Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Adenylate cyclase type 5

Gene

ADCY5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling (PubMed:15385642, PubMed:26206488, PubMed:24700542). Mediates signaling downstream of ADRB1 (PubMed:24700542). Regulates the increase of free cytosolic Ca2+ in response to increased blood glucose levels and contributes to the regulation of Ca2+-dependent insulin secretion (PubMed:24740569).4 Publications

Catalytic activityi

ATP = 3',5'-cyclic AMP + diphosphate.3 Publications

Cofactori

Mg2+1 Publication, Mn2+1 PublicationNote: Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).By similarity

Enzyme regulationi

Activated by forskolin (PubMed:24700542). Activated by GNAS. Activity is further increased by interaction with the G-protein beta and gamma subunit complex formed by GNB1 and GNG2 (PubMed:26206488). Is not activated by calmodulin. Inhibited by adenosine and ATP analogs. Inhibited by calcium ions, already at micromolar concentrations (By similarity). Phosphorylation by RAF1 results in its activation (PubMed:15385642).By similarity2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi474Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi474Magnesium 2; catalyticPROSITE-ProRule annotation1
Metal bindingi475Magnesium 2; via carbonyl oxygen; catalyticPROSITE-ProRule annotation1
Metal bindingi518Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi518Magnesium 2; catalyticPROSITE-ProRule annotation1
Binding sitei562ATPBy similarity1
Binding sitei1123ATPBy similarity1
Binding sitei1244ATPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi474 – 479ATPBy similarity6
Nucleotide bindingi516 – 518ATPBy similarity3
Nucleotide bindingi1197 – 1199ATPBy similarity3
Nucleotide bindingi1204 – 1208ATPBy similarity5

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Biological processi

cAMP biosynthesis

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS10626-MONOMER.
BRENDAi4.6.1.1. 2681.
ReactomeiR-HSA-163359. Glucagon signaling in metabolic regulation.
R-HSA-163615. PKA activation.
R-HSA-164378. PKA activation in glucagon signalling.
R-HSA-170660. Adenylate cyclase activating pathway.
R-HSA-170670. Adenylate cyclase inhibitory pathway.
R-HSA-381676. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
R-HSA-400042. Adrenaline,noradrenaline inhibits insulin secretion.
R-HSA-418555. G alpha (s) signalling events.
R-HSA-418594. G alpha (i) signalling events.
R-HSA-418597. G alpha (z) signalling events.
R-HSA-432040. Vasopressin regulates renal water homeostasis via Aquaporins.
R-HSA-5610787. Hedgehog 'off' state.
SIGNORiO95622.

Names & Taxonomyi

Protein namesi
Recommended name:
Adenylate cyclase type 5 (EC:4.6.1.13 Publications)
Alternative name(s):
ATP pyrophosphate-lyase 5
Adenylate cyclase type V
Adenylyl cyclase 5
Short name:
AC51 Publication
Gene namesi
Name:ADCY5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:236. ADCY5.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 195CytoplasmicSequence analysisAdd BLAST195
Transmembranei196 – 216HelicalSequence analysisAdd BLAST21
Transmembranei242 – 262HelicalSequence analysisAdd BLAST21
Transmembranei268 – 288HelicalSequence analysisAdd BLAST21
Transmembranei299 – 319HelicalSequence analysisAdd BLAST21
Transmembranei325 – 345HelicalSequence analysisAdd BLAST21
Transmembranei374 – 394HelicalSequence analysisAdd BLAST21
Topological domaini395 – 769CytoplasmicSequence analysisAdd BLAST375
Transmembranei770 – 790HelicalSequence analysisAdd BLAST21
Transmembranei792 – 812HelicalSequence analysisAdd BLAST21
Transmembranei836 – 856HelicalSequence analysisAdd BLAST21
Topological domaini857 – 909ExtracellularSequence analysisAdd BLAST53
Transmembranei910 – 930HelicalSequence analysisAdd BLAST21
Transmembranei935 – 955HelicalSequence analysisAdd BLAST21
Transmembranei984 – 1004HelicalSequence analysisAdd BLAST21
Topological domaini1005 – 1261CytoplasmicSequence analysisAdd BLAST257

GO - Cellular componenti

  • cilium Source: UniProtKB
  • integral component of membrane Source: UniProtKB
  • intracellular Source: GOC
  • plasma membrane Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cilium, Membrane

Pathology & Biotechi

Involvement in diseasei

Dyskinesia, familial, with facial myokymia (FDFM)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by predominantly perioral and periorbital myokymia, and face, neck and upper limb dystonic/choreic movements. Initially paroxysmal and worsened by stress, the dyskinetic episodes become nearly constant by the end of the third decade of life, but in some individuals, they may diminish in frequency and severity at older ages.
See also OMIM:606703
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073778418R → W in FDFM; increases cAMP production upon activation of ADRB1. 1 Publication1
Natural variantiVAR_068821726A → T in FDFM; increases cAMP production upon activation of ADRB1. 2 PublicationsCorresponds to variant rs796065306dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi111.
MalaCardsiADCY5.
MIMi606703. phenotype.
OpenTargetsiENSG00000173175.
Orphaneti324588. Familial dyskinesia and facial myokymia.
PharmGKBiPA24563.

Chemistry databases

ChEMBLiCHEMBL3189.
GuidetoPHARMACOLOGYi1282.

Polymorphism and mutation databases

BioMutaiADCY5.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001956941 – 1261Adenylate cyclase type 5Add BLAST1261

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei23Omega-N-methylarginineBy similarity1
Modified residuei96PhosphoserineBy similarity1
Modified residuei155PhosphoserineBy similarity1
Modified residuei666PhosphoserineBy similarity1
Modified residuei754PhosphoserineBy similarity1
Glycosylationi870N-linked (GlcNAc...)Sequence analysis1
Glycosylationi887N-linked (GlcNAc...)Sequence analysis1
Modified residuei1011PhosphothreonineBy similarity1

Post-translational modificationi

Phosphorylated by RAF1.1 Publication

Keywords - PTMi

Glycoprotein, Methylation, Phosphoprotein

Proteomic databases

MaxQBiO95622.
PaxDbiO95622.
PeptideAtlasiO95622.
PRIDEiO95622.

PTM databases

iPTMnetiO95622.
PhosphoSitePlusiO95622.

Expressioni

Tissue specificityi

Detected in pancreas islets (at protein level). Detected in pancreas islets.1 Publication

Gene expression databases

BgeeiENSG00000173175.
CleanExiHS_ADCY5.
ExpressionAtlasiO95622. baseline and differential.
GenevisibleiO95622. HS.

Organism-specific databases

HPAiHPA017730.

Interactioni

Subunit structurei

Interacts with GNAS, GNB1 and GNG2 (PubMed:26206488). Part of a complex containing AKAP5, ADCY6, PDE4C and PKD2 (By similarity). Interacts with RAF1 (PubMed:15385642).By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi106624. 13 interactors.
STRINGi9606.ENSP00000419361.

Chemistry databases

BindingDBiO95622.

Structurei

3D structure databases

ProteinModelPortaliO95622.
SMRiO95622.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini469 – 596Guanylate cyclase 1PROSITE-ProRule annotationAdd BLAST128
Domaini1071 – 1210Guanylate cyclase 2PROSITE-ProRule annotationAdd BLAST140

Domaini

The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal guanylate cyclase domains have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two domains. Both contribute substrate-binding residues, but the catalytic metal ions are bound exclusively via the N-terminal guanylate cyclase domain.By similarity

Sequence similaritiesi

Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.PROSITE-ProRule annotation
Contains 2 guanylate cyclase domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3619. Eukaryota.
COG2114. LUCA.
GeneTreeiENSGT00760000119042.
HOGENOMiHOG000006941.
HOVERGENiHBG050458.
InParanoidiO95622.
KOiK08045.
OMAiFMCNSKD.
OrthoDBiEOG091G05JR.
PhylomeDBiO95622.
TreeFamiTF313845.

Family and domain databases

Gene3Di3.30.70.1230. 2 hits.
InterProiIPR001054. A/G_cyclase.
IPR018297. A/G_cyclase_CS.
IPR032628. AC_N.
IPR030672. Adcy.
IPR009398. Adcy_conserved_dom.
IPR029787. Nucleotide_cyclase.
[Graphical view]
PfamiPF16214. AC_N. 1 hit.
PF06327. DUF1053. 1 hit.
PF00211. Guanylate_cyc. 2 hits.
[Graphical view]
PIRSFiPIRSF039050. Ade_cyc. 1 hit.
SMARTiSM00044. CYCc. 2 hits.
[Graphical view]
SUPFAMiSSF55073. SSF55073. 2 hits.
PROSITEiPS00452. GUANYLATE_CYCLASE_1. 2 hits.
PS50125. GUANYLATE_CYCLASE_2. 2 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O95622-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSGSKSVSPP GYAAQKTAAP APRGGPEHRS AWGEADSRAN GYPHAPGGSA
60 70 80 90 100
RGSTKKPGGA VTPQQQQRLA SRWRSDDDDD PPLSGDDPLA GGFGFSFRSK
110 120 130 140 150
SAWQERGGDD CGRGSRRQRR GAASGGSTRA PPAGGGGGSA AAAASAGGTE
160 170 180 190 200
VRPRSVEVGL EERRGKGRAA DELEAGAVEG GEGSGDGGSS ADSGSGAGPG
210 220 230 240 250
AVLSLGACCL ALLQIFRSKK FPSDKLERLY QRYFFRLNQS SLTMLMAVLV
260 270 280 290 300
LVCLVMLAFH AARPPLQLPY LAVLAAAVGV ILIMAVLCNR AAFHQDHMGL
310 320 330 340 350
ACYALIAVVL AVQVVGLLLP QPRSASEGIW WTVFFIYTIY TLLPVRMRAA
360 370 380 390 400
VLSGVLLSAL HLAIALRTNA QDQFLLKQLV SNVLIFSCTN IVGVCTHYPA
410 420 430 440 450
EVSQRQAFQE TRECIQARLH SQRENQQQER LLLSVLPRHV AMEMKADINA
460 470 480 490 500
KQEDMMFHKI YIQKHDNVSI LFADIEGFTS LASQCTAQEL VMTLNELFAR
510 520 530 540 550
FDKLAAENHC LRIKILGDCY YCVSGLPEAR ADHAHCCVEM GMDMIEAISL
560 570 580 590 600
VREVTGVNVN MRVGIHSGRV HCGVLGLRKW QFDVWSNDVT LANHMEAGGK
610 620 630 640 650
AGRIHITKAT LNYLNGDYEV EPGCGGERNA YLKEHSIETF LILRCTQKRK
660 670 680 690 700
EEKAMIAKMN RQRTNSIGHN PPHWGAERPF YNHLGGNQVS KEMKRMGFED
710 720 730 740 750
PKDKNAQESA NPEDEVDEFL GRAIDARSID RLRSEHVRKF LLTFREPDLE
760 770 780 790 800
KKYSKQVDDR FGAYVACASL VFLFICFVQI TIVPHSIFML SFYLTCSLLL
810 820 830 840 850
TLVVFVSVIY SCVKLFPSPL QTLSRKIVRS KMNSTLVGVF TITLVFLAAF
860 870 880 890 900
VNMFTCNSRD LLGCLAQEHN ISASQVNACH VAESAVNYSL GDEQGFCGSP
910 920 930 940 950
WPNCNFPEYF TYSVLLSLLA CSVFLQISCI GKLVLMLAIE LIYVLIVEVP
960 970 980 990 1000
GVTLFDNADL LVTANAIDFF NNGTSQCPEH ATKVALKVVT PIIISVFVLA
1010 1020 1030 1040 1050
LYLHAQQVES TARLDFLWKL QATEEKEEME ELQAYNRRLL HNILPKDVAA
1060 1070 1080 1090 1100
HFLARERRND ELYYQSCECV AVMFASIANF SEFYVELEAN NEGVECLRLL
1110 1120 1130 1140 1150
NEIIADFDEI ISEDRFRQLE KIKTIGSTYM AASGLNDSTY DKVGKTHIKA
1160 1170 1180 1190 1200
LADFAMKLMD QMKYINEHSF NNFQMKIGLN IGPVVAGVIG ARKPQYDIWG
1210 1220 1230 1240 1250
NTVNVASRMD STGVPDRIQV TTDMYQVLAA NTYQLECRGV VKVKGKGEMM
1260
TYFLNGGPPL S
Length:1,261
Mass (Da):138,908
Last modified:November 28, 2006 - v3
Checksum:iC50492A0B053694F
GO
Isoform 2 (identifier: O95622-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-28: MSGSKSVSPPGYAAQKTAAPAPRGGPEH → MKSQKEGCCSRGDLSIQTGPGGEWAPRR
     29-378: Missing.

Note: No experimental confirmation available.
Show »
Length:911
Mass (Da):102,606
Checksum:iCA9E766B744A6222
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073778418R → W in FDFM; increases cAMP production upon activation of ADRB1. 1 Publication1
Natural variantiVAR_068821726A → T in FDFM; increases cAMP production upon activation of ADRB1. 2 PublicationsCorresponds to variant rs796065306dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0429141 – 28MSGSK…GGPEH → MKSQKEGCCSRGDLSIQTGP GGEWAPRR in isoform 2. 1 PublicationAdd BLAST28
Alternative sequenceiVSP_04291529 – 378Missing in isoform 2. 1 PublicationAdd BLAST350

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK303070 mRNA. Translation: BAH13892.1.
AC025571 Genomic DNA. No translation available.
AC112503 Genomic DNA. No translation available.
AF497517 mRNA. Translation: AAM94374.1.
U65473 mRNA. Translation: AAD00121.1.
BK000371 mRNA. Translation: DAA00057.1.
CCDSiCCDS3022.1. [O95622-1]
CCDS56274.1. [O95622-2]
RefSeqiNP_001186571.1. NM_001199642.1. [O95622-2]
NP_899200.1. NM_183357.2. [O95622-1]
UniGeneiHs.593292.

Genome annotation databases

EnsembliENST00000309879; ENSP00000308685; ENSG00000173175. [O95622-2]
ENST00000462833; ENSP00000419361; ENSG00000173175. [O95622-1]
GeneIDi111.
KEGGihsa:111.
UCSCiuc003egh.3. human. [O95622-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK303070 mRNA. Translation: BAH13892.1.
AC025571 Genomic DNA. No translation available.
AC112503 Genomic DNA. No translation available.
AF497517 mRNA. Translation: AAM94374.1.
U65473 mRNA. Translation: AAD00121.1.
BK000371 mRNA. Translation: DAA00057.1.
CCDSiCCDS3022.1. [O95622-1]
CCDS56274.1. [O95622-2]
RefSeqiNP_001186571.1. NM_001199642.1. [O95622-2]
NP_899200.1. NM_183357.2. [O95622-1]
UniGeneiHs.593292.

3D structure databases

ProteinModelPortaliO95622.
SMRiO95622.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106624. 13 interactors.
STRINGi9606.ENSP00000419361.

Chemistry databases

BindingDBiO95622.
ChEMBLiCHEMBL3189.
GuidetoPHARMACOLOGYi1282.

PTM databases

iPTMnetiO95622.
PhosphoSitePlusiO95622.

Polymorphism and mutation databases

BioMutaiADCY5.

Proteomic databases

MaxQBiO95622.
PaxDbiO95622.
PeptideAtlasiO95622.
PRIDEiO95622.

Protocols and materials databases

DNASUi111.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000309879; ENSP00000308685; ENSG00000173175. [O95622-2]
ENST00000462833; ENSP00000419361; ENSG00000173175. [O95622-1]
GeneIDi111.
KEGGihsa:111.
UCSCiuc003egh.3. human. [O95622-1]

Organism-specific databases

CTDi111.
DisGeNETi111.
GeneCardsiADCY5.
H-InvDBHIX0003612.
HGNCiHGNC:236. ADCY5.
HPAiHPA017730.
MalaCardsiADCY5.
MIMi600293. gene.
606703. phenotype.
neXtProtiNX_O95622.
OpenTargetsiENSG00000173175.
Orphaneti324588. Familial dyskinesia and facial myokymia.
PharmGKBiPA24563.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3619. Eukaryota.
COG2114. LUCA.
GeneTreeiENSGT00760000119042.
HOGENOMiHOG000006941.
HOVERGENiHBG050458.
InParanoidiO95622.
KOiK08045.
OMAiFMCNSKD.
OrthoDBiEOG091G05JR.
PhylomeDBiO95622.
TreeFamiTF313845.

Enzyme and pathway databases

BioCyciZFISH:HS10626-MONOMER.
BRENDAi4.6.1.1. 2681.
ReactomeiR-HSA-163359. Glucagon signaling in metabolic regulation.
R-HSA-163615. PKA activation.
R-HSA-164378. PKA activation in glucagon signalling.
R-HSA-170660. Adenylate cyclase activating pathway.
R-HSA-170670. Adenylate cyclase inhibitory pathway.
R-HSA-381676. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
R-HSA-400042. Adrenaline,noradrenaline inhibits insulin secretion.
R-HSA-418555. G alpha (s) signalling events.
R-HSA-418594. G alpha (i) signalling events.
R-HSA-418597. G alpha (z) signalling events.
R-HSA-432040. Vasopressin regulates renal water homeostasis via Aquaporins.
R-HSA-5610787. Hedgehog 'off' state.
SIGNORiO95622.

Miscellaneous databases

ChiTaRSiADCY5. human.
GeneWikiiADCY5.
GenomeRNAii111.
PROiO95622.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000173175.
CleanExiHS_ADCY5.
ExpressionAtlasiO95622. baseline and differential.
GenevisibleiO95622. HS.

Family and domain databases

Gene3Di3.30.70.1230. 2 hits.
InterProiIPR001054. A/G_cyclase.
IPR018297. A/G_cyclase_CS.
IPR032628. AC_N.
IPR030672. Adcy.
IPR009398. Adcy_conserved_dom.
IPR029787. Nucleotide_cyclase.
[Graphical view]
PfamiPF16214. AC_N. 1 hit.
PF06327. DUF1053. 1 hit.
PF00211. Guanylate_cyc. 2 hits.
[Graphical view]
PIRSFiPIRSF039050. Ade_cyc. 1 hit.
SMARTiSM00044. CYCc. 2 hits.
[Graphical view]
SUPFAMiSSF55073. SSF55073. 2 hits.
PROSITEiPS00452. GUANYLATE_CYCLASE_1. 2 hits.
PS50125. GUANYLATE_CYCLASE_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiADCY5_HUMAN
AccessioniPrimary (citable) accession number: O95622
Secondary accession number(s): B7Z8A6, Q7RTV7, Q8NFM3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 28, 2006
Last modified: November 30, 2016
This is version 154 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.