Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Adhesion G protein-coupled receptor A2

Gene

Adgra2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Endothelial receptor which functions as a WNT7-specific coactivator of canonical Wnt signaling (PubMed:25373781, PubMed:25558062). Required for normal endothelial cell sprouting and migration in the forebrain and neural tube (PubMed:21071672, PubMed:21282641, PubMed:21421844, PubMed:25373781). Has a major role in establishing the blood-brain barrier (PubMed:21421844, PubMed:25373781). Binds to the glycosaminoglycans heparin, heparin sulfate, chondroitin sulfate and dermatan sulfate (By similarity).By similarity5 Publications

GO - Molecular functioni

GO - Biological processi

  • angiogenesis Source: MGI
  • cell surface receptor signaling pathway Source: InterPro
  • central nervous system development Source: UniProtKB
  • endothelial cell migration Source: UniProtKB
  • negative regulation of vascular endothelial growth factor signaling pathway Source: MGI
  • positive regulation of endothelial cell migration Source: MGI
  • regulation of angiogenesis Source: UniProtKB
  • regulation of chemotaxis Source: UniProtKB
  • regulation of establishment of blood-brain barrier Source: MGI
  • sprouting angiogenesis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Angiogenesis

Names & Taxonomyi

Protein namesi
Recommended name:
Adhesion G protein-coupled receptor A2Imported
Alternative name(s):
G-protein coupled receptor 124Imported
Tumor endothelial marker 51 Publication
Gene namesi
Name:Adgra2Imported
Synonyms:Gpr124Imported, Tem51 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:1925810. Adgra2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini34 – 769ExtracellularBy similarityAdd BLAST736
Transmembranei770 – 790Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini791 – 805CytoplasmicSequence analysisAdd BLAST15
Transmembranei806 – 826Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini827 – 830ExtracellularSequence analysis4
Transmembranei831 – 851Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini852 – 884CytoplasmicSequence analysisAdd BLAST33
Transmembranei885 – 905Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini906 – 922ExtracellularSequence analysisAdd BLAST17
Transmembranei923 – 943Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini944 – 1016CytoplasmicSequence analysisAdd BLAST73
Transmembranei1017 – 1037Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini1038 – 1044ExtracellularSequence analysis7
Transmembranei1045 – 1065Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini1066 – 1336CytoplasmicBy similarityAdd BLAST271

GO - Cellular componenti

  • cell surface Source: MGI
  • filopodium Source: UniProtKB-SubCell
  • integral component of membrane Source: UniProtKB-KW
  • plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane

Pathology & Biotechi

Disruption phenotypei

No viable adults (PubMed:21071672, PubMed:21282641, PubMed:21421844). Beginning at E11, deficient embryos exhibit completely penetrant, progressive CNS hemorrhage originating in forebrain telencephalon and ventral neural tube leading to embryonic lethality from E15.5 (PubMed:21071672, PubMed:21282641, PubMed:21421844). Embryos at E11.5 display selective CNS-specific vascular patterning defects, with markedly reduced angiogenic sprouting into the forebrain telencephalon and thickening of the underlying periventricular vascular plexus rendering the telencephalon virtually avascular (PubMed:21071672, PubMed:21282641, PubMed:21421844, PubMed:25373781). Remaining CNS vessels show significantly increased permeability (PubMed:21421844). Lung size is reduced in E15.5 embryos (PubMed:21282641). Cleft palate is present at E15.5 or later (PubMed:21282641).3 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi364D → E: No effect on potentiation of WNT7A signaling. 1 Publication1
Mutagenesisi1333 – 1336Missing : Fails to interact with DLG1. No effect on cell surface localization. 1 Publication4

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 33Sequence analysisAdd BLAST33
ChainiPRO_000001289934 – 1336Adhesion G protein-coupled receptor A2Add BLAST1303

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi84N-linked (GlcNAc...)Sequence analysis1
Glycosylationi101N-linked (GlcNAc...)Sequence analysis1
Glycosylationi162N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi268 ↔ 328PROSITE-ProRule annotation
Glycosylationi275N-linked (GlcNAc...)Sequence analysis1
Glycosylationi602N-linked (GlcNAc...)Sequence analysis1
Glycosylationi691N-linked (GlcNAc...)Sequence analysis1
Glycosylationi735N-linked (GlcNAc...)Sequence analysis1
Modified residuei1104PhosphoserineBy similarity1

Post-translational modificationi

Glycosylated.By similarity
Proteolytically cleaved into two subunits, an extracellular subunit and a seven-transmembrane subunit. Cleaved by thrombin (F2) and MMP1. Also cleaved by MMP9, with lower efficiency. Presence of the protein disulfide-isomerase P4HB at the cell surface is additionally required for shedding of the extracellular subunit, suggesting that the subunits are linked by disulfide bonds. Shedding is enhanced by the growth factor FGF2 and may promote cell survival during angiogenesis.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei369 – 370Cleavage; by thrombinBy similarity2
Sitei398 – 399Cleavage; by thrombinBy similarity2

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ91ZV8.
PaxDbiQ91ZV8.
PRIDEiQ91ZV8.

PTM databases

iPTMnetiQ91ZV8.
PhosphoSitePlusiQ91ZV8.

Expressioni

Tissue specificityi

Abundantly expressed in the vasculature of the developing embryo (PubMed:11559528, PubMed:21071672, PubMed:21282641). Expression in normal adult tissues is specifically vascular with endothelial expression in CNS, including brain and retina and more widespread pericyte expression in the brain and organs, including the kidney, pancreas and corpus luteum (PubMed:21071672).3 Publications

Developmental stagei

At embryonic day 10 (E10) expressed in a wide variety of tissues with relatively more abundant expression in limb buds (PubMed:18848646). At E10.5-E12.5, detected in vessels of the developing CNS and perineural vascular plexus (PNVP) (PubMed:21282641). Expressed in both endothelial cells and pericytes, most prominently in brain and neural tube, and to a lesser degrees in non-CNS embryonic organs, including the liver, heart, and kidney (PubMed:18848646, PubMed:21282641). Expressed also in embryonic epithelium of lung and esophagus and in mesenchyme (PubMed:18848646, PubMed:21282641). Detected in mesenchyme of the palatal shelf at E12.5 (PubMed:21282641).2 Publications

Inductioni

Up-regulated by the growth factors activin AB (INHBA: INHBB dimer) and TGFB1 in vitro.1 Publication

Gene expression databases

BgeeiENSMUSG00000031486.
CleanExiMM_GPR124.
ExpressionAtlasiQ91ZV8. baseline and differential.
GenevisibleiQ91ZV8. MM.

Interactioni

Subunit structurei

Interacts (via PDZ-binding motif) with DLG1 (via PDZ domains) (PubMed:25558062). The cleaved extracellular subunit interacts with the integrin heterodimer ITGAV:ITGB3 (By similarity).By similarity1 Publication

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000033876.

Structurei

3D structure databases

ProteinModelPortaliQ91ZV8.
SMRiQ91ZV8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati85 – 106LRR 1Sequence analysisAdd BLAST22
Repeati109 – 130LRR 2Sequence analysisAdd BLAST22
Repeati133 – 154LRR 3Sequence analysisAdd BLAST22
Repeati157 – 178LRR 4Sequence analysisAdd BLAST22
Domaini190 – 241LRRCTSequence analysisAdd BLAST52
Domaini247 – 344Ig-likePROSITE-ProRule annotationAdd BLAST98
Domaini708 – 756GPSPROSITE-ProRule annotationAdd BLAST49

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi362 – 364RGDBy similarity3
Motifi1333 – 1336PDZ-binding1 Publication4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi777 – 782Poly-LeuSequence analysis6
Compositional biasi1126 – 1129Poly-ProSequence analysis4

Domaini

The leucine-rich repeats (LRRs) are important for potentiation of WNT7 signaling.1 Publication
The RGD motif is involved in integrin ITGAV:ITGB3 binding.By similarity

Sequence similaritiesi

Contains 1 GPS domain.PROSITE-ProRule annotation
Contains 4 LRR (leucine-rich) repeats.Curated
Contains 1 LRRCT domain.Curated

Keywords - Domaini

Immunoglobulin domain, Leucine-rich repeat, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0619. Eukaryota.
COG4886. LUCA.
GeneTreeiENSGT00860000133701.
HOGENOMiHOG000112767.
HOVERGENiHBG051777.
InParanoidiQ91ZV8.
KOiK08461.
OMAiRTLCAYP.
OrthoDBiEOG091G03GB.
PhylomeDBiQ91ZV8.
TreeFamiTF331206.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
3.80.10.10. 1 hit.
InterProiIPR000483. Cys-rich_flank_reg_C.
IPR017981. GPCR_2-like.
IPR001879. GPCR_2_extracellular_dom.
IPR000832. GPCR_2_secretin-like.
IPR017983. GPCR_2_secretin-like_CS.
IPR000203. GPS.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
[Graphical view]
PfamiPF00002. 7tm_2. 1 hit.
PF01825. GPS. 1 hit.
PF13855. LRR_8. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 1 hit.
SM00369. LRR_TYP. 4 hits.
SM00082. LRRCT. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
SSF52058. SSF52058. 1 hit.
PROSITEiPS00650. 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.
PS50835. IG_LIKE. 1 hit.
PS51450. LRR. 3 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q91ZV8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGAGGRRMPV PPARLLLLPL LPCLLLLAPG TRGAPGCPVP IRGCKCSGER
60 70 80 90 100
PKGLSGGAHN PARRRVVCGG GDLPEPPDPG LLPNGTITLL LSNNKITGLR
110 120 130 140 150
NGSFLGLSLL EKLDLRSNVI STVQPGAFLG LGELKRLDLS NNRIGCLTSE
160 170 180 190 200
TFQGLPRLLR LNISGNIYSS LQPGVFDELP ALKIVDFGTE FLTCDCRLRW
210 220 230 240 250
LLPWARNHSL QLSERTLCAY PSALHAHALS SLQESQLRCE GALELHTHYL
260 270 280 290 300
IPSLRQVVFQ GDRLPFQCSA SYLGNDTRIH WYHNGAPMES DEQAGIVLAE
310 320 330 340 350
NLIHDCTFIT SELTLSHIGV WASGEWECSV STVQGNTSKK VEIVVLETSA
360 370 380 390 400
SYCPAERVTN NRGDFRWPRT LAGITAYQSC LQYPFTSVPL SGGAPGTRAS
410 420 430 440 450
RRCDRAGRWE PGDYSHCLYT NDITRVLYTF VLMPINASNA LTLAHQLRVY
460 470 480 490 500
TAEAASFSDM MDVVYVAQMI QKFLGYVDQI KELVEVMVDM ASNLMLVDEH
510 520 530 540 550
LLWLAQREDK ACSGIVGALE RIGGAALSPH AQHISVNSRN VALEAYLIKP
560 570 580 590 600
HSYVGLTCTA FQRREVGVSG AQPSSVGQDA PVEPEPLADQ QLRFRCTTGR
610 620 630 640 650
PNISLSSFHI KNSVALASIQ LPPSLFSTLP AALAPPVPPD CTLQLLVFRN
660 670 680 690 700
GRLFRSHGNN TSRPGAAGPG KRRGVATPVI FAGTSGCGVG NLTEPVAVSL
710 720 730 740 750
RHWAEGADPM AAWWNQDGPG GWSSEGCRLR YSQPNVSSLY CQHLGNVAVL
760 770 780 790 800
MELNAFPREA GGSGAGLHPV VYPCTALLLL CLFSTIITYI LNHSSIHVSR
810 820 830 840 850
KGWHMLLNLC FHMAMTSAVF VGGVTLTNYQ MVCQAVGITL HYSSLSSLLW
860 870 880 890 900
MGVKARVLHK ELSWRAPPLE EGEAAPPGPR PMLRFYLIAG GIPLIICGIT
910 920 930 940 950
AAVNIHNYRD HSPYCWLVWR PSLGAFYIPV ALILPITWIY FLCAGLHLRS
960 970 980 990 1000
HVAQNPKQGN RISLEPGEEL RGSTRLRSSG VLLNDSGSLL ATVSAGVGTP
1010 1020 1030 1040 1050
APPEDGDGVY SPGVQLGALM TTHFLYLAMW ACGALAVSQR WLPRVVCSCL
1060 1070 1080 1090 1100
YGVAASALGL FVFTHHCARR RDVRASWRAC CPPASPSASH VPARALPTAT
1110 1120 1130 1140 1150
EDGSPVLGEG PASLKSSPSG SSGRAPPPPC KLTNLQVAQS QVCEASVAAR
1160 1170 1180 1190 1200
GDGEPEPTGS RGSLAPRHHN NLHHGRRVHK SRAKGHRAGE TGGKSRLKAL
1210 1220 1230 1240 1250
RAGTSPGAPE LLSSESGSLH NSPSDSYPGS SRNSPGDGLP LEGEPMLTPS
1260 1270 1280 1290 1300
EGSDTSAAPI AETGRPGQRR SASRDNLKGS GSALERESKR RSYPLNTTSL
1310 1320 1330
NGAPKGGKYE DASVTGAEAI AGGSMKTGLW KSETTV
Length:1,336
Mass (Da):143,170
Last modified:January 20, 2009 - v2
Checksum:iC65354E5331F049F
GO

Sequence cautioni

The sequence AAI38452 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAI38453 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAL11996 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF378759 mRNA. Translation: AAL11996.1. Different initiation.
BC138451 mRNA. Translation: AAI38452.1. Different initiation.
BC138452 mRNA. Translation: AAI38453.1. Different initiation.
CCDSiCCDS22210.2.
RefSeqiNP_473385.2. NM_054044.2.
UniGeneiMm.87046.

Genome annotation databases

EnsembliENSMUST00000033876; ENSMUSP00000033876; ENSMUSG00000031486.
GeneIDi78560.
KEGGimmu:78560.
UCSCiuc009lhx.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF378759 mRNA. Translation: AAL11996.1. Different initiation.
BC138451 mRNA. Translation: AAI38452.1. Different initiation.
BC138452 mRNA. Translation: AAI38453.1. Different initiation.
CCDSiCCDS22210.2.
RefSeqiNP_473385.2. NM_054044.2.
UniGeneiMm.87046.

3D structure databases

ProteinModelPortaliQ91ZV8.
SMRiQ91ZV8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000033876.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiQ91ZV8.
PhosphoSitePlusiQ91ZV8.

Proteomic databases

MaxQBiQ91ZV8.
PaxDbiQ91ZV8.
PRIDEiQ91ZV8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000033876; ENSMUSP00000033876; ENSMUSG00000031486.
GeneIDi78560.
KEGGimmu:78560.
UCSCiuc009lhx.2. mouse.

Organism-specific databases

CTDi25960.
MGIiMGI:1925810. Adgra2.

Phylogenomic databases

eggNOGiKOG0619. Eukaryota.
COG4886. LUCA.
GeneTreeiENSGT00860000133701.
HOGENOMiHOG000112767.
HOVERGENiHBG051777.
InParanoidiQ91ZV8.
KOiK08461.
OMAiRTLCAYP.
OrthoDBiEOG091G03GB.
PhylomeDBiQ91ZV8.
TreeFamiTF331206.

Miscellaneous databases

PROiQ91ZV8.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000031486.
CleanExiMM_GPR124.
ExpressionAtlasiQ91ZV8. baseline and differential.
GenevisibleiQ91ZV8. MM.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
3.80.10.10. 1 hit.
InterProiIPR000483. Cys-rich_flank_reg_C.
IPR017981. GPCR_2-like.
IPR001879. GPCR_2_extracellular_dom.
IPR000832. GPCR_2_secretin-like.
IPR017983. GPCR_2_secretin-like_CS.
IPR000203. GPS.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
[Graphical view]
PfamiPF00002. 7tm_2. 1 hit.
PF01825. GPS. 1 hit.
PF13855. LRR_8. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 1 hit.
SM00369. LRR_TYP. 4 hits.
SM00082. LRRCT. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
SSF52058. SSF52058. 1 hit.
PROSITEiPS00650. 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.
PS50835. IG_LIKE. 1 hit.
PS51450. LRR. 3 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAGRA2_MOUSE
AccessioniPrimary (citable) accession number: Q91ZV8
Secondary accession number(s): B2RRK0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: January 20, 2009
Last modified: November 30, 2016
This is version 126 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

It is uncertain whether Met-1 or Met-8 is the initiator.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. 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.