LRRC4_MOUSE
ID LRRC4_MOUSE Reviewed; 652 AA.
AC Q99PH1; Q149E5; Q8VI35;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Leucine-rich repeat-containing protein 4;
DE AltName: Full=Brain tumor-associated protein MBAG1;
DE AltName: Full=Netrin-G2 ligand;
DE Short=NGL-2;
DE Flags: Precursor;
GN Name=Lrrc4;
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/J;
RA Wang J., Qian J., Dong L., Li X., Tan C., Li J., Zhang B., Zhang X.,
RA Bin L., Zhou J., Li G.;
RT "Identification and expression analysis of LRRC4, a novel member of
RT leucine-rich repeat (LRR) superfamily.";
RL Sheng Wu Hua Xue Yu Sheng Wu Wu Li Jin Zhan 29:233-239(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ;
RX PubMed=15967442; DOI=10.1016/j.febslet.2005.05.058;
RA Zhang Q., Wang J., Fan S., Wang L., Cao L., Tang K., Peng C., Li Z., Li W.,
RA Gan K., Liu Z., Li X., Shen S., Li G.;
RT "Expression and functional characterization of LRRC4, a novel brain-
RT specific member of the LRR superfamily.";
RL FEBS Lett. 579:3674-3682(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 FUNCTION, AND INTERACTION WITH NTNG2 AND DLG4.
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 [5]
RP TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=17785411; DOI=10.1073/pnas.0706919104;
RA Nishimura-Akiyoshi S., Niimi K., Nakashiba T., Itohara S.;
RT "Axonal netrin-Gs transneuronally determine lamina-specific subdendritic
RT segments.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:14801-14806(2007).
RN [6]
RP INTERACTION WITH NTNG2, AND DISRUPTION PHENOTYPE.
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).
CC -!- FUNCTION: Synaptic adhesion protein. Regulates the formation of
CC exitatory synapses through the recruitment of pre-and-postsynaptic
CC proteins. Organize the lamina/pathway-specific differentiation of
CC dendrites. Plays an important role for auditory synaptic responses.
CC Involved in the suppression of glioma. {ECO:0000269|PubMed:15967442,
CC ECO:0000269|PubMed:16980967, ECO:0000269|PubMed:17785411}.
CC -!- SUBUNIT: Interacts (via LRR repeats) with NTNG2. Interacts with DLG4.
CC Forms a complex with DLG4 and with NMDA receptors.
CC {ECO:0000269|PubMed:16980967, ECO:0000269|PubMed:17973922}.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC Postsynaptic cell membrane {ECO:0000250}. Note=LRRC4 and DLG4 are
CC interdependent for synaptic localization. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in brain. In the
CC hippocampus, parietal cortex and piriform cortex expressed in proximal
CC segments of CA1 pyramidal neurons. {ECO:0000269|PubMed:15967442,
CC ECO:0000269|PubMed:17785411}.
CC -!- DOMAIN: The last 4 C-terminal residues bind to the first 2 PDZ domains
CC of DLG4.
CC -!- PTM: N-glycosylated. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice dysplay impaired startle response to
CC acoustic stimulus. {ECO:0000269|PubMed:17973922}.
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DR EMBL; AF300458; AAL67671.1; -; mRNA.
DR EMBL; DQ177325; AAG60620.2; -; mRNA.
DR EMBL; BC117834; AAI17835.1; -; mRNA.
DR CCDS; CCDS39448.1; -.
DR RefSeq; NP_619623.2; NM_138682.2.
DR AlphaFoldDB; Q99PH1; -.
DR SMR; Q99PH1; -.
DR BioGRID; 228675; 1.
DR DIP; DIP-46449N; -.
DR IntAct; Q99PH1; 1.
DR STRING; 10090.ENSMUSP00000062158; -.
DR GlyConnect; 2469; 4 N-Linked glycans (3 sites).
DR GlyGen; Q99PH1; 8 sites, 3 N-linked glycans (3 sites).
DR PhosphoSitePlus; Q99PH1; -.
DR jPOST; Q99PH1; -.
DR PaxDb; Q99PH1; -.
DR PRIDE; Q99PH1; -.
DR ProteomicsDB; 290170; -.
DR Antibodypedia; 55653; 109 antibodies from 25 providers.
DR DNASU; 192198; -.
DR Ensembl; ENSMUST00000062304; ENSMUSP00000062158; ENSMUSG00000049939.
DR GeneID; 192198; -.
DR KEGG; mmu:192198; -.
DR UCSC; uc009bcu.1; mouse.
DR CTD; 64101; -.
DR MGI; MGI:2182081; Lrrc4.
DR VEuPathDB; HostDB:ENSMUSG00000049939; -.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000159260; -.
DR HOGENOM; CLU_000288_18_24_1; -.
DR InParanoid; Q99PH1; -.
DR OMA; QVWILCV; -.
DR OrthoDB; 282791at2759; -.
DR PhylomeDB; Q99PH1; -.
DR TreeFam; TF324303; -.
DR BioGRID-ORCS; 192198; 1 hit in 73 CRISPR screens.
DR PRO; PR:Q99PH1; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q99PH1; protein.
DR Bgee; ENSMUSG00000049939; Expressed in interventricular septum and 152 other tissues.
DR ExpressionAtlas; Q99PH1; baseline and differential.
DR Genevisible; Q99PH1; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0043197; C:dendritic spine; IDA:MGI.
DR GO; GO:0060076; C:excitatory synapse; IDA:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; IMP:SynGO.
DR GO; GO:0099061; C:integral component of postsynaptic density membrane; IDA:SynGO.
DR GO; GO:0044309; C:neuron spine; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0045211; C:postsynaptic membrane; IDA:MGI.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IDA:SynGO.
DR GO; GO:0045202; C:synapse; IDA:MGI.
DR GO; GO:1904861; P:excitatory synapse assembly; IMP:MGI.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IMP:SynGO.
DR GO; GO:0097119; P:postsynaptic density protein 95 clustering; IDA:MGI.
DR GO; GO:0050808; P:synapse organization; IDA:MGI.
DR GO; GO:0099560; P:synaptic membrane adhesion; ISO:MGI.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR000483; Cys-rich_flank_reg_C.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR026882; Lrrc4.
DR InterPro; IPR000372; LRRNT.
DR PANTHER; PTHR24369:SF9; PTHR24369:SF9; 1.
DR Pfam; PF07679; I-set; 1.
DR Pfam; PF13855; LRR_8; 3.
DR SMART; SM00409; IG; 1.
DR SMART; SM00408; IGc2; 1.
DR SMART; SM00369; LRR_TYP; 7.
DR SMART; SM00082; LRRCT; 1.
DR SMART; SM00013; LRRNT; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS51450; LRR; 7.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; Glycoprotein; Immunoglobulin domain;
KW Leucine-rich repeat; Membrane; Postsynaptic cell membrane;
KW Reference proteome; Repeat; Signal; Synapse; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..40
FT /evidence="ECO:0000255"
FT CHAIN 41..652
FT /note="Leucine-rich repeat-containing protein 4"
FT /id="PRO_0000014834"
FT TOPO_DOM 41..526
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 527..547
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 548..652
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 41..74
FT /note="LRRNT"
FT REPEAT 75..96
FT /note="LRR 1"
FT REPEAT 99..120
FT /note="LRR 2"
FT REPEAT 123..144
FT /note="LRR 3"
FT REPEAT 147..168
FT /note="LRR 4"
FT REPEAT 171..193
FT /note="LRR 5"
FT REPEAT 196..217
FT /note="LRR 6"
FT REPEAT 218..239
FT /note="LRR 7"
FT REPEAT 242..263
FT /note="LRR 8"
FT REPEAT 266..287
FT /note="LRR 9"
FT DOMAIN 299..351
FT /note="LRRCT"
FT DOMAIN 352..441
FT /note="Ig-like"
FT CARBOHYD 276
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 321
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 362
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 387
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 409
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 433
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 439
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 449
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 45..51
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 49..60
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 303..328
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 305..349
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 373..423
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT CONFLICT 252..256
FT /note="QVSLI -> H (in Ref. 1; AAL67671)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 652 AA; 72619 MW; 9D2807A1AEE30062 CRC64;
MKLLWQVTVH HTWNAVLLPV VYLTAQVWIL CAAIAAAASA GPQNCPSVCS CSNQFSKVVC
TRRGLSEVPQ GIPSNTRYLN LMENNIQMIQ ADTFRHLHHL EVLQLGRNSI RQIEVGAFNG
LASLNTLELF DNWLTVIPSG AFEYLSKLRE LWLRNNPIES IPSYAFNRVP SLMRLDLGEL
KKLEYISEGA FEGLFNLKYL NLGMCNIKDM PNLTPLVGLE ELEMSGNHFP EIRPGSFHGL
SSLKKLWVMN SQVSLIERNA FDGLASLVEL NLAHNNLSSL PHDLFTPLRY LVELHLHHNP
WNCDCDILWL AWWLREYIPT NSTCCGRCHA PMHMRGRYLV EVDQAAFQCS APFIMDAPRD
LNISEDRMAE LKCRTPPMSS VKWLLPNGTV LSHASRHPRI SVLNDGTLNF SRVLLIDTGV
YTCMVTNVAG NSNASAYLNV SSAELNTPNF SFFTTVTVET TEISPEDITR KYKPVPTTST
GYQPAYTTST TVLIQTTRVP KQVPVPSTDT TDKMQTSLDE VMKTTKIIIG CFVAVTLLAA
AMLIVFYKLR KRHQQRSTVT AARTVEIIQV DEDIPAAAPA AATAAPSGVS GEGAVVLPTI
HDHINYNTYK PAHGAHWTEN SLGNSLHPTV TTISEPYIIQ THTKDKVQET QI
