ADCY5

Protein identityUniProt · HPA

UniProt accession

O95622

Gene

ADCY5

Ensembl

ENSG00000173175

Chromosome

3

Canonical length

1261 aa

Protein class

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

Subcellular location

Vesicles,Plasma membrane,Primary cilium

OverviewNCBI Gene

This gene encodes a member of the membrane-bound adenylyl cyclase enzymes. Adenylyl cyclases mediate G protein-coupled receptor signaling through the synthesis of the second messenger cAMP. Activity of the encoded protein is stimulated by the Gs alpha subunit of G protein-coupled receptors and is inhibited by protein kinase A, calcium and Gi alpha subunits. Single nucleotide polymorphisms in this gene may be associated with low birth weight and type 2 diabetes. Alternatively spliced transcript variants that encode different isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

Canonical amino-acid sequenceUniProt

1261 residues, UniProt reviewed canonical sequence.

>O95622|ADCY5
     1  MSGSKSVSPP GYAAQKTAAP APRGGPEHRS AWGEADSRAN GYPHAPGGSA RGSTKKPGGA
    61  VTPQQQQRLA SRWRSDDDDD PPLSGDDPLA GGFGFSFRSK SAWQERGGDD CGRGSRRQRR
   121  GAASGGSTRA PPAGGGGGSA AAAASAGGTE VRPRSVEVGL EERRGKGRAA DELEAGAVEG
   181  GEGSGDGGSS ADSGSGAGPG AVLSLGACCL ALLQIFRSKK FPSDKLERLY QRYFFRLNQS
   241  SLTMLMAVLV LVCLVMLAFH AARPPLQLPY LAVLAAAVGV ILIMAVLCNR AAFHQDHMGL
   301  ACYALIAVVL AVQVVGLLLP QPRSASEGIW WTVFFIYTIY TLLPVRMRAA VLSGVLLSAL
   361  HLAIALRTNA QDQFLLKQLV SNVLIFSCTN IVGVCTHYPA EVSQRQAFQE TRECIQARLH
   421  SQRENQQQER LLLSVLPRHV AMEMKADINA KQEDMMFHKI YIQKHDNVSI LFADIEGFTS
   481  LASQCTAQEL VMTLNELFAR FDKLAAENHC LRIKILGDCY YCVSGLPEAR ADHAHCCVEM
   541  GMDMIEAISL VREVTGVNVN MRVGIHSGRV HCGVLGLRKW QFDVWSNDVT LANHMEAGGK
   601  AGRIHITKAT LNYLNGDYEV EPGCGGERNA YLKEHSIETF LILRCTQKRK EEKAMIAKMN
   661  RQRTNSIGHN PPHWGAERPF YNHLGGNQVS KEMKRMGFED PKDKNAQESA NPEDEVDEFL
   721  GRAIDARSID RLRSEHVRKF LLTFREPDLE KKYSKQVDDR FGAYVACASL VFLFICFVQI
   781  TIVPHSIFML SFYLTCSLLL TLVVFVSVIY SCVKLFPSPL QTLSRKIVRS KMNSTLVGVF
   841  TITLVFLAAF VNMFTCNSRD LLGCLAQEHN ISASQVNACH VAESAVNYSL GDEQGFCGSP
   901  WPNCNFPEYF TYSVLLSLLA CSVFLQISCI GKLVLMLAIE LIYVLIVEVP GVTLFDNADL
   961  LVTANAIDFF NNGTSQCPEH ATKVALKVVT PIIISVFVLA LYLHAQQVES TARLDFLWKL
  1021  QATEEKEEME ELQAYNRRLL HNILPKDVAA HFLARERRND ELYYQSCECV AVMFASIANF
  1081  SEFYVELEAN NEGVECLRLL NEIIADFDEI ISEDRFRQLE KIKTIGSTYM AASGLNDSTY
  1141  DKVGKTHIKA LADFAMKLMD QMKYINEHSF NNFQMKIGLN IGPVVAGVIG ARKPQYDIWG
  1201  NTVNVASRMD STGVPDRIQV TTDMYQVLAA NTYQLECRGV VKVKGKGEMM TYFLNGGPPL
  1261  S

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ADCY5 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)

0.34

Highest tissue expression

99 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ADCY5.

Disease | AllUniProt

Conditions ADCY5 is implicated in, by any mechanism.

• Dyskinesia with orofacial involvement, autosomal recessive (DSKOR) MIM:619647
• Dyskinesia with orofacial involvement, autosomal dominant (DSKOD) MIM:606703
• Neurodevelopmental disorder with hyperkinetic movements and dyskinesia (NEDHYD) MIM:619651

Disease | GeneticClinVar

56 pathogenic / likely-pathogenic of 960 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Dyskinesia with orofacial involvement, autosomal dominant
• Inborn genetic diseases
• Neurodevelopmental disorder with hyperkinetic movements and dyskinesia
• Dyskinesia with orofacial involvement, autosomal recessive
• ADCY5-related disorder

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)

0.25

gnomAD pLI

1

gnomAD missense Z

3.4

DepMap mean gene effect

0.06

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% 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-inhibiting dopamine receptor signaling pathway
• cAMP biosynthetic process
• cellular response to forskolin
• cellular response to glucagon stimulus
• G protein-coupled adenosine receptor signaling pathway
• intracellular signal transduction
• locomotory behavior
• neuromuscular process controlling balance
• positive regulation of cytosolic calcium ion concentration
• regulation of insulin secretion involved in cellular response to glucose stimulus
• renal water homeostasis
• vascular endothelial cell response to laminar fluid shear stress

Molecular functions

• adenylate cyclase activity
• adenylate cyclase binding
• ATP binding
• metal ion binding
• scaffold protein binding

Cellular components

• cilium
• membrane
• plasma membrane

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
• Intellectual disability
• Lyase
• Magnesium
• Membrane
• Metal-binding
• Methylation
• Nucleotide-binding
• Phosphoprotein
• Repeat
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of ADCY5 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• GNAS
• GNB1
• GNG2
• RAF1