SHSA6_HUMAN
ID SHSA6_HUMAN Reviewed; 500 AA.
AC Q6ZSJ9; B3KXV5; Q4PL63;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAR-2008, sequence version 2.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Protein shisa-6 {ECO:0000305};
DE Flags: Precursor;
GN Name=SHISA6 {ECO:0000312|HGNC:HGNC:34491};
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=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 103-500 (ISOFORM 1), AND
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 220-500 (ISOFORM 3).
RC TISSUE=Subthalamic nucleus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 209-500 (ISOFORM 2).
RA Lin L., Nong W., Zhou G., Ke R., Shen C., Zhong G., Zheng Z., Liang M.,
RA Wen S., Li H., Yang S.;
RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP IDENTIFICATION, AND TISSUE SPECIFICITY.
RX PubMed=16473350; DOI=10.1016/j.expneurol.2005.12.023;
RA Joergensen J.R., Juliusson B., Henriksen K.F., Hansen C., Knudsen S.,
RA Petersen T.N., Blom N., Seiger A., Wahlberg L.U.;
RT "Identification of novel genes regulated in the developing human ventral
RT mesencephalon.";
RL Exp. Neurol. 198:427-437(2006).
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. May play a role in self-renewal and
CC differentiation of spermatogonial stem cells by inhibiting canonical
CC Wnt signaling pathway. {ECO:0000250|UniProtKB:Q3UH99}.
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. Interacts (via PDZ-binding motif) with DLG4/PSD-95 (via PDZ
CC domain); the interaction is direct. {ECO:0000250|UniProtKB:Q3UH99}.
CC -!- INTERACTION:
CC Q6ZSJ9; Q49AR9: ANKS1A; NbExp=3; IntAct=EBI-12037847, EBI-11954519;
CC Q6ZSJ9; Q9H6L4: ARMC7; NbExp=3; IntAct=EBI-12037847, EBI-742909;
CC Q6ZSJ9; O95817: BAG3; NbExp=5; IntAct=EBI-12037847, EBI-747185;
CC Q6ZSJ9; Q9H257-2: CARD9; NbExp=3; IntAct=EBI-12037847, EBI-11530605;
CC Q6ZSJ9; Q2TAC2-2: CCDC57; NbExp=3; IntAct=EBI-12037847, EBI-10961624;
CC Q6ZSJ9; P38936: CDKN1A; NbExp=3; IntAct=EBI-12037847, EBI-375077;
CC Q6ZSJ9; O76071: CIAO1; NbExp=3; IntAct=EBI-12037847, EBI-725145;
CC Q6ZSJ9; P56545-3: CTBP2; NbExp=3; IntAct=EBI-12037847, EBI-10171902;
CC Q6ZSJ9; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-12037847, EBI-3867333;
CC Q6ZSJ9; Q9NQT4: EXOSC5; NbExp=3; IntAct=EBI-12037847, EBI-371876;
CC Q6ZSJ9; Q8WUP2: FBLIM1; NbExp=3; IntAct=EBI-12037847, EBI-3864120;
CC Q6ZSJ9; Q08379: GOLGA2; NbExp=3; IntAct=EBI-12037847, EBI-618309;
CC Q6ZSJ9; O75031: HSF2BP; NbExp=3; IntAct=EBI-12037847, EBI-7116203;
CC Q6ZSJ9; Q92993: KAT5; NbExp=3; IntAct=EBI-12037847, EBI-399080;
CC Q6ZSJ9; Q9HAQ2: KIF9; NbExp=3; IntAct=EBI-12037847, EBI-8472129;
CC Q6ZSJ9; Q9BVG8-5: KIFC3; NbExp=3; IntAct=EBI-12037847, EBI-14069005;
CC Q6ZSJ9; Q15323: KRT31; NbExp=3; IntAct=EBI-12037847, EBI-948001;
CC Q6ZSJ9; Q9BYR6: KRTAP3-3; NbExp=3; IntAct=EBI-12037847, EBI-3957694;
CC Q6ZSJ9; Q8TAP4-4: LMO3; NbExp=3; IntAct=EBI-12037847, EBI-11742507;
CC Q6ZSJ9; P46934-3: NEDD4; NbExp=3; IntAct=EBI-12037847, EBI-11980721;
CC Q6ZSJ9; O43482: OIP5; NbExp=6; IntAct=EBI-12037847, EBI-536879;
CC Q6ZSJ9; Q99471: PFDN5; NbExp=3; IntAct=EBI-12037847, EBI-357275;
CC Q6ZSJ9; Q58EX7: PLEKHG4; NbExp=3; IntAct=EBI-12037847, EBI-949255;
CC Q6ZSJ9; Q96GM5: SMARCD1; NbExp=3; IntAct=EBI-12037847, EBI-358489;
CC Q6ZSJ9; Q08117-2: TLE5; NbExp=3; IntAct=EBI-12037847, EBI-11741437;
CC Q6ZSJ9; Q15654: TRIP6; NbExp=3; IntAct=EBI-12037847, EBI-742327;
CC Q6ZSJ9; Q96PN8: TSSK3; NbExp=3; IntAct=EBI-12037847, EBI-3918381;
CC Q6ZSJ9; Q6DKK2: TTC19; NbExp=3; IntAct=EBI-12037847, EBI-948354;
CC Q6ZSJ9; P57075-2: UBASH3A; NbExp=3; IntAct=EBI-12037847, EBI-7353612;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000250|UniProtKB:Q3UH99}. Postsynaptic density
CC {ECO:0000250|UniProtKB:Q3UH99}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6ZSJ9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6ZSJ9-2; Sequence=VSP_032565;
CC Name=3;
CC IsoId=Q6ZSJ9-3; Sequence=VSP_040558;
CC -!- TISSUE SPECIFICITY: Expressed in the developing ventral mesencephalon.
CC {ECO:0000269|PubMed:16473350}.
CC -!- DOMAIN: The PDZ-binding motif interacts with PDZ-domain of scaffolding
CC protein DLG4. {ECO:0000250|UniProtKB:Q3UH99}.
CC -!- SIMILARITY: Belongs to the shisa family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC86949.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAG54617.1; Type=Erroneous initiation; Note=Truncated N-terminus.; 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; AC005725; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC007510; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC055825; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK127379; BAC86949.1; ALT_INIT; mRNA.
DR EMBL; AK128003; BAG54617.1; ALT_INIT; mRNA.
DR EMBL; DQ070854; AAY68487.1; -; mRNA.
DR CCDS; CCDS45615.1; -. [Q6ZSJ9-3]
DR CCDS; CCDS54089.1; -. [Q6ZSJ9-2]
DR CCDS; CCDS54090.1; -. [Q6ZSJ9-1]
DR RefSeq; NP_001166932.1; NM_001173461.1. [Q6ZSJ9-1]
DR RefSeq; NP_001166933.1; NM_001173462.1. [Q6ZSJ9-2]
DR RefSeq; NP_997269.2; NM_207386.3. [Q6ZSJ9-3]
DR AlphaFoldDB; Q6ZSJ9; -.
DR SMR; Q6ZSJ9; -.
DR BioGRID; 132648; 40.
DR IntAct; Q6ZSJ9; 30.
DR MINT; Q6ZSJ9; -.
DR STRING; 9606.ENSP00000390084; -.
DR TCDB; 8.A.83.1.1; the shisa6 regulator of short-term neuronal synaptic plasticity (shisa) family.
DR GlyGen; Q6ZSJ9; 3 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q6ZSJ9; -.
DR PhosphoSitePlus; Q6ZSJ9; -.
DR BioMuta; SHISA6; -.
DR DMDM; 172046182; -.
DR MassIVE; Q6ZSJ9; -.
DR PeptideAtlas; Q6ZSJ9; -.
DR PRIDE; Q6ZSJ9; -.
DR Antibodypedia; 6361; 81 antibodies from 21 providers.
DR DNASU; 388336; -.
DR Ensembl; ENST00000409168.7; ENSP00000387157.3; ENSG00000188803.15. [Q6ZSJ9-1]
DR Ensembl; ENST00000432116.7; ENSP00000388659.3; ENSG00000188803.15. [Q6ZSJ9-2]
DR Ensembl; ENST00000441885.8; ENSP00000390084.3; ENSG00000188803.15. [Q6ZSJ9-3]
DR GeneID; 388336; -.
DR KEGG; hsa:388336; -.
DR MANE-Select; ENST00000441885.8; ENSP00000390084.3; NM_207386.4; NP_997269.2. [Q6ZSJ9-3]
DR UCSC; uc002gna.4; human. [Q6ZSJ9-1]
DR CTD; 388336; -.
DR DisGeNET; 388336; -.
DR GeneCards; SHISA6; -.
DR HGNC; HGNC:34491; SHISA6.
DR HPA; ENSG00000188803; Tissue enhanced (brain, cervix).
DR MIM; 617327; gene.
DR neXtProt; NX_Q6ZSJ9; -.
DR OpenTargets; ENSG00000188803; -.
DR PharmGKB; PA165432740; -.
DR VEuPathDB; HostDB:ENSG00000188803; -.
DR eggNOG; ENOG502QUEF; Eukaryota.
DR GeneTree; ENSGT00940000156854; -.
DR HOGENOM; CLU_025677_1_0_1; -.
DR InParanoid; Q6ZSJ9; -.
DR OMA; FECNNTN; -.
DR OrthoDB; 372505at2759; -.
DR PhylomeDB; Q6ZSJ9; -.
DR TreeFam; TF330800; -.
DR PathwayCommons; Q6ZSJ9; -.
DR SignaLink; Q6ZSJ9; -.
DR BioGRID-ORCS; 388336; 12 hits in 1057 CRISPR screens.
DR ChiTaRS; SHISA6; human.
DR GenomeRNAi; 388336; -.
DR Pharos; Q6ZSJ9; Tdark.
DR PRO; PR:Q6ZSJ9; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q6ZSJ9; protein.
DR Bgee; ENSG00000188803; Expressed in lateral nuclear group of thalamus and 118 other tissues.
DR ExpressionAtlas; Q6ZSJ9; baseline and differential.
DR Genevisible; Q6ZSJ9; 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:0099061; C:integral component of postsynaptic density membrane; IEA:Ensembl.
DR GO; GO:0014069; C:postsynaptic density; ISS:UniProtKB.
DR GO; GO:0045211; C:postsynaptic membrane; IBA:GO_Central.
DR GO; GO:0035255; F:ionotropic glutamate receptor binding; ISS:UniProtKB.
DR GO; GO:0030165; F:PDZ domain binding; IEA:Ensembl.
DR GO; GO:0098976; P:excitatory chemical synaptic transmission; ISS:UniProtKB.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0098970; P:postsynaptic neurotransmitter receptor diffusion trapping; IEA:Ensembl.
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: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 GO; GO:0007283; P:spermatogenesis; ISS: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; Glycoprotein; Membrane; Phosphoprotein;
KW Reference proteome; Signal; Synapse; Transmembrane; Transmembrane helix;
KW Wnt signaling pathway.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..500
FT /note="Protein shisa-6"
FT /id="PRO_0000326154"
FT TOPO_DOM 26..174
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 175..195
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 196..500
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 52..73
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 240..269
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 349..378
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 444..470
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 497..500
FT /note="PDZ-binding"
FT /evidence="ECO:0000250|UniProtKB:Q3UH99"
FT COMPBIAS 445..467
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 391
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UH99"
FT MOD_RES 397
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UH99"
FT MOD_RES 409
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UH99"
FT MOD_RES 433
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q3UH99"
FT MOD_RES 477
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q3UH99"
FT CARBOHYD 32
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 59
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 266
FT /note="P -> PGHYGKDAYRSGGPDLHNFISSGFVTLGRGHTK (in isoform
FT 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_032565"
FT VAR_SEQ 266
FT /note="P -> PGHYGKDAYRSGGPDLHNFISSGFVTLGRGHTKGDHQYNHPILSSVT
FT QIPPH (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_040558"
FT CONFLICT 250
FT /note="S -> P (in Ref. 3; AAY68487)"
FT /evidence="ECO:0000305"
FT CONFLICT 297..299
FT /note="PPS -> SPP (in Ref. 3; AAY68487)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 500 AA; 55764 MW; 3DEF68C298A101CB CRC64;
MALRRLLLLL LLSLESLDLL PSVHGARGRA ANRTLSAGGA AVGGRRAGGA LARGGRELNG
TARAPGIPEA GSRRGQPAAA VAAAASAAVT YETCWGYYDV SGQYDKEFEC NNSESGYLYC
CGTCYYRFCC KKRHEKLDQR QCTNYQSPVW VQTPSTKVVS PGPENKYDPE KDKTNFTVYI
TCGVIAFVIV AGVFAKVSYD KAHRPPREMN IHRALADILR QQGPIPIAHC ERETISAIDT
SPKENTPVRS SSKNHYTPVR TAKQTPEKPR MNNILTSATE PYDLSFSRSF QNLAHLPPSY
ESAVKTNPSK YSSLKRLTDK EADEYYMRRR HLPDLAARGT LPLNVIQMSQ QKPLPRERPR
RPIRAMSQDR VLSPDRGLPD EFSMPYDRIL SDEQLLSTER LHSQDPLLSP ERTAFPEQSL
SRAISHTDVF VSTPVLDRYR MSKMHSHPSA SNNSYATLGQ SQTAAKRHAF ASRRHNTVEQ
LHYIPGHHTC YTASKTEVTV
