O94910 (LPHN1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Latrophilin-1

Alternative name(s):
Calcium-independent alpha-latrotoxin receptor 1
Short name=CIRL-1
Lectomedin-2

Gene names

Name:	LPHN1
Synonyms:	KIAA0821, LEC2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1474 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Calcium-independent receptor of high affinity for alpha-latrotoxin, an excitatory neurotoxin present in black widow spider venom which triggers massive exocytosis from neurons and neuroendocrine cells. Receptor for TENM2 that mediates heterophilic synaptic cell-cell contact and postsynaptic specialization. Receptor propably implicated in the regulation of exocytosis By similarity.
Subunit structure	Forms a heterodimer, consisting of a large extracellular region (p120) non-covalently linked to a seven-transmembrane moiety (p85). Interacts with syntaxin and with proteins of the SHANK family via the PDZ domain By similarity.
Subcellular location	Cell membrane; Multi-pass membrane protein. Cell projection › axon By similarity. Cell projection › growth cone By similarity. Cell junction › synapse By similarity. Cell junction › synapse › presynaptic cell membrane By similarity. Cell junction › synapse › synaptosome By similarity. Note: Colocalizes with TENM2 on the cell surface, across intercellular junctions and on nerve terminals near synaptic clefts By similarity.
Domain	The extracellular domain coupled to the a single transmembrane region are sufficient for full responsiveness to alpha-latrotoxin By similarity.
Post-translational modification	Autoproteolytically cleaved into 2 subunits, an extracellular subunit and a seven-transmembrane subunit. This proteolytic processing takes place early in the biosynthetic pathway, either in the endoplasmic reticulum or in the early compartment of the Golgi apparatus By similarity.
Sequence similarities	Belongs to the G-protein coupled receptor 2 family. LN-TM7 subfamily. Contains 1 GPS domain. Contains 1 olfactomedin-like domain. Contains 1 SUEL-type lectin domain.
Sequence caution	The sequence BAA74844.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Cell projection Membrane Synapse Synaptosome
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Ligand	Lectin
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor signaling pathway Traceable author statement PubMed 15203201. Source: GDB calcium-mediated signaling using intracellular calcium source Inferred from sequence or structural similarity. Source: UniProtKB heterophilic cell-cell adhesion Inferred from sequence or structural similarity. Source: UniProtKB neuropeptide signaling pathway Inferred from electronic annotation. Source: InterPro positive regulation of synapse maturation Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	axon Inferred from sequence or structural similarity. Source: UniProtKB cell junction Inferred from electronic annotation. Source: UniProtKB-KW growth cone Inferred from sequence or structural similarity. Source: UniProtKB integral component of membrane Traceable author statement PubMed 15203201. Source: GDB neuron projection Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB presynaptic membrane Inferred from sequence or structural similarity. Source: UniProtKB synapse Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	G-protein coupled receptor activity Traceable author statement PubMed 15203201. Source: GDB carbohydrate binding Inferred from electronic annotation. Source: InterPro cell adhesion molecule binding Inferred from sequence or structural similarity. Source: UniProtKB latrotoxin receptor activity Inferred from sequence or structural similarity. Source: UniProtKB protein binding Inferred from physical interaction PubMed 21078624. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CACNA1A	O00555	2	EBI-3389315,EBI-766279

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O94910-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O94910-2)

The sequence of this isoform differs from the canonical sequence as follows:
     132-137: KVEQKV → I

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 24	24	By similarity
	Chain	25 – 1474	1450	Latrophilin-1		PRO_0000012907
Regions
	Topological domain	25 – 858	834	Extracellular Potential
	Transmembrane	859 – 879	21	Helical; Name=1; Potential
	Topological domain	880 – 893	14	Cytoplasmic Potential
	Transmembrane	894 – 914	21	Helical; Name=2; Potential
	Topological domain	915 – 920	6	Extracellular Potential
	Transmembrane	921 – 941	21	Helical; Name=3; Potential
	Topological domain	942 – 964	23	Cytoplasmic Potential
	Transmembrane	965 – 985	21	Helical; Name=4; Potential
	Topological domain	986 – 1002	17	Extracellular Potential
	Transmembrane	1003 – 1023	21	Helical; Name=5; Potential
	Topological domain	1024 – 1050	27	Cytoplasmic Potential
	Transmembrane	1051 – 1071	21	Helical; Name=6; Potential
	Topological domain	1072 – 1075	4	Extracellular Potential
	Transmembrane	1076 – 1096	21	Helical; Name=7; Potential
	Topological domain	1097 – 1474	378	Cytoplasmic Potential
	Domain	40 – 129	90	SUEL-type lectin
	Domain	139 – 398	260	Olfactomedin-like
	Domain	799 – 850	52	GPS
	Region	117 – 120	4	Carbohydrate binding By similarity
	Compositional bias	413 – 416	4	Poly-Thr
	Compositional bias	1303 – 1314	12	Poly-Pro
	Compositional bias	1315 – 1318	4	Poly-Gly
	Compositional bias	1410 – 1420	11	Poly-Pro
Sites
	Binding site	42	1	Carbohydrate By similarity
	Site	838 – 839	2	Cleavage; by autocatalysis By similarity
Amino acid modifications
	Glycosylation	98	1	N-linked (GlcNAc...) Potential
	Glycosylation	531	1	N-linked (GlcNAc...) Potential
	Glycosylation	640	1	N-linked (GlcNAc...) Potential
	Glycosylation	742	1	N-linked (GlcNAc...) Potential
	Glycosylation	801	1	N-linked (GlcNAc...) Potential
	Glycosylation	806	1	N-linked (GlcNAc...) Potential
	Glycosylation	827	1	N-linked (GlcNAc...) Potential
	Disulfide bond	41 ↔ 71		By similarity
	Disulfide bond	50 ↔ 128		By similarity
	Disulfide bond	83 ↔ 115		By similarity
	Disulfide bond	96 ↔ 102		By similarity
	Disulfide bond	140 ↔ 322		By similarity
	Disulfide bond	480 ↔ 515		By similarity
	Disulfide bond	503 ↔ 532		By similarity
	Disulfide bond	802 ↔ 833		By similarity
	Disulfide bond	821 ↔ 835		By similarity
Natural variations
	Alternative sequence	132 – 137	6	KVEQKV → I in isoform 2.		VSP_010099
	Natural variant	595	1	E → Q. Corresponds to variant rs34759320 [ dbSNP | Ensembl ].		VAR_049463
Experimental info
	Sequence conflict	1321	1	E → V in AAH02974. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: 6152EB2DE1385F5C	FASTA	1,474	162,717
	10 20 30 40 50 60 MARLAAVLWN LCVTAVLVTS ATQGLSRAGL PFGLMRRELA CEGYPIELRC PGSDVIMVEN 70 80 90 100 110 120 ANYGRTDDKI CDADPFQMEN VQCYLPDAFK IMSQRCNNRT QCVVVAGSDA FPDPCPGTYK 130 140 150 160 170 180 YLEVQYDCVP YKVEQKVFVC PGTLQKVLEP TSTHESEHQS GAWCKDPLQA GDRIYVMPWI 190 200 210 220 230 240 PYRTDTLTEY ASWEDYVAAR HTTTYRLPNR VDGTGFVVYD GAVFYNKERT RNIVKYDLRT 250 260 270 280 290 300 RIKSGETVIN TANYHDTSPY RWGGKTDIDL AVDENGLWVI YATEGNNGRL VVSQLNPYTL 310 320 330 340 350 360 RFEGTWETGY DKRSASNAFM VCGVLYVLRS VYVDDDSEAA GNRVDYAFNT NANREEPVSL 370 380 390 400 410 420 TFPNPYQFIS SVDYNPRDNQ LYVWNNYFVV RYSLEFGPPD PSAGPATSPP LSTTTTARPT 430 440 450 460 470 480 PLTSTASPAA TTPLRRAPLT THPVGAINQL GPDLPPATAP VPSTRRPPAP NLHVSPELFC 490 500 510 520 530 540 EPREVRRVQW PATQQGMLVE RPCPKGTRGI ASFQCLPALG LWNPRGPDLS NCTSPWVNQV 550 560 570 580 590 600 AQKIKSGENA ANIASELARH TRGSIYAGDV SSSVKLMEQL LDILDAQLQA LRPIERESAG 610 620 630 640 650 660 KNYNKMHKRE RTCKDYIKAV VETVDNLLRP EALESWKDMN ATEQVHTATM LLDVLEEGAF 670 680 690 700 710 720 LLADNVREPA RFLAAKENVV LEVTVLNTEG QVQELVFPQE EYPRKNSIQL SAKTIKQNSR 730 740 750 760 770 780 NGVVKVVFIL YNNLGLFLST ENATVKLAGE AGPGGPGGAS LVVNSQVIAA SINKESSRVF 790 800 810 820 830 840 LMDPVIFTVA HLEDKNHFNA NCSFWNYSER SMLGYWSTQG CRLVESNKTH TTCACSHLTN 850 860 870 880 890 900 FAVLMAHREI YQGRINELLL SVITWVGIVI SLVCLAICIS TFCFLRGLQT DRNTIHKNLC 910 920 930 940 950 960 INLFLAELLF LVGIDKTQYE IACPIFAGLL HYFFLAAFSW LCLEGVHLYL LLVEVFESEY 970 980 990 1000 1010 1020 SRTKYYYLGG YCFPALVVGI AAAIDYRSYG TEKACWLRVD NYFIWSFIGP VSFVIVVNLV 1030 1040 1050 1060 1070 1080 FLMVTLHKMI RSSSVLKPDS SRLDNIKSWA LGAIALLFLL GLTWAFGLLF INKESVVMAY 1090 1100 1110 1120 1130 1140 LFTTFNAFQG VFIFVFHCAL QKKVHKEYSK CLRHSYCCIR SPPGGTHGSL KTSAMRSNTR 1150 1160 1170 1180 1190 1200 YYTGTQSRIR RMWNDTVRKQ TESSFMAGDI NSTPTLNRGT MGNHLLTNPV LQPRGGTSPY 1210 1220 1230 1240 1250 1260 NTLIAESVGF NPSSPPVFNS PGSYREPKHP LGGREACGMD TLPLNGNFNN SYSLRSGDFP 1270 1280 1290 1300 1310 1320 PGDGGPEPPR GRNLADAAAF EKMIISELVH NNLRGSSSAA KGPPPPEPPV PPVPGGGGEE 1330 1340 1350 1360 1370 1380 EAGGPGGADR AEIELLYKAL EEPLLLPRAQ SVLYQSDLDE SESCTAEDGA TSRPLSSPPG 1390 1400 1410 1420 1430 1440 RDSLYASGAN LRDSPSYPDS SPEGPSEALP PPPPAPPGPP EIYYTSRPPA LVARNPLQGY 1450 1460 1470 YQVRRPSHEG YLAAPGLEGP GPDGDGQMQL VTSL
	Isoform 2 [UniParc]. Checksum: 4907D329A56E57FF	FASTA	1,469	162,118
	10 20 30 40 50 60 MARLAAVLWN LCVTAVLVTS ATQGLSRAGL PFGLMRRELA CEGYPIELRC PGSDVIMVEN 70 80 90 100 110 120 ANYGRTDDKI CDADPFQMEN VQCYLPDAFK IMSQRCNNRT QCVVVAGSDA FPDPCPGTYK 130 140 150 160 170 180 YLEVQYDCVP YIFVCPGTLQ KVLEPTSTHE SEHQSGAWCK DPLQAGDRIY VMPWIPYRTD 190 200 210 220 230 240 TLTEYASWED YVAARHTTTY RLPNRVDGTG FVVYDGAVFY NKERTRNIVK YDLRTRIKSG 250 260 270 280 290 300 ETVINTANYH DTSPYRWGGK TDIDLAVDEN GLWVIYATEG NNGRLVVSQL NPYTLRFEGT 310 320 330 340 350 360 WETGYDKRSA SNAFMVCGVL YVLRSVYVDD DSEAAGNRVD YAFNTNANRE EPVSLTFPNP 370 380 390 400 410 420 YQFISSVDYN PRDNQLYVWN NYFVVRYSLE FGPPDPSAGP ATSPPLSTTT TARPTPLTST 430 440 450 460 470 480 ASPAATTPLR RAPLTTHPVG AINQLGPDLP PATAPVPSTR RPPAPNLHVS PELFCEPREV 490 500 510 520 530 540 RRVQWPATQQ GMLVERPCPK GTRGIASFQC LPALGLWNPR GPDLSNCTSP WVNQVAQKIK 550 560 570 580 590 600 SGENAANIAS ELARHTRGSI YAGDVSSSVK LMEQLLDILD AQLQALRPIE RESAGKNYNK 610 620 630 640 650 660 MHKRERTCKD YIKAVVETVD NLLRPEALES WKDMNATEQV HTATMLLDVL EEGAFLLADN 670 680 690 700 710 720 VREPARFLAA KENVVLEVTV LNTEGQVQEL VFPQEEYPRK NSIQLSAKTI KQNSRNGVVK 730 740 750 760 770 780 VVFILYNNLG LFLSTENATV KLAGEAGPGG PGGASLVVNS QVIAASINKE SSRVFLMDPV 790 800 810 820 830 840 IFTVAHLEDK NHFNANCSFW NYSERSMLGY WSTQGCRLVE SNKTHTTCAC SHLTNFAVLM 850 860 870 880 890 900 AHREIYQGRI NELLLSVITW VGIVISLVCL AICISTFCFL RGLQTDRNTI HKNLCINLFL 910 920 930 940 950 960 AELLFLVGID KTQYEIACPI FAGLLHYFFL AAFSWLCLEG VHLYLLLVEV FESEYSRTKY 970 980 990 1000 1010 1020 YYLGGYCFPA LVVGIAAAID YRSYGTEKAC WLRVDNYFIW SFIGPVSFVI VVNLVFLMVT 1030 1040 1050 1060 1070 1080 LHKMIRSSSV LKPDSSRLDN IKSWALGAIA LLFLLGLTWA FGLLFINKES VVMAYLFTTF 1090 1100 1110 1120 1130 1140 NAFQGVFIFV FHCALQKKVH KEYSKCLRHS YCCIRSPPGG THGSLKTSAM RSNTRYYTGT 1150 1160 1170 1180 1190 1200 QSRIRRMWND TVRKQTESSF MAGDINSTPT LNRGTMGNHL LTNPVLQPRG GTSPYNTLIA 1210 1220 1230 1240 1250 1260 ESVGFNPSSP PVFNSPGSYR EPKHPLGGRE ACGMDTLPLN GNFNNSYSLR SGDFPPGDGG 1270 1280 1290 1300 1310 1320 PEPPRGRNLA DAAAFEKMII SELVHNNLRG SSSAAKGPPP PEPPVPPVPG GGGEEEAGGP 1330 1340 1350 1360 1370 1380 GGADRAEIEL LYKALEEPLL LPRAQSVLYQ SDLDESESCT AEDGATSRPL SSPPGRDSLY 1390 1400 1410 1420 1430 1440 ASGANLRDSP SYPDSSPEGP SEALPPPPPA PPGPPEIYYT SRPPALVARN PLQGYYQVRR 1450 1460 PSHEGYLAAP GLEGPGPDGD GQMQLVTSL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Douangpanya J., Puri K., Hayflick J. Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[2]	"Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:355-364(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[3]	"Genome-wide discovery and analysis of human seven transmembrane helix receptor genes." Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S., Tsutsumi S., Aburatani H., Asai K., Akiyama Y. Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 636-1474. Tissue: Brain and Lung.
[5]	"Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry." Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C. Anal. Chem. 76:2763-2772(2004) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF307079 mRNA. Translation: AAG27461.1. AB020628 mRNA. Translation: BAA74844.2. Different initiation. AB065919 Genomic DNA. Translation: BAC06134.1. BC002974 mRNA. Translation: AAH02974.1. BC007587 mRNA. Translation: AAH07587.1.
CCDS	CCDS12307.1. [O94910-2] CCDS32928.1. [O94910-1]
RefSeq	NP_001008701.1. NM_001008701.2. [O94910-1] NP_055736.2. NM_014921.4. [O94910-2]
UniGene	Hs.94229.
3D structure databases
ProteinModelPortal	O94910.
SMR	O94910. Positions 29-134, 474-838, 861-1100.
ModBase	Search...
MobiDB	Search...
Protein-protein interaction databases
BioGrid	116528. 4 interactions.
IntAct	O94910. 2 interactions.
STRING	9606.ENSP00000340688.
Protein family/group databases
MEROPS	S63.013.
GPCRDB	Search...
PTM databases
PhosphoSite	O94910.
Proteomic databases
MaxQB	O94910.
PaxDb	O94910.
PRIDE	O94910.
Protocols and materials databases
DNASU	22859.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000340736; ENSP00000340688; ENSG00000072071. [O94910-1] ENST00000361434; ENSP00000355328; ENSG00000072071. [O94910-2]
GeneID	22859.
KEGG	hsa:22859.
UCSC	uc010xnn.2. human. [O94910-1] uc010xno.2. human. [O94910-2]
Organism-specific databases
CTD	22859.
GeneCards	GC19M014258.
HGNC	HGNC:20973. LPHN1.
HPA	HPA037974.
neXtProt	NX_O94910.
PharmGKB	PA134868822.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG253931.
HOGENOM	HOG000049065.
HOVERGEN	HBG052337.
InParanoid	O94910.
KO	K04592.
OMA	DRIYVMP.
OrthoDB	EOG76DTRK.
PhylomeDB	O94910.
TreeFam	TF351999.
Gene expression databases
ArrayExpress	O94910.
Bgee	O94910.
CleanEx	HS_LPHN1.
Genevestigator	O94910.
Family and domain databases
InterPro	IPR022624. DUF3497. IPR017981. GPCR_2-like. IPR001879. GPCR_2_extracellular_dom. IPR003924. GPCR_2_latrophilin. IPR003334. GPCR_2_latrophilin_rcpt_C. IPR000832. GPCR_2_secretin-like. IPR017983. GPCR_2_secretin-like_CS. IPR000203. GPS. IPR000922. Lectin_gal-bd_dom. IPR003112. Olfac-like. [Graphical view]
Pfam	PF00002. 7tm_2. 1 hit. PF12003. DUF3497. 1 hit. PF02140. Gal_Lectin. 1 hit. PF01825. GPS. 1 hit. PF02793. HRM. 1 hit. PF02354. Latrophilin. 1 hit. PF02191. OLF. 1 hit. [Graphical view]
PRINTS	PR00249. GPCRSECRETIN. PR01444. LATROPHILIN.
SMART	SM00303. GPS. 1 hit. SM00008. HormR. 1 hit. SM00284. OLF. 1 hit. [Graphical view]
PROSITE	PS00650. G_PROTEIN_RECEP_F2_2. 1 hit. PS50227. G_PROTEIN_RECEP_F2_3. 1 hit. PS50261. G_PROTEIN_RECEP_F2_4. 1 hit. PS50221. GPS. 1 hit. PS51132. OLF. 1 hit. PS50228. SUEL_LECTIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GeneWiki	LPHN1.
GenomeRNAi	22859.
NextBio	43351.
PRO	O94910.

Entry information

Entry name

LPHN1_HUMAN

Accession

Primary (citable) accession number: O94910
Secondary accession number(s): Q96IE7, Q9BU07, Q9HAR3

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 26, 2004
Last sequence update:	May 1, 1999
Last modified:	July 9, 2014
This is version 127 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.