LYPD6_HUMAN
ID LYPD6_HUMAN Reviewed; 171 AA.
AC Q86Y78; B3KWC0; Q4G121; Q53TR3; Q659B1;
DT 09-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Ly6/PLAUR domain-containing protein 6;
DE Flags: Precursor;
GN Name=LYPD6; ORFNames=UNQ3023/PRO9821;
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 1), SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=19653121; DOI=10.1007/s11033-009-9663-7;
RA Zhang Y., Lang Q., Li J., Xie F., Wan B., Yu L.;
RT "Identification and characterization of human LYPD6, a new member of the
RT Ly-6 superfamily.";
RL Mol. Biol. Rep. 37:2055-2062(2010).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Testis;
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 [7]
RP PROTEIN SEQUENCE OF 23-37.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 94-171.
RC TISSUE=Amygdala;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [9]
RP FUNCTION, AND INTERACTION WITH CHRNA3; CHRNA4; CHRNA5; CHRNA6; CHRNA7;
RP CHRNB2 AND CHRNB4.
RX PubMed=27344019; DOI=10.1111/jnc.13718;
RA Arvaniti M., Jensen M.M., Soni N., Wang H., Klein A.B., Thiriet N.,
RA Pinborg L.H., Muldoon P.P., Wienecke J., Imad Damaj M., Kohlmeier K.A.,
RA Gondre-Lewis M.C., Mikkelsen J.D., Thomsen M.S.;
RT "Functional interaction between Lypd6 and nicotinic acetylcholine
RT receptors.";
RL J. Neurochem. 138:806-820(2016).
CC -!- FUNCTION: Acts as a modulator of nicotinic acetylcholine receptors
CC (nAChRs) function in the brain. Inhibits nicotine-induced Ca(2+) influx
CC through nAChRs (PubMed:27344019). Acts as a positive regulator of
CC Wnt/beta-catenin signaling (By similarity).
CC {ECO:0000250|UniProtKB:Q66IA6, ECO:0000269|PubMed:27344019}.
CC -!- SUBUNIT: Interacts with nicotinic acetylcholine receptors (nAChRs)
CC including CHRNA3, CHRNA4, CHRNA5, CHRNA6, CHRNA7, CHRNB2 and CHRNB4
CC (PubMed:27344019). {ECO:0000269|PubMed:27344019}.
CC -!- INTERACTION:
CC Q86Y78; Q9UHA2: SS18L2; NbExp=3; IntAct=EBI-14035066, EBI-10962400;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}. Cytoplasm
CC {ECO:0000269|PubMed:19653121}. Cell membrane
CC {ECO:0000250|UniProtKB:Q66IA6}; Lipid-anchor, GPI-anchor
CC {ECO:0000250|UniProtKB:Q66IA6}. Synapse, synaptosome
CC {ECO:0000250|UniProtKB:D3ZTT2}. Membrane raft
CC {ECO:0000250|UniProtKB:Q66IA6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q86Y78-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86Y78-2; Sequence=VSP_039306, VSP_039307;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highly expressed in brain and heart.
CC {ECO:0000269|PubMed:19653121}.
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DR EMBL; AY358623; AAQ88986.1; -; mRNA.
DR EMBL; AK124733; BAG54082.1; -; mRNA.
DR EMBL; AC007394; AAY14698.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX11539.1; -; Genomic_DNA.
DR EMBL; BC032836; AAH32836.1; -; mRNA.
DR EMBL; BC047013; AAH47013.1; -; mRNA.
DR EMBL; AL831852; CAH56278.1; -; mRNA.
DR CCDS; CCDS2188.1; -. [Q86Y78-1]
DR RefSeq; NP_001182614.1; NM_001195685.1. [Q86Y78-1]
DR RefSeq; NP_919298.1; NM_194317.3. [Q86Y78-1]
DR PDB; 6GBI; X-ray; 1.25 A; A=46-141.
DR PDB; 6IB6; NMR; -; A=47-141.
DR PDBsum; 6GBI; -.
DR PDBsum; 6IB6; -.
DR AlphaFoldDB; Q86Y78; -.
DR SMR; Q86Y78; -.
DR BioGRID; 126242; 59.
DR IntAct; Q86Y78; 31.
DR STRING; 9606.ENSP00000334463; -.
DR GlyGen; Q86Y78; 2 sites.
DR iPTMnet; Q86Y78; -.
DR PhosphoSitePlus; Q86Y78; -.
DR BioMuta; LYPD6; -.
DR DMDM; 55583932; -.
DR MassIVE; Q86Y78; -.
DR PaxDb; Q86Y78; -.
DR PeptideAtlas; Q86Y78; -.
DR PRIDE; Q86Y78; -.
DR Antibodypedia; 33640; 68 antibodies from 14 providers.
DR DNASU; 130574; -.
DR Ensembl; ENST00000334166.9; ENSP00000334463.4; ENSG00000187123.15. [Q86Y78-1]
DR Ensembl; ENST00000392854.4; ENSP00000376594.4; ENSG00000187123.15. [Q86Y78-2]
DR Ensembl; ENST00000409381.5; ENSP00000386413.1; ENSG00000187123.15. [Q86Y78-1]
DR Ensembl; ENST00000418762.5; ENSP00000396855.1; ENSG00000187123.15. [Q86Y78-2]
DR Ensembl; ENST00000651933.1; ENSP00000498455.1; ENSG00000187123.15. [Q86Y78-1]
DR GeneID; 130574; -.
DR KEGG; hsa:130574; -.
DR MANE-Select; ENST00000334166.9; ENSP00000334463.4; NM_194317.5; NP_919298.1.
DR UCSC; uc002twy.4; human. [Q86Y78-1]
DR CTD; 130574; -.
DR DisGeNET; 130574; -.
DR GeneCards; LYPD6; -.
DR HGNC; HGNC:28751; LYPD6.
DR HPA; ENSG00000187123; Tissue enhanced (brain, placenta).
DR MIM; 613359; gene.
DR neXtProt; NX_Q86Y78; -.
DR OpenTargets; ENSG00000187123; -.
DR PharmGKB; PA147357619; -.
DR VEuPathDB; HostDB:ENSG00000187123; -.
DR eggNOG; ENOG502RYB5; Eukaryota.
DR GeneTree; ENSGT00390000000220; -.
DR HOGENOM; CLU_105474_1_0_1; -.
DR InParanoid; Q86Y78; -.
DR OMA; AWPTVAW; -.
DR OrthoDB; 1296179at2759; -.
DR PhylomeDB; Q86Y78; -.
DR TreeFam; TF332443; -.
DR PathwayCommons; Q86Y78; -.
DR SignaLink; Q86Y78; -.
DR BioGRID-ORCS; 130574; 12 hits in 1062 CRISPR screens.
DR ChiTaRS; LYPD6; human.
DR GenomeRNAi; 130574; -.
DR Pharos; Q86Y78; Tbio.
DR PRO; PR:Q86Y78; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q86Y78; protein.
DR Bgee; ENSG00000187123; Expressed in sperm and 113 other tissues.
DR ExpressionAtlas; Q86Y78; baseline and differential.
DR Genevisible; Q86Y78; HS.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0043005; C:neuron projection; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
DR GO; GO:0030550; F:acetylcholine receptor inhibitor activity; IDA:UniProtKB.
DR GO; GO:0030548; F:acetylcholine receptor regulator activity; IBA:GO_Central.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IBA:GO_Central.
DR Gene3D; 2.10.60.10; -; 1.
DR InterPro; IPR031574; LYPD6.
DR InterPro; IPR039457; LYPD6-like.
DR InterPro; IPR045860; Snake_toxin-like_sf.
DR PANTHER; PTHR31171; PTHR31171; 1.
DR PANTHER; PTHR31171:SF0; PTHR31171:SF0; 1.
DR SUPFAM; SSF57302; SSF57302; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Cytoplasm;
KW Direct protein sequencing; Glycoprotein; GPI-anchor; Lipoprotein; Membrane;
KW Reference proteome; Secreted; Signal; Synapse; Synaptosome.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 23..171
FT /note="Ly6/PLAUR domain-containing protein 6"
FT /id="PRO_0000036178"
FT DOMAIN 47..141
FT /note="UPAR/Ly6"
FT CARBOHYD 134
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 147
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 73..76
FT /note="ETRY -> GTMI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_039306"
FT VAR_SEQ 77..171
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_039307"
FT CONFLICT 73
FT /note="E -> V (in Ref. 3; BAG54082)"
FT /evidence="ECO:0000305"
FT STRAND 52..57
FT /evidence="ECO:0007829|PDB:6GBI"
FT HELIX 58..63
FT /evidence="ECO:0007829|PDB:6GBI"
FT STRAND 76..84
FT /evidence="ECO:0007829|PDB:6GBI"
FT STRAND 85..87
FT /evidence="ECO:0007829|PDB:6IB6"
FT STRAND 89..97
FT /evidence="ECO:0007829|PDB:6GBI"
FT HELIX 99..102
FT /evidence="ECO:0007829|PDB:6GBI"
FT STRAND 106..109
FT /evidence="ECO:0007829|PDB:6GBI"
FT STRAND 112..114
FT /evidence="ECO:0007829|PDB:6IB6"
FT STRAND 115..122
FT /evidence="ECO:0007829|PDB:6GBI"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:6IB6"
FT TURN 135..137
FT /evidence="ECO:0007829|PDB:6GBI"
FT STRAND 138..141
FT /evidence="ECO:0007829|PDB:6GBI"
SQ SEQUENCE 171 AA; 19118 MW; 1BAEEE9CD18F5470 CRC64;
MEPGPALAWL LLLSLLADCL KAAQSRDFTV KDIIYLHPST TPYPGGFKCF TCEKAADNYE
CNRWAPDIYC PRETRYCYTQ HTMEVTGNSI SVTKRCVPLE ECLSTGCRDS EHEGHKVCTS
CCEGNICNLP LPRNETDATF ATTSPINQTN GHPRCMSVIV SCLWLWLGLM L
