LYNX1_MOUSE
ID LYNX1_MOUSE Reviewed; 116 AA.
AC P0DP60; Q08EF7; Q3TRB5; Q9WVC2;
DT 05-JUL-2017, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2017, sequence version 1.
DT 03-AUG-2022, entry version 31.
DE RecName: Full=Ly-6/neurotoxin-like protein 1 {ECO:0000305};
DE AltName: Full=GC26 {ECO:0000303|PubMed:10402197};
DE Flags: Precursor;
GN Name=Lynx1 {ECO:0000312|MGI:MGI:1345180};
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], FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RC STRAIN=C57BL/6J; TISSUE=Cerebellum;
RX PubMed=10402197; DOI=10.1016/s0896-6273(00)80757-6;
RA Miwa J.M., Ibanez-Tallon I., Crabtree G.W., Sanchez R., Sali A., Role L.W.,
RA Heintz N.;
RT "Lynx1, an endogenous toxin-like modulator of nicotinic acetylcholine
RT receptors in the mammalian CNS.";
RL Neuron 23:105-114(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129;
RA Miwa J.M., Fletcher C.F., Copeland N.G., Jenkins N.A., Heintz N.;
RT "Genetic mapping and characterization of Lynx1: a new member of the
RT Ly6/neurotoxin superfamily.";
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RC TISSUE=Hippocampus, Medulla oblongata, Spinal cord, and Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N;
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 [6]
RP FUNCTION, TISSUE SPECIFICITY, AND INTERACTION WITH CHRNA7 AND CHRNA4.
RX PubMed=11906696; DOI=10.1016/s0896-6273(02)00632-3;
RA Ibanez-Tallon I., Miwa J.M., Wang H.L., Adams N.C., Crabtree G.W.,
RA Sine S.M., Heintz N.;
RT "Novel modulation of neuronal nicotinic acetylcholine receptors by
RT association with the endogenous prototoxin lynx1.";
RL Neuron 33:893-903(2002).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=16950157; DOI=10.1016/j.neuron.2006.07.025;
RA Miwa J.M., Stevens T.R., King S.L., Caldarone B.J., Ibanez-Tallon I.,
RA Xiao C., Fitzsimonds R.M., Pavlides C., Lester H.A., Picciotto M.R.,
RA Heintz N.;
RT "The prototoxin lynx1 acts on nicotinic acetylcholine receptors to balance
RT neuronal activity and survival in vivo.";
RL Neuron 51:587-600(2006).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=21071629; DOI=10.1126/science.1195320;
RA Morishita H., Miwa J.M., Heintz N., Hensch T.K.;
RT "Lynx1, a cholinergic brake, limits plasticity in adult visual cortex.";
RL Science 330:1238-1240(2010).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CHRNA4.
RX PubMed=25193667; DOI=10.1074/jbc.m114.573667;
RA Nichols W.A., Henderson B.J., Yu C., Parker R.L., Richards C.I.,
RA Lester H.A., Miwa J.M.;
RT "Lynx1 shifts alpha4beta2 nicotinic receptor subunit stoichiometry by
RT affecting assembly in the endoplasmic reticulum.";
RL J. Biol. Chem. 289:31423-31432(2014).
CC -!- FUNCTION: Acts in different tissues through interaction to nicotinic
CC acetylcholine receptors (nAChRs) (PubMed:10402197). The proposed role
CC as modulator of nAChR activity seems to be dependent on the nAChR
CC subtype and stoichiometry, and to involve an effect on nAChR
CC trafficking and its cell surface expression, and on single channel
CC properties of the nAChR inserted in the plasma membrane.Modulates
CC functional properties of nicotinic acetylcholine receptors (nAChRs) to
CC prevent excessive excitation, and hence neurodegeneration. Enhances
CC desensitization by increasing both the rate and extent of
CC desensitization of alpha-4:beta-2-containing nAChRs and slowing
CC recovery from desensitization. Promotes large amplitude ACh-evoked
CC currents through alpha-4:beta-2 nAChRs (PubMed:10402197,
CC PubMed:11906696). Is involved in regulation of the nAChR pentameric
CC assembly in the endoplasmic reticulum. Shifts stoichiometry from high
CC sensitivity alpha-4(2):beta-2(3) to low sensitivity alpha-4(3):beta-
CC 2(2) nAChR (PubMed:25193667). In vitro modulates alpha-3:beta-4-
CC containing nAChRs. Reduces cell surface expression of (alpha-3:beta-
CC 4)(2):beta-4 and (alpha-3:beta-4)(2):alpha-5 nAChRs suggesting an
CC interaction with nAChR alpha-3(-):(+)beta-4 subunit interfaces and an
CC allosteric mode. Corresponding single channel effects characterized by
CC decreased unitary conductance, altered burst proportions and enhanced
CC desensitization/inactivation seem to depend on nAChR alpha:alpha
CC subunit interfaces and are greater in (alpha-3:beta-2)(2):alpha-3 when
CC compared to (alpha-3:beta-2)(2):alpha-5 nAChRs (By similarity).
CC Prevents plasticity in the primary visual cortex late in life
CC (PubMed:21071629). {ECO:0000250|UniProtKB:P0DP58,
CC ECO:0000269|PubMed:10402197, ECO:0000269|PubMed:11906696,
CC ECO:0000269|PubMed:21071629, ECO:0000269|PubMed:25193667}.
CC -!- SUBUNIT: Interacts with nAChRs containing alpha-4:beta-2
CC (CHRNA4:CHRNB2) and alpha-7 (CHRNA7) subunits (PubMed:11906696).
CC Interacts with CHRNA4 probably in the endoplasmic reticulum prior to
CC nAChR pentameric assembly (PubMed:19468303).
CC {ECO:0000269|PubMed:11906696, ECO:0000269|PubMed:19468303}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000255}; Lipid-anchor, GPI-
CC anchor {ECO:0000255}. Cell projection, dendrite
CC {ECO:0000269|PubMed:10402197}. Endoplasmic reticulum
CC {ECO:0000269|PubMed:25193667}. Note=Detected in Purkinje cells soma and
CC proximal dendrites. {ECO:0000269|PubMed:10402197}.
CC -!- TISSUE SPECIFICITY: Expressed in neurons of multiple regions in the
CC CNS, including the cerebral cortex, thalamus, substantia nigra,
CC cerebellum, amygdala and hippocampus (PubMed:10402197,
CC PubMed:11906696). Also expressed in kidney, heart and thymus, but at
CC lower levels than in the brain (PubMed:10402197). Expressed in the
CC primary visual cortex (V1) and the lateral geniculate nucleus (at
CC protein level) (PubMed:21071629). {ECO:0000269|PubMed:10402197,
CC ECO:0000269|PubMed:11906696, ECO:0000269|PubMed:21071629}.
CC -!- DEVELOPMENTAL STAGE: Expressed at very low levels at birth and
CC undergoes a marked up-regulation between postnatal days 10 and 20
CC (PubMed:10402197). Up-regulated in the visual cortex between postnatal
CC day 28 (P28) and P60, when experience-dependent brain plasticity
CC declines (PubMed:21071629). {ECO:0000269|PubMed:10402197,
CC ECO:0000269|PubMed:21071629}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice show no gross abnormalities in size,
CC viability, CNS morphology or longevity, but demonstrate enhanced
CC performance in learning ability and memory and are more responsive to
CC nicotine. Aging mutant mice exhibit a vacuolating neurodegeneration
CC that is exacerbated by nicotine. {ECO:0000269|PubMed:16950157}.
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DR EMBL; AF141377; AAD38939.1; -; mRNA.
DR EMBL; AF169202; AAF16899.1; -; Genomic_DNA.
DR EMBL; AK013827; BAB29006.1; -; mRNA.
DR EMBL; AK161907; BAE36629.1; -; mRNA.
DR EMBL; AK165295; BAE38124.1; -; mRNA.
DR EMBL; AK165314; BAE38132.1; -; mRNA.
DR EMBL; AC118022; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC037541; AAH37541.1; -; mRNA.
DR CCDS; CCDS27530.1; -.
DR RefSeq; NP_035968.1; NM_011838.4.
DR AlphaFoldDB; P0DP60; -.
DR SMR; P0DP60; -.
DR STRING; 10090.ENSMUSP00000023259; -.
DR PhosphoSitePlus; P0DP60; -.
DR PRIDE; P0DP60; -.
DR ProteomicsDB; 292132; -.
DR Antibodypedia; 21624; 31 antibodies from 14 providers.
DR DNASU; 23936; -.
DR Ensembl; ENSMUST00000023259; ENSMUSP00000023259; ENSMUSG00000022594.
DR GeneID; 23936; -.
DR KEGG; mmu:23936; -.
DR CTD; 66004; -.
DR MGI; MGI:1345180; Lynx1.
DR VEuPathDB; HostDB:ENSMUSG00000022594; -.
DR eggNOG; ENOG502SD2S; Eukaryota.
DR GeneTree; ENSGT00730000111571; -.
DR OMA; YTPYRMK; -.
DR OrthoDB; 1593386at2759; -.
DR ChiTaRS; Lynx1; mouse.
DR PRO; PR:P0DP60; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; P0DP60; protein.
DR Bgee; ENSMUSG00000022594; Expressed in interventricular septum and 179 other tissues.
DR ExpressionAtlas; P0DP60; baseline and differential.
DR Genevisible; Q9WVC2; MM.
DR GO; GO:0031225; C:anchored component of membrane; IBA:GO_Central.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0033130; F:acetylcholine receptor binding; ISS:UniProtKB.
DR GO; GO:0030550; F:acetylcholine receptor inhibitor activity; IDA:MGI.
DR GO; GO:0030548; F:acetylcholine receptor regulator activity; ISS:UniProtKB.
DR GO; GO:0008200; F:ion channel inhibitor activity; IDA:MGI.
DR GO; GO:0099601; P:regulation of neurotransmitter receptor activity; ISS:UniProtKB.
DR GO; GO:0007271; P:synaptic transmission, cholinergic; IDA:MGI.
DR CDD; cd00117; LU; 1.
DR Gene3D; 2.10.60.10; -; 1.
DR InterPro; IPR016054; LY6_UPA_recep-like.
DR InterPro; IPR045860; Snake_toxin-like_sf.
DR InterPro; IPR035076; Toxin/TOLIP.
DR Pfam; PF00087; Toxin_TOLIP; 1.
DR SMART; SM00134; LU; 1.
DR SUPFAM; SSF57302; SSF57302; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Disulfide bond; Endoplasmic reticulum;
KW Glycoprotein; GPI-anchor; Lipoprotein; Membrane; Reference proteome;
KW Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..92
FT /note="Ly-6/neurotoxin-like protein 1"
FT /evidence="ECO:0000255"
FT /id="PRO_0000036158"
FT PROPEP 93..116
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000440643"
FT DOMAIN 21..104
FT /note="UPAR/Ly6"
FT /evidence="ECO:0000255"
FT LIPID 92
FT /note="GPI-anchor amidated asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 23..46
FT /evidence="ECO:0000250|UniProtKB:P0DP58"
FT DISULFID 26..33
FT /evidence="ECO:0000250|UniProtKB:P0DP58"
FT DISULFID 39..64
FT /evidence="ECO:0000250|UniProtKB:P0DP58"
FT DISULFID 68..85
FT /evidence="ECO:0000250|UniProtKB:P0DP58"
FT DISULFID 86..91
FT /evidence="ECO:0000250|UniProtKB:P0DP58"
SQ SEQUENCE 116 AA; 12835 MW; DAF442FC1A34DE85 CRC64;
MTHLLTVFLV ALMGLPVAQA LECHVCAYNG DNCFKPMRCP AMATYCMTTR TYFTPYRMKV
RKSCVPSCFE TVYDGYSKHA SATSCCQYYL CNGAGFATPV TLALVPALLA TFWSLL
