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Protein

Adhesion G protein-coupled receptor L4

Gene

ADGRL4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Endothelial orphan receptor that acts as a key regulator of angiogenesis.1 Publication

GO - Molecular functioni

  • calcium ion binding Source: InterPro
  • G-protein coupled receptor activity Source: GDB

GO - Biological processi

  • cell surface receptor signaling pathway Source: InterPro
  • G-protein coupled receptor signaling pathway Source: GDB
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Ligandi

Calcium

Enzyme and pathway databases

BioCyciZFISH:ENSG00000162618-MONOMER.

Protein family/group databases

MEROPSiP02.013.
TCDBi9.A.14.6.3. the g-protein-coupled receptor (gpcr) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Adhesion G protein-coupled receptor L41 Publication
Alternative name(s):
EGF, latrophilin and seven transmembrane domain-containing protein 1
EGF-TM7-latrophilin-related protein
Short name:
ETL protein
Gene namesi
Name:ADGRL41 Publication
Synonyms:ELTD1, ETL
ORF Names:UNQ202/PRO228
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:20822. ADGRL4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini20 – 432ExtracellularCuratedAdd BLAST413
Transmembranei433 – 453Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini454 – 460CytoplasmicCurated7
Transmembranei461 – 481Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini482 – 499ExtracellularCuratedAdd BLAST18
Transmembranei500 – 520Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini521 – 532CytoplasmicCuratedAdd BLAST12
Transmembranei533 – 553Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini554 – 573ExtracellularCuratedAdd BLAST20
Transmembranei574 – 594Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini595 – 618CytoplasmicCuratedAdd BLAST24
Transmembranei619 – 639Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini640 – 646ExtracellularCurated7
Transmembranei647 – 667Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini668 – 690CytoplasmicCuratedAdd BLAST23

GO - Cellular componenti

  • cytoplasmic vesicle Source: UniProtKB
  • integral component of membrane Source: GDB
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi64123.
OpenTargetsiENSG00000162618.
PharmGKBiPA134946418.

Polymorphism and mutation databases

BioMutaiELTD1.
DMDMi212276505.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
ChainiPRO_000001287020 – 690Adhesion G protein-coupled receptor L4Add BLAST671

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi21N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi22 ↔ 33PROSITE-ProRule annotation
Disulfide bondi27 ↔ 42PROSITE-ProRule annotation
Disulfide bondi44 ↔ 56PROSITE-ProRule annotation
Disulfide bondi62 ↔ 75PROSITE-ProRule annotation
Glycosylationi64N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi69 ↔ 84PROSITE-ProRule annotation
Glycosylationi74N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi86 ↔ 107PROSITE-ProRule annotation
Glycosylationi127N-linked (GlcNAc...)Sequence analysis1
Glycosylationi177N-linked (GlcNAc...)Sequence analysis1
Glycosylationi188N-linked (GlcNAc...)Sequence analysis1
Glycosylationi249N-linked (GlcNAc...)1 Publication1
Glycosylationi381N-linked (GlcNAc...)Sequence analysis1
Glycosylationi395N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

Glycosylated.1 Publication
Proteolytically cleaved into 2 subunits, an extracellular alpha subunit and a seven-transmembrane subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei406 – 407CleavageBy similarity2

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ9HBW9.
PaxDbiQ9HBW9.
PeptideAtlasiQ9HBW9.
PRIDEiQ9HBW9.

PTM databases

iPTMnetiQ9HBW9.
PhosphoSitePlusiQ9HBW9.

Expressioni

Tissue specificityi

Detected in the majority of epithelial cells in tumor and normal tissues. Expressed also in human umbilical vein endothelial cells.1 Publication

Developmental stagei

Up-regulated in the adult heart.1 Publication

Inductioni

Up-regulated in tumor endothelial cells. Up-regulated by DLL4.1 Publication

Gene expression databases

BgeeiENSG00000162618.
CleanExiHS_ELTD1.
ExpressionAtlasiQ9HBW9. baseline and differential.
GenevisibleiQ9HBW9. HS.

Organism-specific databases

HPAiHPA025229.

Interactioni

Subunit structurei

Heterodimer of 2 chains generated by proteolytic processing; the large extracellular N-terminal fragment and the membrane-bound C-terminal fragment predominantly remain associated and non-covalently linked.By similarity1 Publication

Protein-protein interaction databases

BioGridi122076. 1 interactor.
IntActiQ9HBW9. 1 interactor.
STRINGi9606.ENSP00000359778.

Structurei

3D structure databases

ProteinModelPortaliQ9HBW9.
SMRiQ9HBW9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini20 – 57EGF-like 1PROSITE-ProRule annotationAdd BLAST38
Domaini58 – 108EGF-like 2; calcium-bindingPROSITE-ProRule annotationAdd BLAST51
Domaini367 – 418GPSPROSITE-ProRule annotationAdd BLAST52

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi326 – 329Poly-Glu4

Domaini

The transmembrane domain is not required for cleavage, but it is required for dimer formation.By similarity

Sequence similaritiesi

Contains 2 EGF-like domains.PROSITE-ProRule annotation
Contains 1 GPS domain.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4193. Eukaryota.
ENOG410XSD2. LUCA.
GeneTreeiENSGT00830000128227.
HOGENOMiHOG000112361.
HOVERGENiHBG101117.
InParanoidiQ9HBW9.
KOiK04595.
OMAiHLTKLMH.
OrthoDBiEOG091G00GJ.
PhylomeDBiQ9HBW9.
TreeFamiTF316380.

Family and domain databases

Gene3Di2.40.155.10. 1 hit.
InterProiIPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR032471. GAIN_dom_N.
IPR023413. GFP-like.
IPR017981. GPCR_2-like.
IPR000832. GPCR_2_secretin-like.
IPR017983. GPCR_2_secretin-like_CS.
IPR000203. GPS.
[Graphical view]
PfamiPF00002. 7tm_2. 1 hit.
PF07645. EGF_CA. 1 hit.
PF16489. GAIN. 1 hit.
PF01825. GPS. 1 hit.
[Graphical view]
PRINTSiPR00249. GPCRSECRETIN.
SMARTiSM00181. EGF. 2 hits.
SM00179. EGF_CA. 1 hit.
SM00303. GPS. 1 hit.
[Graphical view]
PROSITEiPS00010. ASX_HYDROXYL. 1 hit.
PS00018. EF_HAND_1. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 2 hits.
PS01187. EGF_CA. 1 hit.
PS00650. G_PROTEIN_RECEP_F2_2. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
PS50221. GPS. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q9HBW9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKRLPLLVVF STLLNCSYTQ NCTKTPCLPN AKCEIRNGIE ACYCNMGFSG
60 70 80 90 100
NGVTICEDDN ECGNLTQSCG ENANCTNTEG SYYCMCVPGF RSSSNQDRFI
110 120 130 140 150
TNDGTVCIEN VNANCHLDNV CIAANINKTL TKIRSIKEPV ALLQEVYRNS
160 170 180 190 200
VTDLSPTDII TYIEILAESS SLLGYKNNTI SAKDTLSNST LTEFVKTVNN
210 220 230 240 250
FVQRDTFVVW DKLSVNHRRT HLTKLMHTVE QATLRISQSF QKTTEFDTNS
260 270 280 290 300
TDIALKVFFF DSYNMKHIHP HMNMDGDYIN IFPKRKAAYD SNGNVAVAFV
310 320 330 340 350
YYKSIGPLLS SSDNFLLKPQ NYDNSEEEER VISSVISVSM SSNPPTLYEL
360 370 380 390 400
EKITFTLSHR KVTDRYRSLC AFWNYSPDTM NGSWSSEGCE LTYSNETHTS
410 420 430 440 450
CRCNHLTHFA ILMSSGPSIG IKDYNILTRI TQLGIIISLI CLAICIFTFW
460 470 480 490 500
FFSEIQSTRT TIHKNLCCSL FLAELVFLVG INTNTNKLFC SIIAGLLHYF
510 520 530 540 550
FLAAFAWMCI EGIHLYLIVV GVIYNKGFLH KNFYIFGYLS PAVVVGFSAA
560 570 580 590 600
LGYRYYGTTK VCWLSTENNF IWSFIGPACL IILVNLLAFG VIIYKVFRHT
610 620 630 640 650
AGLKPEVSCF ENIRSCARGA LALLFLLGTT WIFGVLHVVH ASVVTAYLFT
660 670 680 690
VSNAFQGMFI FLFLCVLSRK IQEEYYRLFK NVPCCFGCLR
Length:690
Mass (Da):77,811
Last modified:November 4, 2008 - v3
Checksum:i38BFEEBCEADDEFC8
GO

Sequence cautioni

The sequence AAG33021 differs from that shown. Reason: Erroneous initiation.Curated
The sequence AAH25721 differs from that shown. Reason: Erroneous initiation.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_047072300V → L.3 PublicationsCorresponds to variant rs12754818dbSNPEnsembl.1
Natural variantiVAR_047073599H → Q.Corresponds to variant rs1968956dbSNPEnsembl.1
Natural variantiVAR_047074620A → G.1 PublicationCorresponds to variant rs2275902dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB032017 mRNA. Translation: BAD83584.1.
AY358360 mRNA. Translation: AAQ88726.1.
AL596269, AC098651, AC099674 Genomic DNA. Translation: CAI13205.1.
CH471059 Genomic DNA. Translation: EAX06345.1.
BC025721 mRNA. Translation: AAH25721.1. Different initiation.
AF192403 mRNA. Translation: AAG33021.1. Different initiation.
CCDSiCCDS41352.1.
RefSeqiNP_071442.2. NM_022159.3.
UniGeneiHs.132314.

Genome annotation databases

EnsembliENST00000370742; ENSP00000359778; ENSG00000162618.
GeneIDi64123.
KEGGihsa:64123.
UCSCiuc001diq.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB032017 mRNA. Translation: BAD83584.1.
AY358360 mRNA. Translation: AAQ88726.1.
AL596269, AC098651, AC099674 Genomic DNA. Translation: CAI13205.1.
CH471059 Genomic DNA. Translation: EAX06345.1.
BC025721 mRNA. Translation: AAH25721.1. Different initiation.
AF192403 mRNA. Translation: AAG33021.1. Different initiation.
CCDSiCCDS41352.1.
RefSeqiNP_071442.2. NM_022159.3.
UniGeneiHs.132314.

3D structure databases

ProteinModelPortaliQ9HBW9.
SMRiQ9HBW9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122076. 1 interactor.
IntActiQ9HBW9. 1 interactor.
STRINGi9606.ENSP00000359778.

Protein family/group databases

MEROPSiP02.013.
TCDBi9.A.14.6.3. the g-protein-coupled receptor (gpcr) family.
GPCRDBiSearch...

PTM databases

iPTMnetiQ9HBW9.
PhosphoSitePlusiQ9HBW9.

Polymorphism and mutation databases

BioMutaiELTD1.
DMDMi212276505.

Proteomic databases

EPDiQ9HBW9.
PaxDbiQ9HBW9.
PeptideAtlasiQ9HBW9.
PRIDEiQ9HBW9.

Protocols and materials databases

DNASUi64123.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000370742; ENSP00000359778; ENSG00000162618.
GeneIDi64123.
KEGGihsa:64123.
UCSCiuc001diq.5. human.

Organism-specific databases

CTDi64123.
DisGeNETi64123.
GeneCardsiADGRL4.
H-InvDBHIX0000724.
HGNCiHGNC:20822. ADGRL4.
HPAiHPA025229.
MIMi616419. gene.
neXtProtiNX_Q9HBW9.
OpenTargetsiENSG00000162618.
PharmGKBiPA134946418.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4193. Eukaryota.
ENOG410XSD2. LUCA.
GeneTreeiENSGT00830000128227.
HOGENOMiHOG000112361.
HOVERGENiHBG101117.
InParanoidiQ9HBW9.
KOiK04595.
OMAiHLTKLMH.
OrthoDBiEOG091G00GJ.
PhylomeDBiQ9HBW9.
TreeFamiTF316380.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000162618-MONOMER.

Miscellaneous databases

GeneWikiiELTD1.
GenomeRNAii64123.
PROiQ9HBW9.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000162618.
CleanExiHS_ELTD1.
ExpressionAtlasiQ9HBW9. baseline and differential.
GenevisibleiQ9HBW9. HS.

Family and domain databases

Gene3Di2.40.155.10. 1 hit.
InterProiIPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR032471. GAIN_dom_N.
IPR023413. GFP-like.
IPR017981. GPCR_2-like.
IPR000832. GPCR_2_secretin-like.
IPR017983. GPCR_2_secretin-like_CS.
IPR000203. GPS.
[Graphical view]
PfamiPF00002. 7tm_2. 1 hit.
PF07645. EGF_CA. 1 hit.
PF16489. GAIN. 1 hit.
PF01825. GPS. 1 hit.
[Graphical view]
PRINTSiPR00249. GPCRSECRETIN.
SMARTiSM00181. EGF. 2 hits.
SM00179. EGF_CA. 1 hit.
SM00303. GPS. 1 hit.
[Graphical view]
PROSITEiPS00010. ASX_HYDROXYL. 1 hit.
PS00018. EF_HAND_1. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 2 hits.
PS01187. EGF_CA. 1 hit.
PS00650. G_PROTEIN_RECEP_F2_2. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
PS50221. GPS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAGRL4_HUMAN
AccessioniPrimary (citable) accession number: Q9HBW9
Secondary accession number(s): B1AR71, Q5KU34
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 16, 2004
Last sequence update: November 4, 2008
Last modified: November 2, 2016
This is version 143 of the entry and version 3 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 1
    Human chromosome 1: 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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.