NETO2_HUMAN
ID NETO2_HUMAN Reviewed; 525 AA.
AC Q8NC67; J3KNF1; Q7Z381; Q8ND51; Q96SP4; Q9NVY8;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 165.
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; ORFNames=UNQ1926/PRO4401;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 35-525 (ISOFORM 1).
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).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 378-525.
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 378-525.
RC TISSUE=Ovary;
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 [7]
RP PROTEIN SEQUENCE OF 23-37.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
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 -!- INTERACTION:
CC Q8NC67-2; P26378-2: ELAVL4; NbExp=3; IntAct=EBI-25852289, EBI-21603100;
CC Q8NC67-2; P22607: FGFR3; NbExp=3; IntAct=EBI-25852289, EBI-348399;
CC Q8NC67-2; P06396: GSN; NbExp=3; IntAct=EBI-25852289, EBI-351506;
CC Q8NC67-2; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-25852289, EBI-5235340;
CC Q8NC67-2; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-25852289, EBI-741480;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8NC67-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NC67-2; Sequence=VSP_012856, VSP_012857;
CC Name=3;
CC IsoId=Q8NC67-3; Sequence=VSP_053795;
CC -!- PTM: N-glycosylated. {ECO:0000250}.
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DR EMBL; AY358718; AAQ89080.1; -; mRNA.
DR EMBL; AK001292; BAA91604.1; -; mRNA.
DR EMBL; AK027478; BAB55141.1; -; mRNA.
DR EMBL; AK027630; BAB55247.1; -; mRNA.
DR EMBL; AK074937; BAC11303.1; -; mRNA.
DR EMBL; AL834404; CAD39066.1; -; mRNA.
DR EMBL; BX538063; CAD97994.1; -; mRNA.
DR EMBL; CR457255; CAG33536.1; -; mRNA.
DR EMBL; AC007338; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC007494; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC012381; AAH12381.1; -; mRNA.
DR CCDS; CCDS10727.1; -. [Q8NC67-1]
DR CCDS; CCDS58460.1; -. [Q8NC67-3]
DR RefSeq; NP_001188406.1; NM_001201477.1. [Q8NC67-3]
DR RefSeq; NP_060562.3; NM_018092.4. [Q8NC67-1]
DR AlphaFoldDB; Q8NC67; -.
DR SMR; Q8NC67; -.
DR BioGRID; 123589; 62.
DR IntAct; Q8NC67; 36.
DR STRING; 9606.ENSP00000455169; -.
DR TCDB; 8.A.47.1.2; the neuropilin and tolloid-like (neto) family.
DR GlyGen; Q8NC67; 2 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q8NC67; -.
DR PhosphoSitePlus; Q8NC67; -.
DR BioMuta; NETO2; -.
DR DMDM; 59798464; -.
DR EPD; Q8NC67; -.
DR MassIVE; Q8NC67; -.
DR MaxQB; Q8NC67; -.
DR PaxDb; Q8NC67; -.
DR PeptideAtlas; Q8NC67; -.
DR PRIDE; Q8NC67; -.
DR ProteomicsDB; 72857; -. [Q8NC67-1]
DR ProteomicsDB; 72858; -. [Q8NC67-2]
DR Antibodypedia; 2630; 196 antibodies from 28 providers.
DR DNASU; 81831; -.
DR Ensembl; ENST00000303155.9; ENSP00000306726.5; ENSG00000171208.10. [Q8NC67-3]
DR Ensembl; ENST00000562435.6; ENSP00000455169.1; ENSG00000171208.10. [Q8NC67-1]
DR GeneID; 81831; -.
DR KEGG; hsa:81831; -.
DR MANE-Select; ENST00000562435.6; ENSP00000455169.1; NM_018092.5; NP_060562.3.
DR UCSC; uc002eer.3; human. [Q8NC67-1]
DR CTD; 81831; -.
DR DisGeNET; 81831; -.
DR GeneCards; NETO2; -.
DR HGNC; HGNC:14644; NETO2.
DR HPA; ENSG00000171208; Tissue enhanced (lymphoid).
DR MIM; 607974; gene.
DR neXtProt; NX_Q8NC67; -.
DR OpenTargets; ENSG00000171208; -.
DR PharmGKB; PA31559; -.
DR VEuPathDB; HostDB:ENSG00000171208; -.
DR eggNOG; ENOG502QW0Z; Eukaryota.
DR GeneTree; ENSGT00940000156041; -.
DR HOGENOM; CLU_015228_0_1_1; -.
DR InParanoid; Q8NC67; -.
DR OMA; KECIYVL; -.
DR OrthoDB; 477476at2759; -.
DR PhylomeDB; Q8NC67; -.
DR PathwayCommons; Q8NC67; -.
DR SignaLink; Q8NC67; -.
DR SIGNOR; Q8NC67; -.
DR BioGRID-ORCS; 81831; 19 hits in 1066 CRISPR screens.
DR ChiTaRS; NETO2; human.
DR GenomeRNAi; 81831; -.
DR Pharos; Q8NC67; Tbio.
DR PRO; PR:Q8NC67; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q8NC67; protein.
DR Bgee; ENSG00000171208; Expressed in secondary oocyte and 149 other tissues.
DR ExpressionAtlas; Q8NC67; baseline and differential.
DR Genevisible; Q8NC67; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0014069; C:postsynaptic density; IBA:GO_Central.
DR GO; GO:0035255; F:ionotropic glutamate receptor binding; IBA:GO_Central.
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; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Membrane; Phosphoprotein; Receptor; Reference proteome;
KW Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 23..525
FT /note="Neuropilin and tolloid-like protein 2"
FT /id="PRO_0000021801"
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:0000250|UniProtKB:Q8BNJ6"
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..324
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_012856"
FT VAR_SEQ 169..175
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_053795"
FT VAR_SEQ 325..333
FT /note="PWDENHCKE -> MLFTSFVEQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_012857"
FT VARIANT 456
FT /note="S -> T (in dbSNP:rs2231983)"
FT /id="VAR_051232"
FT CONFLICT 211
FT /note="I -> V (in Ref. 3; CAD97994)"
FT /evidence="ECO:0000305"
FT CONFLICT 278
FT /note="E -> G (in Ref. 3; CAD97994)"
FT /evidence="ECO:0000305"
FT CONFLICT 424
FT /note="K -> R (in Ref. 2; BAB55247)"
FT /evidence="ECO:0000305"
FT CONFLICT 461
FT /note="F -> L (in Ref. 2; BAB55247)"
FT /evidence="ECO:0000305"
FT CONFLICT 482
FT /note="S -> G (in Ref. 3; CAD97994)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 525 AA; 59393 MW; EA6F98C3A88220EA CRC64;
MALERLCSVL KVLLITVLVV EGIAVAQKTQ DGQNIGIKHI PATQCGIWVR TSNGGHFASP
NYPDSYPPNK ECIYILEAAP RQRIELTFDE HYYIEPSFEC RFDHLEVRDG PFGFSPLIDR
YCGVKSPPLI RSTGRFMWIK FSSDEELEGL GFRAKYSFIP DPDFTYLGGI LNPIPDCQFE
LSGADGIVRS SQVEQEEKTK PGQAVDCIWT IKATPKAKIY LRFLDYQMEH SNECKRNFVA
VYDGSSSIEN LKAKFCSTVA NDVMLKTGIG VIRMWADEGS RLSRFRMLFT SFVEPPCTSS
TFFCHSNMCI NNSLVCNGVQ NCAYPWDENH CKEKKKAGVF EQITKTHGTI IGITSGIVLV
LLIISILVQV KQPRKKVMAC KTAFNKTGFQ EVFDPPHYEL FSLRDKEISA DLADLSEELD
NYQKMRRSST ASRCIHDHHC GSQASSVKQS RTNLSSMELP FRNDFAQPQP MKTFNSTFKK
SSYTFKQGHE CPEQALEDRV MEEIPCEIYV RGREDSAQAS ISIDF
