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Protein

Lysophosphatidic acid receptor 1

Gene

LPAR1

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

Functioni

Receptor for lysophosphatidic acid (LPA) (PubMed:9070858, PubMed:19306925, PubMed:25025571, PubMed:26091040). Plays a role in the reorganization of the actin cytoskeleton, cell migration, differentiation and proliferation, and thereby contributes to the responses to tissue damage and infectious agents. Activates downstream signaling cascades via the G(i)/G(o), G(12)/G(13), and G(q) families of heteromeric G proteins. Signaling inhibits adenylyl cyclase activity and decreases cellular cAMP levels (PubMed:26091040). Signaling triggers an increase of cytoplasmic Ca2+ levels (PubMed:19656035, PubMed:19733258, PubMed:26091040). Activates RALA; this leads to the activation of phospholipase C (PLC) and the formation of inositol 1,4,5-trisphosphate (PubMed:19306925). Signaling mediates activation of down-stream MAP kinases (By similarity). Contributes to the regulation of cell shape. Promotes Rho-dependent reorganization of the actin cytoskeleton in neuronal cells and neurite retraction (PubMed:26091040). Promotes the activation of Rho and the formation of actin stress fibers (PubMed:26091040). Promotes formation of lamellipodia at the leading edge of migrating cells via activation of RAC1 (By similarity). Through its function as lysophosphatidic acid receptor, plays a role in chemotaxis and cell migration, including responses to injury and wounding (PubMed:18066075, PubMed:19656035, PubMed:19733258). Plays a role in triggering inflammation in response to bacterial lipopolysaccharide (LPS) via its interaction with CD14. Promotes cell proliferation in response to lysophosphatidic acid. Required for normal skeleton development. May play a role in osteoblast differentiation. Required for normal brain development. Required for normal proliferation, survival and maturation of newly formed neurons in the adult dentate gyrus. Plays a role in pain perception and in the initiation of neuropathic pain (By similarity).By similarity2 Publications7 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei39 – 391Lysophosphatidic acid1 Publication
Binding sitei210 – 2101Lysophosphatidic acid1 Publication

GO - Molecular functioni

  • G-protein coupled receptor activity Source: ProtInc
  • lysophosphatidic acid binding Source: UniProtKB
  • lysophosphatidic acid receptor activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Ligandi

Lipid-binding

Enzyme and pathway databases

ReactomeiR-HSA-416476. G alpha (q) signalling events.
R-HSA-418594. G alpha (i) signalling events.
R-HSA-419408. Lysosphingolipid and LPA receptors.
SIGNORiQ92633.

Chemistry

SwissLipidsiSLP:000001567.

Names & Taxonomyi

Protein namesi
Recommended name:
Lysophosphatidic acid receptor 1
Short name:
LPA receptor 1
Short name:
LPA-1
Alternative name(s):
Lysophosphatidic acid receptor Edg-21 Publication
Gene namesi
Name:LPAR1
Synonyms:EDG2, LPA1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:3166. LPAR1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 5050ExtracellularAdd
BLAST
Transmembranei51 – 7525Helical; Name=1Add
BLAST
Topological domaini76 – 838Cytoplasmic
Transmembranei84 – 10724Helical; Name=2Add
BLAST
Topological domaini108 – 12114ExtracellularAdd
BLAST
Transmembranei122 – 14423Helical; Name=3Add
BLAST
Topological domaini145 – 16319CytoplasmicAdd
BLAST
Transmembranei164 – 18421Helical; Name=4Add
BLAST
Topological domaini185 – 20420ExtracellularAdd
BLAST
Transmembranei205 – 22521Helical; Name=5Add
BLAST
Topological domaini226 – 25530CytoplasmicAdd
BLAST
Transmembranei256 – 28025Helical; Name=6Add
BLAST
Topological domaini281 – 29414ExtracellularAdd
BLAST
Transmembranei295 – 31521Helical; Name=7Add
BLAST
Topological domaini316 – 36449CytoplasmicAdd
BLAST

GO - Cellular componenti

  • cell surface Source: UniProtKB
  • dendritic shaft Source: Ensembl
  • dendritic spine Source: Ensembl
  • endosome Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • neuronal cell body Source: Ensembl
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi85 – 851Y → A: Impairs localization at the cell membrane. 1 Publication
Mutagenesisi87 – 871L → A: Impairs localization at the cell membrane. 1 Publication
Mutagenesisi325 – 3262IL → AA: Impairs localization at the cell membrane. 1 Publication

Organism-specific databases

PharmGKBiPA162394187.

Chemistry

ChEMBLiCHEMBL3819.
GuidetoPHARMACOLOGYi272.

Polymorphism and mutation databases

BioMutaiLPAR1.
DMDMi26454626.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 364364Lysophosphatidic acid receptor 1PRO_0000069417Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi24 ↔ 190Combined sources
Glycosylationi27 – 271N-linked (GlcNAc...)Sequence analysis
Glycosylationi35 – 351N-linked (GlcNAc...)Sequence analysis
Disulfide bondi188 ↔ 195Combined sources
Disulfide bondi284 ↔ 287Combined sources
Modified residuei341 – 3411PhosphoserineCombined sources
Modified residuei351 – 3511PhosphothreonineBy similarity

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ92633.
PaxDbiQ92633.
PeptideAtlasiQ92633.
PRIDEiQ92633.

PTM databases

iPTMnetiQ92633.
PhosphoSiteiQ92633.
SwissPalmiQ92633.

Expressioni

Tissue specificityi

Expressed in many adult organs, including brain, heart, colon, small intestine, placenta, prostate, ovary, pancreas, testes, spleen, skeletal muscle, and kidney. Little or no expression in liver, lung, thymus, or peripheral blood leukocytes (PubMed:9070858). Detected in lung fibroblasts from bronchoalveolar fluid from patients with idiopathic pulmonary fibrosis (PubMed:18066075). Detected in bone marrow-derived mesenchymal stem cells (PubMed:19733258).3 Publications

Gene expression databases

BgeeiENSG00000198121.
CleanExiHS_LPAR1.
ExpressionAtlasiQ92633. baseline and differential.
GenevisibleiQ92633. HS.

Organism-specific databases

HPAiHPA050667.

Interactioni

Subunit structurei

Interacts with RALA and ADRBK1 (PubMed:19306925). Interacts with GNAQ and GNA13. Interacts with CD14; the interaction is enhanced by exposure to bacterial lipopolysaccharide (LPS) (By similarity).By similarity1 Publication

Protein-protein interaction databases

BioGridi108226. 143 interactions.
IntActiQ92633. 2 interactions.
STRINGi9606.ENSP00000351755.

Chemistry

BindingDBiQ92633.

Structurei

Secondary structure

1
364
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi30 – 367Combined sources
Helixi47 – 7630Combined sources
Helixi78 – 803Combined sources
Helixi83 – 10624Combined sources
Helixi110 – 1134Combined sources
Helixi118 – 15134Combined sources
Helixi158 – 17821Combined sources
Helixi181 – 1833Combined sources
Helixi192 – 1943Combined sources
Helixi204 – 23229Combined sources
Helixi248 – 28336Combined sources
Turni285 – 2873Combined sources
Helixi294 – 31421Combined sources
Helixi316 – 32611Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4Z34X-ray3.00A2-232[»]
A248-326[»]
4Z35X-ray2.90A2-232[»]
A248-326[»]
4Z36X-ray2.90A2-232[»]
A249-326[»]
ProteinModelPortaliQ92633.
SMRiQ92633. Positions 23-232, 248-326.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni124 – 1296Lysophosphatidic acid binding1 Publication

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000118804.
HOGENOMiHOG000233501.
HOVERGENiHBG103071.
InParanoidiQ92633.
KOiK04289.
OMAiCCQRQEN.
OrthoDBiEOG091G0DD4.
PhylomeDBiQ92633.
TreeFamiTF330052.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR004065. LPA_rcpt.
IPR002277. LPA_rcpt_EDG2.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR01148. EDG2RECEPTOR.
PR00237. GPCRRHODOPSN.
PR01527. LPARECEPTOR.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q92633-1) [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
MAAISTSIPV ISQPQFTAMN EPQCFYNESI AFFYNRSGKH LATEWNTVSK
60 70 80 90 100
LVMGLGITVC IFIMLANLLV MVAIYVNRRF HFPIYYLMAN LAAADFFAGL
110 120 130 140 150
AYFYLMFNTG PNTRRLTVST WLLRQGLIDT SLTASVANLL AIAIERHITV
160 170 180 190 200
FRMQLHTRMS NRRVVVVIVV IWTMAIVMGA IPSVGWNCIC DIENCSNMAP
210 220 230 240 250
LYSDSYLVFW AIFNLVTFVV MVVLYAHIFG YVRQRTMRMS RHSSGPRRNR
260 270 280 290 300
DTMMSLLKTV VIVLGAFIIC WTPGLVLLLL DVCCPQCDVL AYEKFFLLLA
310 320 330 340 350
EFNSAMNPII YSYRDKEMSA TFRQILCCQR SENPTGPTEG SDRSASSLNH
360
TILAGVHSND HSVV
Length:364
Mass (Da):41,109
Last modified:December 6, 2002 - v3
Checksum:i4CA6262FD00DFE74
GO
Isoform 2 (identifier: Q92633-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-15: MAAISTSIPVISQPQ → MLLLLIPAHSSVLENE

Note: No experimental confirmation available.
Show »
Length:365
Mass (Da):41,346
Checksum:i91E76F133A9EB55B
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti340 – 3401G → S in AAC51139 (PubMed:9070858).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti77 – 771N → S.
Corresponds to variant rs11542862 [ dbSNP | Ensembl ].
VAR_049414

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1515MAAIS…ISQPQ → MLLLLIPAHSSVLENE in isoform 2. 1 PublicationVSP_057046Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U80811 mRNA. Translation: AAC51139.1.
Y09479 mRNA. Translation: CAA70686.1.
Y09479 mRNA. Translation: CAA70687.1.
U78192 mRNA. Translation: AAC00530.1.
AY322546 mRNA. Translation: AAP84359.1.
AK296374 mRNA. Translation: BAG59048.1.
AC007157 Genomic DNA. No translation available.
AL157881 Genomic DNA. No translation available.
AL442064 Genomic DNA. No translation available.
BC030615 mRNA. Translation: AAH30615.1.
BC036034 mRNA. Translation: AAH36034.1.
CCDSiCCDS6777.1. [Q92633-1]
PIRiJC5293.
RefSeqiNP_001392.2. NM_001401.3. [Q92633-1]
NP_476500.1. NM_057159.2. [Q92633-1]
XP_005251838.1. XM_005251781.3. [Q92633-1]
XP_005251839.1. XM_005251782.3. [Q92633-1]
UniGeneiHs.126667.

Genome annotation databases

EnsembliENST00000358883; ENSP00000351755; ENSG00000198121. [Q92633-1]
ENST00000374430; ENSP00000363552; ENSG00000198121. [Q92633-1]
ENST00000374431; ENSP00000363553; ENSG00000198121. [Q92633-1]
GeneIDi1902.
KEGGihsa:1902.
UCSCiuc004bfa.4. human. [Q92633-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U80811 mRNA. Translation: AAC51139.1.
Y09479 mRNA. Translation: CAA70686.1.
Y09479 mRNA. Translation: CAA70687.1.
U78192 mRNA. Translation: AAC00530.1.
AY322546 mRNA. Translation: AAP84359.1.
AK296374 mRNA. Translation: BAG59048.1.
AC007157 Genomic DNA. No translation available.
AL157881 Genomic DNA. No translation available.
AL442064 Genomic DNA. No translation available.
BC030615 mRNA. Translation: AAH30615.1.
BC036034 mRNA. Translation: AAH36034.1.
CCDSiCCDS6777.1. [Q92633-1]
PIRiJC5293.
RefSeqiNP_001392.2. NM_001401.3. [Q92633-1]
NP_476500.1. NM_057159.2. [Q92633-1]
XP_005251838.1. XM_005251781.3. [Q92633-1]
XP_005251839.1. XM_005251782.3. [Q92633-1]
UniGeneiHs.126667.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4Z34X-ray3.00A2-232[»]
A248-326[»]
4Z35X-ray2.90A2-232[»]
A248-326[»]
4Z36X-ray2.90A2-232[»]
A249-326[»]
ProteinModelPortaliQ92633.
SMRiQ92633. Positions 23-232, 248-326.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108226. 143 interactions.
IntActiQ92633. 2 interactions.
STRINGi9606.ENSP00000351755.

Chemistry

BindingDBiQ92633.
ChEMBLiCHEMBL3819.
GuidetoPHARMACOLOGYi272.
SwissLipidsiSLP:000001567.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiQ92633.
PhosphoSiteiQ92633.
SwissPalmiQ92633.

Polymorphism and mutation databases

BioMutaiLPAR1.
DMDMi26454626.

Proteomic databases

MaxQBiQ92633.
PaxDbiQ92633.
PeptideAtlasiQ92633.
PRIDEiQ92633.

Protocols and materials databases

DNASUi1902.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000358883; ENSP00000351755; ENSG00000198121. [Q92633-1]
ENST00000374430; ENSP00000363552; ENSG00000198121. [Q92633-1]
ENST00000374431; ENSP00000363553; ENSG00000198121. [Q92633-1]
GeneIDi1902.
KEGGihsa:1902.
UCSCiuc004bfa.4. human. [Q92633-1]

Organism-specific databases

CTDi1902.
GeneCardsiLPAR1.
HGNCiHGNC:3166. LPAR1.
HPAiHPA050667.
MIMi602282. gene.
neXtProtiNX_Q92633.
PharmGKBiPA162394187.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000118804.
HOGENOMiHOG000233501.
HOVERGENiHBG103071.
InParanoidiQ92633.
KOiK04289.
OMAiCCQRQEN.
OrthoDBiEOG091G0DD4.
PhylomeDBiQ92633.
TreeFamiTF330052.

Enzyme and pathway databases

ReactomeiR-HSA-416476. G alpha (q) signalling events.
R-HSA-418594. G alpha (i) signalling events.
R-HSA-419408. Lysosphingolipid and LPA receptors.
SIGNORiQ92633.

Miscellaneous databases

ChiTaRSiLPAR1. human.
GeneWikiiLPAR1.
GenomeRNAii1902.
PROiQ92633.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000198121.
CleanExiHS_LPAR1.
ExpressionAtlasiQ92633. baseline and differential.
GenevisibleiQ92633. HS.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR004065. LPA_rcpt.
IPR002277. LPA_rcpt_EDG2.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR01148. EDG2RECEPTOR.
PR00237. GPCRRHODOPSN.
PR01527. LPARECEPTOR.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLPAR1_HUMAN
AccessioniPrimary (citable) accession number: Q92633
Secondary accession number(s): B4DK36
, O00656, O00722, P78351
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: December 6, 2002
Last modified: September 7, 2016
This is version 156 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 9
    Human chromosome 9: 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

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.