NETO1_HUMAN
ID NETO1_HUMAN Reviewed; 533 AA.
AC Q8TDF5; Q86W85; Q8ND78; Q8TDF4;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 31-MAY-2011, sequence version 2.
DT 03-AUG-2022, entry version 167.
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 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 [MRNA] (ISOFORMS 1; 2 AND 3), VARIANT ASN-481, AND
RP TISSUE SPECIFICITY.
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT ASN-481.
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 34-533 (ISOFORM 3), AND VARIANT
RP ASN-481.
RC TISSUE=Brain;
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).
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 (By similarity). {ECO:0000250}.
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 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane {ECO:0000305}; Single-
CC pass type I membrane protein {ECO:0000305}. Postsynaptic density
CC membrane {ECO:0000250}. Note=Component of the postsynaptic density
CC (PSD) of excitatory synapses. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cell membrane {ECO:0000305}; Single-
CC pass type I membrane protein {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Secreted {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=3;
CC IsoId=Q8TDF5-3; Sequence=Displayed;
CC Name=1; Synonyms=Soluble, sNETO1;
CC IsoId=Q8TDF5-1; Sequence=VSP_012853, VSP_012854, VSP_012855;
CC Name=2;
CC IsoId=Q8TDF5-2; Sequence=VSP_012853;
CC -!- TISSUE SPECIFICITY: Isoform 1 and isoform 2 are retina-specific.
CC Isoform 3 is found in retina as well as at lower levels in adult and
CC fetal brain. {ECO:0000269|PubMed:11943477}.
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DR EMBL; AF448838; AAM18026.1; -; mRNA.
DR EMBL; AF448839; AAM18027.1; -; mRNA.
DR EMBL; AC023301; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC091138; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC050329; AAH50329.1; -; mRNA.
DR EMBL; AL834354; CAD39019.1; -; mRNA.
DR CCDS; CCDS12000.1; -. [Q8TDF5-3]
DR CCDS; CCDS42444.1; -. [Q8TDF5-1]
DR RefSeq; NP_001188394.1; NM_001201465.1. [Q8TDF5-3]
DR RefSeq; NP_620416.1; NM_138966.3. [Q8TDF5-3]
DR RefSeq; NP_620552.1; NM_138999.1. [Q8TDF5-1]
DR RefSeq; XP_005266831.1; XM_005266774.4.
DR RefSeq; XP_016881506.1; XM_017026017.1. [Q8TDF5-3]
DR RefSeq; XP_016881507.1; XM_017026018.1. [Q8TDF5-3]
DR AlphaFoldDB; Q8TDF5; -.
DR SMR; Q8TDF5; -.
DR BioGRID; 123590; 7.
DR STRING; 9606.ENSP00000313088; -.
DR TCDB; 8.A.47.1.1; the neuropilin and tolloid-like (neto) family.
DR GlyGen; Q8TDF5; 3 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q8TDF5; -.
DR PhosphoSitePlus; Q8TDF5; -.
DR BioMuta; NETO1; -.
DR DMDM; 334302837; -.
DR MassIVE; Q8TDF5; -.
DR MaxQB; Q8TDF5; -.
DR PaxDb; Q8TDF5; -.
DR PeptideAtlas; Q8TDF5; -.
DR PRIDE; Q8TDF5; -.
DR ProteomicsDB; 74273; -. [Q8TDF5-3]
DR ProteomicsDB; 74274; -. [Q8TDF5-1]
DR ProteomicsDB; 74275; -. [Q8TDF5-2]
DR Antibodypedia; 23286; 118 antibodies from 29 providers.
DR DNASU; 81832; -.
DR Ensembl; ENST00000327305.11; ENSP00000313088.6; ENSG00000166342.19. [Q8TDF5-3]
DR Ensembl; ENST00000397929.5; ENSP00000381024.1; ENSG00000166342.19. [Q8TDF5-1]
DR Ensembl; ENST00000583169.5; ENSP00000464312.1; ENSG00000166342.19. [Q8TDF5-3]
DR GeneID; 81832; -.
DR KEGG; hsa:81832; -.
DR MANE-Select; ENST00000327305.11; ENSP00000313088.6; NM_138966.5; NP_620416.2.
DR UCSC; uc002lkw.3; human. [Q8TDF5-3]
DR CTD; 81832; -.
DR DisGeNET; 81832; -.
DR GeneCards; NETO1; -.
DR HGNC; HGNC:13823; NETO1.
DR HPA; ENSG00000166342; Group enriched (brain, retina).
DR MIM; 607973; gene.
DR neXtProt; NX_Q8TDF5; -.
DR OpenTargets; ENSG00000166342; -.
DR PharmGKB; PA31558; -.
DR VEuPathDB; HostDB:ENSG00000166342; -.
DR eggNOG; ENOG502QUD4; Eukaryota.
DR GeneTree; ENSGT00940000156700; -.
DR HOGENOM; CLU_015228_0_0_1; -.
DR InParanoid; Q8TDF5; -.
DR OMA; KPLVQPM; -.
DR PhylomeDB; Q8TDF5; -.
DR PathwayCommons; Q8TDF5; -.
DR BioGRID-ORCS; 81832; 9 hits in 1063 CRISPR screens.
DR ChiTaRS; NETO1; human.
DR GenomeRNAi; 81832; -.
DR Pharos; Q8TDF5; Tbio.
DR PRO; PR:Q8TDF5; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q8TDF5; protein.
DR Bgee; ENSG00000166342; Expressed in prefrontal cortex and 107 other tissues.
DR ExpressionAtlas; Q8TDF5; baseline and differential.
DR Genevisible; Q8TDF5; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0060076; C:excitatory synapse; ISS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
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:0098839; C:postsynaptic density membrane; ISS:SynGO.
DR GO; GO:0035255; F:ionotropic glutamate receptor binding; IBA:GO_Central.
DR GO; GO:0007613; P:memory; ISS:UniProtKB.
DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; IBA:GO_Central.
DR GO; GO:0097120; P:receptor localization to synapse; IEA:Ensembl.
DR GO; GO:2000312; P:regulation of kainate selective glutamate receptor activity; IDA:SynGO.
DR GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; ISS:UniProtKB.
DR GO; GO:0008542; P:visual learning; ISS: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 2: Evidence at transcript level;
KW Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein;
KW Membrane; Phosphoprotein; Postsynaptic cell membrane; Receptor;
KW Reference proteome; Repeat; Secreted; Signal; Synapse; Transmembrane;
KW 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_0000021799"
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:0000250|UniProtKB:Q8R4I7"
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 VAR_SEQ 1..10
FT /note="MIHGRSVLHI -> MLAEPFPKV (in isoform 1 and isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:11943477"
FT /id="VSP_012853"
FT VAR_SEQ 157
FT /note="D -> E (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:11943477"
FT /id="VSP_012854"
FT VAR_SEQ 158..533
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:11943477"
FT /id="VSP_012855"
FT VARIANT 481
FT /note="S -> N (in dbSNP:rs922999)"
FT /evidence="ECO:0000269|PubMed:11943477,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17974005"
FT /id="VAR_051230"
FT VARIANT 487
FT /note="A -> G (in dbSNP:rs17086286)"
FT /id="VAR_051231"
FT CONFLICT 140
FT /note="D -> A (in Ref. 3; AAH50329)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 533 AA; 60191 MW; 763EBE7BAF06EAC8 CRC64;
MIHGRSVLHI VASLIILHLS GATKKGTEKQ TTSETQKSVQ CGTWTKHAEG GIFTSPNYPS
KYPPDRECIY IIEAAPRQCI ELYFDEKYSI EPSWECKFDH IEVRDGPFGF SPIIGRFCGQ
QNPPVIKSSG RFLWIKFFAD GELESMGFSA RYNFTPDPDF KDLGALKPLP ACEFEMGGSE
GIVESIQIMK EGKATASEAV DCKWYIRAPP RSKIYLRFLD YEMQNSNECK RNFVAVYDGS
SSVEDLKAKF CSTVANDVML RTGLGVIRMW ADEGSRNSRF QMLFTSFQEP PCEGNTFFCH
SNMCINNTLV CNGLQNCVYP WDENHCKEKR KTSLLDQLTN TSGTVIGVTS CIVIILIIIS
VIVQIKQPRK KYVQRKSDFD QTVFQEVFEP PHYELCTLRG TGATADFADV ADDFENYHKL
RRSSSKCIHD HHCGSQLSST KGSRSNLSTR DASILTEMPT QPGKPLIPPM NRRNILVMKH
SYSQDAADAC DIDEIEEVPT TSHRLSRHDK AVQRFCLIGS LSKHESEYNT TRV
