ADIPOR1 (adiponectin receptor 1)

2009-05-01 Virginia Kaklamani , Christos Mantzoros Affiliation

Identity

HGNC

ADIPOR1

LOCATION

1q32.1

LOCUSID

51094

ALIAS

ACDCR1,CGI-45,CGI45,PAQR1,TESBP1A

FUSION GENES

Show Gene Fusions

DNA/RNA

Genomic structure of ADIPOR1. Blue boxes indicate exons.

Description

Eight exons spanning 17.5 kb. Transcription is from telomere to centromere.

Transcription

Transcription produces 11 different mRNAs, 10 alternatively spliced variants and 1 unspliced form. There are 6 probable alternative promoters, 2 non overlapping alternative last exons and 8 validated alternative polyadenylation sites. The mRNAs appear to differ by truncation of the 5 end, truncation of the 3 end, presence or absence of 6 cassette exons, overlapping exons with different boundaries. 9 spliced and the unspliced mRNAs putatively encode good proteins, altogether 9 different isoforms (3 complete, 6 partial), some containing Hly-III related proteins domain (Pfam) some transmembrane domains (Psort2); 1 of the 3 complete proteins appears to be secreted. The remaining mRNA variant (spliced) appears not to encode a good protein.

Proteins

Description

Receptor for globular and full-length adiponectin (APM1), an essential hormone secreted by adipocytes that counteracts the effects of insulin.

Expression

Widely expressed. Highly expressed in adipose tissue and skeletal muscle. Expressed at intermediate level in brain, heart, spleen, kidney, liver, placenta, lung and peripheral blood leukocytes. Weakly expressed in colon, thymus and small intestine. We have also shown expression in normal and cancerous breast tissue as well as in other cancers such as prostate, colon, endometrial. It is also present in several cell lines.

Localisation

ADIPOR1 localizes to the plasma membrane.

Function

Receptor for globular and full-length adiponectin (APM1), an essential hormone secreted by adipocytes that acts as an antidiabetic. Probably involved in metabolic pathways that regulate lipid metabolism such as fatty acid oxidation. Mediates increased AMPK, PPARa ligand activity, fatty acid oxidation and glucose uptake by adiponectin. Has some high-affinity for globular adiponectin but low-affinity for full-length adiponectin.

Homology

The mouse, human, and rat Adipor1 protein (ADIPOR1) contains 375 amino acids. Human and mouse ADIPOR1 share 96.8% identity.

Mutations

Note

One functional polymorphism has been described. Rs7539542 has been found to modulate expression of ADIPOR1 mRNA (Soccio et al., 2006).

Implicated in

Entity name

Breast Cancer

Note

Adiponectin has been implicated in breast cancer. The breast cancer cell lines MCF-7, MDB-MB-231 and T47D were found to express both adiponectin receptors ADIPOR1/ADIPOR2 (Dieudonne et al., 2006; Korner et al., 2007) and exposure of T47D cells to adiponectin, significantly inhibited their proliferation (Korner et al., 2007). rs2232853 CT genotype (OR=1.67; 95% CI 1.23-2.26) and the combination of rs7539542 GC (OR=0.59; 95% CI 0.36-0.98) and CC genotypes (OR=0.57; 95% CI 0.35-0.94) were significantly associated with breast cancer risk. The high expressing rs2241766 G allele (GG and GT genotypes) was associated with decreased breast cancer risk (OR=0.64; 95% CI 0.49-0.83). The low expressing rs1501299 G allele was associated with increased breast cancer risk: for TG: OR=1.59; 95% CI 1.03-2.48, for GG: OR= 1.80; 95% CI 1.14-2.85.

Entity name

Colon Cancer

Note

Adiponectin has also been implicated in colon cancer risk. rs266729 polymorphism was significantly associated with colon cancer risk: the RR for the GG/CG genotypes was rs266729 was associated with a reduced colorectal cancer risk: O.R. 0.73, 95% CI (0.53-0.99) (Kaklamani et al., 2008).

Entity name

Endometrial Cancer

Note

Adiponectin levels have been shown to correlate with endometrial cancer risk (Petridou et al., 2003; Dal et al., 2004).

Entity name

Prostate Cancer

Note

Adiponectin levels have been shown to correlate with prostate cancer risk (Barb et al., 2007; Arisan et al., 2009).

Bibliography

Pubmed ID	Last Year	Title	Authors
19322011	2009	Serum adipocytokine levels in prostate cancer patients.	Arisan ED et al
18265479	2007	Adiponectin in relation to malignancies: a review of existing basic research and clinical evidence.	Barb D et al
15001602	2004	Circulating adiponectin and endometrial cancer risk.	Dal Maso L et al
16678125	2006	Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells.	Dieudonne MN et al
18827209	2008	Variants of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes and colorectal cancer risk.	Kaklamani VG et al
17192291	2007	Total and high-molecular-weight adiponectin in breast cancer: in vitro and in vivo studies.	Körner A et al
12629074	2003	Plasma adiponectin concentrations in relation to endometrial cancer: a case-control study in Greece.	Petridou E et al
17003341	2006	Common haplotypes at the adiponectin receptor 1 (ADIPOR1) locus are associated with increased risk of coronary artery disease in type 2 diabetes.	Soccio T et al

Other Information

Locus ID:

NCBI: 51094
MIM: 607945
HGNC: 24040
Ensembl: ENSG00000159346

Variants:

dbSNP: 51094
ClinVar: 51094
TCGA: ENSG00000159346
COSMIC: ADIPOR1

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000159346	ENST00000340990	Q96A54
ENSG00000159346	ENST00000367254	F8W782
ENSG00000159346	ENST00000417068	C9JNM5
ENSG00000159346	ENST00000426229	C9J0W7

Expression (GTEx)

100

150

200

250

300

350

400

450

500

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Adipocytokine signaling pathway	KEGG	ko04920
Adipocytokine signaling pathway	KEGG	hsa04920
Non-alcoholic fatty liver disease (NAFLD)	KEGG	hsa04932
Non-alcoholic fatty liver disease (NAFLD)	KEGG	ko04932
AMPK signaling pathway	KEGG	hsa04152
AMPK signaling pathway	KEGG	ko04152
Metabolism	REACTOME	R-HSA-1430728
Integration of energy metabolism	REACTOME	R-HSA-163685
AMPK inhibits chREBP transcriptional activation activity	REACTOME	R-HSA-163680
Longevity regulating pathway	KEGG	hsa04211

References

Pubmed ID	Year	Title	Citations
12802337	2003	Cloning of adiponectin receptors that mediate antidiabetic metabolic effects.	639
16622416	2006	APPL1 binds to adiponectin receptors and mediates adiponectin signalling and function.	202
15454091	2004	Adiponectin and its receptors are expressed in bone-forming cells.	108
20682687	2010	Common variants in 40 genes assessed for diabetes incidence and response to metformin and lifestyle intervention in the diabetes prevention program.	88
19913121	2009	Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.	85
16678125	2006	Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells.	83
23813974	2013	The large non-coding RNA ANRIL, which is associated with atherosclerosis, periodontitis and several forms of cancer, regulates ADIPOR1, VAMP3 and C11ORF10.	71
23355630	2013	Molecular pathways: adiponectin and leptin signaling in cancer.	68
17911635	2007	Adiponectin enhances IL-6 production in human synovial fibroblast via an AdipoR1 receptor, AMPK, p38, and NF-kappa B pathway.	62
19109202	2009	Adiponectin and functional adiponectin receptor 1 are expressed by airway epithelial cells in chronic obstructive pulmonary disease.	58

Citation

Virginia Kaklamani ; Christos Mantzoros

ADIPOR1 (adiponectin receptor 1)

Atlas Genet Cytogenet Oncol Haematol. 2009-05-01

Online version: http://atlasgeneticsoncology.org/gene/44512/adipor1id44512ch1q32