NETO1_MOUSE
ID NETO1_MOUSE Reviewed; 533 AA.
AC Q8R4I7; Q80X39; Q8C4S3; Q8CCM2;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 2.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Neuropilin and tolloid-like protein 1;
DE AltName: Full=Brain-specific transmembrane protein containing 2 CUB and 1 LDL-receptor class A domains protein 1;
DE Flags: Precursor;
GN Name=Neto1; Synonyms=Btcl1;
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].
RC TISSUE=Retina;
RX PubMed=11943477; DOI=10.1016/s0378-1119(02)00438-9;
RA Stoehr H., Berger C., Froehlich S., Weber B.H.F.;
RT "A novel gene encoding a putative transmembrane protein with two
RT extracellular CUB domains and a low-density lipoprotein class A module:
RT isolation of alternatively spliced isoforms in retina and brain.";
RL Gene 286:223-231(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=12810072; DOI=10.1016/s0006-291x(03)01035-0;
RA Michishita M., Ikeda T., Nakashiba T., Ogawa M., Tashiro K., Honjo T.,
RA Doi K., Itohara S., Endo S.;
RT "A novel gene, Btcl1, encoding CUB and LDLa domains is expressed in
RT restricted areas of mouse brain.";
RL Biochem. Biophys. Res. Commun. 306:680-686(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Head, and Olfactory bulb;
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 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 [5]
RP DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-417, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [8]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, SUBCELLULAR LOCATION,
RP AND INTERACTION WITH GRIN2A; GRIN2B; DLG2; DLG3 AND DLG4.
RX PubMed=19243221; DOI=10.1371/journal.pbio.1000041;
RA Ng D., Pitcher G.M., Szilard R.K., Sertie A., Kanisek M., Clapcote S.J.,
RA Lipina T., Kalia L.V., Joo D., McKerlie C., Cortez M., Roder J.C.,
RA Salter M.W., McInnes R.R.;
RT "Neto1 is a novel CUB-domain NMDA receptor-interacting protein required for
RT synaptic plasticity and learning.";
RL PLoS Biol. 7:E41-E41(2009).
CC -!- FUNCTION: Involved in the development and/or maintenance of neuronal
CC circuitry. Accessory subunit of the neuronal N-methyl-D-aspartate
CC receptor (NMDAR) critical for maintaining the abundance of GRIN2A-
CC containing NMDARs in the postsynaptic density. Regulates long-term NMDA
CC receptor-dependent synaptic plasticity and cognition, at least in the
CC context of spatial learning and memory. {ECO:0000269|PubMed:12810072,
CC ECO:0000269|PubMed:19243221}.
CC -!- SUBUNIT: Interacts with PLZ domains of DLG2, DLG3 and DLG4 via its C-
CC terminal TRV domain. Interacts with GRIN2A and GRIN2B via its CUB
CC domains. {ECO:0000269|PubMed:19243221}.
CC -!- INTERACTION:
CC Q8R4I7; Q62108: Dlg4; NbExp=7; IntAct=EBI-2314926, EBI-300895;
CC Q8R4I7; P78352: DLG4; Xeno; NbExp=2; IntAct=EBI-2314926, EBI-80389;
CC Q8R4I7; Q00959: Grin2a; Xeno; NbExp=4; IntAct=EBI-2314926, EBI-630970;
CC Q8R4I7; Q00960: Grin2b; Xeno; NbExp=2; IntAct=EBI-2314926, EBI-396905;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}. Postsynaptic density membrane
CC {ECO:0000269|PubMed:19243221}. Note=Component of the postsynaptic
CC density (PSD) of excitatory synapses.
CC -!- TISSUE SPECIFICITY: Expressed only in brain. Present throughout the
CC central nervous system. Highly expressed in the hippocampal CA3 region,
CC olfactory bulb and tubercle, caudate putamen, and neocortex in the
CC adult brain. {ECO:0000269|PubMed:12810072, ECO:0000269|PubMed:15464227,
CC ECO:0000269|PubMed:19243221}.
CC -!- DEVELOPMENTAL STAGE: Observed restrictively in brain throughout
CC embryonic and postnatal stages. Expression pattern in brain slightly
CC changes from 13 dpc to postnatal day 21 (P21). Expressed in both
CC cerebrum and cerebellum throughout P0 to P35. In the cerebrum
CC expression reached a plateau at P14 while expression in the cerebellum
CC remains constant throughout all postnatal stages.
CC {ECO:0000269|PubMed:12810072, ECO:0000269|PubMed:15464227}.
CC -!- DISRUPTION PHENOTYPE: Depressed long-term potentiation (LTP) at
CC Schaffer collateral-CA1 synapses, NMDAR-dependent spatial learning and
CC memory. Rescued by the ampakine CX546 at physiological doses.
CC {ECO:0000269|PubMed:19243221}.
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DR EMBL; AF448840; AAM18028.1; -; mRNA.
DR EMBL; AY138990; AAN38318.1; -; mRNA.
DR EMBL; AK032510; BAC27902.1; -; mRNA.
DR EMBL; AK081325; BAC38196.1; -; mRNA.
DR EMBL; BC051145; AAH51145.1; -; mRNA.
DR CCDS; CCDS29387.1; -.
DR RefSeq; NP_659195.3; NM_144946.4.
DR RefSeq; XP_006526543.1; XM_006526480.3.
DR RefSeq; XP_006526544.1; XM_006526481.3.
DR RefSeq; XP_006526545.1; XM_006526482.3.
DR RefSeq; XP_017173396.1; XM_017317907.1.
DR RefSeq; XP_017173397.1; XM_017317908.1.
DR AlphaFoldDB; Q8R4I7; -.
DR SMR; Q8R4I7; -.
DR BioGRID; 232925; 1.
DR DIP; DIP-48395N; -.
DR IntAct; Q8R4I7; 10.
DR STRING; 10090.ENSMUSP00000057340; -.
DR GlyGen; Q8R4I7; 2 sites.
DR iPTMnet; Q8R4I7; -.
DR PhosphoSitePlus; Q8R4I7; -.
DR PaxDb; Q8R4I7; -.
DR PeptideAtlas; Q8R4I7; -.
DR PRIDE; Q8R4I7; -.
DR ProteomicsDB; 287381; -.
DR Antibodypedia; 23286; 118 antibodies from 29 providers.
DR DNASU; 246317; -.
DR Ensembl; ENSMUST00000058829; ENSMUSP00000057340; ENSMUSG00000050321.
DR GeneID; 246317; -.
DR KEGG; mmu:246317; -.
DR UCSC; uc008fuz.2; mouse.
DR CTD; 81832; -.
DR MGI; MGI:2180216; Neto1.
DR VEuPathDB; HostDB:ENSMUSG00000050321; -.
DR eggNOG; ENOG502QUD4; Eukaryota.
DR GeneTree; ENSGT00940000156700; -.
DR HOGENOM; CLU_015228_0_0_1; -.
DR InParanoid; Q8R4I7; -.
DR OMA; KPLVQPM; -.
DR OrthoDB; 477476at2759; -.
DR PhylomeDB; Q8R4I7; -.
DR BioGRID-ORCS; 246317; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Neto1; mouse.
DR PRO; PR:Q8R4I7; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q8R4I7; protein.
DR Bgee; ENSMUSG00000050321; Expressed in dorsal striatum and 105 other tissues.
DR ExpressionAtlas; Q8R4I7; baseline and differential.
DR Genevisible; Q8R4I7; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0060076; C:excitatory synapse; IDA:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0099061; C:integral component of postsynaptic density membrane; IDA:SynGO.
DR GO; GO:0014069; C:postsynaptic density; IDA:UniProtKB.
DR GO; GO:0098839; C:postsynaptic density membrane; IDA:SynGO.
DR GO; GO:0045202; C:synapse; IDA:MGI.
DR GO; GO:0035255; F:ionotropic glutamate receptor binding; IPI:MGI.
DR GO; GO:0007613; P:memory; IMP:UniProtKB.
DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; IMP:MGI.
DR GO; GO:0097120; P:receptor localization to synapse; IMP:MGI.
DR GO; GO:2000312; P:regulation of kainate selective glutamate receptor activity; ISO:MGI.
DR GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; IMP:UniProtKB.
DR GO; GO:0008542; P:visual learning; IMP:UniProtKB.
DR CDD; cd00041; CUB; 2.
DR CDD; cd00112; LDLa; 1.
DR Gene3D; 2.60.120.290; -; 2.
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; IPR028867; NETO1.
DR InterPro; IPR035914; Sperma_CUB_dom_sf.
DR PANTHER; PTHR45645:SF3; PTHR45645:SF3; 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 Cell membrane; Disulfide bond; Glycoprotein; Membrane; Phosphoprotein;
KW Postsynaptic cell membrane; Receptor; Reference proteome; Repeat; Signal;
KW Synapse; Transmembrane; Transmembrane helix.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..533
FT /note="Neuropilin and tolloid-like protein 1"
FT /id="PRO_0000021800"
FT TOPO_DOM 23..344
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 345..365
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 366..533
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 41..155
FT /note="CUB 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 172..287
FT /note="CUB 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 291..327
FT /note="LDL-receptor class A"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT MOTIF 531..533
FT /note="PDZ-binding"
FT MOD_RES 417
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18034455"
FT CARBOHYD 306
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 340
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 41..68
FT /evidence="ECO:0000250"
FT DISULFID 96..118
FT /evidence="ECO:0000250"
FT DISULFID 172..202
FT /evidence="ECO:0000250"
FT DISULFID 229..251
FT /evidence="ECO:0000250"
FT DISULFID 292..304
FT /evidence="ECO:0000250"
FT DISULFID 299..317
FT /evidence="ECO:0000250"
FT DISULFID 311..326
FT /evidence="ECO:0000250"
FT CONFLICT 80
FT /note="I -> F (in Ref. 3; BAC38196)"
FT /evidence="ECO:0000305"
FT CONFLICT 514
FT /note="R -> Q (in Ref. 1; AAM18028 and 3; BAC38196)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 533 AA; 60242 MW; 6375B395421D558F CRC64;
MIYGRSLFHI IASLIILHSS GATKKGTEKQ ITPETQKSVQ CGTWTKHAEG GVFTSPNYPS
KYPPDRECVY IIEAAPRQCI ELYFDEKYSI EPSWECKFDH IEVRDGPFGF SPIIGRFCGQ
QNPPVIKSSG RFLWIKFFAD GELESMGFSA RYNFTPDPDF KDLGVLKPLP ACEFEMGGPE
GIVESIQILK EGKASASEAV DCKWYIRAPP RSKIYLRFLD YEMQNSNECK RNFVAVYDGS
SSVEDLKAKF CSTVANDVML RTGLGVIRMW ADEGSRNSRF QMLFTSFQEP PCEGNTFFCH
SNMCINNTLV CNGLQNCVYP WDENHCKEKR KTSLLDQLTN TSGTVIGVTS CIVIILIIVS
VIVQIKQPRK KYVQRKSDFD QTVFQEVFEP PHYELCTLRG TGATADFADV AEDFENYHKL
RRSSSKCIHD HHCGSQLSSA KGSRSNLSTR DASILAEIPT QPVKPLIPPV NRRNILVMKH
NYSQDAADAC DIDEIEEVPT TSHRLSRHEK SVQRFCLIGS LSKHESEYNT TRV
