NRX3B_HUMAN
ID NRX3B_HUMAN Reviewed; 637 AA.
AC Q9HDB5; A5PKW8; A8MPU5; B3KPM7; Q6NUR0; Q8IUD8;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 4.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Neurexin-3-beta;
DE AltName: Full=Neurexin III-beta;
DE Contains:
DE RecName: Full=Neurexin-3-beta, soluble form;
DE Contains:
DE RecName: Full=Neurexin-3-beta, C-terminal fragment;
DE Short=NRXN3-CTF;
DE Flags: Precursor;
GN Name=NRXN3; Synonyms=KIAA0743;
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] (ISOFORM 3B).
RC TISSUE=Heart;
RX PubMed=12379233; DOI=10.1016/s0006-291x(02)02403-8;
RA Occhi G., Rampazzo A., Beffagna G., Antonio Danieli G.;
RT "Identification and characterization of heart-specific splicing of human
RT neurexin 3 mRNA (NRXN3).";
RL Biochem. Biophys. Res. Commun. 298:151-155(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING.
RX PubMed=11944992; DOI=10.1006/geno.2002.6734;
RA Rowen L., Young J., Birditt B., Kaur A., Madan A., Philipps D.L., Qin S.,
RA Minx P., Wilson R.K., Hood L., Graveley B.R.;
RT "Analysis of the human neurexin genes: alternative splicing and the
RT generation of protein diversity.";
RL Genomics 79:587-597(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1B).
RC TISSUE=Teratocarcinoma;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2B).
RC TISSUE=Stomach;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2B).
RC TISSUE=Placenta;
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 [8]
RP TISSUE SPECIFICITY.
RX PubMed=19926856; DOI=10.1073/pnas.0809510106;
RA Bottos A., Destro E., Rissone A., Graziano S., Cordara G., Assenzio B.,
RA Cera M.R., Mascia L., Bussolino F., Arese M.;
RT "The synaptic proteins neurexins and neuroligins are widely expressed in
RT the vascular system and contribute to its functions.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:20782-20787(2009).
RN [9]
RP PROTEOLYTIC PROCESSING.
RX PubMed=21084300; DOI=10.1074/jbc.m110.142521;
RA Bot N., Schweizer C., Ben Halima S., Fraering P.C.;
RT "Processing of the synaptic cell adhesion molecule neurexin-3beta by
RT Alzheimer disease alpha- and gamma-secretases.";
RL J. Biol. Chem. 286:2762-2773(2011).
CC -!- FUNCTION: Neuronal cell surface protein that may be involved in cell
CC recognition and cell adhesion. May play a role in angiogenesis (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Weakly interacts with CBLN1 and CBLN2 (By similarity). Very
CC weak binding, if any, with CBLN4 (By similarity).
CC {ECO:0000250|UniProtKB:Q8C985}.
CC -!- INTERACTION:
CC Q9HDB5-2; Q3KNR5: PAX4; NbExp=3; IntAct=EBI-18040962, EBI-10240813;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=7;
CC Comment=A number of isoforms, alpha-type and beta-type, are produced
CC by alternative promoter usage. Beta-type isoforms differ from
CC alpha-type isoforms in their N-terminus. Additional isoforms produced
CC by alternative splicing seem to exist.;
CC Name=1b;
CC IsoId=Q9HDB5-1; Sequence=Displayed;
CC Name=2b;
CC IsoId=Q9HDB5-2; Sequence=VSP_036465, VSP_036466;
CC Name=3b;
CC IsoId=Q9HDB5-3; Sequence=VSP_035644, VSP_035646, VSP_035647;
CC Name=4b;
CC IsoId=Q9HDB5-4; Sequence=VSP_035644, VSP_040988;
CC Name=1a;
CC IsoId=Q9Y4C0-1; Sequence=External;
CC Name=3a;
CC IsoId=Q9Y4C0-3; Sequence=External;
CC Name=4a;
CC IsoId=Q9Y4C0-4; Sequence=External;
CC -!- TISSUE SPECIFICITY: Expressed in the blood vessel walls (at protein
CC level). {ECO:0000269|PubMed:19926856}.
CC -!- PTM: Proccessed by alpha-secretase leading to the formation of an
CC extracellular soluble protein as well as a C-terminal membrane-embedded
CC fragment (CTF). Proteolysis of these CTFs by gamma-secretase releases
CC intracellular domains (ICDs) and extracellular peptides.
CC -!- MISCELLANEOUS: [Isoform 2b]: Produced by alternative splicing.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3b]: Produced by alternative splicing.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 4b]: Produced by alternative splicing.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the neurexin family. {ECO:0000305}.
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DR EMBL; AJ493127; CAD37989.1; -; mRNA.
DR EMBL; AF123462; AAD13621.1; -; Genomic_DNA.
DR EMBL; AK056530; BAG51739.1; -; mRNA.
DR EMBL; AL833739; CAH56254.1; -; mRNA.
DR EMBL; AC008056; AAF09143.1; -; Genomic_DNA.
DR EMBL; AC012099; AAF15058.1; -; Genomic_DNA.
DR EMBL; AC018514; AAF99808.1; -; Genomic_DNA.
DR EMBL; CH471061; EAW81313.1; -; Genomic_DNA.
DR EMBL; CH471061; EAW81315.1; -; Genomic_DNA.
DR EMBL; BC059368; AAH59368.1; -; mRNA.
DR EMBL; BC068469; AAH68469.1; -; mRNA.
DR EMBL; BC142649; AAI42650.1; -; mRNA.
DR EMBL; BC150194; AAI50195.1; -; mRNA.
DR CCDS; CCDS45145.1; -. [Q9HDB5-4]
DR CCDS; CCDS61515.1; -. [Q9HDB5-1]
DR CCDS; CCDS9871.1; -. [Q9HDB5-2]
DR RefSeq; NP_001098720.1; NM_001105250.2. [Q9HDB5-4]
DR RefSeq; NP_001258949.1; NM_001272020.1. [Q9HDB5-1]
DR RefSeq; NP_004787.2; NM_004796.5.
DR RefSeq; NP_620426.2; NM_138970.4. [Q9HDB5-2]
DR AlphaFoldDB; Q9HDB5; -.
DR SMR; Q9HDB5; -.
DR BioGRID; 114770; 22.
DR IntAct; Q9HDB5; 9.
DR MINT; Q9HDB5; -.
DR iPTMnet; Q9HDB5; -.
DR PhosphoSitePlus; Q9HDB5; -.
DR BioMuta; NRXN3; -.
DR DMDM; 218512141; -.
DR EPD; Q9HDB5; -.
DR MassIVE; Q9HDB5; -.
DR PeptideAtlas; Q9HDB5; -.
DR PRIDE; Q9HDB5; -.
DR ProteomicsDB; 81844; -. [Q9HDB5-1]
DR ProteomicsDB; 81845; -. [Q9HDB5-2]
DR ProteomicsDB; 81846; -. [Q9HDB5-3]
DR ProteomicsDB; 81847; -. [Q9HDB5-4]
DR Antibodypedia; 106; 252 antibodies from 31 providers.
DR DNASU; 9369; -.
DR Ensembl; ENST00000281127.11; ENSP00000281127.7; ENSG00000021645.20. [Q9HDB5-2]
DR Ensembl; ENST00000428277.6; ENSP00000394426.2; ENSG00000021645.20. [Q9HDB5-4]
DR Ensembl; ENST00000557594.5; ENSP00000451672.1; ENSG00000021645.20. [Q9HDB5-1]
DR GeneID; 9369; -.
DR KEGG; hsa:9369; -.
DR UCSC; uc001xuq.4; human. [Q9HDB5-1]
DR CTD; 9369; -.
DR DisGeNET; 9369; -.
DR GeneCards; NRXN3; -.
DR HGNC; HGNC:8010; NRXN3.
DR HPA; ENSG00000021645; Tissue enhanced (brain, retina).
DR MIM; 600567; gene.
DR neXtProt; NX_Q9HDB5; -.
DR OpenTargets; ENSG00000021645; -.
DR PharmGKB; PA31788; -.
DR VEuPathDB; HostDB:ENSG00000021645; -.
DR GeneTree; ENSGT00940000154618; -.
DR HOGENOM; CLU_025785_2_0_1; -.
DR OrthoDB; 35129at2759; -.
DR PathwayCommons; Q9HDB5; -.
DR Reactome; R-HSA-6794361; Neurexins and neuroligins.
DR SignaLink; Q9HDB5; -.
DR SIGNOR; Q9HDB5; -.
DR BioGRID-ORCS; 9369; 10 hits in 1067 CRISPR screens.
DR ChiTaRS; NRXN3; human.
DR GeneWiki; NRXN3; -.
DR GenomeRNAi; 9369; -.
DR Pharos; Q9HDB5; Tbio.
DR Proteomes; UP000005640; Chromosome 14.
DR Bgee; ENSG00000021645; Expressed in cerebellar vermis and 162 other tissues.
DR ExpressionAtlas; Q9HDB5; baseline and differential.
DR Genevisible; Q9HDB5; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0050839; F:cell adhesion molecule binding; TAS:BHF-UCL.
DR GO; GO:0097109; F:neuroligin family protein binding; TAS:BHF-UCL.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; NAS:BHF-UCL.
DR GO; GO:0030534; P:adult behavior; IGI:BHF-UCL.
DR GO; GO:0001525; P:angiogenesis; ISS:UniProtKB.
DR GO; GO:0007612; P:learning; IGI:BHF-UCL.
DR GO; GO:0007158; P:neuron cell-cell adhesion; TAS:BHF-UCL.
DR GO; GO:0007165; P:signal transduction; NAS:BHF-UCL.
DR GO; GO:0035176; P:social behavior; IGI:BHF-UCL.
DR GO; GO:0071625; P:vocalization behavior; IGI:BHF-UCL.
DR CDD; cd00110; LamG; 1.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR001791; Laminin_G.
DR InterPro; IPR003585; Neurexin-like.
DR InterPro; IPR027789; Syndecan/Neurexin_dom.
DR Pfam; PF02210; Laminin_G_2; 1.
DR Pfam; PF01034; Syndecan; 1.
DR SMART; SM00294; 4.1m; 1.
DR SMART; SM00282; LamG; 1.
DR SUPFAM; SSF49899; SSF49899; 1.
DR PROSITE; PS50025; LAM_G_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Alternative promoter usage; Alternative splicing; Angiogenesis;
KW Cell adhesion; Glycoprotein; Membrane; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..35
FT /evidence="ECO:0000250"
FT CHAIN 36..637
FT /note="Neurexin-3-beta"
FT /id="PRO_0000019502"
FT CHAIN 36..550
FT /note="Neurexin-3-beta, soluble form"
FT /id="PRO_0000412543"
FT CHAIN 551..637
FT /note="Neurexin-3-beta, C-terminal fragment"
FT /id="PRO_0000412544"
FT TOPO_DOM 36..562
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 563..583
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 584..637
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 85..255
FT /note="Laminin G-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122"
FT REGION 43..65
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 289..310
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 605..637
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 619..637
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 184
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 252
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 296
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 200
FT /note="T -> TGNTDNERFQMVKQKIPFKYNRPVEEWLQEK (in isoform 3b
FT and isoform 4b)"
FT /evidence="ECO:0000303|PubMed:12379233"
FT /id="VSP_035644"
FT VAR_SEQ 328
FT /note="S -> ST (in isoform 2b)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_036465"
FT VAR_SEQ 329..537
FT /note="TGGELVIPLLVEDPLATPPIATRAPSITLPPTFRPLLTIIETTKDSLSMTSE
FT AGLPCLSDQGSDGCDDDGLVISGYGSGETFDSNLPPTDDEDFYTTFSLVTDKSLSTSIF
FT EGGYKAHAPKWESKDFRPNKVSETSRTTTTSLSPELIRFTASSSSGMVPKLPAGKMNNR
FT DLKPQPDIVLLPLPTAYELDSTKLKSPLITSPMFRNVPT -> GRS (in isoform
FT 2b)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_036466"
FT VAR_SEQ 329..536
FT /note="Missing (in isoform 4b)"
FT /evidence="ECO:0000305"
FT /id="VSP_040988"
FT VAR_SEQ 329..367
FT /note="TGGELVIPLLVEDPLATPPIATRAPSITLPPTFRPLLTI -> GRSARSSNA
FT ARSLRAALTWTWRLTYTFTPIIFISCVVH (in isoform 3b)"
FT /evidence="ECO:0000303|PubMed:12379233"
FT /id="VSP_035646"
FT VAR_SEQ 368..637
FT /note="Missing (in isoform 3b)"
FT /evidence="ECO:0000303|PubMed:12379233"
FT /id="VSP_035647"
SQ SEQUENCE 637 AA; 69305 MW; A0F100DA9D72A149 CRC64;
MHLRIHARRS PPRRPAWTLG IWFLFWGCIV SSVWSSSNVA SSSSTSSSPG SHSQHEHHFH
GSKHHSVPIS IYRSPVSLRG GHAGATYIFG KSGGLILYTW PANDRPSTRS DRLAVGFSTT
VKDGILVRID SAPGLGDFLQ LHIEQGKIGV VFNIGTVDIS IKEERTPVND GKYHVVRFTR
NGGNATLQVD NWPVNEHYPT GRQLTIFNTQ AQIAIGGKDK GRLFQGQLSG LYYDGLKVLN
MAAENNPNIK INGSVRLVGE VPSILGTTQT TSMPPEMSTT VMETTTTMAT TTTRKNRSTA
SIQPTSDDLV SSAECSSDDE DFVECEPSTG GELVIPLLVE DPLATPPIAT RAPSITLPPT
FRPLLTIIET TKDSLSMTSE AGLPCLSDQG SDGCDDDGLV ISGYGSGETF DSNLPPTDDE
DFYTTFSLVT DKSLSTSIFE GGYKAHAPKW ESKDFRPNKV SETSRTTTTS LSPELIRFTA
SSSSGMVPKL PAGKMNNRDL KPQPDIVLLP LPTAYELDST KLKSPLITSP MFRNVPTANP
TEPGIRRVPG ASEVIRESSS TTGMVVGIVA AAALCILILL YAMYKYRNRD EGSYQVDETR
NYISNSAQSN GTLMKEKQQS SKSGHKKQKN KDREYYV
