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O88917 (LPHN1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Latrophilin-1
Alternative name(s):
Calcium-independent alpha-latrotoxin receptor 1
Short name=CIRL-1
Gene names
Name:Lphn1
Synonyms:Cirl, Cirl1, Cl1
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length1515 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 propably implicated in the regulation of exocytosis.

Isoform 2:Receptor for TENM2 that mediates heterophilic synaptic cell-cell contact and postsynaptic specialization.

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. Isoform 2 interacts with TENM2. Ref.2 Ref.6 Ref.9

Subcellular location

Cell membrane; Multi-pass membrane protein Ref.9 Ref.10.

Isoform 2: Cell membrane. Cell projectionaxon. Cell projectiongrowth cone. Cell junctionsynapse. Cell junctionsynapsepresynaptic cell membrane. Cell junctionsynapsesynaptosome. Note: Colocalizes with TENM2 on the cell surface, across intercellular junctions and on nerve terminals near synaptic clefts. Ref.9 Ref.10

Tissue specificity

Expressed in the brain (at protein level). Brain specific distribution but low levels are also detected in most tissues. Ref.1 Ref.9

Domain

The extracellular domain coupled to the a single transmembrane region are sufficient for full responsiveness to alpha-latrotoxin.

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. Ref.2 Ref.10

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.

Ontologies

Keywords
   Cellular componentCell junction
Cell membrane
Cell projection
Membrane
Synapse
Synaptosome
   Coding sequence diversityAlternative splicing
   DomainSignal
Transmembrane
Transmembrane helix
   LigandLectin
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processbrain development

Inferred from expression pattern PubMed 10964907. Source: RGD

calcium-mediated signaling using intracellular calcium source

Inferred from direct assay Ref.9. Source: UniProtKB

heterophilic cell-cell adhesion

Inferred from direct assay Ref.9. Source: UniProtKB

neuropeptide signaling pathway

Inferred from electronic annotation. Source: InterPro

positive regulation of synapse maturation

Inferred from direct assay Ref.9. Source: UniProtKB

synaptic vesicle exocytosis

Traceable author statement Ref.3. Source: RGD

   Cellular_componentaxon

Inferred from direct assay Ref.9. Source: UniProtKB

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

growth cone

Inferred from direct assay Ref.9. Source: UniProtKB

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

neuron projection

Inferred from direct assay Ref.9. Source: UniProtKB

plasma membrane

Inferred from direct assay Ref.9. Source: UniProtKB

postsynaptic density

Inferred from direct assay PubMed 10964907. Source: RGD

presynaptic membrane

Inferred from direct assay Ref.9. Source: UniProtKB

synapse

Inferred from direct assay Ref.9. Source: UniProtKB

   Molecular_functionG-protein coupled receptor activity

Inferred from direct assay Ref.3. Source: RGD

carbohydrate binding

Inferred from electronic annotation. Source: InterPro

cell adhesion molecule binding

Inferred from direct assay Ref.9. Source: UniProtKB

latrotoxin receptor activity

Inferred from direct assay Ref.3. Source: RGD

protein binding

Inferred from physical interaction PubMed 10964907Ref.3. Source: RGD

toxic substance binding

Inferred from physical interaction Ref.3. Source: RGD

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O88917-1)

Also known as: CL1BB;

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: O88917-2)

Also known as: CL1AA;

The sequence of this isoform differs from the canonical sequence as follows:
     132-137: KVEQKV → I
     1146-1189: Missing.
Isoform 3 (identifier: O88917-3)

Also known as: CL1AB;

The sequence of this isoform differs from the canonical sequence as follows:
     132-137: KVEQKV → I
Isoform 4 (identifier: O88917-4)

Also known as: CL1BA;

The sequence of this isoform differs from the canonical sequence as follows:
     1146-1189: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Ref.2
Chain25 – 15151491Latrophilin-1
PRO_0000012908

Regions

Topological domain25 – 857833Extracellular Potential
Transmembrane858 – 87821Helical; Name=1; Potential
Topological domain879 – 89214Cytoplasmic Potential
Transmembrane893 – 91321Helical; Name=2; Potential
Topological domain914 – 9196Extracellular Potential
Transmembrane920 – 94021Helical; Name=3; Potential
Topological domain941 – 96424Cytoplasmic Potential
Transmembrane965 – 98521Helical; Name=4; Potential
Topological domain986 – 100116Extracellular Potential
Transmembrane1002 – 102221Helical; Name=5; Potential
Topological domain1023 – 104927Cytoplasmic Potential
Transmembrane1050 – 107021Helical; Name=6; Potential
Topological domain1071 – 10744Extracellular Potential
Transmembrane1075 – 109521Helical; Name=7; Potential
Topological domain1096 – 1515420Cytoplasmic Potential
Domain40 – 12990SUEL-type lectin
Domain139 – 398260Olfactomedin-like
Domain798 – 84952GPS
Region117 – 1204Carbohydrate binding By similarity
Compositional bias413 – 4164Poly-Thr
Compositional bias1451 – 146111Poly-Pro

Sites

Binding site421Carbohydrate By similarity
Site837 – 8382Cleavage; by autocatalysis

Amino acid modifications

Glycosylation981N-linked (GlcNAc...) Potential
Glycosylation5311N-linked (GlcNAc...) Ref.10
Glycosylation6401N-linked (GlcNAc...) Ref.10
Glycosylation7411N-linked (GlcNAc...) Ref.10
Glycosylation8001N-linked (GlcNAc...) Ref.10
Glycosylation8051N-linked (GlcNAc...) Potential
Glycosylation8261N-linked (GlcNAc...) Ref.10
Disulfide bond41 ↔ 71 By similarity
Disulfide bond50 ↔ 128 By similarity
Disulfide bond83 ↔ 115 By similarity
Disulfide bond96 ↔ 102 By similarity
Disulfide bond140 ↔ 322 By similarity
Disulfide bond480 ↔ 515 Ref.10
Disulfide bond503 ↔ 532 Ref.10
Disulfide bond801 ↔ 832 Ref.10
Disulfide bond820 ↔ 834 Ref.10

Natural variations

Alternative sequence132 – 1376KVEQKV → I in isoform 2 and isoform 3.
VSP_050398
Alternative sequence1146 – 118944Missing in isoform 2 and isoform 4.
VSP_050399

Experimental info

Mutagenesis8021S → R: Strongly reduced cleavage. Ref.10
Mutagenesis8041W → I: Abolishes cleavage. Ref.10
Mutagenesis8151W → S: Abolishes cleavage. Abolishes cell surface localization. Ref.7
Mutagenesis8341C → S: Strongly reduced cleavage. Ref.7 Ref.10
Mutagenesis8341C → W: Abolishes cleavage. Abolishes cell surface localization. Ref.7 Ref.10
Mutagenesis8361H → S: Abolishes cleavage. No effect on cell surface localization. Ref.10
Mutagenesis8371L → A: Abolishes cleavage. No effect on cell surface localization. Ref.10
Mutagenesis8381T → G: Abolishes cleavage. No effect on cell surface localization. Ref.7 Ref.10
Mutagenesis8381T → P: Abolishes cleavage. Abolishes cell surface localization. Ref.7 Ref.10
Mutagenesis8401F → A: Strongly reduced cleavage. Ref.10

Secondary structure

....................................................... 1515
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (CL1BB) [UniParc].

Last modified November 1, 1998. Version 1.
Checksum: 0BF3B900C54F17B7

FASTA1,515166,615
        10         20         30         40         50         60 
MARLAAALWS LCVTTVLVTS 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 
AFPNPYQFVS SVDYNPRDNQ LYVWNNYFVV RYSLEFGPPD PSAGPATSPP LSTTTTARPT 

       430        440        450        460        470        480 
PLTSTASPAA TTPLRRAPLT THPVGAINQL GPDLPPATAP APSTRRPPAP 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 RFLAAKQNVV LEVTVLSTEG QVQELVFPQE YASESSIQLS ANTIKQNSRN 

       730        740        750        760        770        780 
GVVKVVFILY NNLGLFLSTE NATVKLAGEA GTGGPGGASL VVNSQVIAAS INKESSRVFL 

       790        800        810        820        830        840 
MDPVIFTVAH LEAKNHFNAN CSFWNYSERS MLGYWSTQGC RLVESNKTHT TCACSHLTNF 

       850        860        870        880        890        900 
AVLMAHREIY QGRINELLLS VITWVGIVIS LVCLAICIST FCFLRGLQTD RNTIHKNLCI 

       910        920        930        940        950        960 
NLFLAELLFL VGIDKTQYEV ACPIFAGLLH YFFLAAFSWL CLEGVHLYLL LVEVFESEYS 

       970        980        990       1000       1010       1020 
RTKYYYLGGY CFPALVVGIA AAIDYRSYGT EKACWLRVDN YFIWSFIGPV SFVIVVNLVF 

      1030       1040       1050       1060       1070       1080 
LMVTLHKMIR SSSVLKPDSS RLDNIKSWAL GAIALLFLLG LTWAFGLLFI NKESVVMAYL 

      1090       1100       1110       1120       1130       1140 
FTTFNAFQGV FIFVFHCALQ KKVHKEYSKC LRHSYCCIRS PPGGAHGSLK TSAMRSNTRY 

      1150       1160       1170       1180       1190       1200 
YTGTQVPGQG RHIHQVSLGP RGRSALPESQ KDPGGQSGPG DPLTFGLCPS RIRRMWNDTV 

      1210       1220       1230       1240       1250       1260 
RKQTESSFMA GDINSTPTLN RGTMGNHLLT NPVLQPRGGT SPYNTLIAES VGFNPSSPPV 

      1270       1280       1290       1300       1310       1320 
FNSPGSYREP KHPLGGREAC GMDTLPLNGN FNNSYSLRSG DFPPGDGGPE PPRGRNLADA 

      1330       1340       1350       1360       1370       1380 
AAFEKMIISE LVHNNLRGAS GGAKGPPPEP PVPPVPGVSE DEAGGPGGAD RAEIELLYKA 

      1390       1400       1410       1420       1430       1440 
LEEPLLLPRA QSVLYQSDLD ESESCTAEDG ATSRPLSSPP GRDSLYASGA NLRDSPSYPD 

      1450       1460       1470       1480       1490       1500 
SSPEGPNEAL PPPPPAPPGP PEIYYTSRPP ALVARNPLQG YYQVRRPSHE GYLAAPSLEG 

      1510 
PGPDGDGQMQ LVTSL 

« Hide

Isoform 2 (CL1AA) [UniParc].

Checksum: 5926609E031565F9
Show »

FASTA1,466161,545
Isoform 3 (CL1AB) [UniParc].

Checksum: 6A22505113DFCD5B
Show »

FASTA1,510166,016
Isoform 4 (CL1BA) [UniParc].

Checksum: 9F560F544B4191C6
Show »

FASTA1,471162,144

References

« Hide 'large scale' references
[1]"Alpha-latrotoxin receptor CIRL/latrophilin 1 (CL1) defines an unusual family of ubiquitous G-protein-linked receptors. G-protein coupling not required for triggering exocytosis."
Sugita S., Ichtchenko K., Khvotchev M., Suedhof T.C.
J. Biol. Chem. 273:32715-32724(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), TISSUE SPECIFICITY.
[2]"Alpha-latrotoxin stimulates exocytosis by the interaction with a neuronal G-protein-coupled receptor."
Krasnoperov V.G., Bittner M.A., Beavis R., Kuang Y., Salnikow K.V., Chepurny O.G., Little A.R., Plotnikov A.N., Wu D., Holz R.W., Petrenko A.G.
Neuron 18:925-937(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), PROTEIN SEQUENCE OF N-TERMINUS, PROTEIN SEQUENCE OF 838-850, PROTEOLYTIC PROCESSING, INTERACTION WITH SYNTAXIN.
[3]"Alpha-latrotoxin receptor, latrophilin, is a novel member of the secretin family of G protein-coupled receptors."
Lelianova V.G., Davletov B.A., Sterling A., Rahman M.A., Grishin E.V., Totty N.F., Ushkaryov Y.A.
J. Biol. Chem. 272:21504-21508(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PARTIAL PROTEIN SEQUENCE.
[4]"Isolation and biochemical characterization of a Ca2+-independent alpha-latrotoxin-binding protein."
Davletov B.A., Shamotienko O.G., Lelianova V.G., Grishin E.V., Ushkaryov Y.A.
J. Biol. Chem. 271:23239-23245(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION (ISOFORM 2).
Strain: Sprague-Dawley.
Tissue: Brain.
[5]"Structural requirements for alpha-latrotoxin binding and alpha-latrotoxin-stimulated secretion. A study with calcium-independent receptor of alpha-latrotoxin (CIRL) deletion mutants."
Krasnoperov V., Bittner M.A., Holz R.W., Chepurny O., Petrenko A.G.
J. Biol. Chem. 274:3590-3596(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[6]"The G protein-coupled receptor CL1 interacts directly with proteins of the Shank family."
Tobaben S., Suedhof T.C., Stahl B.
J. Biol. Chem. 275:36204-36210(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PROTEINS OF THE SHANK FAMILY.
[7]"Post-translational proteolytic processing of the calcium-independent receptor of alpha-latrotoxin (CIRL), a natural chimera of the cell adhesion protein and the G protein-coupled receptor. Role of the G protein-coupled receptor proteolysis site (GPS) motif."
Krasnoperov V., Lu Y., Buryanovsky L., Neubert T.A., Ichtchenko K., Petrenko A.G.
J. Biol. Chem. 277:46518-46526(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF TRP-815; CYS-834 AND THR-838.
[8]"Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites."
Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.
Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"Latrophilin 1 and its endogenous ligand Lasso/teneurin-2 form a high-affinity transsynaptic receptor pair with signaling capabilities."
Silva J.P., Lelianova V.G., Ermolyuk Y.S., Vysokov N., Hitchen P.G., Berninghausen O., Rahman M.A., Zangrandi A., Fidalgo S., Tonevitsky A.G., Dell A., Volynski K.E., Ushkaryov Y.A.
Proc. Natl. Acad. Sci. U.S.A. 108:12113-12118(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: TENM2 LIGAND-BINDING, INTERACTION WITH TENM2, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[10]"A novel evolutionarily conserved domain of cell-adhesion GPCRs mediates autoproteolysis."
Arac D., Boucard A.A., Bolliger M.F., Nguyen J., Soltis S.M., Sudhof T.C., Brunger A.T.
EMBO J. 31:1364-1378(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 460-850, GLYCOSYLATION AT ASN-531; ASN-640; ASN-741; ASN-800 AND ASN-826, DISULFIDE BONDS, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-802; TRP-804; CYS-834; HIS-836; LEU-837; THR-838 AND PHE-840, AUTOCATALYTIC PROCESSING.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF081144 mRNA. Translation: AAC62650.1.
AF081145 mRNA. Translation: AAC62651.1.
AF081146 mRNA. Translation: AAC62652.1.
AF081147 mRNA. Translation: AAC62653.1.
U72487 mRNA. Translation: AAC53268.1.
U78105 mRNA. Translation: AAC98700.1.
PIRT17138.
T17145.
T17149.
T17156.
RefSeqNP_075251.1. NM_022962.1. [O88917-4]
UniGeneRn.10776.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4DLQX-ray1.85A460-837[»]
B838-850[»]
ProteinModelPortalO88917.
SMRO88917. Positions 29-134.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid249249. 2 interactions.
IntActO88917. 1 interaction.
MINTMINT-143437.

Chemistry

GuidetoPHARMACOLOGY206.

Protein family/group databases

MEROPSS63.013.
GPCRDBSearch...

PTM databases

PhosphoSiteO88917.

Proteomic databases

PaxDbO88917.
PRIDEO88917.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID65096.
KEGGrno:65096.

Organism-specific databases

CTD22859.
RGD620768. Lphn1.

Phylogenomic databases

eggNOGNOG253931.
HOGENOMHOG000049065.
HOVERGENHBG052337.
InParanoidO88917.
KOK04592.
PhylomeDBO88917.

Gene expression databases

GenevestigatorO88917.

Family and domain databases

InterProIPR022624. 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]
PfamPF00002. 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]
PRINTSPR00249. GPCRSECRETIN.
PR01444. LATROPHILIN.
SMARTSM00303. GPS. 1 hit.
SM00008. HormR. 1 hit.
SM00284. OLF. 1 hit.
[Graphical view]
PROSITEPS00650. 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]
ProtoNetSearch...

Other

NextBio613919.
PROO88917.

Entry information

Entry nameLPHN1_RAT
AccessionPrimary (citable) accession number: O88917
Secondary accession number(s): O09026, O35818, O88916
Entry history
Integrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: November 1, 1998
Last modified: June 11, 2014
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries