NRX2A_HUMAN
ID NRX2A_HUMAN Reviewed; 1712 AA.
AC Q9P2S2; A7E2C1; Q9Y2D6;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Neurexin-2;
DE AltName: Full=Neurexin II-alpha;
DE AltName: Full=Neurexin-2-alpha;
DE Flags: Precursor;
GN Name=NRXN2; Synonyms=KIAA0921;
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 1A).
RC TISSUE=Fetal brain;
RA Seki N., Yoshikawa T., Azuma T., Muramatsu M., Saito T.;
RT "Human neurexin II.";
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2A).
RC TISSUE=Brain;
RX PubMed=10231032; DOI=10.1093/dnares/6.1.63;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:63-70(1999).
RN [3]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2A).
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).
CC -!- FUNCTION: Neuronal cell surface protein that may be involved in cell
CC recognition and cell adhesion. May mediate intracellular signaling.
CC -!- SUBUNIT: The laminin G-like domain 1 binds to NXPH1. Interacts with
CC PATJ (By similarity). Interacts with CBLN1, CBLN2 and, less avidly,
CC with CBLN4 (By similarity). Isoforms alpha 2C bind to alpha-
CC dystroglycan (By similarity). Interacts (via Laminin G-like 1 domain)
CC with IGSF21 (Ig-like 1 domain) in a trans-interaction manner (By
CC similarity). {ECO:0000250|UniProtKB:E9Q7X7,
CC ECO:0000250|UniProtKB:Q63374}.
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=3;
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=1a;
CC IsoId=Q9P2S2-1; Sequence=Displayed;
CC Name=2a; Synonyms=Alpha-2B;
CC IsoId=Q9P2S2-2; Sequence=VSP_003505, VSP_003506, VSP_003507,
CC VSP_003508;
CC Name=1b;
CC IsoId=P58401-1; Sequence=External;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in brain.
CC -!- SIMILARITY: Belongs to the neurexin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA76765.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB035266; BAA94075.1; -; mRNA.
DR EMBL; AB023138; BAA76765.2; ALT_INIT; mRNA.
DR EMBL; AC044790; AAK68154.1; -; Genomic_DNA.
DR EMBL; BC150275; AAI50276.1; -; mRNA.
DR CCDS; CCDS31597.1; -. [Q9P2S2-2]
DR CCDS; CCDS8077.1; -. [Q9P2S2-1]
DR RefSeq; NP_055895.1; NM_015080.3. [Q9P2S2-1]
DR RefSeq; NP_620060.1; NM_138732.2. [Q9P2S2-2]
DR AlphaFoldDB; Q9P2S2; -.
DR SMR; Q9P2S2; -.
DR BioGRID; 114780; 6.
DR IntAct; Q9P2S2; 3.
DR MINT; Q9P2S2; -.
DR STRING; 9606.ENSP00000265459; -.
DR GlyGen; Q9P2S2; 6 sites, 3 O-linked glycans (2 sites).
DR iPTMnet; Q9P2S2; -.
DR PhosphoSitePlus; Q9P2S2; -.
DR BioMuta; NRXN2; -.
DR DMDM; 17369343; -.
DR jPOST; Q9P2S2; -.
DR MassIVE; Q9P2S2; -.
DR PaxDb; Q9P2S2; -.
DR PeptideAtlas; Q9P2S2; -.
DR PRIDE; Q9P2S2; -.
DR ProteomicsDB; 83887; -. [Q9P2S2-1]
DR ProteomicsDB; 83888; -. [Q9P2S2-2]
DR Antibodypedia; 63686; 48 antibodies from 7 providers.
DR DNASU; 9379; -.
DR Ensembl; ENST00000265459.11; ENSP00000265459.5; ENSG00000110076.20. [Q9P2S2-1]
DR Ensembl; ENST00000377559.7; ENSP00000366782.3; ENSG00000110076.20. [Q9P2S2-2]
DR GeneID; 9379; -.
DR KEGG; hsa:9379; -.
DR MANE-Select; ENST00000265459.11; ENSP00000265459.5; NM_015080.4; NP_055895.1.
DR UCSC; uc021qkw.2; human. [Q9P2S2-1]
DR CTD; 9379; -.
DR DisGeNET; 9379; -.
DR GeneCards; NRXN2; -.
DR HGNC; HGNC:8009; NRXN2.
DR HPA; ENSG00000110076; Tissue enhanced (brain).
DR MIM; 600566; gene.
DR neXtProt; NX_Q9P2S2; -.
DR OpenTargets; ENSG00000110076; -.
DR PharmGKB; PA31787; -.
DR VEuPathDB; HostDB:ENSG00000110076; -.
DR eggNOG; KOG3514; Eukaryota.
DR GeneTree; ENSGT00940000155978; -.
DR HOGENOM; CLU_001710_1_0_1; -.
DR InParanoid; Q9P2S2; -.
DR OMA; XHAGIGH; -.
DR OrthoDB; 35129at2759; -.
DR PhylomeDB; Q9P2S2; -.
DR TreeFam; TF321302; -.
DR PathwayCommons; Q9P2S2; -.
DR Reactome; R-HSA-6794361; Neurexins and neuroligins.
DR SignaLink; Q9P2S2; -.
DR SIGNOR; Q9P2S2; -.
DR BioGRID-ORCS; 9379; 12 hits in 1069 CRISPR screens.
DR ChiTaRS; NRXN2; human.
DR GenomeRNAi; 9379; -.
DR Pharos; Q9P2S2; Tbio.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9P2S2; protein.
DR Bgee; ENSG00000110076; Expressed in right hemisphere of cerebellum and 137 other tissues.
DR ExpressionAtlas; Q9P2S2; baseline and differential.
DR Genevisible; Q9P2S2; 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:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR GO; GO:0005246; F:calcium channel regulator activity; ISS:BHF-UCL.
DR GO; GO:0050839; F:cell adhesion molecule binding; ISS:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0097109; F:neuroligin family protein binding; ISS:BHF-UCL.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; ISS:BHF-UCL.
DR GO; GO:0030534; P:adult behavior; IMP:BHF-UCL.
DR GO; GO:0007268; P:chemical synaptic transmission; ISS:BHF-UCL.
DR GO; GO:0097116; P:gephyrin clustering involved in postsynaptic density assembly; ISS:BHF-UCL.
DR GO; GO:0097118; P:neuroligin clustering involved in postsynaptic membrane assembly; ISS:BHF-UCL.
DR GO; GO:0007158; P:neuron cell-cell adhesion; TAS:BHF-UCL.
DR GO; GO:0007269; P:neurotransmitter secretion; ISS:BHF-UCL.
DR GO; GO:0097119; P:postsynaptic density protein 95 clustering; ISS:BHF-UCL.
DR GO; GO:0097104; P:postsynaptic membrane assembly; ISS:BHF-UCL.
DR GO; GO:0007165; P:signal transduction; ISS:BHF-UCL.
DR GO; GO:0035176; P:social behavior; IMP:BHF-UCL.
DR GO; GO:0007416; P:synapse assembly; ISS:BHF-UCL.
DR GO; GO:0042297; P:vocal learning; IMP:BHF-UCL.
DR GO; GO:0071625; P:vocalization behavior; IMP:BHF-UCL.
DR CDD; cd00110; LamG; 6.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR001791; Laminin_G.
DR InterPro; IPR003585; Neurexin-like.
DR Pfam; PF02210; Laminin_G_2; 6.
DR SMART; SM00294; 4.1m; 1.
DR SMART; SM00181; EGF; 3.
DR SMART; SM00282; LamG; 6.
DR SUPFAM; SSF49899; SSF49899; 6.
DR PROSITE; PS50026; EGF_3; 3.
DR PROSITE; PS50025; LAM_G_DOMAIN; 6.
PE 2: Evidence at transcript level;
KW Alternative promoter usage; Alternative splicing; Calcium; Cell adhesion;
KW Disulfide bond; EGF-like domain; Glycoprotein; Membrane; Metal-binding;
KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..1712
FT /note="Neurexin-2"
FT /id="PRO_0000019495"
FT TOPO_DOM 29..1636
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1637..1657
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1658..1712
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 29..206
FT /note="Laminin G-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122"
FT DOMAIN 202..242
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 289..486
FT /note="Laminin G-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122"
FT DOMAIN 493..686
FT /note="Laminin G-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122"
FT DOMAIN 690..727
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 732..904
FT /note="Laminin G-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122"
FT DOMAIN 918..1093
FT /note="Laminin G-like 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122"
FT DOMAIN 1096..1133
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1137..1345
FT /note="Laminin G-like 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122"
FT REGION 1373..1392
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1458..1489
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1525..1626
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1679..1712
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1575..1601
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1696..1712
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 335
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 352
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 420
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT CARBOHYD 60
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 338
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 841
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1236
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 206..219
FT /evidence="ECO:0000250"
FT DISULFID 213..229
FT /evidence="ECO:0000250"
FT DISULFID 231..241
FT /evidence="ECO:0000250"
FT DISULFID 450..486
FT /evidence="ECO:0000250"
FT DISULFID 657..686
FT /evidence="ECO:0000250"
FT DISULFID 694..705
FT /evidence="ECO:0000250"
FT DISULFID 699..714
FT /evidence="ECO:0000250"
FT DISULFID 716..726
FT /evidence="ECO:0000250"
FT DISULFID 1065..1093
FT /evidence="ECO:0000250"
FT DISULFID 1100..1111
FT /evidence="ECO:0000250"
FT DISULFID 1105..1120
FT /evidence="ECO:0000250"
FT DISULFID 1122..1132
FT /evidence="ECO:0000250"
FT VAR_SEQ 260..283
FT /note="Missing (in isoform 2a)"
FT /evidence="ECO:0000303|PubMed:10231032,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_003505"
FT VAR_SEQ 393..399
FT /note="Missing (in isoform 2a)"
FT /evidence="ECO:0000303|PubMed:10231032,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_003506"
FT VAR_SEQ 797..806
FT /note="DCLRVGCAPS -> G (in isoform 2a)"
FT /evidence="ECO:0000303|PubMed:10231032,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_003507"
FT VAR_SEQ 1253..1282
FT /note="Missing (in isoform 2a)"
FT /evidence="ECO:0000303|PubMed:10231032,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_003508"
FT VARIANT 81
FT /note="L -> Q (in dbSNP:rs12273892)"
FT /id="VAR_050266"
SQ SEQUENCE 1712 AA; 184982 MW; E4E8EC404DA1D0B0 CRC64;
MASGSRWRPT PPPLLLLLLL ALAARADGLE FGGGPGQWAR YARWAGAASS GELSFSLRTN
ATRALLLYLD DGGDCDFLEL LLVDGRLRLR FTLSCAEPAT LQLDTPVADD RWHMVLLTRD
ARRTALAVDG EARAAEVRSK RREMQVASDL FVGGIPPDVR LSALTLSTVK YEPPFRGLLA
NLKLGERPPA LLGSQGLRGA TADPLCAPAR NPCANGGLCT VLAPGEVGCD CSHTGFGGKF
CSEEEHPMEG PAHLTLNSEV GSLLFSEGGA GRGGAGDVHQ PTKGKEEFVA TFKGNEFFCY
DLSHNPIQSS TDEITLAFRT LQRNGLMLHT GKSADYVNLS LKSGAVWLVI NLGSGAFEAL
VEPVNGKFND NAWHDVRVTR NLRQHAGIGH AMVNKLHYLV TISVDGILTT TGYTQEDYTM
LGSDDFFYIG GSPNTADLPG SPVSNNFMGC LKDVVYKNND FKLELSRLAK EGDPKMKLQG
DLSFRCEDVA ALDPVTFESP EAFVALPRWS AKRTGSISLD FRTTEPNGLL LFSQGRRAGG
GAGSHSSAQR ADYFAMELLD GHLYLLLDMG SGGIKLRASS RKVNDGEWCH VDFQRDGRKG
SISVNSRSTP FLATGDSEIL DLESELYLGG LPEGGRVDLP LPPEVWTAAL RAGYVGCVRD
LFIDGRSRDL RGLAEAQGAV GVAPFCSRET LKQCASAPCR NGGVCREGWN RFICDCIGTG
FLGRVCEREA TVLSYDGSMY MKIMLPNAMH TEAEDVSLRF MSQRAYGLMM ATTSRESADT
LRLELDGGQM KLTVNLDCLR VGCAPSKGPE TLFAGHKLND NEWHTVRVVR RGKSLQLSVD
NVTVEGQMAG AHMRLEFHNI ETGIMTERRF ISVVPSNFIG HLSGLVFNGQ PYMDQCKDGD
ITYCELNARF GLRAIVADPV TFKSRSSYLA LATLQAYASM HLFFQFKTTA PDGLLLFNSG
NGNDFIVIEL VKGYIHYVFD LGNGPSLMKG NSDKPVNDNQ WHNVVVSRDP GNVHTLKIDS
RTVTQHSNGA RNLDLKGELY IGGLSKNMFS NLPKLVASRD GFQGCLASVD LNGRLPDLIA
DALHRIGQVE RGCDGPSTTC TEESCANQGV CLQQWDGFTC DCTMTSYGGP VCNDPGTTYI
FGKGGALITY TWPPNDRPST RMDRLAVGFS THQRSAVLVR VDSASGLGDY LQLHIDQGTV
GVIFNVGTDD ITIDEPNAIV SDGKYHVVRF TRSGGNATLQ VDSWPVNERY PAGNFDNERL
AIARQRIPYR LGRVVDEWLL DKGRQLTIFN SQAAIKIGGR DQGRPFQGQV SGLYYNGLKV
LALAAESDPN VRTEGHLRLV GEGPSVLLSA ETTATTLLAD MATTIMETTT TMATTTTRRG
RSPTLRDSTT QNTDDLLVAS AECPSDDEDL EECEPSTGGE LILPIITEDS LDPPPVATRS
PFVPPPPTFY PFLTGVGATQ DTLPPPAARR PPSGGPCQAE RDDSDCEEPI EASGFASGEV
FDSSLPPTDD EDFYTTFPLV TDRTTLLSPR KPAPRPNLRT DGATGAPGVL FAPSAPAPNL
PAGKMNHRDP LQPLLENPPL GPGAPTSFEP RRPPPLRPGV TSAPGFPHLP TANPTGPGER
GPPGAVEVIR ESSSTTGMVV GIVAAAALCI LILLYAMYKY RNRDEGSYQV DQSRNYISNS
AQSNGAVVKE KAPAAPKTPS KAKKNKDKEY YV
