NTNG2_MOUSE
ID NTNG2_MOUSE Reviewed; 589 AA.
AC Q8R4F1; A2AKX0; Q8R4F2; Q8VIP6; Q8VIP7; Q8VIP8;
DT 19-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Netrin-G2;
DE AltName: Full=Laminet-2;
DE Flags: Precursor;
GN Name=Ntng2; Synonyms=Lmnt2;
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 {ECO:0000305};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2A; 2B AND 2C), FUNCTION, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAB71994.1};
RC TISSUE=Brain {ECO:0000312|EMBL:BAB71994.1};
RX PubMed=11804778; DOI=10.1016/s0925-4773(01)00600-1;
RA Nakashiba T., Nishimura S., Ikeda T., Itohara S.;
RT "Complementary expression and neurite outgrowth activity of netrin-G
RT subfamily members.";
RL Mech. Dev. 111:47-60(2002).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2A AND 2B), TISSUE SPECIFICITY, AND
RP GLYCOSYLATION.
RC TISSUE=Brain {ECO:0000269|PubMed:11906208};
RX PubMed=11906208; DOI=10.1006/mcne.2001.1089;
RA Yin Y., Miner J.H., Sanes J.R.;
RT "Laminets: laminin- and netrin-related genes expressed in distinct neuronal
RT subsets.";
RL Mol. Cell. Neurosci. 19:344-358(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP INTERACTION WITH LRRC4.
RX PubMed=16980967; DOI=10.1038/nn1763;
RA Kim S., Burette A., Chung H.S., Kwon S.-K., Woo J., Lee H.W., Kim K.,
RA Kim H., Weinberg R.J., Kim E.;
RT "NGL family PSD-95-interacting adhesion molecules regulate excitatory
RT synapse formation.";
RL Nat. Neurosci. 9:1294-1301(2006).
RN [6]
RP INTERACTION WITH LRRC4.
RX PubMed=17973922; DOI=10.1111/j.1601-183x.2007.00361.x;
RA Zhang W., Rajan I., Savelieva K.V., Wang C.Y., Vogel P., Kelly M., Xu N.,
RA Hasson B., Jarman W., Lanthorn T.H.;
RT "Netrin-G2 and netrin-G2 ligand are both required for normal auditory
RT responsiveness.";
RL Genes Brain Behav. 7:385-392(2008).
RN [7]
RP FUNCTION.
RX PubMed=31668703; DOI=10.1016/j.ajhg.2019.09.025;
RA Dias C.M., Punetha J., Zheng C., Mazaheri N., Rad A., Efthymiou S.,
RA Petersen A., Dehghani M., Pehlivan D., Partlow J.N., Posey J.E.,
RA Salpietro V., Gezdirici A., Malamiri R.A., Al Menabawy N.M., Selim L.A.,
RA Vahidi Mehrjardi M.Y., Banu S., Polla D.L., Yang E.,
RA Rezazadeh Varaghchi J., Mitani T., van Beusekom E., Najafi M., Sedaghat A.,
RA Keller-Ramey J., Durham L., Coban-Akdemir Z., Karaca E., Orlova V.,
RA Schaeken L.L.M., Sherafat A., Jhangiani S.N., Stanley V., Shariati G.,
RA Galehdari H., Gleeson J.G., Walsh C.A., Lupski J.R., Seiradake E.,
RA Houlden H., van Bokhoven H., Maroofian R.;
RT "Homozygous Missense Variants in NTNG2, Encoding a Presynaptic Netrin-G2
RT Adhesion Protein, Lead to a Distinct Neurodevelopmental Disorder.";
RL Am. J. Hum. Genet. 105:1048-1056(2019).
RN [8]
RP FUNCTION.
RX PubMed=31692205; DOI=10.1002/humu.23945;
RA Heimer G., van Woerden G.M., Barel O., Marek-Yagel D., Kol N.,
RA Munting J.B., Borghei M., Atawneh O.M., Nissenkorn A., Rechavi G.,
RA Anikster Y., Elgersma Y., Kushner S.A., Ben Zeev B.;
RT "Netrin-G2 dysfunction causes a Rett-like phenotype with areflexia.";
RL Hum. Mutat. 41:476-486(2020).
CC -!- FUNCTION: Involved in controlling patterning and neuronal circuit
CC formation at the laminar, cellular, subcellular and synaptic levels.
CC Promotes neurite outgrowth of both axons and dendrites.
CC {ECO:0000269|PubMed:11804778, ECO:0000269|PubMed:31668703,
CC ECO:0000269|PubMed:31692205}.
CC -!- SUBUNIT: Interacts with LRRC4. {ECO:0000269|PubMed:16980967,
CC ECO:0000269|PubMed:17973922}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11804778};
CC Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:11804778}; Extracellular
CC side {ECO:0000269|PubMed:11804778}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=2B {ECO:0000269|PubMed:11906208}; Synonyms=G2b
CC {ECO:0000269|PubMed:11804778};
CC IsoId=Q8R4F1-1; Sequence=Displayed;
CC Name=2A {ECO:0000269|PubMed:11906208}; Synonyms=G2a
CC {ECO:0000269|PubMed:11804778};
CC IsoId=Q8R4F1-2; Sequence=VSP_050562, VSP_050563;
CC Name=2C {ECO:0000305}; Synonyms=G2c {ECO:0000269|PubMed:11804778};
CC IsoId=Q8R4F1-3; Sequence=VSP_050564, VSP_050565;
CC -!- TISSUE SPECIFICITY: Expression is restricted primarily to neurons of
CC the CNS, particularly in the cerebral cortex, habenular nucleus and
CC superior colliculus. Low levels in lung, kidney, heart and spleen.
CC {ECO:0000269|PubMed:11804778, ECO:0000269|PubMed:11906208}.
CC -!- DEVELOPMENTAL STAGE: Expression is detected from embryonic day 9.
CC Strong expression is maintained from embryonic day 14 well into
CC adulthood. {ECO:0000269|PubMed:11804778}.
CC -!- DOMAIN: The laminin N-terminal domain mediates 1:1 binding to NGL
CC ligand with sub-micromolar affinity. Three NGL-binding loops mediate
CC discrimination for LRRC4/NGL2 among other NGLs by binding specifically
CC to its LRR repeats. This specificity drives the sorting of a mixed
CC population of molecules into discrete cell surface subdomains (By
CC similarity). {ECO:0000250}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:11906208}.
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DR EMBL; AB052336; BAB71994.1; -; mRNA.
DR EMBL; AB052337; BAB71995.1; -; mRNA.
DR EMBL; AB052338; BAB71996.1; -; mRNA.
DR EMBL; AF475079; AAL84788.1; -; mRNA.
DR EMBL; AF475080; AAL84789.1; -; mRNA.
DR EMBL; AL772379; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466542; EDL08409.1; -; Genomic_DNA.
DR CCDS; CCDS15851.1; -. [Q8R4F1-2]
DR CCDS; CCDS15852.1; -. [Q8R4F1-1]
DR CCDS; CCDS84499.1; -. [Q8R4F1-3]
DR RefSeq; NP_001292734.1; NM_001305805.1. [Q8R4F1-3]
DR RefSeq; NP_598007.1; NM_133500.2. [Q8R4F1-2]
DR RefSeq; NP_598008.1; NM_133501.2. [Q8R4F1-1]
DR AlphaFoldDB; Q8R4F1; -.
DR SMR; Q8R4F1; -.
DR BioGRID; 228486; 1.
DR IntAct; Q8R4F1; 1.
DR STRING; 10090.ENSMUSP00000035468; -.
DR GlyConnect; 2533; 2 N-Linked glycans (1 site).
DR GlyGen; Q8R4F1; 5 sites, 2 N-linked glycans (1 site).
DR PhosphoSitePlus; Q8R4F1; -.
DR PaxDb; Q8R4F1; -.
DR PRIDE; Q8R4F1; -.
DR ProteomicsDB; 293768; -. [Q8R4F1-1]
DR ProteomicsDB; 293769; -. [Q8R4F1-2]
DR ProteomicsDB; 293770; -. [Q8R4F1-3]
DR Antibodypedia; 31663; 112 antibodies from 26 providers.
DR DNASU; 171171; -.
DR Ensembl; ENSMUST00000048455; ENSMUSP00000035468; ENSMUSG00000035513. [Q8R4F1-1]
DR Ensembl; ENSMUST00000091153; ENSMUSP00000088688; ENSMUSG00000035513. [Q8R4F1-3]
DR Ensembl; ENSMUST00000102873; ENSMUSP00000099937; ENSMUSG00000035513. [Q8R4F1-2]
DR GeneID; 171171; -.
DR KEGG; mmu:171171; -.
DR UCSC; uc008izo.2; mouse. [Q8R4F1-1]
DR UCSC; uc012btf.2; mouse. [Q8R4F1-3]
DR CTD; 84628; -.
DR MGI; MGI:2159341; Ntng2.
DR VEuPathDB; HostDB:ENSMUSG00000035513; -.
DR eggNOG; KOG3512; Eukaryota.
DR GeneTree; ENSGT00940000153601; -.
DR HOGENOM; CLU_039838_1_0_1; -.
DR InParanoid; Q8R4F1; -.
DR OMA; FPNVCDE; -.
DR PhylomeDB; Q8R4F1; -.
DR TreeFam; TF333945; -.
DR Reactome; R-MMU-163125; Post-translational modification: synthesis of GPI-anchored proteins.
DR BioGRID-ORCS; 171171; 2 hits in 58 CRISPR screens.
DR ChiTaRS; Ntng2; mouse.
DR PRO; PR:Q8R4F1; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q8R4F1; protein.
DR Bgee; ENSMUSG00000035513; Expressed in granulocyte and 80 other tissues.
DR ExpressionAtlas; Q8R4F1; baseline and differential.
DR Genevisible; Q8R4F1; MM.
DR GO; GO:0046658; C:anchored component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0099029; C:anchored component of presynaptic active zone membrane; IDA:SynGO.
DR GO; GO:0030424; C:axon; IDA:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0043256; C:laminin complex; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IDA:SynGO.
DR GO; GO:0009887; P:animal organ morphogenesis; IBA:GO_Central.
DR GO; GO:0007409; P:axonogenesis; IDA:MGI.
DR GO; GO:0070831; P:basement membrane assembly; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IMP:SynGO.
DR GO; GO:0098698; P:postsynaptic specialization assembly; IDA:SynGO.
DR GO; GO:2001222; P:regulation of neuron migration; IMP:UniProtKB.
DR GO; GO:0150011; P:regulation of neuron projection arborization; IMP:UniProtKB.
DR GO; GO:0010975; P:regulation of neuron projection development; IMP:UniProtKB.
DR GO; GO:1905606; P:regulation of presynapse assembly; IDA:SynGO.
DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; IBA:GO_Central.
DR GO; GO:0099560; P:synaptic membrane adhesion; IDA:SynGO.
DR GO; GO:0009888; P:tissue development; IBA:GO_Central.
DR CDD; cd00055; EGF_Lam; 3.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR008211; Laminin_N.
DR InterPro; IPR002049; LE_dom.
DR InterPro; IPR036278; Sialidase_sf.
DR Pfam; PF00053; Laminin_EGF; 3.
DR Pfam; PF00055; Laminin_N; 1.
DR SMART; SM00181; EGF; 2.
DR SMART; SM00180; EGF_Lam; 3.
DR SMART; SM00136; LamNT; 1.
DR SUPFAM; SSF50939; SSF50939; 1.
DR PROSITE; PS00022; EGF_1; 3.
DR PROSITE; PS01186; EGF_2; 1.
DR PROSITE; PS50026; EGF_3; 1.
DR PROSITE; PS01248; EGF_LAM_1; 2.
DR PROSITE; PS50027; EGF_LAM_2; 3.
DR PROSITE; PS51117; LAMININ_NTER; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Developmental protein;
KW Differentiation; Disulfide bond; Glycoprotein; GPI-anchor;
KW Laminin EGF-like domain; Lipoprotein; Membrane; Neurogenesis;
KW Reference proteome; Repeat; Signal.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..566
FT /note="Netrin-G2"
FT /id="PRO_0000017097"
FT PROPEP 567..589
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000017098"
FT DOMAIN 35..286
FT /note="Laminin N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00466"
FT DOMAIN 287..346
FT /note="Laminin EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460"
FT DOMAIN 413..468
FT /note="Laminin EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460"
FT DOMAIN 469..513
FT /note="Laminin EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460"
FT REGION 69..88
FT /note="NGL discriminant loop I"
FT /evidence="ECO:0000250"
FT REGION 201..203
FT /note="NGL discriminant loop II"
FT /evidence="ECO:0000250"
FT REGION 264..267
FT /note="NGL discriminant loop III"
FT /evidence="ECO:0000250"
FT LIPID 566
FT /note="GPI-anchor amidated glycine"
FT /evidence="ECO:0000255"
FT CARBOHYD 122
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 128
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 310
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 455
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 482
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 22..39
FT /evidence="ECO:0000250"
FT DISULFID 61..81
FT /evidence="ECO:0000250"
FT DISULFID 69..77
FT /evidence="ECO:0000250"
FT DISULFID 171..195
FT /evidence="ECO:0000250"
FT DISULFID 287..296
FT /evidence="ECO:0000250"
FT DISULFID 289..305
FT /evidence="ECO:0000250"
FT DISULFID 307..316
FT /evidence="ECO:0000250"
FT DISULFID 319..344
FT /evidence="ECO:0000250"
FT DISULFID 413..422
FT /evidence="ECO:0000255"
FT DISULFID 415..433
FT /evidence="ECO:0000255"
FT DISULFID 436..445
FT /evidence="ECO:0000255"
FT DISULFID 448..466
FT /evidence="ECO:0000255"
FT DISULFID 469..481
FT /evidence="ECO:0000255"
FT DISULFID 471..487
FT /evidence="ECO:0000255"
FT DISULFID 489..498
FT /evidence="ECO:0000255"
FT DISULFID 501..511
FT /evidence="ECO:0000255"
FT DISULFID 516..529
FT /evidence="ECO:0000250"
FT DISULFID 523..535
FT /evidence="ECO:0000250"
FT DISULFID 537..546
FT /evidence="ECO:0000250"
FT VAR_SEQ 353..411
FT /note="Missing (in isoform 2A)"
FT /evidence="ECO:0000303|PubMed:11804778,
FT ECO:0000303|PubMed:11906208"
FT /id="VSP_050562"
FT VAR_SEQ 353..377
FT /note="Missing (in isoform 2C)"
FT /evidence="ECO:0000303|PubMed:11804778,
FT ECO:0000303|PubMed:11906208"
FT /id="VSP_050564"
FT VAR_SEQ 378
FT /note="A -> T (in isoform 2C)"
FT /evidence="ECO:0000303|PubMed:11804778,
FT ECO:0000303|PubMed:11906208"
FT /id="VSP_050565"
FT VAR_SEQ 412
FT /note="D -> N (in isoform 2A)"
FT /evidence="ECO:0000303|PubMed:11804778,
FT ECO:0000303|PubMed:11906208"
FT /id="VSP_050563"
FT CONFLICT 41
FT /note="P -> S (in Ref. 2; AAL84788/AAL84789)"
FT /evidence="ECO:0000305"
FT CONFLICT 392
FT /note="S -> F (in Ref. 2; AAL84789)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 589 AA; 66166 MW; F2AB419F0EE074F7 CRC64;
MLRLLALFLH CLPLVSGDYD ICKSWVTTDE GPTWEFYACQ PKVMRLKDYV KVKVEPSGIT
CGDPPERFCS HENPYLCSNE CDASNPDLAH PPRLMFDRED EGLATYWQSV TWSRYPSPLE
ANITLSWNKS VELTDDVVVT FEYGRPTVMV LEKSLDNGRT WQPYQFYAED CMEAFGMSAR
RARDMSPSSA HRVLCTEEYS RWAGSKKEKH VRFEVRDRFA IFAGPDLRNM DNLYTRMESA
KGLKEFFTFT DLRMRLLRPA LGGTYVQREN LYKYFYAISN IEVIGRCKCN LHANLCTVRE
GSLQCECEHN TTGPDCGRCK KNFRTRAWRA GSYLPLPHGS PNACAAAGSA FGSQTKPPTM
APLGDSSFWP QVSSSAEAVA ISVAVPSQAK DSTLFELKPR SPQVIPIEEF QDCECYGHSN
RCSYIDFLNV VTCVSCKHNT RGQHCQHCRL GYYRNGSAEL DDENVCIECN CNQIGSVHDR
CNETGFCECR EGAVGPKCDD CLPTHYWRQG CYPNVCDDDQ LLCQNGGTCQ QNQRCACPPG
YTGIRCEQPR CDLADDAGPD CDRAPGIVPR PDTLLGCLLL LGLAARLAC
