ID   AGRL1_HUMAN             Reviewed;        1474 AA.
AC   O94910; Q96IE7; Q9BU07; Q9HAR3;
DT   26-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 1.
DT   13-FEB-2019, entry version 165.
DE   RecName: Full=Adhesion G protein-coupled receptor L1 {ECO:0000312|HGNC:HGNC:20973};
DE   AltName: Full=Calcium-independent alpha-latrotoxin receptor 1 {ECO:0000250|UniProtKB:O88917};
DE            Short=CIRL-1 {ECO:0000250|UniProtKB:O88917};
DE   AltName: Full=Latrophilin-1 {ECO:0000312|HGNC:HGNC:20973};
DE   AltName: Full=Lectomedin-2;
DE   Flags: Precursor;
GN   Name=ADGRL1 {ECO:0000312|HGNC:HGNC:20973};
GN   Synonyms=KIAA0821 {ECO:0000312|HGNC:HGNC:20973},
GN   LEC2 {ECO:0000250|UniProtKB:Q80TR1},
GN   LPHN1 {ECO:0000312|HGNC:HGNC:20973};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA   Douangpanya J., Puri K., Hayflick J.;
RL   Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Brain;
RX   PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA   Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M.,
RA   Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. XII.
RT   The complete sequences of 100 new cDNA clones from brain which code
RT   for large proteins in vitro.";
RL   DNA Res. 5:355-364(1998).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S.,
RA   Tsutsumi S., Aburatani H., Asai K., Akiyama Y.;
RT   "Genome-wide discovery and analysis of human seven transmembrane helix
RT   receptor genes.";
RL   Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 636-1474.
RC   TISSUE=Brain, and Lung;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Leukemic T-cell;
RX   PubMed=15144186; DOI=10.1021/ac035352d;
RA   Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,
RA   Peters E.C.;
RT   "Robust phosphoproteomic profiling of tyrosine phosphorylation sites
RT   from human T cells using immobilized metal affinity chromatography and
RT   tandem mass spectrometry.";
RL   Anal. Chem. 76:2763-2772(2004).
CC   -!- FUNCTION: Calcium-independent receptor of high affinity for alpha-
CC       latrotoxin, an excitatory neurotoxin present in black widow spider
CC       venom which triggers massive exocytosis from neurons and
CC       neuroendocrine cells. Receptor for TENM2 that mediates
CC       heterophilic synaptic cell-cell contact and postsynaptic
CC       specialization. Receptor probably implicated in the regulation of
CC       exocytosis (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Forms a heterodimer, consisting of a large extracellular
CC       region (p120) non-covalently linked to a seven-transmembrane
CC       moiety (p85). Interacts with syntaxin and with proteins of the
CC       SHANK family via the PDZ domain. Interacts (via extracellular
CC       domain) with FLRT1, FLRT2 and FLRT3 (via extracellular domain) (By
CC       similarity). {ECO:0000250|UniProtKB:O88917,
CC       ECO:0000250|UniProtKB:Q80TR1}.
CC   -!- INTERACTION:
CC       O00555:CACNA1A; NbExp=2; IntAct=EBI-3389315, EBI-766279;
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC       Cell projection, axon {ECO:0000250|UniProtKB:O88917}. Cell
CC       projection, growth cone {ECO:0000250|UniProtKB:O88917}. Cell
CC       junction, synapse {ECO:0000250|UniProtKB:O88917}. Cell junction,
CC       synapse, presynaptic cell membrane {ECO:0000250|UniProtKB:O88917}.
CC       Cell junction, synapse, synaptosome
CC       {ECO:0000250|UniProtKB:O88917}. Note=Colocalizes with TENM2 on the
CC       cell surface, across intercellular junctions and on nerve
CC       terminals near synaptic clefts. {ECO:0000250|UniProtKB:O88917}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=O94910-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=O94910-2; Sequence=VSP_010099;
CC   -!- DOMAIN: The extracellular domain coupled to the a single
CC       transmembrane region are sufficient for full responsiveness to
CC       alpha-latrotoxin. {ECO:0000250}.
CC   -!- PTM: Autoproteolytically cleaved into 2 subunits, an extracellular
CC       subunit and a seven-transmembrane subunit. This proteolytic
CC       processing takes place early in the biosynthetic pathway, either
CC       in the endoplasmic reticulum or in the early compartment of the
CC       Golgi apparatus (By similarity). {ECO:0000250|UniProtKB:O88917}.
CC   -!- SIMILARITY: Belongs to the G-protein coupled receptor 2 family.
CC       Adhesion G-protein coupled receptor (ADGR) subfamily.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA74844.2; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
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DR   EMBL; AF307079; AAG27461.1; -; mRNA.
DR   EMBL; AB020628; BAA74844.2; ALT_INIT; mRNA.
DR   EMBL; AB065919; BAC06134.1; -; Genomic_DNA.
DR   EMBL; BC002974; AAH02974.1; -; mRNA.
DR   EMBL; BC007587; AAH07587.1; -; mRNA.
DR   CCDS; CCDS12307.1; -. [O94910-2]
DR   CCDS; CCDS32928.1; -. [O94910-1]
DR   RefSeq; NP_001008701.1; NM_001008701.2. [O94910-1]
DR   RefSeq; NP_055736.2; NM_014921.4. [O94910-2]
DR   UniGene; Hs.94229; -.
DR   ProteinModelPortal; O94910; -.
DR   SMR; O94910; -.
DR   BioGrid; 116528; 31.
DR   IntAct; O94910; 2.
DR   STRING; 9606.ENSP00000340688; -.
DR   MEROPS; P02.010; -.
DR   iPTMnet; O94910; -.
DR   PhosphoSitePlus; O94910; -.
DR   BioMuta; ADGRL1; -.
DR   EPD; O94910; -.
DR   jPOST; O94910; -.
DR   MaxQB; O94910; -.
DR   PaxDb; O94910; -.
DR   PeptideAtlas; O94910; -.
DR   PRIDE; O94910; -.
DR   ProteomicsDB; 50544; -.
DR   ProteomicsDB; 50545; -. [O94910-2]
DR   DNASU; 22859; -.
DR   Ensembl; ENST00000340736; ENSP00000340688; ENSG00000072071. [O94910-1]
DR   Ensembl; ENST00000361434; ENSP00000355328; ENSG00000072071. [O94910-2]
DR   GeneID; 22859; -.
DR   KEGG; hsa:22859; -.
DR   UCSC; uc010xnn.3; human. [O94910-1]
DR   CTD; 22859; -.
DR   DisGeNET; 22859; -.
DR   EuPathDB; HostDB:ENSG00000072071.16; -.
DR   GeneCards; ADGRL1; -.
DR   HGNC; HGNC:20973; ADGRL1.
DR   HPA; HPA037974; -.
DR   MIM; 616416; gene.
DR   neXtProt; NX_O94910; -.
DR   OpenTargets; ENSG00000072071; -.
DR   PharmGKB; PA134868822; -.
DR   eggNOG; KOG3545; Eukaryota.
DR   eggNOG; KOG4193; Eukaryota.
DR   eggNOG; KOG4729; Eukaryota.
DR   eggNOG; ENOG410XSD2; LUCA.
DR   GeneTree; ENSGT00940000159684; -.
DR   HOGENOM; HOG000049065; -.
DR   HOVERGEN; HBG052337; -.
DR   InParanoid; O94910; -.
DR   KO; K04592; -.
DR   OMA; YIQAVVQ; -.
DR   OrthoDB; 388923at2759; -.
DR   PhylomeDB; O94910; -.
DR   TreeFam; TF351999; -.
DR   GeneWiki; LPHN1; -.
DR   GenomeRNAi; 22859; -.
DR   PRO; PR:O94910; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   Bgee; ENSG00000072071; Expressed in 222 organ(s), highest expression level in frontal cortex.
DR   ExpressionAtlas; O94910; baseline and differential.
DR   Genevisible; O94910; HS.
DR   GO; GO:0030424; C:axon; ISS:UniProtKB.
DR   GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR   GO; GO:0030426; C:growth cone; ISS:UniProtKB.
DR   GO; GO:0016021; C:integral component of membrane; TAS:GDB.
DR   GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR   GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0014069; C:postsynaptic density; IBA:GO_Central.
DR   GO; GO:0042734; C:presynaptic membrane; ISS:UniProtKB.
DR   GO; GO:0045202; C:synapse; ISS:UniProtKB.
DR   GO; GO:0030246; F:carbohydrate binding; IEA:UniProtKB-KW.
DR   GO; GO:0050839; F:cell adhesion molecule binding; ISS:UniProtKB.
DR   GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR   GO; GO:0016524; F:latrotoxin receptor activity; ISS:UniProtKB.
DR   GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0035584; P:calcium-mediated signaling using intracellular calcium source; ISS:UniProtKB.
DR   GO; GO:0007166; P:cell surface receptor signaling pathway; IEA:InterPro.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:GDB.
DR   GO; GO:0007157; P:heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; ISS:UniProtKB.
DR   GO; GO:0051965; P:positive regulation of synapse assembly; IEA:Ensembl.
DR   GO; GO:0090129; P:positive regulation of synapse maturation; ISS:UniProtKB.
DR   Gene3D; 4.10.1240.10; -; 1.
DR   InterPro; IPR032471; GAIN_dom_N.
DR   InterPro; IPR017981; GPCR_2-like.
DR   InterPro; IPR036445; GPCR_2_extracell_dom_sf.
DR   InterPro; IPR001879; GPCR_2_extracellular_dom.
DR   InterPro; IPR003924; GPCR_2_latrophilin.
DR   InterPro; IPR003334; GPCR_2_latrophilin_rcpt_C.
DR   InterPro; IPR000832; GPCR_2_secretin-like.
DR   InterPro; IPR017983; GPCR_2_secretin-like_CS.
DR   InterPro; IPR000203; GPS.
DR   InterPro; IPR031234; Latrophilin-1.
DR   InterPro; IPR000922; Lectin_gal-bd_dom.
DR   InterPro; IPR003112; Olfac-like_dom.
DR   PANTHER; PTHR12011:SF62; PTHR12011:SF62; 1.
DR   Pfam; PF00002; 7tm_2; 1.
DR   Pfam; PF16489; GAIN; 1.
DR   Pfam; PF02140; Gal_Lectin; 1.
DR   Pfam; PF01825; GPS; 1.
DR   Pfam; PF02793; HRM; 1.
DR   Pfam; PF02354; Latrophilin; 1.
DR   Pfam; PF02191; OLF; 1.
DR   PRINTS; PR00249; GPCRSECRETIN.
DR   PRINTS; PR01444; LATROPHILIN.
DR   SMART; SM00303; GPS; 1.
DR   SMART; SM00008; HormR; 1.
DR   SMART; SM00284; OLF; 1.
DR   PROSITE; PS00650; G_PROTEIN_RECEP_F2_2; 1.
DR   PROSITE; PS50227; G_PROTEIN_RECEP_F2_3; 1.
DR   PROSITE; PS50261; G_PROTEIN_RECEP_F2_4; 1.
DR   PROSITE; PS50221; GPS; 1.
DR   PROSITE; PS51132; OLF; 1.
DR   PROSITE; PS50228; SUEL_LECTIN; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Autocatalytic cleavage; Cell junction;
KW   Cell membrane; Cell projection; Complete proteome; Disulfide bond;
KW   G-protein coupled receptor; Glycoprotein; Lectin; Membrane;
KW   Methylation; Phosphoprotein; Polymorphism; Receptor;
KW   Reference proteome; Signal; Synapse; Synaptosome; Transducer;
KW   Transmembrane; Transmembrane helix.
FT   SIGNAL        1     24       {ECO:0000250}.
FT   CHAIN        25   1474       Adhesion G protein-coupled receptor L1.
FT                                /FTId=PRO_0000012907.
FT   TOPO_DOM     25    858       Extracellular. {ECO:0000255}.
FT   TRANSMEM    859    879       Helical; Name=1. {ECO:0000255}.
FT   TOPO_DOM    880    893       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    894    914       Helical; Name=2. {ECO:0000255}.
FT   TOPO_DOM    915    920       Extracellular. {ECO:0000255}.
FT   TRANSMEM    921    941       Helical; Name=3. {ECO:0000255}.
FT   TOPO_DOM    942    964       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    965    985       Helical; Name=4. {ECO:0000255}.
FT   TOPO_DOM    986   1002       Extracellular. {ECO:0000255}.
FT   TRANSMEM   1003   1023       Helical; Name=5. {ECO:0000255}.
FT   TOPO_DOM   1024   1050       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM   1051   1071       Helical; Name=6. {ECO:0000255}.
FT   TOPO_DOM   1072   1075       Extracellular. {ECO:0000255}.
FT   TRANSMEM   1076   1096       Helical; Name=7. {ECO:0000255}.
FT   TOPO_DOM   1097   1474       Cytoplasmic. {ECO:0000255}.
FT   DOMAIN       40    129       SUEL-type lectin. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00260}.
FT   DOMAIN      139    398       Olfactomedin-like. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00446}.
FT   DOMAIN      799    850       GPS. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00098}.
FT   REGION      117    120       Carbohydrate binding. {ECO:0000250}.
FT   COMPBIAS    413    416       Poly-Thr.
FT   COMPBIAS   1303   1314       Poly-Pro.
FT   COMPBIAS   1315   1318       Poly-Gly.
FT   COMPBIAS   1410   1420       Poly-Pro.
FT   BINDING      42     42       Carbohydrate. {ECO:0000250}.
FT   SITE        838    839       Cleavage; by autolysis.
FT                                {ECO:0000250|UniProtKB:O88917}.
FT   MOD_RES    1194   1194       Omega-N-methylarginine.
FT                                {ECO:0000250|UniProtKB:Q80TR1}.
FT   MOD_RES    1220   1220       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q80TR1}.
FT   MOD_RES    1473   1473       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q80TR1}.
FT   CARBOHYD     98     98       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    531    531       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    640    640       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    742    742       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    801    801       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    806    806       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    827    827       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID     41     71       {ECO:0000255|PROSITE-ProRule:PRU00446}.
FT   DISULFID     50    128       {ECO:0000255|PROSITE-ProRule:PRU00446}.
FT   DISULFID     83    115       {ECO:0000255|PROSITE-ProRule:PRU00446}.
FT   DISULFID     96    102       {ECO:0000255|PROSITE-ProRule:PRU00446}.
FT   DISULFID    140    322       {ECO:0000255|PROSITE-ProRule:PRU00446}.
FT   DISULFID    480    515       {ECO:0000255|PROSITE-ProRule:PRU00446}.
FT   DISULFID    503    532       {ECO:0000255|PROSITE-ProRule:PRU00446}.
FT   DISULFID    802    833       {ECO:0000255|PROSITE-ProRule:PRU00446}.
FT   DISULFID    821    835       {ECO:0000255|PROSITE-ProRule:PRU00446}.
FT   VAR_SEQ     132    137       KVEQKV -> I (in isoform 2).
FT                                {ECO:0000303|Ref.1}.
FT                                /FTId=VSP_010099.
FT   VARIANT     595    595       E -> Q (in dbSNP:rs34759320).
FT                                /FTId=VAR_049463.
FT   CONFLICT   1321   1321       E -> V (in Ref. 4; AAH02974).
FT                                {ECO:0000305}.
SQ   SEQUENCE   1474 AA;  162717 MW;  6152EB2DE1385F5C CRC64;
     MARLAAVLWN LCVTAVLVTS ATQGLSRAGL PFGLMRRELA CEGYPIELRC PGSDVIMVEN
     ANYGRTDDKI CDADPFQMEN VQCYLPDAFK IMSQRCNNRT QCVVVAGSDA FPDPCPGTYK
     YLEVQYDCVP YKVEQKVFVC PGTLQKVLEP TSTHESEHQS GAWCKDPLQA GDRIYVMPWI
     PYRTDTLTEY ASWEDYVAAR HTTTYRLPNR VDGTGFVVYD GAVFYNKERT RNIVKYDLRT
     RIKSGETVIN TANYHDTSPY RWGGKTDIDL AVDENGLWVI YATEGNNGRL VVSQLNPYTL
     RFEGTWETGY DKRSASNAFM VCGVLYVLRS VYVDDDSEAA GNRVDYAFNT NANREEPVSL
     TFPNPYQFIS SVDYNPRDNQ LYVWNNYFVV RYSLEFGPPD PSAGPATSPP LSTTTTARPT
     PLTSTASPAA TTPLRRAPLT THPVGAINQL GPDLPPATAP VPSTRRPPAP NLHVSPELFC
     EPREVRRVQW PATQQGMLVE RPCPKGTRGI ASFQCLPALG LWNPRGPDLS NCTSPWVNQV
     AQKIKSGENA ANIASELARH TRGSIYAGDV SSSVKLMEQL LDILDAQLQA LRPIERESAG
     KNYNKMHKRE RTCKDYIKAV VETVDNLLRP EALESWKDMN ATEQVHTATM LLDVLEEGAF
     LLADNVREPA RFLAAKENVV LEVTVLNTEG QVQELVFPQE EYPRKNSIQL SAKTIKQNSR
     NGVVKVVFIL YNNLGLFLST ENATVKLAGE AGPGGPGGAS LVVNSQVIAA SINKESSRVF
     LMDPVIFTVA HLEDKNHFNA NCSFWNYSER SMLGYWSTQG CRLVESNKTH TTCACSHLTN
     FAVLMAHREI YQGRINELLL SVITWVGIVI SLVCLAICIS TFCFLRGLQT DRNTIHKNLC
     INLFLAELLF LVGIDKTQYE IACPIFAGLL HYFFLAAFSW LCLEGVHLYL LLVEVFESEY
     SRTKYYYLGG YCFPALVVGI AAAIDYRSYG TEKACWLRVD NYFIWSFIGP VSFVIVVNLV
     FLMVTLHKMI RSSSVLKPDS SRLDNIKSWA LGAIALLFLL GLTWAFGLLF INKESVVMAY
     LFTTFNAFQG VFIFVFHCAL QKKVHKEYSK CLRHSYCCIR SPPGGTHGSL KTSAMRSNTR
     YYTGTQSRIR RMWNDTVRKQ TESSFMAGDI NSTPTLNRGT MGNHLLTNPV LQPRGGTSPY
     NTLIAESVGF NPSSPPVFNS PGSYREPKHP LGGREACGMD TLPLNGNFNN SYSLRSGDFP
     PGDGGPEPPR GRNLADAAAF EKMIISELVH NNLRGSSSAA KGPPPPEPPV PPVPGGGGEE
     EAGGPGGADR AEIELLYKAL EEPLLLPRAQ SVLYQSDLDE SESCTAEDGA TSRPLSSPPG
     RDSLYASGAN LRDSPSYPDS SPEGPSEALP PPPPAPPGPP EIYYTSRPPA LVARNPLQGY
     YQVRRPSHEG YLAAPGLEGP GPDGDGQMQL VTSL
//