P43657 (LPAR6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Lysophosphatidic acid receptor 6
Short name=LPA receptor 6
Short name=LPA-6

Alternative name(s):
Oleoyl-L-alpha-lysophosphatidic acid receptor
P2Y purinoceptor 5
Short name=P2Y5
Purinergic receptor 5
RB intron encoded G-protein coupled receptor

Gene names

Name:	LPAR6
Synonyms:	P2RY5

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	344 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Binds to oleoyl-L-alpha-lysophosphatidic acid (LPA). Intracellular cAMP is involved in the receptor activation. Important for the maintenance of hair growth and texture. Ref.12
Subcellular location	Cell membrane; Multi-pass membrane protein Ref.12.
Tissue specificity	Expressed ubiquitously, including in skin and hair follicle cells. Detected in both Henle's and Huxley's layers of the inner root sheath of the hair follicle and in suprabasal layers of the epidermis (at protein level). Expressed at low levels in peripheral blood leukocytes. Ref.11 Ref.12 Ref.13
Developmental stage	Markedly up-regulated in promyelocytic HL60 cells induced to differentiate along the monocyte/macrophage pathway. Not detectable in undifferentiated HL60 cells and only low levels after the induction of differentiation along the granulocytic pathway. Ref.11
Involvement in disease	Woolly hair autosomal recessive 1 with or without hypotrichosis (ARWH1) [MIM:278150]: A hair shaft disorder characterized by fine and tightly curled hair. Compared to normal curly hair that is observed in some populations, woolly hair grows slowly and stops growing after a few inches. Under light microscopy, woolly hair shows some structural anomalies, including trichorrexis nodosa and tapered ends. Some individuals exhibit features of hypotrichosis. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13 Hypotrichosis 8 (HYPT8) [MIM:278150]: A condition characterized by the presence of less than the normal amount of hair and abnormal hair follicles and shafts, which are thin and atrophic. The disorder affects the trunk and extremities as well as the scalp, and the eyebrows and eyelashes may also be involved, whereas beard, pubic, and axillary hairs are largely spared. In addition, patients can develop hyperkeratotic follicular papules, erythema, and pruritus in affected areas. In some patients with congenital hypotrichosis, monilethrix-like hairs showing elliptical nodes have been observed. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12
Miscellaneous	This is a nested gene within intron 17 of the retinoblastoma gene.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.
Sequence caution	The sequence L11910 differs from that shown. Reason: Frameshift at position 31.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Hypotrichosis
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from direct assay Ref.12. Source: UniProtKB
Molecular_function	G-protein coupled purinergic nucleotide receptor activity Inferred from electronic annotation. Source: InterPro G-protein coupled receptor activity Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 344	344	Lysophosphatidic acid receptor 6		PRO_0000070025
Regions
	Topological domain	1 – 19	19	Extracellular Potential
	Transmembrane	20 – 46	27	Helical; Name=1; Potential
	Topological domain	47 – 55	9	Cytoplasmic Potential
	Transmembrane	56 – 79	24	Helical; Name=2; Potential
	Topological domain	80 – 92	13	Extracellular Potential
	Transmembrane	93 – 112	20	Helical; Name=3; Potential
	Topological domain	113 – 133	21	Cytoplasmic Potential
	Transmembrane	134 – 154	21	Helical; Name=4; Potential
	Topological domain	155 – 181	27	Extracellular Potential
	Transmembrane	182 – 209	28	Helical; Name=5; Potential
	Topological domain	210 – 227	18	Cytoplasmic Potential
	Transmembrane	228 – 253	26	Helical; Name=6; Potential
	Topological domain	254 – 272	19	Extracellular Potential
	Transmembrane	273 – 292	20	Helical; Name=7; Potential
	Topological domain	293 – 344	52	Cytoplasmic Potential
Amino acid modifications
	Lipidation	284	1	S-palmitoyl cysteine By similarity
	Glycosylation	5	1	N-linked (GlcNAc...) Potential
	Disulfide bond	89 ↔ 168		Potential
Natural variations
	Natural variant	33	1	I → V. Corresponds to variant rs1060585 [ dbSNP | Ensembl ].		VAR_022636
	Natural variant	63	1	D → V in ARWH1. Ref.13		VAR_044326
	Natural variant	137	1	C → W. Ref.7 Corresponds to variant rs4151553 [ dbSNP | Ensembl ].		VAR_016253
	Natural variant	188	1	I → F in ARWH1. Ref.13		VAR_044327
	Natural variant	189	1	E → K in ARWH1. Ref.13		VAR_044328
	Natural variant	307	1	W → C. Corresponds to variant rs17071686 [ dbSNP | Ensembl ].		VAR_049430
Experimental info
	Sequence conflict	242	1	F → I in BAD97109. Ref.6
	Sequence conflict	303	1	K → I in CAD97680. Ref.4
	Sequence conflict	344	1	A → G in CAD97687. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P43657 [UniParc]. Last modified August 22, 2003. Version 3. Checksum: 699212F3C1249433	FASTA	344	39,392
	10 20 30 40 50 60 MVSVNSSHCF YNDSFKYTLY GCMFSMVFVL GLISNCVAIY IFICVLKVRN ETTTYMINLA 70 80 90 100 110 120 MSDLLFVFTL PFRIFYFTTR NWPFGDLLCK ISVMLFYTNM YGSILFLTCI SVDRFLAIVY 130 140 150 160 170 180 PFKSKTLRTK RNAKIVCTGV WLTVIGGSAP AVFVQSTHSQ GNNASEACFE NFPEATWKTY 190 200 210 220 230 240 LSRIVIFIEI VGFFIPLILN VTCSSMVLKT LTKPVTLSRS KINKTKVLKM IFVHLIIFCF 250 260 270 280 290 300 CFVPYNINLI LYSLVRTQTF VNCSVVAAVR TMYPITLCIA VSNCCFDPIV YYFTSDTIQN 310 320 330 340 SIKMKNWSVR RSDFRFSEVH GAENFIQHNL QTLKSKIFDN ESAA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete genomic sequence of the human retinoblastoma susceptibility gene." Toguchida J., McGee T.L., Paterson J.C., Eagle J.R., Tucker S., Yandell D.W., Dryja T.P. Genomics 17:535-543(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Intron 17 of the human retinoblastoma susceptibility gene encodes an actively transcribed G protein-coupled receptor gene." Herzog H., Darby K., Hort Y.J., Shine J. Genome Res. 6:858-861(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"The human purinergic receptor P2Y5 is encoded in intron 17 of the retinoblastoma gene." Bohm S.K., Trumpp A., Khitin L.M., Kong W., Payan D.G., Bunnett N.W. Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Endometrium and Heart.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Subthalamic nucleus.
[6]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Thymus.
[7]	NIEHS SNPs program Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT TRP-137.
[8]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain, Placenta and Testis.
[11]	"Expression of purinergic receptors (ionotropic P2X1-7 and metabotropic P2Y1-11) during myeloid differentiation of HL60 cells." Adrian K., Bernhard M.K., Breitinger H.-G., Ogilvie A. Biochim. Biophys. Acta 1492:127-138(2000) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[12]	"G protein-coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth." Pasternack S.M., von Kuegelgen I., Aboud K.A., Lee Y.-A., Rueschendorf F., Voss K., Hillmer A.M., Molderings G.J., Franz T., Ramirez A., Nuernberg P., Noethen M.M., Betz R.C. Nat. Genet. 40:329-334(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INVOLVEMENT IN HYPT8.
[13]	"Disruption of P2RY5, an orphan G protein-coupled receptor, underlies autosomal recessive woolly hair." Shimomura Y., Wajid M., Ishii Y., Shapiro L., Petukhova L., Gordon D., Christiano A.M. Nat. Genet. 40:335-339(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ARWH1 VAL-63; PHE-188 AND LYS-189, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L11910 Genomic DNA. No translation available. L78805 Genomic DNA. Translation: AAL40065.1. AF000546 mRNA. Translation: AAB62190.1. BX537392 mRNA. Translation: CAD97634.1. BX537438 mRNA. Translation: CAD97680.1. BX537445 mRNA. Translation: CAD97687.1. AK122856 mRNA. Translation: BAG53764.1. AK223389 mRNA. Translation: BAD97109.1. AF551763 Genomic DNA. Translation: AAN64134.1. AL392048 Genomic DNA. Translation: CAH72247.1. CH471075 Genomic DNA. Translation: EAX08796.1. BC040850 mRNA. Translation: AAH40850.1. BC045651 mRNA. Translation: AAH45651.1. BC070295 mRNA. Translation: AAH70295.1. BC106756 mRNA. Translation: AAI06757.1.
IPI	IPI00019955.
PIR	T09508.
RefSeq	NP_001155969.1. NM_001162497.1. NP_001155970.1. NM_001162498.1. NP_005758.2. NM_005767.5.
UniGene	Hs.123464.
3D structure databases
ProteinModelPortal	P43657.
ModBase	Search...
Protein-protein interaction databases
IntAct	P43657. 1 interaction.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	P43657.
Polymorphism databases
DMDM	34223726.
Proteomic databases
PaxDb	P43657.
PRIDE	P43657.
Protocols and materials databases
DNASU	10161.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000345941; ENSP00000344353; ENSG00000139679. ENST00000378434; ENSP00000367691; ENSG00000139679.
GeneID	10161.
KEGG	hsa:10161.
UCSC	uc001vce.3. human.
Organism-specific databases
CTD	10161.
GeneCards	GC13M048963.
HGNC	HGNC:15520. LPAR6.
HPA	HPA028934.
MIM	278150. phenotype. 609239. gene.
neXtProt	NX_P43657.
Orphanet	55654. Hypotrichosis simplex. 170. Woolly hair.
PharmGKB	PA165505129.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG289230.
HOVERGEN	HBG101917.
InParanoid	P43657.
KO	K04273.
OMA	FRIFYFA.
OrthoDB	EOG4Q58PX.
PhylomeDB	P43657.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	P43657.
Bgee	P43657.
Genevestigator	P43657.
GermOnline	ENSG00000139679. Homo sapiens.
Family and domain databases
InterPro	IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. IPR002188. P2Y5_purnocptor. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00237. GPCRRHODOPSN. PR01067. P2Y5ORPHANR.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	10161.
NextBio	38470.
SOURCE	Search...

Entry information

Entry name

LPAR6_HUMAN

Accession

Primary (citable) accession number: P43657
Secondary accession number(s): A4FTW9 , B3KVF2, O15133, Q3KPF5, Q53FA0, Q5VW44, Q7Z3S0, Q7Z3S6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	August 22, 2003
Last modified:	May 1, 2013
This is version 118 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.