ID   SHSA5_HUMAN             Reviewed;         240 AA.
AC   Q8N114; B3KW99; F8W9N8; Q69YY9; Q7Z433; Q8NHL9; Q96MW8; Q9BV58;
DT   04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 1.
DT   27-MAR-2024, entry version 146.
DE   RecName: Full=Protein shisa-5;
DE   AltName: Full=Putative NF-kappa-B-activating protein 120;
DE   AltName: Full=Scotin;
DE   Flags: Precursor;
GN   Name=SHISA5; Synonyms=SCOTIN; ORFNames=PSEC0133;
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 [GENOMIC DNA / MRNA] (ISOFORM 1), FUNCTION, INDUCTION,
RP   DOMAIN, AND SUBCELLULAR LOCATION.
RX   PubMed=12135983; DOI=10.1083/jcb.200203006;
RA   Bourdon J.-C., Renzing J., Robertson P.L., Fernandes K.N., Lane D.P.;
RT   "Scotin, a novel p53-inducible proapoptotic protein located in the ER and
RT   the nuclear membrane.";
RL   J. Cell Biol. 158:235-246(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC   TISSUE=Lung;
RX   PubMed=12761501; DOI=10.1038/sj.onc.1206406;
RA   Matsuda A., Suzuki Y., Honda G., Muramatsu S., Matsuzaki O., Nagano Y.,
RA   Doi T., Shimotohno K., Harada T., Nishida E., Hayashi H., Sugano S.;
RT   "Large-scale identification and characterization of human genes that
RT   activate NF-kappaB and MAPK signaling pathways.";
RL   Oncogene 22:3307-3318(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Amygdala, Placenta, and Teratocarcinoma;
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4).
RC   TISSUE=Brain, and Kidney;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15372022; DOI=10.1038/nature02919;
RA   Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA   Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA   She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA   Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA   Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA   Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA   Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA   Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA   Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA   Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA   Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA   Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA   Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT   "The DNA sequence and comparative analysis of human chromosome 5.";
RL   Nature 431:268-274(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC   TISSUE=Placenta;
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   [8]
RP   INTERACTION WITH PDCD6.
RX   PubMed=17889823; DOI=10.1016/j.abb.2007.07.028;
RA   Draeby I., Woods Y.L., la Cour J.M., Mollerup J., Bourdon J.C.,
RA   Berchtold M.W.;
RT   "The calcium binding protein ALG-2 binds and stabilizes Scotin, a p53-
RT   inducible gene product localized at the endoplasmic reticulum membrane.";
RL   Arch. Biochem. Biophys. 467:87-94(2007).
CC   -!- FUNCTION: Can induce apoptosis in a caspase-dependent manner and plays
CC       a role in p53/TP53-dependent apoptosis. {ECO:0000269|PubMed:12135983}.
CC   -!- SUBUNIT: Interacts with PDCD6; PDCD6 can stabilze SHISA5.
CC       {ECO:0000269|PubMed:17889823}.
CC   -!- INTERACTION:
CC       Q8N114; Q9NZC7: WWOX; NbExp=2; IntAct=EBI-2115556, EBI-4320739;
CC       Q8N114; P12815: Pdcd6; Xeno; NbExp=5; IntAct=EBI-2115556, EBI-309164;
CC       Q8N114-3; Q15041: ARL6IP1; NbExp=3; IntAct=EBI-13369834, EBI-714543;
CC       Q8N114-3; Q6ICB0: DESI1; NbExp=3; IntAct=EBI-13369834, EBI-2806959;
CC       Q8N114-3; P57086: SCAND1; NbExp=3; IntAct=EBI-13369834, EBI-745846;
CC       Q8N114-3; O43765: SGTA; NbExp=3; IntAct=EBI-13369834, EBI-347996;
CC       Q8N114-3; Q96EQ0: SGTB; NbExp=3; IntAct=EBI-13369834, EBI-744081;
CC       Q8N114-3; Q9NYZ1: TVP23B; NbExp=3; IntAct=EBI-13369834, EBI-11343401;
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000269|PubMed:12135983}; Single-pass type I membrane protein
CC       {ECO:0000269|PubMed:12135983}. Nucleus membrane
CC       {ECO:0000269|PubMed:12135983}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=5;
CC       Name=1;
CC         IsoId=Q8N114-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8N114-2; Sequence=VSP_029954;
CC       Name=3;
CC         IsoId=Q8N114-3; Sequence=VSP_029953, VSP_029955;
CC       Name=4;
CC         IsoId=Q8N114-4; Sequence=VSP_029953, VSP_029955, VSP_029956;
CC       Name=5;
CC         IsoId=Q8N114-5; Sequence=VSP_055712;
CC   -!- INDUCTION: Induced in a p53/TP53-dependent manner in response to
CC       cellular stress. {ECO:0000269|PubMed:12135983}.
CC   -!- DOMAIN: The proline-rich region is required for endoplasmic reticulum
CC       localization. {ECO:0000269|PubMed:12135983}.
CC   -!- SIMILARITY: Belongs to the shisa family. {ECO:0000305}.
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DR   EMBL; AF520698; AAM74232.1; -; mRNA.
DR   EMBL; AH011688; AAM74235.1; -; Genomic_DNA.
DR   EMBL; AB097007; BAC77360.1; -; mRNA.
DR   EMBL; AK056328; BAB71152.1; -; mRNA.
DR   EMBL; AK075441; BAC11623.1; -; mRNA.
DR   EMBL; AK124652; BAG54061.1; -; mRNA.
DR   EMBL; AL117413; CAH10718.1; -; mRNA.
DR   EMBL; AL832568; CAH10587.1; -; mRNA.
DR   EMBL; AC104448; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC134772; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471055; EAW64885.1; -; Genomic_DNA.
DR   EMBL; CH471055; EAW64887.1; -; Genomic_DNA.
DR   EMBL; BC001463; AAH01463.2; -; mRNA.
DR   CCDS; CCDS2770.1; -. [Q8N114-1]
DR   CCDS; CCDS63621.1; -. [Q8N114-3]
DR   CCDS; CCDS63622.1; -. [Q8N114-2]
DR   CCDS; CCDS63623.1; -. [Q8N114-5]
DR   RefSeq; NP_001258994.1; NM_001272065.1. [Q8N114-5]
DR   RefSeq; NP_001258995.1; NM_001272066.1. [Q8N114-2]
DR   RefSeq; NP_001258996.1; NM_001272067.1. [Q8N114-2]
DR   RefSeq; NP_001258997.1; NM_001272068.1. [Q8N114-2]
DR   RefSeq; NP_001259011.1; NM_001272082.1. [Q8N114-3]
DR   RefSeq; NP_001259012.1; NM_001272083.1. [Q8N114-4]
DR   RefSeq; NP_057563.3; NM_016479.4. [Q8N114-1]
DR   RefSeq; XP_005265262.1; XM_005265205.1.
DR   RefSeq; XP_006713251.1; XM_006713188.2.
DR   RefSeq; XP_011532098.1; XM_011533796.1.
DR   AlphaFoldDB; Q8N114; -.
DR   BioGRID; 119403; 12.
DR   ELM; Q8N114; -.
DR   IntAct; Q8N114; 10.
DR   STRING; 9606.ENSP00000296444; -.
DR   TCDB; 8.A.83.1.7; the shisa6 regulator of short-term neuronal synaptic plasticity (shisa) family.
DR   GlyCosmos; Q8N114; 1 site, 1 glycan.
DR   GlyGen; Q8N114; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q8N114; -.
DR   PhosphoSitePlus; Q8N114; -.
DR   BioMuta; SHISA5; -.
DR   DMDM; 74714697; -.
DR   EPD; Q8N114; -.
DR   jPOST; Q8N114; -.
DR   MassIVE; Q8N114; -.
DR   PaxDb; 9606-ENSP00000296444; -.
DR   PeptideAtlas; Q8N114; -.
DR   ProteomicsDB; 30355; -.
DR   ProteomicsDB; 71515; -. [Q8N114-1]
DR   ProteomicsDB; 71516; -. [Q8N114-2]
DR   ProteomicsDB; 71517; -. [Q8N114-3]
DR   Antibodypedia; 30112; 176 antibodies from 18 providers.
DR   DNASU; 51246; -.
DR   Ensembl; ENST00000296444.7; ENSP00000296444.2; ENSG00000164054.17. [Q8N114-1]
DR   Ensembl; ENST00000426002.5; ENSP00000390388.1; ENSG00000164054.17. [Q8N114-3]
DR   Ensembl; ENST00000442747.5; ENSP00000408223.1; ENSG00000164054.17. [Q8N114-2]
DR   Ensembl; ENST00000443308.6; ENSP00000395373.2; ENSG00000164054.17. [Q8N114-5]
DR   Ensembl; ENST00000444115.5; ENSP00000407957.1; ENSG00000164054.17. [Q8N114-2]
DR   Ensembl; ENST00000619810.4; ENSP00000484992.1; ENSG00000164054.17. [Q8N114-2]
DR   GeneID; 51246; -.
DR   KEGG; hsa:51246; -.
DR   MANE-Select; ENST00000296444.7; ENSP00000296444.2; NM_016479.6; NP_057563.3.
DR   UCSC; uc003ctm.4; human. [Q8N114-1]
DR   AGR; HGNC:30376; -.
DR   CTD; 51246; -.
DR   DisGeNET; 51246; -.
DR   GeneCards; SHISA5; -.
DR   HGNC; HGNC:30376; SHISA5.
DR   HPA; ENSG00000164054; Low tissue specificity.
DR   MIM; 607290; gene.
DR   neXtProt; NX_Q8N114; -.
DR   OpenTargets; ENSG00000164054; -.
DR   PharmGKB; PA162403295; -.
DR   VEuPathDB; HostDB:ENSG00000164054; -.
DR   eggNOG; ENOG502S2Y4; Eukaryota.
DR   GeneTree; ENSGT00390000008296; -.
DR   HOGENOM; CLU_093192_1_0_1; -.
DR   InParanoid; Q8N114; -.
DR   OMA; MCRKPQP; -.
DR   OrthoDB; 5266769at2759; -.
DR   PhylomeDB; Q8N114; -.
DR   TreeFam; TF332572; -.
DR   PathwayCommons; Q8N114; -.
DR   Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR   Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR   SignaLink; Q8N114; -.
DR   BioGRID-ORCS; 51246; 17 hits in 1162 CRISPR screens.
DR   ChiTaRS; SHISA5; human.
DR   GenomeRNAi; 51246; -.
DR   Pharos; Q8N114; Tbio.
DR   PRO; PR:Q8N114; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   RNAct; Q8N114; Protein.
DR   Bgee; ENSG00000164054; Expressed in oviduct epithelium and 183 other cell types or tissues.
DR   ExpressionAtlas; Q8N114; baseline and differential.
DR   GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0050699; F:WW domain binding; IPI:UniProtKB.
DR   GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IEA:Ensembl.
DR   GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; HMP:UniProtKB.
DR   InterPro; IPR026910; Shisa.
DR   PANTHER; PTHR31395:SF14; PROTEIN SHISA-5; 1.
DR   PANTHER; PTHR31395; SHISA; 1.
DR   Pfam; PF13908; Shisa; 1.
DR   Genevisible; Q8N114; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Apoptosis; Endoplasmic reticulum; Membrane; Nucleus;
KW   Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..28
FT                   /evidence="ECO:0000255"
FT   CHAIN           29..240
FT                   /note="Protein shisa-5"
FT                   /id="PRO_0000312878"
FT   TOPO_DOM        29..105
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        106..126
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        127..240
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         1..103
FT                   /note="Missing (in isoform 3 and isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:12761501,
FT                   ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:17974005"
FT                   /id="VSP_029953"
FT   VAR_SEQ         1..31
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_029954"
FT   VAR_SEQ         71..77
FT                   /note="Missing (in isoform 5)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_055712"
FT   VAR_SEQ         104
FT                   /note="S -> M (in isoform 3 and isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:12761501,
FT                   ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:17974005"
FT                   /id="VSP_029955"
FT   VAR_SEQ         216..240
FT                   /note="GAAAPYPASQPPYNPAYMDAPKAAL -> ECPCQL (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:17974005"
FT                   /id="VSP_029956"
FT   VARIANT         216
FT                   /note="G -> R (in dbSNP:rs35750010)"
FT                   /id="VAR_054031"
SQ   SEQUENCE   240 AA;  25582 MW;  7C4A8E7A2AD8E272 CRC64;
     MTAPVPAPRI LLPLLLLLLL TPPPGARGEV CMASRGLSLF PESCPDFCCG TCDDQYCCSD
     VLKKFVWSEE RCAVPEASVP ASVEPVEQLG SALRFRPGYN DPMSGFGATL AVGLTIFVLS
     VVTIIICFTC SCCCLYKTCR RPRPVVTTTT STTVVHAPYP QPPSVPPSYP GPSYQGYHTM
     PPQPGMPAAP YPMQYPPPYP AQPMGPPAYH ETLAGGAAAP YPASQPPYNP AYMDAPKAAL
//