LRIG1_MOUSE
ID LRIG1_MOUSE Reviewed; 1091 AA.
AC P70193; E9QL89;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Leucine-rich repeats and immunoglobulin-like domains protein 1;
DE Short=LIG-1;
DE Flags: Precursor;
GN Name=Lrig1;
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], AND TISSUE SPECIFICITY.
RX PubMed=8798419; DOI=10.1074/jbc.271.37.22522;
RA Suzuki Y., Sato N., Tohyama M., Wanaka A., Takagi T.;
RT "cDNA cloning of a novel membrane glycoprotein that is expressed
RT specifically in glial cells in the mouse brain. LIG-1, a protein with
RT leucine-rich repeats and immunoglobulin-like domains.";
RL J. Biol. Chem. 271:22522-22527(1996).
RN [2]
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 [3]
RP DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12067728; DOI=10.1016/s0014-5793(02)02824-7;
RA Suzuki Y., Miura H., Tanemura A., Kobayashi K., Kondoh G., Sano S.,
RA Ozawa K., Inui S., Nakata A., Takagi T., Tohyama M., Yoshikawa K.,
RA Itami S.;
RT "Targeted disruption of LIG-1 gene results in psoriasiform epidermal
RT hyperplasia.";
RL FEBS Lett. 521:67-71(2002).
CC -!- FUNCTION: Acts as a feedback negative regulator of signaling by
CC receptor tyrosine kinases, through a mechanism that involves
CC enhancement of receptor ubiquitination and accelerated intracellular
CC degradation. {ECO:0000250|UniProtKB:Q96JA1}.
CC -!- SUBUNIT: Interacts (via extracellular LRR and Ig-like domains) with
CC EGFR/ERBB1, ERBB2, ERBB3 and ERBB4 (via extracellular domain). The
CC physiological relevance of the interaction is controversial; LRIG1 may
CC have low affinity for EGFR, and interaction may occur only when high
CC levels of both proteins are present. {ECO:0000250|UniProtKB:Q96JA1}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12067728};
CC Single-pass type I membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Detected in brain (at protein level)
CC (PubMed:12067728). Predominantly expressed in the brain, restricted to
CC a small subset of glial cells, such as Bergmann glial cells of the
CC cerebellum and glial cells in the nerve fiber layer of the olfactory
CC bulb. Expressed also in the skin. Low expression is detected in the
CC thymus and heart. No expression in the kidney, liver, lung or small
CC intestine. {ECO:0000269|PubMed:12067728, ECO:0000269|PubMed:8798419}.
CC -!- DOMAIN: Contains LRR and Ig-domains that can mediate low-affinity
CC interaction with EGFR. The LRRs and the Ig-domains are each sufficient
CC for EGFR/ERBB1 binding. This interaction is abolished only when both
CC the LRRs and the Ig-domains are deleted.
CC {ECO:0000250|UniProtKB:Q96JA1}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice are born at the expected Mendelian
CC rate and initially display no visible phenotype. One to four months
CC after birth, they develop skin abnormalities including alopecia and
CC epidermal hyperplasia that are reminiscent of psoriasis.
CC {ECO:0000269|PubMed:12067728}.
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DR EMBL; D78572; BAA11416.1; -; mRNA.
DR EMBL; AC122272; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC155330; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS20380.1; -.
DR PIR; A58532; A58532.
DR RefSeq; NP_032403.2; NM_008377.2.
DR AlphaFoldDB; P70193; -.
DR SMR; P70193; -.
DR BioGRID; 200652; 3.
DR IntAct; P70193; 2.
DR STRING; 10090.ENSMUSP00000098686; -.
DR GlyConnect; 2474; 1 N-Linked glycan (1 site).
DR GlyGen; P70193; 7 sites, 1 N-linked glycan (1 site).
DR iPTMnet; P70193; -.
DR PhosphoSitePlus; P70193; -.
DR MaxQB; P70193; -.
DR PaxDb; P70193; -.
DR PRIDE; P70193; -.
DR ProteomicsDB; 292034; -.
DR Antibodypedia; 55087; 235 antibodies from 30 providers.
DR DNASU; 16206; -.
DR Ensembl; ENSMUST00000032105; ENSMUSP00000032105; ENSMUSG00000030029.
DR Ensembl; ENSMUST00000101126; ENSMUSP00000098686; ENSMUSG00000030029.
DR Ensembl; ENSMUST00000204645; ENSMUSP00000144963; ENSMUSG00000030029.
DR GeneID; 16206; -.
DR KEGG; mmu:16206; -.
DR UCSC; uc009czu.1; mouse.
DR CTD; 26018; -.
DR MGI; MGI:107935; Lrig1.
DR VEuPathDB; HostDB:ENSMUSG00000030029; -.
DR eggNOG; KOG4194; Eukaryota.
DR GeneTree; ENSGT00940000158502; -.
DR HOGENOM; CLU_000288_18_24_1; -.
DR InParanoid; P70193; -.
DR OMA; QDIAIRT; -.
DR OrthoDB; 161719at2759; -.
DR PhylomeDB; P70193; -.
DR TreeFam; TF325380; -.
DR Reactome; R-MMU-177929; Signaling by EGFR.
DR Reactome; R-MMU-6807004; Negative regulation of MET activity.
DR BioGRID-ORCS; 16206; 4 hits in 74 CRISPR screens.
DR ChiTaRS; Lrig1; mouse.
DR PRO; PR:P70193; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; P70193; protein.
DR Bgee; ENSMUSG00000030029; Expressed in hindlimb stylopod muscle and 133 other tissues.
DR Genevisible; P70193; MM.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0022405; P:hair cycle process; IMP:MGI.
DR GO; GO:0060384; P:innervation; IGI:MGI.
DR GO; GO:0032474; P:otolith morphogenesis; IGI:MGI.
DR GO; GO:0007605; P:sensory perception of sound; IMP:MGI.
DR Gene3D; 2.60.40.10; -; 3.
DR Gene3D; 3.80.10.10; -; 2.
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; IPR000372; LRRNT.
DR Pfam; PF07679; I-set; 2.
DR Pfam; PF13855; LRR_8; 5.
DR Pfam; PF01463; LRRCT; 1.
DR Pfam; PF01462; LRRNT; 1.
DR SMART; SM00409; IG; 3.
DR SMART; SM00408; IGc2; 3.
DR SMART; SM00369; LRR_TYP; 14.
DR SMART; SM00082; LRRCT; 1.
DR SMART; SM00013; LRRNT; 1.
DR SUPFAM; SSF48726; SSF48726; 3.
DR PROSITE; PS50835; IG_LIKE; 3.
DR PROSITE; PS51450; LRR; 14.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; Glycoprotein; Immunoglobulin domain;
KW Leucine-rich repeat; Membrane; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..34
FT /evidence="ECO:0000255"
FT CHAIN 35..1091
FT /note="Leucine-rich repeats and immunoglobulin-like domains
FT protein 1"
FT /id="PRO_0000014828"
FT TOPO_DOM 35..796
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 797..817
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 818..1091
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 35..70
FT /note="LRRNT"
FT REPEAT 71..92
FT /note="LRR 1"
FT REPEAT 95..116
FT /note="LRR 2"
FT REPEAT 118..139
FT /note="LRR 3"
FT REPEAT 142..163
FT /note="LRR 4"
FT REPEAT 166..187
FT /note="LRR 5"
FT REPEAT 191..212
FT /note="LRR 6"
FT REPEAT 214..235
FT /note="LRR 7"
FT REPEAT 238..259
FT /note="LRR 8"
FT REPEAT 262..283
FT /note="LRR 9"
FT REPEAT 286..307
FT /note="LRR 10"
FT REPEAT 310..331
FT /note="LRR 11"
FT REPEAT 334..355
FT /note="LRR 12"
FT REPEAT 358..380
FT /note="LRR 13"
FT REPEAT 385..406
FT /note="LRR 14"
FT REPEAT 409..430
FT /note="LRR 15"
FT DOMAIN 442..493
FT /note="LRRCT"
FT DOMAIN 497..596
FT /note="Ig-like C2-type 1"
FT DOMAIN 601..690
FT /note="Ig-like C2-type 2"
FT DOMAIN 695..781
FT /note="Ig-like C2-type 3"
FT REGION 912..990
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1059..1091
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 921..939
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 975..989
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 76
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 152
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 248
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 294
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 320
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 385
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 686
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 47..56
FT /evidence="ECO:0000250|UniProtKB:Q96JA1"
FT DISULFID 446..470
FT /evidence="ECO:0000250|UniProtKB:Q96JA1"
FT DISULFID 448..491
FT /evidence="ECO:0000250|UniProtKB:Q96JA1"
FT DISULFID 518..579
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 622..674
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 716..765
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT CONFLICT 38
FT /note="G -> R (in Ref. 1; BAA11416)"
FT /evidence="ECO:0000305"
FT CONFLICT 52
FT /note="D -> N (in Ref. 1; BAA11416)"
FT /evidence="ECO:0000305"
FT CONFLICT 114
FT /note="A -> T (in Ref. 1; BAA11416)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1091 AA; 119156 MW; 938BF3C154520DC0 CRC64;
MARPGPGVLG APRLAPRLLL WLLLLLLQWP ESAGAQAGPR APCAAACTCA GDSLDCSGRG
LATLPRDLPS WTRSLNLSYN RLSEIDSAAF EDLTNLQEVY LNSNELTAIP SLGAASIGVV
SLFLQHNKIL SVDGSQLKSY LSLEVLDLSS NNITEIRSSC FPNGLRIREL NLASNRISIL
ESGAFDGLSR SLLTLRLSKN RITQLPVKAF KLPRLTQLDL NRNRIRLIEG LTFQGLDSLE
VLRLQRNNIS RLTDGAFWGL SKMHVLHLEY NSLVEVNSGS LYGLTALHQL HLSNNSISRI
QRDGWSFCQK LHELILSFNN LTRLDEESLA ELSSLSILRL SHNAISHIAE GAFKGLKSLR
VLDLDHNEIS GTIEDTSGAF TGLDNLSKLT LFGNKIKSVA KRAFSGLESL EHLNLGENAI
RSVQFDAFAK MKNLKELYIS SESFLCDCQL KWLPPWLMGR MLQAFVTATC AHPESLKGQS
IFSVLPDSFV CDDFPKPQII TQPETTMAVV GKDIRFTCSA ASSSSSPMTF AWKKDNEVLA
NADMENFAHV RAQDGEVMEY TTILHLRHVT FGHEGRYQCI ITNHFGSTYS HKARLTVNVL
PSFTKIPHDI AIRTGTTARL ECAATGHPNP QIAWQKDGGT DFPAARERRM HVMPDDDVFF
ITDVKIDDMG VYSCTAQNSA GSVSANATLT VLETPSLAVP LEDRVVTVGE TVAFQCKATG
SPTPRITWLK GGRPLSLTER HHFTPGNQLL VVQNVMIDDA GRYTCEMSNP LGTERAHSQL
SILPTPGCRK DGTTVGIFTI AVVCSIVLTS LVWVCIIYQT RKKSEEYSVT NTDETIVPPD
VPSYLSSQGT LSDRQETVVR TEGGHQANGH IESNGVCLRD PSLFPEVDIH STTCRQPKLC
VGYTREPWKV TEKADRTAAP HTTAHSGSAV CSDCSTDTAY HPQPVPRDSG QPGTASSQEL
RQHDREYSPH HPYSGTADGS HTLSGGSLYP SNHDRILPSL KNKAASADGN GDSSWTLAKL
HEADCIDLKP SPTLASGSPE LMEDAISTEA QHLLVSNGHL PKACDSSPES VPLKGQITGK
RRGPLLLAPR S
