SHSA7_HUMAN
ID SHSA7_HUMAN Reviewed; 538 AA.
AC A6NL88;
DT 22-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-MAR-2009, sequence version 3.
DT 03-AUG-2022, entry version 99.
DE RecName: Full=Protein shisa-7 {ECO:0000305};
DE AltName: Full=Cystine-knot AMPAR modulating protein of 59 kDa {ECO:0000250|UniProtKB:Q8C3Q5};
DE Short=CKAMP59;
DE AltName: Full=GABA(A) receptor auxiliary subunit Shisa7;
DE AltName: Full=Protein shisa-6-like;
DE Flags: Precursor;
GN Name=SHISA7 {ECO:0000312|HGNC:HGNC:35409};
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 207-362.
RA Stevens M., Wei C., Gross S.S., McPherson J., Brent M.R.;
RT "Exhaustive RT-PCR and sequencing of all novel TWINSCAN predictions in
RT human.";
RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Transmembrane protein that regulates gamma-aminobutyric acid
CC type A receptor (GABA(A)R) trafficking, channel deactivation kinetics
CC and pharmacology, necessary for fast inhibitory transmission in the
CC brain. Enhances the action of benzodiazepine, a primary GABA(A)Rs
CC target drug, in the brain. May affect channel kinetics of AMPA-type
CC glutamate receptors (AMPAR), the brain's main excitatory
CC neurotransmitter, necessary for synaptic hippocampal plasticity, and
CC memory recall. May regulate the induction and maintenance of long-term
CC potentiation at Schaffer collaterals/CA3-CA1 excitatory synapses.
CC {ECO:0000250|UniProtKB:Q8C3Q5}.
CC -!- SUBUNIT: Interacts with GABA(A)R (GABA type A receptor) subunits
CC GABRA1, GABRA2 and GABRG2; the interaction is direct. Does not interact
CC with GABRB2 and GABRB3 subunits. May interact with AMPAR subunits
CC GRIA1, GRIA2 and GRIA3 and AMPAR auxiliary proteins SHISA6 and SHISA7.
CC May interact (via PDZ-binding motif) with DLG4/PSD-95 (via PDZ domain);
CC the interaction is direct. {ECO:0000250|UniProtKB:Q8C3Q5}.
CC -!- SUBCELLULAR LOCATION: Postsynaptic density membrane
CC {ECO:0000250|UniProtKB:Q8C3Q5}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:Q8C3Q5}. Note=Localizes at GABAergic inhibitory
CC synapses and colocalizes with gephyrin in hippocampal neurons.
CC {ECO:0000250|UniProtKB:Q8C3Q5}.
CC -!- DOMAIN: The PDZ-binding motif interacts with PDZ-domain of scaffolding
CC protein DLG4. {ECO:0000250|UniProtKB:Q8C3Q5}.
CC -!- DOMAIN: The GRID (GABA(A)R-interacting domain) is critical for its
CC subcellular localization and interaction with GABA(A)R.
CC {ECO:0000250|UniProtKB:Q8C3Q5}.
CC -!- SIMILARITY: Belongs to the shisa family. {ECO:0000305}.
CC -!- CAUTION: SHISA7 has been reported to interact with AMPAR subunit GRIA1
CC in heterologous conditions and in the brain (By similarity). However,
CC it was later demonstrated that SHISA7 does not colocalize neither
CC interact with AMPAR, but with GABA(A)R (By similarity). Therefore
CC additional experiments are needed to understand the discrepancy for
CC SHISA7 function. {ECO:0000250|UniProtKB:Q8C3Q5, ECO:0000305}.
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DR EMBL; AC135592; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; DY654595; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; DY654596; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; DY654895; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; DY654896; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS46193.1; -.
DR RefSeq; NP_001138648.1; NM_001145176.1.
DR AlphaFoldDB; A6NL88; -.
DR SMR; A6NL88; -.
DR STRING; 9606.ENSP00000365503; -.
DR TCDB; 8.A.83.1.4; the shisa6 regulator of short-term neuronal synaptic plasticity (shisa) family.
DR GlyGen; A6NL88; 2 sites.
DR iPTMnet; A6NL88; -.
DR PhosphoSitePlus; A6NL88; -.
DR BioMuta; SHISA7; -.
DR MassIVE; A6NL88; -.
DR PaxDb; A6NL88; -.
DR PeptideAtlas; A6NL88; -.
DR PRIDE; A6NL88; -.
DR ProteomicsDB; 1458; -.
DR TopDownProteomics; A6NL88; -.
DR Antibodypedia; 52662; 70 antibodies from 18 providers.
DR DNASU; 729956; -.
DR Ensembl; ENST00000376325.10; ENSP00000365503.3; ENSG00000187902.13.
DR GeneID; 729956; -.
DR KEGG; hsa:729956; -.
DR MANE-Select; ENST00000376325.10; ENSP00000365503.3; NM_001145176.2; NP_001138648.1.
DR UCSC; uc002qkz.4; human.
DR CTD; 729956; -.
DR GeneCards; SHISA7; -.
DR HGNC; HGNC:35409; SHISA7.
DR HPA; ENSG00000187902; Tissue enriched (brain).
DR MIM; 617328; gene.
DR neXtProt; NX_A6NL88; -.
DR OpenTargets; ENSG00000187902; -.
DR PharmGKB; PA165394299; -.
DR VEuPathDB; HostDB:ENSG00000187902; -.
DR eggNOG; ENOG502QV92; Eukaryota.
DR GeneTree; ENSGT00940000162254; -.
DR HOGENOM; CLU_025677_2_1_1; -.
DR InParanoid; A6NL88; -.
DR OMA; HNYIHLN; -.
DR OrthoDB; 475894at2759; -.
DR PhylomeDB; A6NL88; -.
DR TreeFam; TF330800; -.
DR PathwayCommons; A6NL88; -.
DR SignaLink; A6NL88; -.
DR BioGRID-ORCS; 729956; 17 hits in 1069 CRISPR screens.
DR GenomeRNAi; 729956; -.
DR Pharos; A6NL88; Tdark.
DR PRO; PR:A6NL88; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; A6NL88; protein.
DR Bgee; ENSG00000187902; Expressed in nucleus accumbens and 70 other tissues.
DR ExpressionAtlas; A6NL88; baseline and differential.
DR Genevisible; A6NL88; HS.
DR GO; GO:0032281; C:AMPA glutamate receptor complex; IBA:GO_Central.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0098985; C:asymmetric, glutamatergic, excitatory synapse; ISS:UniProtKB.
DR GO; GO:0032591; C:dendritic spine membrane; IBA:GO_Central.
DR GO; GO:0099060; C:integral component of postsynaptic specialization membrane; IEA:Ensembl.
DR GO; GO:0014069; C:postsynaptic density; ISS:UniProtKB.
DR GO; GO:0098839; C:postsynaptic density membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0045211; C:postsynaptic membrane; IBA:GO_Central.
DR GO; GO:0050811; F:GABA receptor binding; ISS:UniProtKB.
DR GO; GO:0035255; F:ionotropic glutamate receptor binding; ISS:UniProtKB.
DR GO; GO:0097112; P:gamma-aminobutyric acid receptor clustering; ISS:UniProtKB.
DR GO; GO:0007214; P:gamma-aminobutyric acid signaling pathway; ISS:UniProtKB.
DR GO; GO:0007613; P:memory; ISS:UniProtKB.
DR GO; GO:1900273; P:positive regulation of long-term synaptic potentiation; ISS:UniProtKB.
DR GO; GO:1904717; P:regulation of AMPA glutamate receptor clustering; ISS:UniProtKB.
DR GO; GO:2000311; P:regulation of AMPA receptor activity; IBA:GO_Central.
DR GO; GO:0106040; P:regulation of GABA-A receptor activity; ISS:UniProtKB.
DR GO; GO:0098962; P:regulation of postsynaptic neurotransmitter receptor activity; IEA:Ensembl.
DR GO; GO:0048172; P:regulation of short-term neuronal synaptic plasticity; IBA:GO_Central.
DR InterPro; IPR026910; Shisa.
DR PANTHER; PTHR31774; PTHR31774; 2.
DR Pfam; PF13908; Shisa; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Glycoprotein; Membrane; Phosphoprotein;
KW Postsynaptic cell membrane; Reference proteome; Signal; Synapse;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..538
FT /note="Protein shisa-7"
FT /id="PRO_0000344472"
FT TOPO_DOM 20..186
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 187..207
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 208..538
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 49..73
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 139..178
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 233..262
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 423..505
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 535..538
FT /note="PDZ-binding"
FT /evidence="ECO:0000250|UniProtKB:Q8C3Q5"
FT MOD_RES 417
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8C3Q5"
FT MOD_RES 512
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8C3Q5"
FT CARBOHYD 23
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 59
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 538 AA; 56214 MW; B64A8A543C64CF6B CRC64;
MPALLLLVLL ASSAGQARAR PSNATSAEPA GPLPALLAHL RRLTGALTGG GGAASPGANG
TRTGPAGGAG AAARAPPPAE LCHGYYDVMG QYDATFNCST GSYRFCCGTC HYRFCCEHRH
MRLAQASCSN YDTPRWATTP PPLAGGAGGA GGAGGGPGPG QAGWLEGGRT GGAGGRGGEG
PGGSTAYVVC GVISFALAVG VGAKVAFSKA SRAPRAHRDI NVPRALVDIL RHQAGPGTRP
DRARSSSLTP GIGGPDSMPP RTPKNLYNTV KTPNLDWRAL PPPSPSLHYS TLSCSRSFHN
LSHLPPSYEA AVKSELNRYS SLKRLAEKDL DEAYLKRRPL ELPRGTLPLH ALRRPGTGGG
YRMEAWGGPE ELGLAPAPNP RRVMSQEHLL GDGGRSRYEF TLPRARLVSQ EHLLLSSPEA
LRQSREHLLS PPRSPALPPD PTARASLAAS HSNLLLGPGG PPTPLRGLPP PSSLHAHHHH
ALHGSPQPAW MSDAGGGGGT LARRPPFQRQ GTLEQLQFIP GHHLPQHLRT ASKNEVTV
