein shisa-6"
FT /id="PRO_0000326155"
FT TOPO_DOM 31..180
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 181..201
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 202..525
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 241..294
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 469..495
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 522..525
FT /note="PDZ-binding"
FT /evidence="ECO:0000269|PubMed:26931375"
FT COMPBIAS 245..294
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 470..492
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 416
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 422
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 434
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16452087,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 458
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 502
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 37
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 62
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 272
FT /note="P -> PGHYGKDAYRSGGPDLHNFISSGFVTLGRGHTK (in isoform
FT 2)"
FT /id="VSP_059384"
FT MUTAGEN 522..525
FT /note="Missing: Loss of interaction with PDZ-domain of
FT DLG4."
FT /evidence="ECO:0000269|PubMed:26931375"
SQ SEQUENCE 525 AA; 58426 MW; 1F9706B52F0F3C47 CRC64;
MALRRLLLPP LLLSLLLSLA SLHLPPGADA ARGRSGNRTL NAGAVGGRRA GGALARGGRE
LNSTARASGV PEAGSRRGQS AAAAAAAAAA ASATVTYETC WGYYDVSGQY DKEFECNNSE
SGYLYCCGTC YYRFCCKKRH EKLDQRQCTN YQSPVWVQTP STKVVSPGPE NKYDPEKDKT
NFTVYITCGV IAFVIVAGVF AKVSYDKAHR PPREMNIHRA LADILRQQGP IPIAHCERET
ISAIDTSPKE NTPVRSTSKN HYTPVRTAKQ TPGDRQYNHP ILSSATQTPT HEKPRMNNIL
TSATEPYDLS FSRSYQNLAH LPPSYESAVK TNPSKYSSLK RLTDKEADEY YMRRRHLPDL
AARGTLPLNV IQMSQQKPLP RERPRRPIRA MSQDRVLSPR RGLPDEFGMP YDRILSDEQL
LSTERLHSQD PLLSPERTAF PEQSLSRAIS HTDVFVSTPV LDRYRMTKMH SHPSASNNSY
ATLGQSQTAA KRHAFASRRH NTVEQLHYIP GHHTCYTASK TEVTV
