IGSF8_MOUSE
ID IGSF8_MOUSE Reviewed; 611 AA.
AC Q8R366; Q8R0L7;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 2.
DT 25-MAY-2022, entry version 138.
DE RecName: Full=Immunoglobulin superfamily member 8;
DE Short=IgSF8;
DE AltName: Full=CD81 partner 3;
DE AltName: Full=Glu-Trp-Ile EWI motif-containing protein 2;
DE Short=EWI-2;
DE AltName: Full=Keratinocyte-associated transmembrane protein 4;
DE Short=KCT-4;
DE AltName: Full=Prostaglandin regulatory-like protein;
DE Short=PGRL;
DE AltName: CD_antigen=CD316;
DE Flags: Precursor;
GN Name=Igsf8; Synonyms=Ewi2, Kct4, Pgrl;
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], FUNCTION, INTERACTION WITH CD81, IDENTIFICATION
RP BY MASS SPECTROMETRY, AND DOMAIN.
RX PubMed=11673522; DOI=10.4049/jimmunol.167.9.5115;
RA Clark K.L., Zeng Z., Langford A.L., Bowen S.M., Todd S.C.;
RT "PGRL is a major CD81-associated protein on lymphocytes and distinguishes a
RT new family of cell surface proteins.";
RL J. Immunol. 167:5115-5121(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RX PubMed=12595239; DOI=10.1016/s1044-7431(02)00021-0;
RA Murdoch J.N., Doudney K., Gerrelli D., Wortham N., Paternotte C.,
RA Stanier P., Copp A.J.;
RT "Genomic organization and embryonic expression of Igsf8, an immunoglobulin
RT superfamily member implicated in development of the nervous system and
RT organ epithelia.";
RL Mol. Cell. Neurosci. 22:62-74(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=BALB/cJ;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Colon, and Mammary tumor;
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 [5]
RP FUNCTION, INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=16203089; DOI=10.1016/j.neulet.2005.09.017;
RA Yamada O., Tamura K., Yagihara H., Isotani M., Washizu T., Bonkobara M.;
RT "Neuronal expression of keratinocyte-associated transmembrane protein-4,
RT KCT-4, in mouse brain and its up-regulation by neurite outgrowth of Neuro-
RT 2a cells.";
RL Neurosci. Lett. 392:226-230(2006).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Spleen, and Testis;
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 [7]
RP PALMITOYLATION AT CYS-602 AND CYS-603, DOMAIN, AND SUBCELLULAR LOCATION.
RX PubMed=21609323; DOI=10.1042/bj20101381;
RA He B., Zhang Y.H., Richardson M.M., Zhang J.S., Rubinstein E., Zhang X.A.;
RT "Differential functions of phospholipid binding and palmitoylation of
RT tumour suppressor EWI2/PGRL.";
RL Biochem. J. 437:399-411(2011).
RN [8]
RP INTERACTION WITH CD81, INTERACTION WITH PTGFRN, INTERACTION WITH CD9, AND
RP TISSUE SPECIFICITY.
RX PubMed=23575678; DOI=10.1038/ncomms2675;
RA Charrin S., Latil M., Soave S., Polesskaya A., Chretien F., Boucheix C.,
RA Rubinstein E.;
RT "Normal muscle regeneration requires tight control of muscle cell fusion by
RT tetraspanins CD9 and CD81.";
RL Nat. Commun. 4:1674-1674(2013).
CC -!- FUNCTION: May play a key role in diverse functions ascribed to CD81 and
CC CD9 such as oocytes fertilization or hepatitis C virus function. May
CC regulate proliferation and differentiation of keratinocytes. May be a
CC negative regulator of cell motility: suppresses T-cell mobility
CC coordinately with CD81, associates with CD82 to suppress prostate
CC cancer cell migration, regulates epidermoid cell reaggregation and
CC motility on laminin-5 with CD9 and CD81 as key linkers. May also play a
CC role on integrin-dependent morphology and motility functions. May
CC participate in the regulation of neurite outgrowth and maintenance of
CC the neural network in the adult brain. {ECO:0000269|PubMed:11673522,
CC ECO:0000269|PubMed:16203089}.
CC -!- SUBUNIT: Interacts directly with CD82 and CD9/tetraspanin-29. Also
CC interacts with integrin alpha-3/beta-1 and integrin alpha-4/beta-1 (By
CC similarity). Part of a complex composed of CD9, PTGFRN and CD81
CC (PubMed:23575678). Interacts with CD81/tetraspanin-28. {ECO:0000250,
CC ECO:0000269|PubMed:11673522, ECO:0000269|PubMed:23575678}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21609323};
CC Single-pass membrane protein {ECO:0000269|PubMed:21609323}.
CC -!- TISSUE SPECIFICITY: Expressed in lymphocytes as well as in many tissues
CC with higher expression in brain. Detected in all regions of the brain
CC with weak expression in the pituitary. Expressed selectively by neurons
CC but not by glial cells. Expressed in myoblasts (at protein level).
CC {ECO:0000269|PubMed:16203089, ECO:0000269|PubMed:23575678}.
CC -!- DEVELOPMENTAL STAGE: Expressed at 9.5 dpc in the ventral domain of the
CC neural tube, with dorsal expression apparent at 10.5 dpc, as well as in
CC the dorsal bud of the pancreas. Detected at 11.5 dpc within the
CC ventricular zone of the neural tube in the hindbrain, diencephalon and
CC telencephalon; also detected in the epithelial lining of the bronchi
CC and esophagus. At 12.5 dpc, expressed in the bronchi, in the atrial and
CC ventricular myocardium, the dorsal root ganglia and the epithelial
CC lining of the rectum and bladder. At 15.5 dpc, detected in the
CC developing choroid plexus epithelium, neural retina, olfactory
CC epithelium and developing vomeronasal organ.
CC {ECO:0000269|PubMed:12595239}.
CC -!- INDUCTION: Induced by neurite outgrowth in neuroblastoma cell lines
CC Neuro-2a. {ECO:0000269|PubMed:16203089}.
CC -!- DOMAIN: The Ig-like C2-type domains 3 and 4 are required for
CC interaction with CD81.
CC -!- DOMAIN: The short cytoplasmic domain is very basic, interacts with
CC membrane PIPs, and mediates plasma membrane localization.
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; AF411055; AAL02217.1; -; mRNA.
DR EMBL; AF439263; AAN63626.1; -; mRNA.
DR EMBL; AK146104; BAE26904.1; -; mRNA.
DR EMBL; AK146221; BAE26989.1; -; mRNA.
DR EMBL; AK168363; BAE40298.1; -; mRNA.
DR EMBL; BC026464; AAH26464.1; -; mRNA.
DR EMBL; BC026633; AAH26633.1; -; mRNA.
DR EMBL; BC048387; AAH48387.1; -; mRNA.
DR CCDS; CCDS15511.1; -.
DR RefSeq; NP_536344.1; NM_080419.2.
DR AlphaFoldDB; Q8R366; -.
DR BioGRID; 228282; 29.
DR IntAct; Q8R366; 1.
DR MINT; Q8R366; -.
DR STRING; 10090.ENSMUSP00000041232; -.
DR GlyConnect; 2384; 17 N-Linked glycans (4 sites).
DR GlyGen; Q8R366; 4 sites, 16 N-linked glycans (4 sites).
DR iPTMnet; Q8R366; -.
DR PhosphoSitePlus; Q8R366; -.
DR SwissPalm; Q8R366; -.
DR EPD; Q8R366; -.
DR MaxQB; Q8R366; -.
DR PaxDb; Q8R366; -.
DR PeptideAtlas; Q8R366; -.
DR PRIDE; Q8R366; -.
DR ProteomicsDB; 269546; -.
DR DNASU; 140559; -.
DR GeneID; 140559; -.
DR KEGG; mmu:140559; -.
DR UCSC; uc007dqe.1; mouse.
DR CTD; 93185; -.
DR MGI; MGI:2154090; Igsf8.
DR eggNOG; ENOG502QTUT; Eukaryota.
DR InParanoid; Q8R366; -.
DR OrthoDB; 409194at2759; -.
DR PhylomeDB; Q8R366; -.
DR TreeFam; TF332702; -.
DR BioGRID-ORCS; 140559; 1 hit in 71 CRISPR screens.
DR PRO; PR:Q8R366; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q8R366; protein.
DR GO; GO:0030424; C:axon; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0043209; C:myelin sheath; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; IDA:MGI.
DR GO; GO:2000145; P:regulation of cell motility; IGI:MGI.
DR Gene3D; 2.60.40.10; -; 3.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR013106; Ig_V-set.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 4.
DR SUPFAM; SSF48726; SSF48726; 4.
DR PROSITE; PS50835; IG_LIKE; 2.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; Glycoprotein; Immunoglobulin domain;
KW Lipoprotein; Membrane; Palmitate; Phosphoprotein; Reference proteome;
KW Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..25
FT /evidence="ECO:0000250"
FT CHAIN 26..611
FT /note="Immunoglobulin superfamily member 8"
FT /id="PRO_0000226248"
FT TOPO_DOM 26..577
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 578..598
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 599..611
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 26..143
FT /note="Ig-like C2-type 1"
FT DOMAIN 160..284
FT /note="Ig-like C2-type 2"
FT DOMAIN 301..422
FT /note="Ig-like C2-type 3"
FT DOMAIN 429..554
FT /note="Ig-like C2-type 4"
FT MOTIF 272..274
FT /note="EWI motif"
FT MOD_RES 516
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q969P0"
FT LIPID 602
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:21609323"
FT LIPID 603
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:21609323"
FT CARBOHYD 48
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 137
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 325
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 47..125
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 184..268
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 324..404
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 460..542
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT CONFLICT 20
FT /note="G -> E (in Ref. 3; BAE26989/BAE40298)"
FT /evidence="ECO:0000305"
FT CONFLICT 37
FT /note="R -> Q (in Ref. 3; BAE26904)"
FT /evidence="ECO:0000305"
FT CONFLICT 221
FT /note="R -> H (in Ref. 3; BAE26904 and 4; AAH48387)"
FT /evidence="ECO:0000305"
FT CONFLICT 316
FT /note="P -> A (in Ref. 3; BAE26989/BAE40298)"
FT /evidence="ECO:0000305"
FT CONFLICT 319
FT /note="P -> H (in Ref. 3; BAE26904)"
FT /evidence="ECO:0000305"
FT CONFLICT 470..471
FT /note="GL -> RV (in Ref. 1; AAL02217)"
FT /evidence="ECO:0000305"
FT CONFLICT 489
FT /note="S -> T (in Ref. 1, 3; BAE26904 and 4; AAH48387)"
FT /evidence="ECO:0000305"
FT CONFLICT 547
FT /note="W -> S (in Ref. 3; BAE26904)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 611 AA; 65011 MW; B5581BE0DF01565A CRC64;
MGVPSPTPLS SLLLLLLILG TRCYARQVHV PRGPLYRVAG TAVSISCNVS DYEGPAQQDF
EWFMYRPEAP ATSLGIVSTK DSQFSYAVFG PRVASGDLQV QRLKGDSVVL KIARLQAQDS
GFYECYTPST DTQYLGNYSA KVELRVLPDE LQVSAAPPGP RGRQAATSPS RLTVHEGQEL
ALGCLAQTKT KKHTHLSVSF GRAIPEAPVG RATLQEVVGL RSDMAVEAGA PYAERLASGE
LRLSKEGTDR YRMVVGGAQA GDSGTYHCTA AEWIQDPDGS WVQVAEKRAV LAHVDVQTLS
SQLAVTVGPG ERRIGPGEPL ELLCNVSGAL PPPGRHAAYS VGWEMAPAGA PGPGRLVAQL
DTEGIGSLGP GYEDRHIAME KVASRTYRLR LEAARPADAG TYRCLAKAYV RGSGTRLREA
ASARSRPLPV HVREEGVVLE AVAWLAGGTV YRGETASLLC NISVRGGPPG LRLAASWWVE
RPEEGELSSG PAQLVGGVGQ DGVAELGVRP GGGPVSVELV GPRSHRLRLH GLGPEDEGIY
HCAPSAWVQH ADYSWYQAGS ARSGPVTVYP YTHAVDTLFV PLLVGTGVAL VTGASVLATI
TCCFMKRMRK R
