ADCY8 adenylate cyclase 8 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ADCY8provided by HGNC
Official Full Name: adenylate cyclase 8provided by HGNC
Primary source: HGNC:HGNC:239
See related: Ensembl:ENSG00000155897 MIM:103070; AllianceGenome:HGNC:239
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: AC8; ADCY3; HBAC1
Summary: Adenylate cyclase is a membrane bound enzyme that catalyses the formation of cyclic AMP from ATP. The enzymatic activity is under the control of several hormones, and different polypeptides participate in the transduction of the signal from the receptor to the catalytic moiety. Stimulatory or inhibitory receptors (Rs and Ri) interact with G proteins (Gs and Gi) that exhibit GTPase activity and they modulate the activity of the catalytic subunit of the adenylyl cyclase [provided by RefSeq, Jul 2008]
Expression: Biased expression in brain (RPKM 4.1), lung (RPKM 0.8) and 2 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 8q24.22

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	8	NC_000008.11 (130780301..131040909, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	8	NC_060932.1 (131907547..132167269, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (131792547..132053155, complement)

Chromosome 8 - NC_000008.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Colocalization of caveolin1 and adenylyl cyclase 8 in lipid rafts depends on the cytoskeleton.
Title: Structural and Functional Determinants of AC8 Trafficking, Targeting and Responsiveness in Lipid Raft Microdomains.
Our results provide evidence for new loci influencing abdominal visceral (BBS9, ADCY8, KCNK9) and subcutaneous (MLLT10/DNAJC1/EBLN1) fat, and confirmed a locus (THNSL2) previously reported to be associated with abdominal fat in women
Title: Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat.
Results show that promoter hypermethylation of ADCY8, CDH8, and ZNF582 are correlated with high-grade squamous intraepithelial lesion.
Title: Molecular Pap smear: HPV genotype and DNA methylation of ADCY8, CDH8, and ZNF582 as an integrated biomarker for high-grade cervical cytology.
ADCY8 is required for the physiological activation of glucose-induced signalling pathways in beta cells, for glucose tolerance and for hypothalamic adaptation to a high-fat diet via regulation of islet insulin secretion.
Title: Multilevel control of glucose homeostasis by adenylyl cyclase 8.
ADCY8 is integral for long-term potentiation and synaptic plasticity and is implicated in fear-related learning and memory.
Title: A genome-wide association study of clinical symptoms of dissociation in a trauma-exposed sample.
Polymorphisms ADCY8 are associated with an alcohol-dependent phenotype in females, which is distinguished by comorbid signs of depression.
Title: Genetic markers of comorbid depression and alcoholism in women.
The adenylate cyclase 8 plays a major role in cAMP production.
Title: Gα(h)/transglutaminase-2 activity is required for maximal activation of adenylylcyclase 8 in human and rat glioma cells.
Orai1 and AC8 binding mediates dynamic interplay between Ca2+ and cAMP signaling
Title: Direct binding between Orai1 and AC8 mediates dynamic interplay between Ca2+ and cAMP signaling.
cAMP-mediated pathways are modelled by glucose, and downregulation of the calcium-sensitive ADCY8 plays a central role herein, including signalling via the GLP1R.
Title: Adenylyl cyclase 8 is central to glucagon-like peptide 1 signalling and effects of chronically elevated glucose in rat and human pancreatic beta cells.
Ca2+ entry increase was accompanied by red cell aggregation rise, while adenylyl cyclase-cAMP system stimulation led to red cell deformability increase and its aggregation lowered.
Title: Crosstalk between adenylyl cyclase signaling pathway and Ca2+ regulatory mechanism under red blood cell microrheological changes.

Submit: New GeneRIF Correction See all GeneRIFs (22)

Phenotypes

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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
A genome-wide association study of clinical symptoms of dissociation in a trauma-exposed sample. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association with MRI atrophy measures as a quantitative trait locus for Alzheimer's disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide data reveal novel genes for methotrexate response in a large cohort of juvenile idiopathic arthritis cases. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-85246 (e-PCR)
- UniSTS:184858

SHGC-36821 (e-PCR)
- UniSTS:6180

D8S1092 (e-PCR)
- UniSTS:72521

RH122757 (e-PCR)
- UniSTS:134986

G54644 (e-PCR)
- UniSTS:117845

D8S1765 (e-PCR), detects polymorphism
- UniSTS:45683

G59968 (e-PCR)
- UniSTS:137104

SHGC-147478 (e-PCR)
- UniSTS:175832

D8S1208 (e-PCR)
- UniSTS:150264

SHGC-148407 (e-PCR)
- UniSTS:176377

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables actin binding	ISS Inferred from Sequence or Structural Similarity more info
enables adenylate cyclase activity	IBA Inferred from Biological aspect of Ancestor more info
enables adenylate cyclase activity	TAS Traceable Author Statement more info
enables calcium- and calmodulin-responsive adenylate cyclase activity	ISS Inferred from Sequence or Structural Similarity more info
enables calmodulin binding	ISS Inferred from Sequence or Structural Similarity more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein dimerization activity	ISS Inferred from Sequence or Structural Similarity more info
enables protein heterodimerization activity	ISS Inferred from Sequence or Structural Similarity more info
enables protein homodimerization activity	ISS Inferred from Sequence or Structural Similarity more info
enables protein phosphatase 2A binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in G protein-coupled opioid receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in activation of protein kinase A activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in adenylate cyclase-activating G protein-coupled receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in cAMP biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to calcium ion	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to forskolin	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to glucagon stimulus	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to glucose stimulus	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to morphine	ISS Inferred from Sequence or Structural Similarity more info
involved_in glucose homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in glucose mediated signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in intracellular signal transduction	IEA Inferred from Electronic Annotation more info
involved_in learning or memory	TAS Traceable Author Statement more info	PubMed
involved_in locomotory behavior	ISS Inferred from Sequence or Structural Similarity more info
involved_in long-term memory	IEA Inferred from Electronic Annotation more info
involved_in memory	ISS Inferred from Sequence or Structural Similarity more info
involved_in neuroinflammatory response	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of CREB transcription factor activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of cytosolic calcium ion concentration	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of insulin secretion involved in cellular response to glucose stimulus	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of long-term synaptic depression	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of long-term synaptic potentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of synaptic plasticity	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein complex oligomerization	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein homooligomerization	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of cellular response to stress	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of cytosolic calcium ion concentration	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of insulin secretion	TAS Traceable Author Statement more info
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in Schaffer collateral - CA1 synapse	IEA Inferred from Electronic Annotation more info
colocalizes_with actin cytoskeleton	ISS Inferred from Sequence or Structural Similarity more info
located_in apical plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in axon	ISS Inferred from Sequence or Structural Similarity more info
located_in basolateral plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in caveola	ISS Inferred from Sequence or Structural Similarity more info
located_in clathrin-coated pit	ISS Inferred from Sequence or Structural Similarity more info
located_in clathrin-coated vesicle membrane	IEA Inferred from Electronic Annotation more info
located_in dendrite	ISS Inferred from Sequence or Structural Similarity more info
located_in excitatory synapse	ISS Inferred from Sequence or Structural Similarity more info
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
located_in hippocampal mossy fiber to CA3 synapse	IEA Inferred from Electronic Annotation 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
located_in neuronal cell body membrane	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	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in plasma membrane raft	ISS Inferred from Sequence or Structural Similarity more info
located_in postsynaptic density	ISS Inferred from Sequence or Structural Similarity more info
located_in presynaptic active zone	ISS Inferred from Sequence or Structural Similarity more info
located_in presynaptic membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: adenylate cyclase type 8

Names: ATP pyrophosphate-lyase 8; HEL-S-172mP; adenylate cyclase 8 (brain); adenylate cyclase type VIII; adenylyl cyclase 8; adenylyl cyclase-8, brain; ca(2+)/calmodulin-activated adenylyl cyclase; epididymis secretory sperm binding protein Li 172mP

NP_001106.1

EC 4.6.1.1

XP_005250826.1

EC 4.6.1.1

XP_006716564.1

EC 4.6.1.1

XP_016868495.1

EC 4.6.1.1

XP_016868496.1

EC 4.6.1.1

XP_054215663.1

EC 4.6.1.1

XP_054215664.1

EC 4.6.1.1

XP_054215665.1

EC 4.6.1.1

XP_054215666.1

EC 4.6.1.1

NCBI Reference Sequences (RefSeq)

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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.

mRNA and Protein(s)

NM_001115.3 → NP_001106.1 adenylate cyclase type 8

See identical proteins and their annotated locations for NP_001106.1

Status: REVIEWED

Source sequence(s)

AC087341, AC103726, DQ104739, DR003657, Z35309

Consensus CDS

CCDS6363.1

UniProtKB/Swiss-Prot

P40145

UniProtKB/TrEMBL

A0A0K0K1K3, E7EVL1

Related

ENSP00000286355.5, ENST00000286355.10

Conserved Domains (4) summary

smart00044
Location:366 → 564

CYCc; Adenylyl- / guanylyl cyclase, catalytic domain

pfam00211
Location:973 → 1172

Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain

pfam06327
Location:617 → 711

DUF1053; Domain of Unknown Function (DUF1053)

pfam16214
Location:161 → 400

AC_N; Adenylyl cyclase N-terminal extracellular and transmembrane region

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000008.11 Reference GRCh38.p14 Primary Assembly

Range

130780301..131040909 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017013006.2 → XP_016868495.1 adenylate cyclase type 8 isoform X3

UniProtKB/TrEMBL

E7EVL1
XM_006716501.4 → XP_006716564.1 adenylate cyclase type 8 isoform X2

UniProtKB/TrEMBL

E7EVL1

Conserved Domains (4) summary

smart00044
Location:366 → 564

CYCc; Adenylyl- / guanylyl cyclase, catalytic domain

pfam00211
Location:907 → 1106

Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain

pfam06327
Location:617 → 639

DUF1053; Domain of Unknown Function (DUF1053)

pfam16214
Location:161 → 400

AC_N; Adenylyl cyclase N-terminal extracellular and transmembrane region
XM_005250769.4 → XP_005250826.1 adenylate cyclase type 8 isoform X1

UniProtKB/TrEMBL

E7EVL1

Related

ENSP00000367161.3, ENST00000377928.7

Conserved Domains (4) summary

smart00044
Location:366 → 564

CYCc; Adenylyl- / guanylyl cyclase, catalytic domain

pfam00211
Location:943 → 1142

Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain

pfam06327
Location:617 → 711

DUF1053; Domain of Unknown Function (DUF1053)

pfam16214
Location:161 → 400

AC_N; Adenylyl cyclase N-terminal extracellular and transmembrane region
XM_017013007.2 → XP_016868496.1 adenylate cyclase type 8 isoform X4