LYNX1_HUMAN
ID LYNX1_HUMAN Reviewed; 116 AA.
AC P0DP58; A0A140VJN6; D3DWI7; G3XAC2; Q86SR0; Q9BZG9;
DT 05-JUL-2017, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2017, sequence version 1.
DT 03-AUG-2022, entry version 33.
DE RecName: Full=Ly-6/neurotoxin-like protein 1 {ECO:0000305};
DE AltName: Full=Endogenous prototoxin LYNX1 {ECO:0000303|PubMed:21252236};
DE AltName: Full=Testicular tissue protein Li 112 {ECO:0000312|EMBL:AEE61023.1};
DE Flags: Precursor;
GN Name=LYNX1 {ECO:0000312|HGNC:HGNC:29604};
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 2).
RA Li J.Y.;
RT "Human testis protein.";
RL Submitted (MAR-2010) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-80 (ISOFORM 1).
RA Southan C., Simms M., Narjis S.;
RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP ALTERNATIVE SPLICING (ISOFORMS 1 AND 2).
RX PubMed=26033490; DOI=10.1016/j.intimp.2015.05.030;
RA Moriwaki Y., Takada K., Tsuji S., Kawashima K., Misawa H.;
RT "Transcriptional regulation of SLURP2, a psoriasis-associated gene, is
RT under control of IL-22 in the skin: A special reference to the nested gene
RT LYNX1.";
RL Int. Immunopharmacol. 29:71-75(2015).
RN [6]
RP STRUCTURE BY NMR OF 21-93 (ISOFORM 1), FUNCTION, DISULFIDE BONDS, AND
RP MISCELLANEOUS.
RX PubMed=21252236; DOI=10.1074/jbc.m110.189100;
RA Lyukmanova E.N., Shenkarev Z.O., Shulepko M.A., Mineev K.S., D'Hoedt D.,
RA Kasheverov I.E., Filkin S.Y., Krivolapova A.P., Janickova H., Dolezal V.,
RA Dolgikh D.A., Arseniev A.S., Bertrand D., Tsetlin V.I., Kirpichnikov M.P.;
RT "NMR structure and action on nicotinic acetylcholine receptors of water-
RT soluble domain of human LYNX1.";
RL J. Biol. Chem. 286:10618-10627(2011).
RN [7]
RP FUNCTION.
RX PubMed=28100642; DOI=10.1096/fj.201600733r;
RA George A.A., Bloy A., Miwa J.M., Lindstrom J.M., Lukas R.J., Whiteaker P.;
RT "Isoform-specific mechanisms of alpha3beta4*-nicotinic acetylcholine
RT receptor modulation by the prototoxin lynx1.";
RL FASEB J. 31:1398-1420(2017).
CC -!- FUNCTION: Acts in different tissues through interaction to nicotinic
CC acetylcholine receptors (nAChRs) (PubMed:21252236). 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. Is involved in regulation of
CC the nAChR pentameric assembly in the endoplasmic reticulum. Shifts
CC stoichiometry from high sensitivity alpha-4(2):beta-2(3) to low
CC sensitivity alpha-4(3):beta-2(2) nAChR (By similarity). In vitro
CC modulates alpha-3:beta-4-containing nAChRs. Reduces cell surface
CC expression of (alpha-3:beta-4)(2):beta-4 and (alpha-3:beta-4)(2):alpha-
CC 5 nAChRs suggesting an interaction with nAChR alpha-3(-):(+)beta-4
CC subunit interfaces and an allosteric mode. Corresponding single channel
CC effects characterized by decreased unitary conductance, altered burst
CC proportions and enhanced desensitization/inactivation seem to depend on
CC nAChR alpha:alpha subunit interfaces and are greater in (alpha-3:beta-
CC 2)(2):alpha-3 when compared to (alpha-3:beta-2)(2):alpha-5 nAChRs
CC (PubMed:28100642). Prevents plasticity in the primary visual cortex
CC late in life (By similarity). {ECO:0000250|UniProtKB:P0DP60,
CC ECO:0000269|PubMed:21252236, ECO:0000269|PubMed:28100642}.
CC -!- SUBUNIT: Interacts with nAChRs containing alpha-4:beta-2
CC (CHRNA4:CHRNB2) and alpha-7 (CHRNA7) subunits. Interacts with CHRNA4
CC probably in the endoplasmic reticulum prior to nAChR pentameric
CC assembly (By similarity). {ECO:0000250|UniProtKB:P0DP60}.
CC -!- INTERACTION:
CC P0DP58-2; P55212: CASP6; NbExp=3; IntAct=EBI-21916939, EBI-718729;
CC P0DP58-2; Q8NI60: COQ8A; NbExp=3; IntAct=EBI-21916939, EBI-745535;
CC P0DP58-2; P22607: FGFR3; NbExp=3; IntAct=EBI-21916939, EBI-348399;
CC P0DP58-2; P06396: GSN; NbExp=3; IntAct=EBI-21916939, EBI-351506;
CC P0DP58-2; P13473-2: LAMP2; NbExp=3; IntAct=EBI-21916939, EBI-21591415;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000255}; Lipid-anchor, GPI-
CC anchor {ECO:0000255}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:P0DP60}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:P0DP60}. Note=Detected in Purkinje cells soma
CC and proximal dendrites. {ECO:0000250|UniProtKB:P0DP60}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=LYNX1 {ECO:0000303|Ref.1};
CC IsoId=P0DP58-1, Q9BZG9-2;
CC Sequence=Displayed;
CC Name=2; Synonyms=LYNX1-SLURP2 {ECO:0000303|PubMed:26033490};
CC IsoId=P0DP58-2, Q9BZG9-1;
CC Sequence=VSP_058978;
CC -!- MISCELLANEOUS: Isoform 1 is considered to be an endogenous
CC 'prototoxin', that shares a N-terminal three-finger structure with
CC snake alpha-neurotoxins. {ECO:0000303|PubMed:21252236}.
CC -!- MISCELLANEOUS: [Isoform 2]: Based on a naturally occurring readthrough
CC transcript which produces a LYNX1-SLURP2 fusion protein.
CC {ECO:0000305|PubMed:26033490}.
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DR EMBL; HM005425; AEE61023.1; -; mRNA.
DR EMBL; AC083841; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471162; EAW82299.1; -; Genomic_DNA.
DR EMBL; CH471162; EAW82301.1; -; Genomic_DNA.
DR EMBL; CH471162; EAW82302.1; -; Genomic_DNA.
DR EMBL; CH471162; EAW82303.1; -; Genomic_DNA.
DR EMBL; CH471162; EAW82304.1; -; Genomic_DNA.
DR EMBL; AF321824; AAK01642.1; -; mRNA.
DR CCDS; CCDS6389.1; -.
DR RefSeq; NP_076435.1; NM_023946.3. [P0DP58-2]
DR RefSeq; NP_803252.1; NM_177457.4. [P0DP58-1]
DR RefSeq; NP_803429.1; NM_177476.3. [P0DP58-1]
DR RefSeq; NP_803430.1; NM_177477.3. [P0DP58-1]
DR PDB; 2L03; NMR; -; A=21-93.
DR PDBsum; 2L03; -.
DR AlphaFoldDB; P0DP58; -.
DR SMR; P0DP58; -.
DR IntAct; P0DP58; 24.
DR STRING; 9606.ENSP00000479586; -.
DR iPTMnet; P0DP58; -.
DR PhosphoSitePlus; P0DP58; -.
DR BioMuta; LYNX1; -.
DR jPOST; P0DP58; -.
DR MassIVE; P0DP58; -.
DR PeptideAtlas; P0DP58; -.
DR PRIDE; P0DP58; -.
DR Antibodypedia; 21624; 31 antibodies from 14 providers.
DR DNASU; 66004; -.
DR Ensembl; ENST00000614491.1; ENSP00000477648.1; ENSG00000180155.20. [P0DP58-1]
DR Ensembl; ENST00000620006.4; ENSP00000478402.1; ENSG00000180155.20. [P0DP58-1]
DR Ensembl; ENST00000621401.4; ENSP00000478390.1; ENSG00000180155.20. [P0DP58-1]
DR Ensembl; ENST00000652477.1; ENSP00000498325.1; ENSG00000180155.20. [P0DP58-1]
DR GeneID; 111188157; -.
DR GeneID; 66004; -.
DR KEGG; hsa:111188157; -.
DR KEGG; hsa:66004; -.
DR MANE-Select; ENST00000652477.1; ENSP00000498325.1; NM_177477.4; NP_803430.1.
DR CTD; 111188157; -.
DR CTD; 66004; -.
DR DisGeNET; 111188157; -.
DR DisGeNET; 66004; -.
DR GeneCards; LYNX1; -.
DR HGNC; HGNC:29604; LYNX1.
DR HPA; ENSG00000180155; Tissue enhanced (brain).
DR MIM; 606110; gene.
DR neXtProt; NX_P0DP58; -.
DR OpenTargets; ENSG00000180155; -.
DR VEuPathDB; HostDB:ENSG00000180155; -.
DR eggNOG; ENOG502T3MP; Eukaryota.
DR GeneTree; ENSGT00730000111571; -.
DR GeneTree; ENSGT00940000153378; -.
DR OMA; CIAFATR; -.
DR OrthoDB; 1544318at2759; -.
DR PathwayCommons; P0DP58; -.
DR SignaLink; P0DP58; -.
DR BioGRID-ORCS; 66004; 14 hits in 1072 CRISPR screens.
DR GenomeRNAi; 66004; -.
DR Pharos; P0DP58; Tbio.
DR PRO; PR:P0DP58; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; P0DP58; protein.
DR Bgee; ENSG00000180155; Expressed in apex of heart and 131 other tissues.
DR ExpressionAtlas; P0DP58; baseline and differential.
DR Genevisible; Q9BZG9; HS.
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:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0033130; F:acetylcholine receptor binding; IDA:UniProtKB.
DR GO; GO:0030550; F:acetylcholine receptor inhibitor activity; IBA:GO_Central.
DR GO; GO:0030548; F:acetylcholine receptor regulator activity; IDA:UniProtKB.
DR GO; GO:0099601; P:regulation of neurotransmitter receptor activity; IDA:UniProtKB.
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 3D-structure; Alternative splicing; Cell membrane; Cell projection;
KW Disulfide bond; Endoplasmic reticulum; Glycoprotein; GPI-anchor;
KW Lipoprotein; Membrane; Reference proteome; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..91
FT /note="Ly-6/neurotoxin-like protein 1"
FT /evidence="ECO:0000255"
FT /id="PRO_0000036154"
FT PROPEP 92..116
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000440641"
FT DOMAIN 21..107
FT /note="UPAR/Ly6"
FT /evidence="ECO:0000255"
FT LIPID 91
FT /note="GPI-anchor amidated cysteine"
FT /evidence="ECO:0000255"
FT DISULFID 23..46
FT /evidence="ECO:0000269|PubMed:21252236,
FT ECO:0007744|PDB:2L03"
FT DISULFID 26..33
FT /evidence="ECO:0000269|PubMed:21252236,
FT ECO:0007744|PDB:2L03"
FT DISULFID 39..64
FT /evidence="ECO:0000269|PubMed:21252236,
FT ECO:0007744|PDB:2L03"
FT DISULFID 68..85
FT /evidence="ECO:0000269|PubMed:21252236,
FT ECO:0007744|PDB:2L03"
FT DISULFID 86..91
FT /evidence="ECO:0000269|PubMed:21252236,
FT ECO:0007744|PDB:2L03"
FT VAR_SEQ 52..116
FT /note="YYTPTRMKVSKSCVPRCFETVYDGYSKHASTTSCCQYDLCNGTGLATPATLA
FT LAPILLATLWGLL -> SAAEAIWCHQCTGFGGCSHGSRCLRDSTHCVTTATRVLSNTE
FT DLPLVTKMCHIGCPDIPSLGLGPYVSIACCQTSLCNHD (in isoform 2)"
FT /id="VSP_058978"
FT STRAND 22..24
FT /evidence="ECO:0007829|PDB:2L03"
FT STRAND 26..31
FT /evidence="ECO:0007829|PDB:2L03"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:2L03"
FT STRAND 45..54
FT /evidence="ECO:0007829|PDB:2L03"
FT STRAND 57..66
FT /evidence="ECO:0007829|PDB:2L03"
FT STRAND 75..77
FT /evidence="ECO:0007829|PDB:2L03"
FT STRAND 80..86
FT /evidence="ECO:0007829|PDB:2L03"
FT TURN 89..92
FT /evidence="ECO:0007829|PDB:2L03"
SQ SEQUENCE 116 AA; 12641 MW; BF5827EB64BFE6F6 CRC64;
MTPLLTLILV VLMGLPLAQA LDCHVCAYNG DNCFNPMRCP AMVAYCMTTR TYYTPTRMKV
SKSCVPRCFE TVYDGYSKHA STTSCCQYDL CNGTGLATPA TLALAPILLA TLWGLL
