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P49019 (HCAR3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Hydroxycarboxylic acid receptor 3
Alternative name(s):
G-protein coupled receptor 109B
G-protein coupled receptor HM74
G-protein coupled receptor HM74B
Niacin receptor 2
Nicotinic acid receptor 2
Gene names
Name:HCAR3
Synonyms:GPR109B, HCA3, HM74B, NIACR2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length387 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Receptor for 3-OH-octanoid acid mediates a negative feedback regulation of adipocyte lipolysis to counteract prolipolytic influences under conditions of physiological or pathological increases in beta-oxidation rates. Acts as a low affinity receptor for nicotinic acid. This pharmacological effect requires nicotinic acid doses that are much higher than those provided by a normal diet. Ref.7 Ref.8

Subcellular location

Cell membrane; Multi-pass membrane protein.

Tissue specificity

Expression largely restricted to adipose tissue and spleen. Ref.7

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Ontologies

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 387387Hydroxycarboxylic acid receptor 3
PRO_0000069604

Regions

Topological domain1 – 2828Extracellular Potential
Transmembrane29 – 5022Helical; Name=1; Potential
Topological domain51 – 6313Cytoplasmic Potential
Transmembrane64 – 8522Helical; Name=2; Potential
Topological domain86 – 10217Extracellular Potential
Transmembrane103 – 12321Helical; Name=3; Potential
Topological domain124 – 14219Cytoplasmic Potential
Transmembrane143 – 16321Helical; Name=4; Potential
Topological domain164 – 19431Extracellular Potential
Transmembrane195 – 20915Helical; Name=5; Potential
Topological domain210 – 23627Cytoplasmic Potential
Transmembrane237 – 25620Helical; Name=6; Potential
Topological domain257 – 27317Extracellular Potential
Transmembrane274 – 29825Helical; Name=7; Potential
Topological domain299 – 38789Cytoplasmic Potential

Amino acid modifications

Disulfide bond100 ↔ 177 By similarity

Natural variations

Natural variant1731T → P. Ref.1 Ref.2 Ref.3 Ref.6
Corresponds to variant rs1798192 [ dbSNP | Ensembl ].
VAR_038715
Natural variant1981F → L. Ref.1 Ref.2 Ref.3 Ref.6
Corresponds to variant rs17884481 [ dbSNP | Ensembl ].
VAR_038716
Natural variant2531H → R. Ref.1 Ref.2 Ref.3 Ref.6
VAR_038717
Natural variant3171I → M. Ref.1 Ref.2 Ref.3 Ref.6
VAR_038718
Natural variant3461I → M. Ref.1 Ref.2 Ref.3 Ref.6
Corresponds to variant rs56308926 [ dbSNP | Ensembl ].
VAR_038719
Natural variant3501G → S.
VAR_038720

Experimental info

Mutagenesis1111R → A: Abrogates completely the activation by OH-octanoid acid. Ref.8
Sequence conflict941K → N in BAA01721. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P49019 [UniParc].

Last modified June 26, 2013. Version 3.
Checksum: 887BA427B6134A3F

FASTA38744,478
        10         20         30         40         50         60 
MNRHHLQDHF LEIDKKNCCV FRDDFIAKVL PPVLGLEFIF GLLGNGLALW IFCFHLKSWK 

        70         80         90        100        110        120 
SSRIFLFNLA VADFLLIICL PFVMDYYVRR SDWKFGDIPC RLVLFMFAMN RQGSIIFLTV 

       130        140        150        160        170        180 
VAVDRYFRVV HPHHALNKIS NWTAAIISCL LWGITVGLTV HLLKKKLLIQ NGTANVCISF 

       190        200        210        220        230        240 
SICHTFRWHE AMFLLEFFLP LGIILFCSAR IIWSLRQRQM DRHAKIKRAI TFIMVVAIVF 

       250        260        270        280        290        300 
VICFLPSVVV RIHIFWLLHT SGTQNCEVYR SVDLAFFITL SFTYMNSMLD PVVYYFSSPS 

       310        320        330        340        350        360 
FPNFFSTLIN RCLQRKITGE PDNNRSTSVE LTGDPNKTRG APEALIANSG EPWSPSYLGP 

       370        380 
TSNNHSKKGH CHQEPASLEK QLGCCIE 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning of cDNAs encoding a LD78 receptor and putative leukocyte chemotactic peptide receptors."
Nomura H., Nielsen B.W., Matsushima K.
Int. Immunol. 5:1239-1249(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS PRO-173; LEU-198; ARG-253; MET-317 AND MET-346.
Tissue: Monocyte.
[2]"Genome-wide discovery and analysis of human seven transmembrane helix receptor genes."
Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S., Tsutsumi S., Aburatani H., Asai K., Akiyama Y.
Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS PRO-173; LEU-198; ARG-253; MET-317 AND MET-346.
[3]"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. expand/collapse author list , 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], VARIANTS PRO-173; LEU-198; ARG-253; MET-317 AND MET-346.
Tissue: Neutrophil.
[4]SeattleSNPs variation discovery resource
Submitted (NOV-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"The finished DNA sequence of human chromosome 12."
Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. expand/collapse author list , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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], VARIANTS PRO-173; LEU-198; ARG-253; MET-317 AND MET-346.
Tissue: Pancreas.
[7]"Molecular identification of high and low affinity receptors for nicotinic acid."
Wise A., Foord S.M., Fraser N.J., Barnes A.A., Elshourbagy N., Eilert M., Ignar D.M., Murdock P.R., Steplewski K., Green A., Brown A.J., Dowell S.J., Szekeres P.G., Hassall D.G., Marshall F.H., Wilson S., Pike N.B.
J. Biol. Chem. 278:9869-9874(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, CHARACTERIZATION.
[8]"Deorphanization of GPR109B as a receptor for the beta-oxidation intermediate 3-OH-octanoic acid and its role in the regulation of lipolysis."
Ahmed K., Tunaru S., Langhans C.-D., Hanson J., Michalski C.W., Koelker S., Jones P.M., Okun J.G., Offermanns S.
J. Biol. Chem. 284:21928-21933(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF ARG-111.
[9]"International union of basic and clinical pharmacology. LXXXII: nomenclature and classification of hydroxy-carboxylic acid receptors (GPR81, GPR109A, and GPR109B)."
Offermanns S., Colletti S.L., Lovenberg T.W., Semple G., Wise A., Ijzerman A.P.
Pharmacol. Rev. 63:269-290(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: NOMENCLATURE.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D10923 mRNA. Translation: BAA01721.1.
AB065865 Genomic DNA. Translation: BAC06083.1.
AK290930 mRNA. Translation: BAF83619.1.
AK313212 mRNA. Translation: BAG36027.1.
EU293604 Genomic DNA. Translation: ABX64359.1.
AC026333 Genomic DNA. No translation available.
BC047891 mRNA. Translation: AAH47891.1.
PIRI69202.
RefSeqNP_006009.2. NM_006018.2.
UniGeneHs.458425.

3D structure databases

ProteinModelPortalP49019.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP49019. 1 interaction.

Chemistry

BindingDBP49019.
ChEMBLCHEMBL4421.
DrugBankDB04843. Mepenzolate.
DB00627. Niacin.
GuidetoPHARMACOLOGY313.

Protein family/group databases

GPCRDBSearch...

Polymorphism databases

DMDM519668680.

Proteomic databases

PRIDEP49019.

Protocols and materials databases

DNASU8843.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000528880; ENSP00000436714; ENSG00000255398.
GeneID8843.
KEGGhsa:8843.

Organism-specific databases

CTD8843.
GeneCardsGC12M123200.
H-InvDBHIX0036803.
HGNCHGNC:16824. HCAR3.
HPAHPA028660.
MIM606039. gene.
neXtProtNX_P49019.
PharmGKBPA165512827.
GenAtlasSearch...

Phylogenomic databases

HOVERGENHBG051680.
InParanoidP49019.
KOK08402.
OMATANVCIS.
OrthoDBEOG7R56SR.
PhylomeDBP49019.
TreeFamTF330775.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

CleanExHS_GPR109B.
GenevestigatorP49019.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR028017. HCAR2/3_rcpt.
[Graphical view]
PANTHERPTHR24231:SF22. PTHR24231:SF22. 1 hit.
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00237. GPCRRHODOPSN.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi8843.
NextBio33198.
PROP49019.
SOURCESearch...

Entry information

Entry nameHCAR3_HUMAN
AccessionPrimary (citable) accession number: P49019
Secondary accession number(s): A8K4G5 expand/collapse secondary AC list , B2R830, E9PI97, Q8NGE4
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: June 26, 2013
Last modified: April 16, 2014
This is version 129 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries