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P49019

- HCAR3_HUMAN

UniProt

P49019 - HCAR3_HUMAN

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Protein
Hydroxycarboxylic acid receptor 3
Gene
HCAR3, GPR109B, HCA3, HM74B, NIACR2
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.2 Publications

GO - Molecular functioni

  1. G-protein coupled receptor activity Source: ProtInc

GO - Biological processi

  1. G-protein coupled receptor signaling pathway Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiREACT_163785. Hydroxycarboxylic acid-binding receptors.
REACT_19231. G alpha (i) signalling events.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:HCAR3
Synonyms:GPR109B, HCA3, HM74B, NIACR2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 12

Organism-specific databases

HGNCiHGNC:16824. HCAR3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2828Extracellular Reviewed prediction
Add
BLAST
Transmembranei29 – 5022Helical; Name=1; Reviewed prediction
Add
BLAST
Topological domaini51 – 6313Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei64 – 8522Helical; Name=2; Reviewed prediction
Add
BLAST
Topological domaini86 – 10217Extracellular Reviewed prediction
Add
BLAST
Transmembranei103 – 12321Helical; Name=3; Reviewed prediction
Add
BLAST
Topological domaini124 – 14219Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei143 – 16321Helical; Name=4; Reviewed prediction
Add
BLAST
Topological domaini164 – 19431Extracellular Reviewed prediction
Add
BLAST
Transmembranei195 – 20915Helical; Name=5; Reviewed prediction
Add
BLAST
Topological domaini210 – 23627Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei237 – 25620Helical; Name=6; Reviewed prediction
Add
BLAST
Topological domaini257 – 27317Extracellular Reviewed prediction
Add
BLAST
Transmembranei274 – 29825Helical; Name=7; Reviewed prediction
Add
BLAST
Topological domaini299 – 38789Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. integral component of plasma membrane Source: ProtInc
  2. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi111 – 1111R → A: Abrogates completely the activation by OH-octanoid acid. 1 Publication

Organism-specific databases

PharmGKBiPA165512827.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 387387Hydroxycarboxylic acid receptor 3
PRO_0000069604Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi100 ↔ 177 By similarity

Keywords - PTMi

Disulfide bond

Proteomic databases

PRIDEiP49019.

Expressioni

Tissue specificityi

Expression largely restricted to adipose tissue and spleen.1 Publication

Gene expression databases

CleanExiHS_GPR109B.
GenevestigatoriP49019.

Organism-specific databases

HPAiHPA028660.

Interactioni

Protein-protein interaction databases

IntActiP49019. 1 interaction.

Structurei

3D structure databases

ProteinModelPortaliP49019.
SMRiP49019. Positions 30-311.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

HOVERGENiHBG051680.
InParanoidiP49019.
KOiK08402.
OMAiTANVCIS.
OrthoDBiEOG7R56SR.
PhylomeDBiP49019.
TreeFamiTF330775.

Family and domain databases

Gene3Di1.20.1070.10. 1 hit.
InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR028017. HCAR2/3_rcpt.
[Graphical view]
PANTHERiPTHR24231:SF0. PTHR24231:SF0. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P49019-1 [UniParc]FASTAAdd to Basket

« Hide

MNRHHLQDHF LEIDKKNCCV FRDDFIAKVL PPVLGLEFIF GLLGNGLALW    50
IFCFHLKSWK SSRIFLFNLA VADFLLIICL PFVMDYYVRR SDWKFGDIPC 100
RLVLFMFAMN RQGSIIFLTV VAVDRYFRVV HPHHALNKIS NWTAAIISCL 150
LWGITVGLTV HLLKKKLLIQ NGTANVCISF SICHTFRWHE AMFLLEFFLP 200
LGIILFCSAR IIWSLRQRQM DRHAKIKRAI TFIMVVAIVF VICFLPSVVV 250
RIHIFWLLHT SGTQNCEVYR SVDLAFFITL SFTYMNSMLD PVVYYFSSPS 300
FPNFFSTLIN RCLQRKITGE PDNNRSTSVE LTGDPNKTRG APEALIANSG 350
EPWSPSYLGP TSNNHSKKGH CHQEPASLEK QLGCCIE 387
Length:387
Mass (Da):44,478
Last modified:June 26, 2013 - v3
Checksum:i887BA427B6134A3F
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti173 – 1731T → P.4 Publications
Corresponds to variant rs1798192 [ dbSNP | Ensembl ].
VAR_038715
Natural varianti198 – 1981F → L.4 Publications
Corresponds to variant rs17884481 [ dbSNP | Ensembl ].
VAR_038716
Natural varianti253 – 2531H → R.4 Publications
VAR_038717
Natural varianti317 – 3171I → M.4 Publications
VAR_038718
Natural varianti346 – 3461I → M.4 Publications
Corresponds to variant rs56308926 [ dbSNP | Ensembl ].
VAR_038719
Natural varianti350 – 3501G → S.
VAR_038720

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti94 – 941K → N in BAA01721. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS53842.1.
PIRiI69202.
RefSeqiNP_006009.2. NM_006018.2.
UniGeneiHs.458425.

Genome annotation databases

EnsembliENST00000528880; ENSP00000436714; ENSG00000255398.
GeneIDi8843.
KEGGihsa:8843.

Polymorphism databases

DMDMi519668680.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS53842.1.
PIRi I69202.
RefSeqi NP_006009.2. NM_006018.2.
UniGenei Hs.458425.

3D structure databases

ProteinModelPortali P49019.
SMRi P49019. Positions 30-311.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi P49019. 1 interaction.

Chemistry

BindingDBi P49019.
ChEMBLi CHEMBL4421.
DrugBanki DB04843. Mepenzolate.
DB00627. Niacin.
GuidetoPHARMACOLOGYi 313.

Protein family/group databases

GPCRDBi Search...

Polymorphism databases

DMDMi 519668680.

Proteomic databases

PRIDEi P49019.

Protocols and materials databases

DNASUi 8843.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000528880 ; ENSP00000436714 ; ENSG00000255398 .
GeneIDi 8843.
KEGGi hsa:8843.

Organism-specific databases

CTDi 8843.
GeneCardsi GC12M123200.
H-InvDB HIX0036803.
HGNCi HGNC:16824. HCAR3.
HPAi HPA028660.
MIMi 606039. gene.
neXtProti NX_P49019.
PharmGKBi PA165512827.
GenAtlasi Search...

Phylogenomic databases

HOVERGENi HBG051680.
InParanoidi P49019.
KOi K08402.
OMAi TANVCIS.
OrthoDBi EOG7R56SR.
PhylomeDBi P49019.
TreeFami TF330775.

Enzyme and pathway databases

Reactomei REACT_163785. Hydroxycarboxylic acid-binding receptors.
REACT_19231. G alpha (i) signalling events.

Miscellaneous databases

GenomeRNAii 8843.
NextBioi 33198.
PROi P49019.
SOURCEi Search...

Gene expression databases

CleanExi HS_GPR109B.
Genevestigatori P49019.

Family and domain databases

Gene3Di 1.20.1070.10. 1 hit.
InterProi IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR028017. HCAR2/3_rcpt.
[Graphical view ]
PANTHERi PTHR24231:SF0. PTHR24231:SF0. 1 hit.
Pfami PF00001. 7tm_1. 1 hit.
[Graphical view ]
PRINTSi PR00237. GPCRRHODOPSN.
PROSITEi PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.
    , 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. 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.

Entry informationi

Entry nameiHCAR3_HUMAN
AccessioniPrimary (citable) accession number: P49019
Secondary accession number(s): A8K4G5
, B2R830, E9PI97, Q8NGE4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: June 26, 2013
Last modified: September 3, 2014
This is version 133 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 12
    Human chromosome 12: 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

External Data

Dasty 3

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