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Protein

Adhesion G protein-coupled receptor L3

Gene

ADGRL3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Plays a role in cell-cell adhesion and neuron guidance via its interactions with FLRT2 and FLRT3 that are expressed at the surface of adjacent cells (PubMed:26235030). Plays a role in the development of glutamatergic synapses in the cortex. Important in determining the connectivity rates between the principal neurons in the cortex.By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi264CalciumCombined sources1 Publication1
Metal bindingi312CalciumCombined sources1 Publication1
Metal bindingi313Calcium; via carbonyl oxygenCombined sources1 Publication1
Metal bindingi367Calcium; via carbonyl oxygenCombined sources1 Publication1

GO - Molecular functioni

  • calcium ion binding Source: UniProtKB
  • carbohydrate binding Source: UniProtKB-KW
  • G-protein coupled receptor activity Source: GDB

GO - Biological processi

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer
LigandCalcium, Lectin, Metal-binding

Protein family/group databases

MEROPSiP02.011

Names & Taxonomyi

Protein namesi
Recommended name:
Adhesion G protein-coupled receptor L3Imported
Alternative name(s):
Calcium-independent alpha-latrotoxin receptor 3By similarity
Short name:
CIRL-3By similarity
Latrophilin-3Imported
Lectomedin-3
Gene namesi
Name:ADGRL3Imported
Synonyms:KIAA0768Imported, LEC3Imported, LPHN3Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000150471.15
HGNCiHGNC:20974 ADGRL3
MIMi616417 gene
neXtProtiNX_Q9HAR2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini20 – 866ExtracellularSequence analysisAdd BLAST847
Transmembranei867 – 889Helical; Name=1Sequence analysisAdd BLAST23
Topological domaini890 – 901CytoplasmicSequence analysisAdd BLAST12
Transmembranei902 – 919Helical; Name=2Sequence analysisAdd BLAST18
Topological domaini920 – 933ExtracellularSequence analysisAdd BLAST14
Transmembranei934 – 956Helical; Name=3Sequence analysisAdd BLAST23
Topological domaini957 – 968CytoplasmicSequence analysisAdd BLAST12
Transmembranei969 – 988Helical; Name=4Sequence analysisAdd BLAST20
Topological domaini989 – 1007ExtracellularSequence analysisAdd BLAST19
Transmembranei1008 – 1030Helical; Name=5Sequence analysisAdd BLAST23
Topological domaini1031 – 1049CytoplasmicSequence analysisAdd BLAST19
Transmembranei1050 – 1072Helical; Name=6Sequence analysisAdd BLAST23
Topological domaini1073 – 1081ExtracellularSequence analysis9
Transmembranei1082 – 1104Helical; Name=7Sequence analysisAdd BLAST23
Topological domaini1105 – 1447CytoplasmicSequence analysisAdd BLAST343

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi249 – 252YHDT → AHAA: Strongly reduces FLRT3 binding. Abolishes FLRT3 binding; when associated with A-308. 1 Publication4
Mutagenesisi308R → A: Abolishes FLRT3 binding; when associated with 249-A--A-252. 1 Publication1

Organism-specific databases

DisGeNETi23284
OpenTargetsiENSG00000150471
PharmGKBiPA134968284

Polymorphism and mutation databases

BioMutaiLPHN3
DMDMi47116772

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
ChainiPRO_000001291320 – 1447Adhesion G protein-coupled receptor L3Add BLAST1428

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi36 ↔ 66Combined sources1 Publication
Disulfide bondi45 ↔ 123Combined sources1 Publication
Disulfide bondi78 ↔ 110Combined sources1 Publication
Disulfide bondi91 ↔ 97Combined sources1 Publication
Glycosylationi93N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi135 ↔ 317PROSITE-ProRule annotationCombined sources1 Publication
Glycosylationi464N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi549N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi746N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi759N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi804N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi830N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1076N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei1164PhosphoserineBy similarity1

Post-translational modificationi

Proteolytically cleaved into 2 subunits, an extracellular subunit and a seven-transmembrane subunit.By similarity
O-glycosylated (major) and N-glycosylated.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei841 – 842CleavageBy similarity2

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ9HAR2
PaxDbiQ9HAR2
PeptideAtlasiQ9HAR2
PRIDEiQ9HAR2
ProteomicsDBi81420
81421 [Q9HAR2-2]
81422 [Q9HAR2-3]

PTM databases

iPTMnetiQ9HAR2
PhosphoSitePlusiQ9HAR2
SwissPalmiQ9HAR2

Expressioni

Gene expression databases

BgeeiENSG00000150471
CleanExiHS_LPHN3
ExpressionAtlasiQ9HAR2 baseline and differential
GenevisibleiQ9HAR2 HS

Organism-specific databases

HPAiCAB022698
HPA015027
HPA015762

Interactioni

Subunit structurei

Interacts (via olfactomedin-like domain) with FLRT3 (via extracellular domain); the interaction is direct (PubMed:26235030). Identified in a complex with FLRT3 and UNC5B; does not interact with UNC5B by itself (PubMed:26235030). Identified in a complex with FLRT3 and UNC5D; does not interact with UNC5D by itself (PubMed:26235030). Interacts (via olfactomedin-like domain) with FLRT1 (via extracellular domain). Interacts (via olfactomedin-like domain) with FLRT2 (via extracellular domain). Interacts (via extracellular domain) with TENM1. Interacts (via extracellular domain) with TENM3 (By similarity).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
FLRT3Q9NZU04EBI-2689295,EBI-1057092

Protein-protein interaction databases

BioGridi116882, 10 interactors
CORUMiQ9HAR2
DIPiDIP-56228N
IntActiQ9HAR2, 2 interactors
STRINGi9606.ENSP00000422533

Structurei

3D structure databases

ProteinModelPortaliQ9HAR2
SMRiQ9HAR2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini35 – 124SUEL-type lectinPROSITE-ProRule annotationAdd BLAST90
Domaini134 – 393Olfactomedin-likePROSITE-ProRule annotationAdd BLAST260
Domaini802 – 853GPSPROSITE-ProRule annotationAdd BLAST52

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni249 – 279Interaction with FLRT31 PublicationAdd BLAST31

Domaini

The Olfactomedin-like domain is required for the synapse-promoting function and the interaction with FLRT3. The Olfactomedin-like and the SUEL-type lectin domains are required for the interaction with TENM1 (By similarity).By similarity

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3545 Eukaryota
KOG4193 Eukaryota
KOG4729 Eukaryota
ENOG410XSD2 LUCA
GeneTreeiENSGT00900000140800
HOGENOMiHOG000049065
HOVERGENiHBG052337
InParanoidiQ9HAR2
KOiK04594
PhylomeDBiQ9HAR2
TreeFamiTF351999

Family and domain databases

Gene3Di4.10.1240.10, 1 hit
InterProiView protein in InterPro
IPR032471 GAIN_dom_N
IPR017981 GPCR_2-like
IPR036445 GPCR_2_extracell_dom_sf
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
IPR015630 Latrophilin-3
IPR000922 Lectin_gal-bd_dom
IPR003112 Olfac-like_dom
PANTHERiPTHR12011:SF60 PTHR12011:SF60, 1 hit
PfamiView protein in Pfam
PF00002 7tm_2, 1 hit
PF16489 GAIN, 1 hit
PF02140 Gal_Lectin, 1 hit
PF01825 GPS, 1 hit
PF02793 HRM, 1 hit
PF02354 Latrophilin, 2 hits
PF02191 OLF, 1 hit
PRINTSiPR00249 GPCRSECRETIN
PR01444 LATROPHILIN
SMARTiView protein in SMART
SM00303 GPS, 1 hit
SM00008 HormR, 1 hit
SM00284 OLF, 1 hit
PROSITEiView protein in 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

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9HAR2-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MWPSQLLIFM MLLAPIIHAF SRAPIPMAVV RRELSCESYP IELRCPGTDV
60 70 80 90 100
IMIESANYGR TDDKICDSDP AQMENIRCYL PDAYKIMSQR CNNRTQCAVV
110 120 130 140 150
AGPDVFPDPC PGTYKYLEVQ YECVPYKVEQ KVFLCPGLLK GVYQSEHLFE
160 170 180 190 200
SDHQSGAWCK DPLQASDKIY YMPWTPYRTD TLTEYSSKDD FIAGRPTTTY
210 220 230 240 250
KLPHRVDGTG FVVYDGALFF NKERTRNIVK FDLRTRIKSG EAIIANANYH
260 270 280 290 300
DTSPYRWGGK SDIDLAVDEN GLWVIYATEQ NNGKIVISQL NPYTLRIEGT
310 320 330 340 350
WDTAYDKRSA SNAFMICGIL YVVKSVYEDD DNEATGNKID YIYNTDQSKD
360 370 380 390 400
SLVDVPFPNS YQYIAAVDYN PRDNLLYVWN NYHVVKYSLD FGPLDSRSGQ
410 420 430 440 450
AHHGQVSYIS PPIHLDSELE RPSVKDISTT GPLGMGSTTT STTLRTTTLS
460 470 480 490 500
PGRSTTPSVS GRRNRSTSTP SPAVEVLDDM TTHLPSASSQ IPALEESCEA
510 520 530 540 550
VEAREIMWFK TRQGQIAKQP CPAGTIGVST YLCLAPDGIW DPQGPDLSNC
560 570 580 590 600
SSPWVNHITQ KLKSGETAAN IARELAEQTR NHLNAGDITY SVRAMDQLVG
610 620 630 640 650
LLDVQLRNLT PGGKDSAARS LNKAMVETVN NLLQPQALNA WRDLTTSDQL
660 670 680 690 700
RAATMLLHTV EESAFVLADN LLKTDIVREN TDNIKLEVAR LSTEGNLEDL
710 720 730 740 750
KFPENMGHGS TIQLSANTLK QNGRNGEIRV AFVLYNNLGP YLSTENASMK
760 770 780 790 800
LGTEALSTNH SVIVNSPVIT AAINKEFSNK VYLADPVVFT VKHIKQSEEN
810 820 830 840 850
FNPNCSFWSY SKRTMTGYWS TQGCRLLTTN KTHTTCSCNH LTNFAVLMAH
860 870 880 890 900
VEVKHSDAVH DLLLDVITWV GILLSLVCLL ICIFTFCFFR GLQSDRNTIH
910 920 930 940 950
KNLCISLFVA ELLFLIGINR TDQPIACAVF AALLHFFFLA AFTWMFLEGV
960 970 980 990 1000
QLYIMLVEVF ESEHSRRKYF YLVGYGMPAL IVAVSAAVDY RSYGTDKVCW
1010 1020 1030 1040 1050
LRLDTYFIWS FIGPATLIIM LNVIFLGIAL YKMFHHTAIL KPESGCLDNI
1060 1070 1080 1090 1100
KSWVIGAIAL LCLLGLTWAF GLMYINESTV IMAYLFTIFN SLQGMFIFIF
1110 1120 1130 1140 1150
HCVLQKKVRK EYGKCLRTHC CSGKSTESSI GSGKTSGSRT PGRYSTGSQS
1160 1170 1180 1190 1200
RIRRMWNDTV RKQSESSFIT GDINSSASLN REGLLNNARD TSVMDTLPLN
1210 1220 1230 1240 1250
GNHGNSYSIA SGEYLSNCVQ IIDRGYNHNE TALEKKILKE LTSNYIPSYL
1260 1270 1280 1290 1300
NNHERSSEQN RNLMNKLVNN LGSGREDDAI VLDDATSFNH EESLGLELIH
1310 1320 1330 1340 1350
EESDAPLLPP RVYSTENHQP HHYTRRRIPQ DHSESFFPLL TNEHTEDLQS
1360 1370 1380 1390 1400
PHRDSLYTSM PTLAGVAATE SVTTSTQTEP PPAKCGDAED VYYKSMPNLG
1410 1420 1430 1440
SRNHVHQLHT YYQLGRGSSD GFIVPPNKDG TPPEGSSKGP AHLVTSL
Length:1,447
Mass (Da):161,812
Last modified:May 10, 2004 - v2
Checksum:i54B7E7DBE516447A
GO
Isoform 2 (identifier: Q9HAR2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     623-623: K → KLQKRERSCRAYVQ
     1050-1050: I → INYEDNRPFI
     1183-1218: GLLNNARDTSVMDTLPLNGNHGNSYSIASGEYLSNC → PYRETSMGVKLNIAYQIGASEQCQGYKCHGYSTTEW
     1219-1447: Missing.

Show »
Length:1,240
Mass (Da):139,280
Checksum:iE357F856B07AE142
GO
Isoform 3 (identifier: Q9HAR2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     668-707: ADNLLKTDIV...EDLKFPENMG → VLQVCLPVRE...PLKFRLAKNK
     708-1447: Missing.

Note: No experimental confirmation available.
Show »
Length:707
Mass (Da):79,337
Checksum:i0AB57B9A7361496E
GO
Isoform 4 (identifier: Q9HAR2-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     623-623: K → KLQKRERSCRAYVQ
     1050-1050: I → INYEDNRPFI

Show »
Length:1,469
Mass (Da):164,580
Checksum:i660D0446D584C7F4
GO

Sequence cautioni

The sequence BAA91375 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_064477247A → S1 Publication1
Natural variantiVAR_055934465R → Q1 PublicationCorresponds to variant dbSNP:rs35106420Ensembl.1
Natural variantiVAR_064478770T → M1 Publication1
Natural variantiVAR_064479915L → V1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_010235623K → KLQKRERSCRAYVQ in isoform 2 and isoform 4. 1 Publication1
Alternative sequenceiVSP_010236668 – 707ADNLL…PENMG → VLQVCLPVREQSFLPFFSFF IFFFSFLPFIPLKFRLAKNK in isoform 3. 1 PublicationAdd BLAST40
Alternative sequenceiVSP_010237708 – 1447Missing in isoform 3. 1 PublicationAdd BLAST740
Alternative sequenceiVSP_0102381050I → INYEDNRPFI in isoform 2 and isoform 4. 1 Publication1
Alternative sequenceiVSP_0102391183 – 1218GLLNN…YLSNC → PYRETSMGVKLNIAYQIGAS EQCQGYKCHGYSTTEW in isoform 2. 1 PublicationAdd BLAST36
Alternative sequenceiVSP_0102401219 – 1447Missing in isoform 2. 1 PublicationAdd BLAST229

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF307080 mRNA Translation: AAG27462.1
AK000781 mRNA Translation: BAA91375.1 Different initiation.
AC007511 Genomic DNA No translation available.
AC020741 Genomic DNA No translation available.
AC092643 Genomic DNA No translation available.
AC092663 Genomic DNA No translation available.
AC092668 Genomic DNA No translation available.
AC096723 Genomic DNA No translation available.
AC104813 Genomic DNA No translation available.
AC108161 Genomic DNA No translation available.
AB018311 mRNA Translation: BAA34488.1
CCDSiCCDS54768.1 [Q9HAR2-4]
CCDS82926.1 [Q9HAR2-2]
RefSeqiNP_001309175.1, NM_001322246.1 [Q9HAR2-2]
NP_001309331.1, NM_001322402.1
NP_056051.2, NM_015236.5 [Q9HAR2-4]
UniGeneiHs.28391
Hs.570770

Genome annotation databases

EnsembliENST00000512091; ENSP00000423388; ENSG00000150471 [Q9HAR2-2]
ENST00000514591; ENSP00000422533; ENSG00000150471 [Q9HAR2-4]
GeneIDi23284
KEGGihsa:23284
UCSCiuc003hcq.5 human [Q9HAR2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiAGRL3_HUMAN
AccessioniPrimary (citable) accession number: Q9HAR2
Secondary accession number(s): E9PE04, O94867, Q9NWK5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: May 10, 2004
Last modified: July 18, 2018
This is version 140 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

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