NETO2_MOUSE
ID NETO2_MOUSE Reviewed; 525 AA.
AC Q8BNJ6; B2RX93; Q5VM49; Q8C4Q8;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Neuropilin and tolloid-like protein 2;
DE AltName: Full=Brain-specific transmembrane protein containing 2 CUB and 1 LDL-receptor class A domains protein 2;
DE Flags: Precursor;
GN Name=Neto2; Synonyms=Btcl2;
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), MEMBRANE TOPOLOGY, TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15464227; DOI=10.1016/j.devbrainres.2004.06.012;
RA Michishita M., Ikeda T., Nakashiba T., Ogawa M., Tashiro K., Honjo T.,
RA Doi K., Itohara S., Endo S.;
RT "Expression of Btcl2, a novel member of Btcl gene family, during
RT development of the central nervous system.";
RL Brain Res. Dev. Brain Res. 153:135-142(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Head;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [4]
RP TISSUE SPECIFICITY.
RX PubMed=19217376; DOI=10.1016/j.neuron.2008.12.014;
RA Zhang W., St-Gelais F., Grabner C.P., Trinidad J.C., Sumioka A.,
RA Morimoto-Tomita M., Kim K.S., Straub C., Burlingame A.L., Howe J.R.,
RA Tomita S.;
RT "A transmembrane accessory subunit that modulates kainate-type glutamate
RT receptors.";
RL Neuron 61:385-396(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-409, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE 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).
CC -!- FUNCTION: Accessory subunit of neuronal kainate-sensitive glutamate
CC receptors, GRIK2 and GRIK3. Increases kainate-receptor channel
CC activity, slowing the decay kinetics of the receptors, without
CC affecting their expression at the cell surface, and increasing the open
CC probability of the receptor channels. Modulates the agonist sensitivity
CC of kainate receptors. Slows the decay of kainate receptor-mediated
CC excitatory postsynaptic currents (EPSCs), thus directly influencing
CC synaptic transmission (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with GRIK2 and GRIK3, but neither with AMPA-nor with
CC NMDA-sensitive glutamate receptors. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane {ECO:0000305}; Single-
CC pass type I membrane protein {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane; Multi-pass membrane
CC protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8BNJ6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BNJ6-2; Sequence=VSP_012858, VSP_012859;
CC -!- TISSUE SPECIFICITY: Expressed in brain tissues, including cerebellar
CC granule cells (at protein level). {ECO:0000269|PubMed:15464227,
CC ECO:0000269|PubMed:19217376}.
CC -!- DEVELOPMENTAL STAGE: Observed restrictively in brain throughout
CC embryonic (E) and postnatal stages (P). Expression pattern in brain
CC slightly changes from 13 dpc to P21. {ECO:0000269|PubMed:15464227}.
CC -!- PTM: N-glycosylated. {ECO:0000250}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC38225.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY138991; AAN38319.1; -; mRNA.
DR EMBL; AK081462; BAC38225.1; ALT_INIT; mRNA.
DR EMBL; AK083512; BAC38938.1; -; mRNA.
DR EMBL; BC151050; AAI51051.1; -; mRNA.
DR CCDS; CCDS40423.1; -. [Q8BNJ6-2]
DR CCDS; CCDS90432.1; -. [Q8BNJ6-1]
DR RefSeq; NP_001074793.1; NM_001081324.1. [Q8BNJ6-2]
DR RefSeq; XP_006531500.1; XM_006531437.3. [Q8BNJ6-2]
DR RefSeq; XP_006531502.1; XM_006531439.2.
DR AlphaFoldDB; Q8BNJ6; -.
DR SMR; Q8BNJ6; -.
DR STRING; 10090.ENSMUSP00000105308; -.
DR GlyGen; Q8BNJ6; 1 site.
DR iPTMnet; Q8BNJ6; -.
DR PhosphoSitePlus; Q8BNJ6; -.
DR MaxQB; Q8BNJ6; -.
DR PaxDb; Q8BNJ6; -.
DR PRIDE; Q8BNJ6; -.
DR ProteomicsDB; 252812; -. [Q8BNJ6-1]
DR ProteomicsDB; 252813; -. [Q8BNJ6-2]
DR Antibodypedia; 2630; 196 antibodies from 28 providers.
DR DNASU; 74513; -.
DR Ensembl; ENSMUST00000109686; ENSMUSP00000105308; ENSMUSG00000036902. [Q8BNJ6-2]
DR Ensembl; ENSMUST00000216286; ENSMUSP00000150062; ENSMUSG00000036902. [Q8BNJ6-1]
DR GeneID; 74513; -.
DR KEGG; mmu:74513; -.
DR UCSC; uc009mqc.1; mouse. [Q8BNJ6-2]
DR UCSC; uc009mqe.2; mouse. [Q8BNJ6-1]
DR CTD; 81831; -.
DR MGI; MGI:1921763; Neto2.
DR VEuPathDB; HostDB:ENSMUSG00000036902; -.
DR eggNOG; ENOG502QW0Z; Eukaryota.
DR GeneTree; ENSGT00940000156041; -.
DR HOGENOM; CLU_015228_0_1_1; -.
DR InParanoid; Q8BNJ6; -.
DR OMA; KECIYVL; -.
DR OrthoDB; 477476at2759; -.
DR PhylomeDB; Q8BNJ6; -.
DR BioGRID-ORCS; 74513; 0 hits in 42 CRISPR screens.
DR ChiTaRS; Neto2; mouse.
DR PRO; PR:Q8BNJ6; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q8BNJ6; protein.
DR Bgee; ENSMUSG00000036902; Expressed in cortical plate and 208 other tissues.
DR ExpressionAtlas; Q8BNJ6; baseline and differential.
DR Genevisible; Q8BNJ6; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0014069; C:postsynaptic density; IDA:MGI.
DR GO; GO:0045202; C:synapse; IDA:MGI.
DR GO; GO:0035255; F:ionotropic glutamate receptor binding; IPI:MGI.
DR GO; GO:2000312; P:regulation of kainate selective glutamate receptor activity; IEA:InterPro.
DR CDD; cd00041; CUB; 2.
DR CDD; cd00112; LDLa; 1.
DR Gene3D; 2.60.120.290; -; 2.
DR Gene3D; 4.10.400.10; -; 1.
DR InterPro; IPR000859; CUB_dom.
DR InterPro; IPR036055; LDL_receptor-like_sf.
DR InterPro; IPR023415; LDLR_class-A_CS.
DR InterPro; IPR002172; LDrepeatLR_classA_rpt.
DR InterPro; IPR028868; NETO2.
DR InterPro; IPR035914; Sperma_CUB_dom_sf.
DR PANTHER; PTHR45645:SF22; PTHR45645:SF22; 1.
DR Pfam; PF00431; CUB; 2.
DR Pfam; PF00057; Ldl_recept_a; 1.
DR SMART; SM00042; CUB; 2.
DR SMART; SM00192; LDLa; 1.
DR SUPFAM; SSF49854; SSF49854; 2.
DR SUPFAM; SSF57424; SSF57424; 1.
DR PROSITE; PS01180; CUB; 2.
DR PROSITE; PS01209; LDLRA_1; 1.
DR PROSITE; PS50068; LDLRA_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein;
KW Membrane; Phosphoprotein; Receptor; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..22
FT /evidence="ECO:0000250"
FT CHAIN 23..525
FT /note="Neuropilin and tolloid-like protein 2"
FT /id="PRO_0000021802"
FT TOPO_DOM 23..347
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 348..368
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 369..525
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 45..159
FT /note="CUB 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 177..292
FT /note="CUB 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 296..332
FT /note="LDL-receptor class A"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT MOD_RES 409
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 311
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 45..72
FT /evidence="ECO:0000250"
FT DISULFID 100..122
FT /evidence="ECO:0000250"
FT DISULFID 177..207
FT /evidence="ECO:0000250"
FT DISULFID 234..256
FT /evidence="ECO:0000250"
FT DISULFID 297..309
FT /evidence="ECO:0000250"
FT DISULFID 304..322
FT /evidence="ECO:0000250"
FT DISULFID 316..331
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..11
FT /note="MALEQLCAVLK -> MGTNAVTHSQTLGRAWGILWKNKDGMSQNDQGHHKKT
FT YRINLPGPI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15464227"
FT /id="VSP_012858"
FT VAR_SEQ 169..175
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15464227"
FT /id="VSP_012859"
SQ SEQUENCE 525 AA; 59368 MW; 3E02308F311EC5CE CRC64;
MALEQLCAVL KVLLITVLVV EGIAVAQKTQ DGQNIGIKHI PATQCGIWVR TSNGGHFASP
NYPDSYPPNK ECIYILEAAP RQRIELTFDE RYYIEPSFEC RFDHLEIRDG PFGFSPLIDR
YCGMKSPALI RSTGRFMWIK FSSDEELEGL GFRAKYSFIP DPDFTYLGGI LNPIPDCQFE
LSGADGIVRS SQVEQEEKTK PGQAVDCIWT IKATPKAKIY LRFLDYQMEH SNECKRNFVA
VYDGSSAIEN LKAKFCSTVA NDVMLKTGVG VIRMWADEGS RLSRFRMLFT SFVEPPCTSS
TFFCHSNMCI NNSLVCNGVQ NCAYPWDENH CKEKKKAGLF EQITKTHGTI IGITSGIVLV
LLIISILVQV KQPRKKVMAC KTAFNKTGFQ EVFDPPHYEL FSLREKEISA DLADLSEELD
NYQKLRRSST ASRCIHDHHC GSQASSVKQS RTNLSSMELP FRNDFAQPQP MKTFNSTFKK
SSYTFKQAHE CPEQALEDRV MEEIPCEIYV RGRDDSAQAS ISIDF
