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Protein

Adenylate cyclase type 9

Gene

ADCY9

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

Functioni

Adenylyl cyclase that catalyzes the formation of the signaling molecule cAMP in response to activation of G protein-coupled receptors (PubMed:9628827, PubMed:12972952, PubMed:15879435, PubMed:10987815). Contributes to signaling cascades activated by CRH (corticotropin-releasing factor), corticosteroids and beta-adrenergic receptors (PubMed:9628827).4 Publications

Catalytic activityi

ATP = 3',5'-cyclic AMP + diphosphate.4 Publications

Cofactori

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

Enzyme regulationi

Insensitive to calcium/calmodulin, forskolin and somatostatin. Stimulated by beta-adrenergic receptor activation (PubMed:9628827). Activity is down-regulated by calcium/calcineurin (PubMed:10987815).2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi399Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi399Magnesium 2; catalyticPROSITE-ProRule annotation1
Metal bindingi400Magnesium 2; via carbonyl oxygen; catalyticPROSITE-ProRule annotation1
Metal bindingi443Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi443Magnesium 2; catalyticPROSITE-ProRule annotation1
Binding sitei487ATPBy similarity1
Binding sitei1108ATPBy similarity1
Binding sitei1232ATPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi399 – 404ATPBy similarity6
Nucleotide bindingi441 – 443ATPBy similarity3
Nucleotide bindingi1185 – 1187ATPBy similarity3
Nucleotide bindingi1192 – 1196ATPBy similarity5

GO - Molecular functioni

  • adenylate cyclase activity Source: UniProtKB
  • ATP binding Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Biological processi

cAMP biosynthesis

Keywords - Ligandi

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

Enzyme and pathway databases

BioCyciZFISH:HS08643-MONOMER.
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-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.
SIGNORiO60503.

Names & Taxonomyi

Protein namesi
Recommended name:
Adenylate cyclase type 91 Publication (EC:4.6.1.14 Publications)
Alternative name(s):
ATP pyrophosphate-lyase 9
Adenylate cyclase type IX1 Publication
Short name:
ACIX1 Publication
Adenylyl cyclase 9
Short name:
AC91 Publication
Gene namesi
Name:ADCY9
Synonyms:KIAA0520
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:240. ADCY9.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 117CytoplasmicSequence analysisAdd BLAST117
Transmembranei118 – 138HelicalSequence analysisAdd BLAST21
Topological domaini139 – 141ExtracellularSequence analysis3
Transmembranei142 – 162HelicalSequence analysisAdd BLAST21
Topological domaini163 – 171CytoplasmicSequence analysis9
Transmembranei172 – 192HelicalSequence analysisAdd BLAST21
Topological domaini193 – 215ExtracellularSequence analysisAdd BLAST23
Transmembranei216 – 235HelicalSequence analysisAdd BLAST20
Topological domaini236 – 241CytoplasmicSequence analysis6
Transmembranei242 – 259HelicalSequence analysisAdd BLAST18
Topological domaini260 – 280ExtracellularSequence analysisAdd BLAST21
Transmembranei281 – 301HelicalSequence analysisAdd BLAST21
Topological domaini302 – 786CytoplasmicSequence analysisAdd BLAST485
Transmembranei787 – 807HelicalSequence analysisAdd BLAST21
Topological domaini808 – 818ExtracellularSequence analysisAdd BLAST11
Transmembranei819 – 839HelicalSequence analysisAdd BLAST21
Topological domaini840 – 867CytoplasmicSequence analysisAdd BLAST28
Transmembranei868 – 888HelicalSequence analysisAdd BLAST21
Topological domaini889 – 891ExtracellularSequence analysis3
Transmembranei892 – 912HelicalSequence analysisAdd BLAST21
Topological domaini913 – 920CytoplasmicSequence analysis8
Transmembranei921 – 941HelicalSequence analysisAdd BLAST21
Topological domaini942 – 975ExtracellularSequence analysisAdd BLAST34
Transmembranei976 – 996HelicalSequence analysisAdd BLAST21
Topological domaini997 – 1353CytoplasmicSequence analysisAdd BLAST357

GO - Cellular componenti

  • axon Source: Ensembl
  • dendrite Source: Ensembl
  • integral component of membrane Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • intracellular Source: GOC
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi115.
OpenTargetsiENSG00000162104.
PharmGKBiPA30.

Chemistry databases

ChEMBLiCHEMBL2655.

Polymorphism and mutation databases

BioMutaiADCY9.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001957081 – 1353Adenylate cyclase type 9Add BLAST1353

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi206N-linked (GlcNAc...)Sequence analysis1
Modified residuei610PhosphoserineBy similarity1
Modified residuei688PhosphoserineBy similarity1
Modified residuei691PhosphoserineBy similarity1
Modified residuei706PhosphoserineCombined sources1
Glycosylationi955N-linked (GlcNAc...)Sequence analysis1
Glycosylationi964N-linked (GlcNAc...)Sequence analysis1
Modified residuei1257PhosphoserineCombined sources1
Modified residuei1259PhosphoserineCombined sources1
Modified residuei1295PhosphoserineBy similarity1
Modified residuei1307PhosphoserineCombined sources1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiO60503.
PaxDbiO60503.
PeptideAtlasiO60503.
PRIDEiO60503.

PTM databases

iPTMnetiO60503.
PhosphoSitePlusiO60503.

Expressioni

Tissue specificityi

Detected in skeletal muscle, pancreas, lung, heart, kidney, liver, brain and placenta (PubMed:9628827, PubMed:10987815). Expressed in multiple cells of the lung, with expression highest in airway smooth muscle (PubMed:12972952).3 Publications

Gene expression databases

BgeeiENSG00000162104.
CleanExiHS_ADCY9.
ExpressionAtlasiO60503. baseline and differential.
GenevisibleiO60503. HS.

Organism-specific databases

HPAiHPA041328.
HPA044225.

Interactioni

Protein-protein interaction databases

BioGridi106628. 15 interactors.
IntActiO60503. 3 interactors.
STRINGi9606.ENSP00000294016.

Structurei

3D structure databases

ProteinModelPortaliO60503.
SMRiO60503.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini394 – 521Guanylate cyclase 1PROSITE-ProRule annotationAdd BLAST128
Domaini1058 – 1198Guanylate cyclase 2PROSITE-ProRule annotationAdd BLAST141

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

eggNOGiKOG3618. Eukaryota.
COG2114. LUCA.
GeneTreeiENSGT00760000119042.
HOVERGENiHBG050459.
InParanoidiO60503.
KOiK08049.
OMAiWHICLAV.
OrthoDBiEOG091G0285.
PhylomeDBiO60503.
TreeFamiTF313845.

Family and domain databases

Gene3Di3.30.70.1230. 2 hits.
InterProiIPR001054. A/G_cyclase.
IPR018297. A/G_cyclase_CS.
IPR029787. Nucleotide_cyclase.
[Graphical view]
PfamiPF00211. Guanylate_cyc. 2 hits.
[Graphical view]
SMARTiSM00044. CYCc. 2 hits.
[Graphical view]
SUPFAMiSSF55073. SSF55073. 2 hits.
PROSITEiPS00452. GUANYLATE_CYCLASE_1. 2 hits.
PS50125. GUANYLATE_CYCLASE_2. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O60503-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASPPHQQLL HHHSTEVSCD SSGDSNSVRV KINPKQLSSN SHPKHCKYSI
60 70 80 90 100
SSSCSSSGDS GGVPRRVGGG GRLRRQKKLP QLFERASSRW WDPKFDSVNL
110 120 130 140 150
EEACLERCFP QTQRRFRYAL FYIGFACLLW SIYFAVHMRS RLIVMVAPAL
160 170 180 190 200
CFLLVCVGFF LFTFTKLYAR HYAWTSLALT LLVFALTLAA QFQVLTPVSG
210 220 230 240 250
RGDSSNLTAT ARPTDTCLSQ VGSFSMCIEV LFLLYTVMHL PLYLSLCLGV
260 270 280 290 300
AYSVLFETFG YHFRDEACFP SPGAGALHWE LLSRGLLHGC IHAIGVHLFV
310 320 330 340 350
MSQVRSRSTF LKVGQSIMHG KDLEVEKALK ERMIHSVMPR IIADDLMKQG
360 370 380 390 400
DEESENSVKR HATSSPKNRK KKSSIQKAPI AFRPFKMQQI EEVSILFADI
410 420 430 440 450
VGFTKMSANK SAHALVGLLN DLFGRFDRLC EETKCEKIST LGDCYYCVAG
460 470 480 490 500
CPEPRADHAY CCIEMGLGMI KAIEQFCQEK KEMVNMRVGV HTGTVLCGIL
510 520 530 540 550
GMRRFKFDVW SNDVNLANLM EQLGVAGKVH ISEATAKYLD DRYEMEDGKV
560 570 580 590 600
IERLGQSVVA DQLKGLKTYL ISGQRAKESR CSCAEALLSG FEVIDGSQVS
610 620 630 640 650
SGPRGQGTAS SGNVSDLAQT VKTFDNLKTC PSCGITFAPK SEAGAEGGAP
660 670 680 690 700
QNGCQDEHKN STKASGGPNP KTQNGLLSPP QEEKLTNSQT SLCEILQEKG
710 720 730 740 750
RWAGVSLDQS ALLPLRFKNI REKTDAHFVD VIKEDSLMKD YFFKPPINQF
760 770 780 790 800
SLNFLDQELE RSYRTSYQEE VIKNSPVKTF ASPTFSSLLD VFLSTTVFLT
810 820 830 840 850
LSTTCFLKYE AATVPPPPAA LAVFSAALLL EVLSLAVSIR MVFFLEDVMA
860 870 880 890 900
CTKRLLEWIA GWLPRHCIGA ILVSLPALAV YSHVTSEYET NIHFPVFTGS
910 920 930 940 950
AALIAVVHYC NFCQLSSWMR SSLATVVGAG PLLLLYVSLC PDSSVLTSPL
960 970 980 990 1000
DAVQNFSSER NPCNSSVPRD LRRPASLIGQ EVVLVFFLLL LLVWFLNREF
1010 1020 1030 1040 1050
EVSYRLHYHG DVEADLHRTK IQSMRDQADW LLRNIIPYHV AEQLKVSQTY
1060 1070 1080 1090 1100
SKNHDSGGVI FASIVNFSEF YEENYEGGKE CYRVLNELIG DFDELLSKPD
1110 1120 1130 1140 1150
YSSIEKIKTI GATYMAASGL NTAQAQDGSH PQEHLQILFE FAKEMMRVVD
1160 1170 1180 1190 1200
DFNNNMLWFN FKLRVGFNHG PLTAGVIGTT KLLYDIWGDT VNIASRMDTT
1210 1220 1230 1240 1250
GVECRIQVSE ESYRVLSKMG YDFDYRGTVN VKGKGQMKTY LYPKCTDHRV
1260 1270 1280 1290 1300
IPQHQLSISP DIRVQVDGSI GRSPTDEIAN LVPSVQYVDK TSLGSDSSTQ
1310 1320 1330 1340 1350
AKDAHLSPKR PWKEPVKAEE RGRFGKAIEK DDCDETGIEE ANELTKLNVS

KSV
Length:1,353
Mass (Da):150,701
Last modified:December 13, 2002 - v4
Checksum:i4CBF051EA49B5B7B
GO

Sequence cautioni

The sequence AAC24201 differs from that shown. Reason: Frameshift at position 1252.Curated
The sequence BAA25446 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti493G → R in CAB65084 (PubMed:10987815).Curated1
Sequence conflicti884V → A in CAB65084 (PubMed:10987815).Curated1
Sequence conflicti1308P → R in CAB65084 (PubMed:10987815).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_023750772I → M Common polymorphism; found in 37.5% of the Asian population, in 30% of the Caucasian population and in 16.3% of the African-American population; reduced adenylyl cyclase activity in response to stimulation of the beta-adregnergic receptor by Mn(2+) agonists isoproteronol and NaF; increased albuterol-stimulated adenylyl cyclase activity in the presence of corticosteroid. 2 PublicationsCorresponds to variant rs2230739dbSNPEnsembl.1
Natural variantiVAR_0708871154N → S.3 PublicationsCorresponds to variant rs61731445dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF036927 mRNA. Translation: AAC24201.1. Frameshift.
DQ008441 mRNA. Translation: AAY27880.1.
DQ005545 mRNA. Translation: AAY21237.1.
AJ133123 mRNA. Translation: CAB65084.1.
AY028959
, AY028949, AY028950, AY028951, AY028952, AY028953, AY028954, AY028955, AY028956, AY028957 Genomic DNA. Translation: AAK29464.1.
AB011092 mRNA. Translation: BAA25446.3. Different initiation.
CH471112 Genomic DNA. Translation: EAW85331.1.
CH471112 Genomic DNA. Translation: EAW85332.1.
BC136657 mRNA. Translation: AAI36658.1.
BC136658 mRNA. Translation: AAI36659.1.
BC151207 mRNA. Translation: AAI51208.1.
BC151229 mRNA. Translation: AAI51230.1.
CCDSiCCDS32382.1.
RefSeqiNP_001107.2. NM_001116.3.
UniGeneiHs.391860.
Hs.610484.

Genome annotation databases

EnsembliENST00000294016; ENSP00000294016; ENSG00000162104.
GeneIDi115.
KEGGihsa:115.
UCSCiuc002cvx.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF036927 mRNA. Translation: AAC24201.1. Frameshift.
DQ008441 mRNA. Translation: AAY27880.1.
DQ005545 mRNA. Translation: AAY21237.1.
AJ133123 mRNA. Translation: CAB65084.1.
AY028959
, AY028949, AY028950, AY028951, AY028952, AY028953, AY028954, AY028955, AY028956, AY028957 Genomic DNA. Translation: AAK29464.1.
AB011092 mRNA. Translation: BAA25446.3. Different initiation.
CH471112 Genomic DNA. Translation: EAW85331.1.
CH471112 Genomic DNA. Translation: EAW85332.1.
BC136657 mRNA. Translation: AAI36658.1.
BC136658 mRNA. Translation: AAI36659.1.
BC151207 mRNA. Translation: AAI51208.1.
BC151229 mRNA. Translation: AAI51230.1.
CCDSiCCDS32382.1.
RefSeqiNP_001107.2. NM_001116.3.
UniGeneiHs.391860.
Hs.610484.

3D structure databases

ProteinModelPortaliO60503.
SMRiO60503.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106628. 15 interactors.
IntActiO60503. 3 interactors.
STRINGi9606.ENSP00000294016.

Chemistry databases

ChEMBLiCHEMBL2655.

PTM databases

iPTMnetiO60503.
PhosphoSitePlusiO60503.

Polymorphism and mutation databases

BioMutaiADCY9.

Proteomic databases

MaxQBiO60503.
PaxDbiO60503.
PeptideAtlasiO60503.
PRIDEiO60503.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000294016; ENSP00000294016; ENSG00000162104.
GeneIDi115.
KEGGihsa:115.
UCSCiuc002cvx.4. human.

Organism-specific databases

CTDi115.
DisGeNETi115.
GeneCardsiADCY9.
HGNCiHGNC:240. ADCY9.
HPAiHPA041328.
HPA044225.
MIMi603302. gene.
neXtProtiNX_O60503.
OpenTargetsiENSG00000162104.
PharmGKBiPA30.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3618. Eukaryota.
COG2114. LUCA.
GeneTreeiENSGT00760000119042.
HOVERGENiHBG050459.
InParanoidiO60503.
KOiK08049.
OMAiWHICLAV.
OrthoDBiEOG091G0285.
PhylomeDBiO60503.
TreeFamiTF313845.

Enzyme and pathway databases

BioCyciZFISH:HS08643-MONOMER.
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-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.
SIGNORiO60503.

Miscellaneous databases

ChiTaRSiADCY9. human.
GeneWikiiADCY9.
GenomeRNAii115.
PROiO60503.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000162104.
CleanExiHS_ADCY9.
ExpressionAtlasiO60503. baseline and differential.
GenevisibleiO60503. HS.

Family and domain databases

Gene3Di3.30.70.1230. 2 hits.
InterProiIPR001054. A/G_cyclase.
IPR018297. A/G_cyclase_CS.
IPR029787. Nucleotide_cyclase.
[Graphical view]
PfamiPF00211. Guanylate_cyc. 2 hits.
[Graphical view]
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 nameiADCY9_HUMAN
AccessioniPrimary (citable) accession number: O60503
Secondary accession number(s): A7E2V5
, A7E2X2, D3DUD1, O60273, Q4ZHT9, Q4ZIR5, Q9BWT4, Q9UGP2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: December 13, 2002
Last modified: November 2, 2016
This is version 150 of the entry and version 4 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 16
    Human chromosome 16: 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.