ADCY2 adenylate cyclase 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ADCY2provided by HGNC
Official Full Name: adenylate cyclase 2provided by HGNC
Primary source: HGNC:HGNC:233
See related: Ensembl:ENSG00000078295 MIM:103071; AllianceGenome:HGNC:233
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: AC2; HBAC2
Summary: This gene encodes a member of the family of adenylate cyclases, which are membrane-associated enzymes that catalyze the formation of the secondary messenger cyclic adenosine monophosphate (cAMP). This enzyme is insensitive to Ca(2+)/calmodulin, and is stimulated by the G protein beta and gamma subunit complex. [provided by RefSeq, Jul 2008]
Expression: Biased expression in brain (RPKM 19.2), prostate (RPKM 3.0) and 6 other tissues See more
Orthologs: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 5p15.31

Exon count:: 26

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (7396138..7830081)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (7334987..7769222)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (7396251..7830194)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

circSLC25A13 acts as a ceRNA to regulate AML progression via miR-616-3p/ADCY2 axis.
Title: circSLC25A13 acts as a ceRNA to regulate AML progression via miR-616-3p/ADCY2 axis.
Association of adenylate cyclase-2 gene polymorphism with bipolar disorder.
Title: Association of adenylate cyclase-2 gene polymorphism with bipolar disorder.
Investigation of the impact of an ADCY2 polymorphism as a predictive biomarker in bipolar disorder, suicide tendency and response to lithium carbonate therapy: the first report from Iran.
Title: Investigation of the impact of an ADCY2 polymorphism as a predictive biomarker in bipolar disorder, suicide tendency and response to lithium carbonate therapy: the first report from Iran.
In patients receiving capecitabine monotherapy, rs4702484, located in ADCY2 and close to MTRR, was associated with slightly reduced PFS for homozygous wild-type patients (CC 6.2 vs. CT 8.0 months; P=0.018).
Title: Clinical validation study of genetic markers for capecitabine efficacy in metastatic colorectal cancer patients.
Our present study defines an AC2 cAMP signaling compartment that specifically regulates IL-6 expression in bronchial smooth muscle cells.
Title: Non-raft adenylyl cyclase 2 defines a cAMP signaling compartment that selectively regulates IL-6 expression in airway smooth muscle cells: differential regulation of gene expression by AC isoforms.
AKAP79, PKC, PKA and PDE4 participate in a Gq-linked muscarinic receptor and adenylate cyclase 2 cAMP signalling complex.
Title: AKAP79, PKC, PKA and PDE4 participate in a Gq-linked muscarinic receptor and adenylate cyclase 2 cAMP signalling complex.
AGS3 reduced D(2L)DR-mediated sensitization of AC1 and AC2.
Title: Differential effects of AGS3 expression on D(2L) dopamine receptor-mediated adenylyl cyclase signaling.
A replication of association between two SNPs previously associated with COPD (CHRNA3/5 and IREB2), as well as an association with COPD of one locus initially associated with lung function (ADCY2).
Title: CHRNA3/5, IREB2, and ADCY2 are associated with severe chronic obstructive pulmonary disease in Poland.
Data suggest that SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK are potential prognostic markers in colorectal cancer.
Title: SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK are prognosis-related in colorectal cancer.
AC2 and AC4 isoforms, stimulated by GTP binding protein betagamma subunits, are expressed in bronchial nonlipid raft membrane fractions where they colocalize with and couple to prostanoid EP2 receptors.
Title: Human bronchial smooth muscle cells express adenylyl cyclase isoforms 2, 4, and 6 in distinct membrane microdomains.

Submit: New GeneRIF Correction See all GeneRIFs (14)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Gene-alcohol interactions identify several novel blood pressure loci including a promising locus near SLC16A9. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study reveals two new risk loci for bipolar disorder. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of novel germline polymorphisms governing capecitabine sensitivity. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

Go to the top of the page Help

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	The addition of HIV-1 gp120 with TNF-alpha to human B-cells stimulates cAMP production in a dose-dependent manner	PubMed
Envelope transmembrane glycoprotein gp41	env	Secretion of IL-10 is upregulated by HIV-1 gp41 in monocytes through activation of cAMP/adenylate cyclase and p70 (S6)-kinase; up-regulation of IL-10 is paralleled by an enhanced expression of the chemokine receptor CCR5	PubMed
Nef	nef	HIV-1 induces the upregulation of complement factor C3 in astrocytes and neurons through signaling pathways that involve protein kinase C and adenylate cyclase activation, which is an effect that may contribute to the pathogenesis of AIDS in the brain	PubMed
Tat	tat	HIV-1 Tat inhibits adenylyl cyclase activity in microglia and astrocyte cultures from neonatal rat brain, suggesting that Tat inhibition of cAMP synthesis may contribute to neuronal degeneration and cell death associated with HIV infection	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

SHGC-30499 (e-PCR)
- UniSTS:167687

SHGC-23973 (e-PCR)
- UniSTS:776

STS-L21993 (e-PCR)
- UniSTS:47387

D5S676 (e-PCR), detects polymorphism
- UniSTS:8745

D8S2278 (e-PCR)
- UniSTS:473906

D8S2279 (e-PCR)
- UniSTS:473907

SHGC-152285 (e-PCR)
- UniSTS:177460

D5S2717 (e-PCR)
- UniSTS:7737

SHGC-153179 (e-PCR)
- UniSTS:182589

SHGC-149779 (e-PCR)
- UniSTS:177215

L18426 (e-PCR)
- UniSTS:34648

SHGC-147265 (e-PCR)
- UniSTS:175706

D5S2572 (e-PCR)
- UniSTS:7535

RH79802 (e-PCR)
- UniSTS:88688

ADCY2_4036 (e-PCR)
- UniSTS:462711

SHGC-156108 (e-PCR)
- UniSTS:184190

SHGC-111957 (e-PCR)
- UniSTS:168838

ADCY2 (e-PCR)
- UniSTS:479881

D11S3114 (e-PCR)
- UniSTS:152207

RH15976 (e-PCR)
- UniSTS:33935

D5S676 (e-PCR), detects polymorphism
- UniSTS:18835

SHGC-149093 (e-PCR)
- UniSTS:176795

D5S1953 (e-PCR), detects polymorphism
- UniSTS:26017

RH26804 (e-PCR)
- UniSTS:85668

D5S1866 (e-PCR)
- UniSTS:41386

SHGC-146119 (e-PCR)
- UniSTS:175018

D5S1736 (e-PCR)
- UniSTS:4269

RH78017 (e-PCR)
- UniSTS:78769

GDB:631813 (e-PCR)
- UniSTS:158430

D5S1607E (e-PCR)
- UniSTS:151028

D5S2784 (e-PCR)
- UniSTS:473852

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables adenylate cyclase activity	IBA Inferred from Biological aspect of Ancestor more info
enables adenylate cyclase activity	ISS Inferred from Sequence or Structural Similarity more info
enables adenylate cyclase activity	NAS Non-traceable Author Statement more info	PubMed
enables adenylate cyclase binding	ISS Inferred from Sequence or Structural Similarity more info
enables magnesium ion binding	ISS Inferred from Sequence or Structural Similarity more info
enables manganese ion binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in adenylate cyclase-activating G protein-coupled receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in adenylate cyclase-activating G protein-coupled receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in adenylate cyclase-modulating G protein-coupled receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in cAMP biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in cAMP biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in cAMP-mediated signaling	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to forskolin	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in dendrite	ISS Inferred from Sequence or Structural Similarity more info
located_in membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in membrane raft	ISS Inferred from Sequence or Structural Similarity more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

Go to the top of the page Help

Preferred Names: adenylate cyclase type 2

Names: 3',5'-cyclic AMP synthetase; ATP pyrophosphate-lyase 2; adenylate cyclase 2 (brain); adenylate cyclase II; adenylate cyclase type II; adenylyl cyclase 2; type II adenylate cyclase

NP_065433.2

EC 4.6.1.1

XP_011512244.1

EC 4.6.1.1

XP_047272601.1

EC 4.6.1.1

XP_047272602.1

EC 4.6.1.1

XP_047272603.1

EC 4.6.1.1

XP_054207440.1

EC 4.6.1.1

XP_054207441.1

EC 4.6.1.1

XP_054207442.1

EC 4.6.1.1

XP_054207443.1

EC 4.6.1.1

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_046913.1 RefSeqGene

Range

4909..438852

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_020546.3 → NP_065433.2 adenylate cyclase type 2

See identical proteins and their annotated locations for NP_065433.2

Status: REVIEWED

Source sequence(s)

AC010346, AC024577, AF070583, BC111743, BE677757, DB029098, DB481853

Consensus CDS

CCDS3872.2

UniProtKB/Swiss-Prot

B7Z2C1, Q08462, Q2NKL8, Q9UDB2, Q9UPU2

UniProtKB/TrEMBL

B4E1Z0

Related

ENSP00000342952.4, ENST00000338316.9

Conserved Domains (4) summary

smart00044
Location:236 → 439

CYCc; Adenylyl- / guanylyl cyclase, catalytic domain

pfam00211
Location:878 → 1077

Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain

pfam06327
Location:495 → 599

DUF1053; Domain of Unknown Function (DUF1053)

pfam16214
Location:33 → 260

AC_N; Adenylyl cyclase N-terminal extracellular and transmembrane region

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000005.10 Reference GRCh38.p14 Primary Assembly

Range

7396138..7830081

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011513942.3 → XP_011512244.1 adenylate cyclase type 2 isoform X2

UniProtKB/TrEMBL

B4E1Z0

Conserved Domains (4) summary

smart00044
Location:236 → 439

CYCc; Adenylyl- / guanylyl cyclase, catalytic domain

pfam00211
Location:832 → 1031

Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain

pfam06327
Location:495 → 599

DUF1053; Domain of Unknown Function (DUF1053)

pfam16214
Location:33 → 260

AC_N; Adenylyl cyclase N-terminal extracellular and transmembrane region
XM_047416645.1 → XP_047272601.1 adenylate cyclase type 2 isoform X1
XM_047416646.1 → XP_047272602.1 adenylate cyclase type 2 isoform X3
XM_047416647.1 → XP_047272603.1 adenylate cyclase type 2 isoform X4