ADCY6

Protein identityUniProt · HPA

UniProt accession

O43306

Gene

ADCY6

Ensembl

ENSG00000174233

Chromosome

12

Canonical length

1168 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Golgi apparatus

OverviewNCBI Gene

This gene encodes a member of the adenylyl cyclase family of proteins, which are required for the synthesis of cyclic AMP. All members of this family have an intracellular N-terminus, a tandem repeat of six transmembrane domains separated by a cytoplasmic loop, and a C-terminal cytoplasmic domain. The two cytoplasmic regions bind ATP and form the catalytic core of the protein. Adenylyl cyclases are important effectors of transmembrane signaling pathways and are regulated by the activity of G protein coupled receptor signaling. This protein belongs to a small subclass of adenylyl cyclase proteins that are functionally related and are inhibited by protein kinase A, calcium ions and nitric oxide. A mutation in this gene is associated with arthrogryposis multiplex congenita. [provided by RefSeq, May 2015]

Canonical amino-acid sequenceUniProt

1168 residues, UniProt reviewed canonical sequence.

>O43306|ADCY6
     1  MSWFSGLLVP KVDERKTAWG ERNGQKRSRR RGTRAGGFCT PRYMSCLRDA EPPSPTPAGP
    61  PRCPWQDDAF IRRGGPGKGK ELGLRAVALG FEDTEVTTTA GGTAEVAPDA VPRSGRSCWR
   121  RLVQVFQSKQ FRSAKLERLY QRYFFQMNQS SLTLLMAVLV LLTAVLLAFH AAPARPQPAY
   181  VALLACAAAL FVGLMVVCNR HSFRQDSMWV VSYVVLGILA AVQVGGALAA DPRSPSAGLW
   241  CPVFFVYIAY TLLPIRMRAA VLSGLGLSTL HLILAWQLNR GDAFLWKQLG ANVLLFLCTN
   301  VIGICTHYPA EVSQRQAFQE TRGYIQARLH LQHENRQQER LLLSVLPQHV AMEMKEDINT
   361  KKEDMMFHKI YIQKHDNVSI LFADIEGFTS LASQCTAQEL VMTLNELFAR FDKLAAENHC
   421  LRIKILGDCY YCVSGLPEAR ADHAHCCVEM GVDMIEAISL VREVTGVNVN MRVGIHSGRV
   481  HCGVLGLRKW QFDVWSNDVT LANHMEAGGR AGRIHITRAT LQYLNGDYEV EPGRGGERNA
   541  YLKEQHIETF LILGASQKRK EEKAMLAKLQ RTRANSMEGL MPRWVPDRAF SRTKDSKAFR
   601  QMGIDDSSKD NRGTQDALNP EDEVDEFLSR AIDARSIDQL RKDHVRRFLL TFQREDLEKK
   661  YSRKVDPRFG AYVACALLVF CFICFIQLLI FPHSTLMLGI YASIFLLLLI TVLICAVYSC
   721  GSLFPKALQR LSRSIVRSRA HSTAVGIFSV LLVFTSAIAN MFTCNHTPIR SCAARMLNLT
   781  PADITACHLQ QLNYSLGLDA PLCEGTMPTC SFPEYFIGNM LLSLLASSVF LHISSIGKLA
   841  MIFVLGLIYL VLLLLGPPAT IFDNYDLLLG VHGLASSNET FDGLDCPAAG RVALKYMTPV
   901  ILLVFALALY LHAQQVESTA RLDFLWKLQA TGEKEEMEEL QAYNRRLLHN ILPKDVAAHF
   961  LARERRNDEL YYQSCECVAV MFASIANFSE FYVELEANNE GVECLRLLNE IIADFDEIIS
  1021  EERFRQLEKI KTIGSTYMAA SGLNASTYDQ VGRSHITALA DYAMRLMEQM KHINEHSFNN
  1081  FQMKIGLNMG PVVAGVIGAR KPQYDIWGNT VNVSSRMDST GVPDRIQVTT DLYQVLAAKG
  1141  YQLECRGVVK VKGKGEMTTY FLNGGPSS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ADCY6 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

12

Mean surface accessibility (rSASA)

0.3

Highest tissue expression

54 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ADCY6.

Disease | AllUniProt

Conditions ADCY6 is implicated in, by any mechanism.

• Lethal congenital contracture syndrome 8 (LCCS8) MIM:616287

Disease | GeneticClinVar

3 pathogenic / likely-pathogenic of 221 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Lethal congenital contracture syndrome 8

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.44

gnomAD pLI

0.01

gnomAD missense Z

2.68

DepMap mean gene effect

0

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adenylate cyclase-activating dopamine receptor signaling pathway
• adenylate cyclase-activating G protein-coupled receptor signaling pathway
• adenylate cyclase-activating serotonin receptor signaling pathway
• adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
• adenylate cyclase-inhibiting serotonin receptor signaling pathway
• blood vessel diameter maintenance
• cAMP biosynthetic process
• cellular response to catecholamine stimulus
• cellular response to forskolin
• cellular response to glucagon stimulus
• cellular response to prostaglandin E stimulus
• cellular response to vasopressin
• intracellular signal transduction
• negative regulation of neuron projection development
• negative regulation of urine volume
• renal water homeostasis
• vascular endothelial cell response to laminar fluid shear stress

Molecular functions

• adenylate cyclase activity
• ATP binding
• metal ion binding
• protein kinase binding
• protein kinase C binding

Cellular components

• cilium
• membrane
• plasma membrane
• stereocilium

Protein domainsUniProt · Pfam · InterPro

• Adenylyl cyclase class-3/4/guanylyl cyclase
• Adenylate cyclase, conserved domain
• Adenylyl cyclase class-4/guanylyl cyclase, conserved site
• Nucleotide cyclase
• Adenylate cyclase
• Adenylate cyclase, N-terminal
• Adenylate and Guanylate cyclase catalytic domain
• Adenylate cyclase, conserved domain
• Adenylyl cyclase N-terminal extracellular and transmembrane region

KeywordsUniProt

• ATP-binding
• cAMP biosynthesis
• Cell membrane
• Cell projection
• Cilium
• Glycoprotein
• Lyase
• Magnesium
• Manganese
• Membrane
• Metal-binding
• Nucleotide-binding
• Phosphoprotein
• Repeat
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of ADCY6 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• RAF1