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O43306

- ADCY6_HUMAN

UniProt

O43306 - ADCY6_HUMAN

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Protein

Adenylate cyclase type 6

Gene

ADCY6

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

Functioni

Membrane-bound, calcium-inhibitable adenylyl cyclase.By similarity

Catalytic activityi

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

Cofactori

Binds 2 magnesium ions per subunit.By similarity

Enzyme regulationi

Inhibition by calcium in the submicromolar concentration range (By similarity). Phosphorylation by RAF1 results in its activation.By similarity1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi384 – 3841Magnesium 1PROSITE-ProRule annotation
Metal bindingi384 – 3841Magnesium 2PROSITE-ProRule annotation
Metal bindingi385 – 3851Magnesium 2; via carbonyl oxygenPROSITE-ProRule annotation
Metal bindingi428 – 4281Magnesium 1PROSITE-ProRule annotation
Metal bindingi428 – 4281Magnesium 2PROSITE-ProRule annotation

GO - Molecular functioni

  1. adenylate cyclase activity Source: BHF-UCL
  2. ATP binding Source: UniProtKB-KW
  3. metal ion binding Source: UniProtKB-KW
  4. protein kinase binding Source: BHF-UCL

GO - Biological processi

  1. activation of phospholipase C activity Source: Reactome
  2. activation of protein kinase A activity Source: Reactome
  3. adenylate cyclase-activating G-protein coupled receptor signaling pathway Source: Reactome
  4. adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway Source: Reactome
  5. cAMP biosynthetic process Source: BHF-UCL
  6. cellular response to catecholamine stimulus Source: BHF-UCL
  7. cellular response to glucagon stimulus Source: Reactome
  8. cellular response to prostaglandin E stimulus Source: BHF-UCL
  9. dopamine receptor signaling pathway Source: BHF-UCL
  10. energy reserve metabolic process Source: Reactome
  11. epidermal growth factor receptor signaling pathway Source: Reactome
  12. fibroblast growth factor receptor signaling pathway Source: Reactome
  13. innate immune response Source: Reactome
  14. intracellular signal transduction Source: InterPro
  15. negative regulation of neuron projection development Source: ParkinsonsUK-UCL
  16. neurotrophin TRK receptor signaling pathway Source: Reactome
  17. signal transduction Source: Reactome
  18. small molecule metabolic process Source: Reactome
  19. synaptic transmission Source: Reactome
  20. transmembrane transport Source: Reactome
  21. water transport Source: Reactome
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

BRENDAi4.6.1.1. 2681.
ReactomeiREACT_15312. Adenylate cyclase activating pathway.
REACT_15333. Adenylate cyclase inhibitory pathway.
REACT_15530. PKA activation.
REACT_1665. Glucagon signaling in metabolic regulation.
REACT_18274. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
REACT_18339. Adrenaline,noradrenaline inhibits insulin secretion.
REACT_19231. G alpha (i) signalling events.
REACT_19327. G alpha (s) signalling events.
REACT_19333. G alpha (z) signalling events.
REACT_1946. PKA activation in glucagon signalling.
REACT_24023. Regulation of water balance by renal Aquaporins.

Names & Taxonomyi

Protein namesi
Recommended name:
Adenylate cyclase type 6 (EC:4.6.1.1)
Alternative name(s):
ATP pyrophosphate-lyase 6
Adenylate cyclase type VI
Adenylyl cyclase 6
Ca(2+)-inhibitable adenylyl cyclase
Gene namesi
Name:ADCY6
Synonyms:KIAA0422
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 12

Organism-specific databases

HGNCiHGNC:237. ADCY6.

Subcellular locationi

GO - Cellular componenti

  1. cilium Source: UniProtKB-KW
  2. integral component of membrane Source: UniProtKB-KW
  3. membrane Source: BHF-UCL
  4. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Cilium, Membrane

Pathology & Biotechi

Organism-specific databases

Orphaneti2680. Hypomyelination neuropathy - arthrogryposis.
PharmGKBiPA27.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11681168Adenylate cyclase type 6PRO_0000195699Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei556 – 5561PhosphoserineBy similarity
Modified residuei576 – 5761Phosphoserine1 Publication
Modified residuei662 – 6621PhosphoserineBy similarity
Glycosylationi793 – 7931N-linked (GlcNAc...)Sequence Analysis
Modified residuei919 – 9191PhosphothreonineBy similarity

Post-translational modificationi

Phosphorylated by RAF1.2 Publications

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiO43306.
PaxDbiO43306.
PRIDEiO43306.

PTM databases

PhosphoSiteiO43306.

Expressioni

Gene expression databases

BgeeiO43306.
CleanExiHS_ADCY6.
ExpressionAtlasiO43306. baseline and differential.
GenevestigatoriO43306.

Organism-specific databases

HPAiCAB018365.

Interactioni

Subunit structurei

Part of a complex containing AKAP5, ADCY5, PDE4C and PKD2 (By similarity). Interacts with RAF1.By similarity1 Publication

Protein-protein interaction databases

BioGridi106625. 9 interactions.
IntActiO43306. 1 interaction.
MINTiMINT-2856766.
STRINGi9606.ENSP00000311405.

Structurei

3D structure databases

ProteinModelPortaliO43306.
SMRiO43306. Positions 364-553, 970-1145.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 151151CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini306 – 673368CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini760 – 81960ExtracellularSequence AnalysisAdd
BLAST
Topological domaini914 – 1168255CytoplasmicSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei152 – 16817HelicalSequence AnalysisAdd
BLAST
Transmembranei181 – 19717HelicalSequence AnalysisAdd
BLAST
Transmembranei214 – 23017HelicalSequence AnalysisAdd
BLAST
Transmembranei239 – 25517HelicalSequence AnalysisAdd
BLAST
Transmembranei259 – 27517HelicalSequence AnalysisAdd
BLAST
Transmembranei289 – 30517HelicalSequence AnalysisAdd
BLAST
Transmembranei674 – 69118HelicalSequence AnalysisAdd
BLAST
Transmembranei702 – 71817HelicalSequence AnalysisAdd
BLAST
Transmembranei743 – 75917HelicalSequence AnalysisAdd
BLAST
Transmembranei820 – 83617HelicalSequence AnalysisAdd
BLAST
Transmembranei839 – 85517HelicalSequence AnalysisAdd
BLAST
Transmembranei897 – 91317HelicalSequence AnalysisAdd
BLAST

Family & Domainsi

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

eggNOGiCOG2114.
GeneTreeiENSGT00760000119042.
HOGENOMiHOG000006941.
HOVERGENiHBG050458.
InParanoidiO43306.
KOiK08046.
OMAiRSCWRRL.
OrthoDBiEOG7B8S30.
PhylomeDBiO43306.
TreeFamiTF313845.

Family and domain databases

Gene3Di3.30.70.1230. 2 hits.
InterProiIPR001054. A/G_cyclase.
IPR018297. A/G_cyclase_CS.
IPR009398. Adenylate_cyclase-like.
IPR029787. Nucleotide_cyclase.
[Graphical view]
PfamiPF06327. DUF1053. 1 hit.
PF00211. 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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: O43306-1) [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
MSWFSGLLVP KVDERKTAWG ERNGQKRSRR RGTRAGGFCT PRYMSCLRDA
60 70 80 90 100
EPPSPTPAGP PRCPWQDDAF IRRGGPGKGK ELGLRAVALG FEDTEVTTTA
110 120 130 140 150
GGTAEVAPDA VPRSGRSCWR RLVQVFQSKQ FRSAKLERLY QRYFFQMNQS
160 170 180 190 200
SLTLLMAVLV LLTAVLLAFH AAPARPQPAY VALLACAAAL FVGLMVVCNR
210 220 230 240 250
HSFRQDSMWV VSYVVLGILA AVQVGGALAA DPRSPSAGLW CPVFFVYIAY
260 270 280 290 300
TLLPIRMRAA VLSGLGLSTL HLILAWQLNR GDAFLWKQLG ANVLLFLCTN
310 320 330 340 350
VIGICTHYPA EVSQRQAFQE TRGYIQARLH LQHENRQQER LLLSVLPQHV
360 370 380 390 400
AMEMKEDINT KKEDMMFHKI YIQKHDNVSI LFADIEGFTS LASQCTAQEL
410 420 430 440 450
VMTLNELFAR FDKLAAENHC LRIKILGDCY YCVSGLPEAR ADHAHCCVEM
460 470 480 490 500
GVDMIEAISL VREVTGVNVN MRVGIHSGRV HCGVLGLRKW QFDVWSNDVT
510 520 530 540 550
LANHMEAGGR AGRIHITRAT LQYLNGDYEV EPGRGGERNA YLKEQHIETF
560 570 580 590 600
LILGASQKRK EEKAMLAKLQ RTRANSMEGL MPRWVPDRAF SRTKDSKAFR
610 620 630 640 650
QMGIDDSSKD NRGTQDALNP EDEVDEFLSR AIDARSIDQL RKDHVRRFLL
660 670 680 690 700
TFQREDLEKK YSRKVDPRFG AYVACALLVF CFICFIQLLI FPHSTLMLGI
710 720 730 740 750
YASIFLLLLI TVLICAVYSC GSLFPKALQR LSRSIVRSRA HSTAVGIFSV
760 770 780 790 800
LLVFTSAIAN MFTCNHTPIR SCAARMLNLT PADITACHLQ QLNYSLGLDA
810 820 830 840 850
PLCEGTMPTC SFPEYFIGNM LLSLLASSVF LHISSIGKLA MIFVLGLIYL
860 870 880 890 900
VLLLLGPPAT IFDNYDLLLG VHGLASSNET FDGLDCPAAG RVALKYMTPV
910 920 930 940 950
ILLVFALALY LHAQQVESTA RLDFLWKLQA TGEKEEMEEL QAYNRRLLHN
960 970 980 990 1000
ILPKDVAAHF LARERRNDEL YYQSCECVAV MFASIANFSE FYVELEANNE
1010 1020 1030 1040 1050
GVECLRLLNE IIADFDEIIS EERFRQLEKI KTIGSTYMAA SGLNASTYDQ
1060 1070 1080 1090 1100
VGRSHITALA DYAMRLMEQM KHINEHSFNN FQMKIGLNMG PVVAGVIGAR
1110 1120 1130 1140 1150
KPQYDIWGNT VNVSSRMDST GVPDRIQVTT DLYQVLAAKG YQLECRGVVK
1160
VKGKGEMTTY FLNGGPSS
Length:1,168
Mass (Da):130,615
Last modified:January 11, 2001 - v2
Checksum:i127BB6E67F73AA61
GO
Isoform 2 (identifier: O43306-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     762-814: Missing.

Note: No experimental confirmation available.

Show »
Length:1,115
Mass (Da):124,865
Checksum:iD1D26C1E15FAC0B0
GO

Sequence cautioni

The sequence BAA24852.2 differs from that shown. Reason: Erroneous initiation.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti674 – 6741A → S.
Corresponds to variant rs3730071 [ dbSNP | Ensembl ].
VAR_048249

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei762 – 81453Missing in isoform 2. 1 PublicationVSP_000244Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF250226 mRNA. Translation: AAF82478.1.
AB007882 mRNA. Translation: BAA24852.2. Different initiation.
BC064923 mRNA. No translation available.
CCDSiCCDS8767.1. [O43306-1]
CCDS8768.1. [O43306-2]
RefSeqiNP_056085.1. NM_015270.3. [O43306-1]
NP_066193.1. NM_020983.2. [O43306-2]
XP_005268662.1. XM_005268605.1. [O43306-1]
XP_006719273.1. XM_006719210.1. [O43306-1]
UniGeneiHs.525401.
Hs.694408.

Genome annotation databases

EnsembliENST00000307885; ENSP00000311405; ENSG00000174233. [O43306-1]
ENST00000357869; ENSP00000350536; ENSG00000174233. [O43306-2]
ENST00000550422; ENSP00000446730; ENSG00000174233. [O43306-2]
GeneIDi112.
KEGGihsa:112.
UCSCiuc001rsh.4. human. [O43306-1]
uc001rsi.4. human. [O43306-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF250226 mRNA. Translation: AAF82478.1 .
AB007882 mRNA. Translation: BAA24852.2 . Different initiation.
BC064923 mRNA. No translation available.
CCDSi CCDS8767.1. [O43306-1 ]
CCDS8768.1. [O43306-2 ]
RefSeqi NP_056085.1. NM_015270.3. [O43306-1 ]
NP_066193.1. NM_020983.2. [O43306-2 ]
XP_005268662.1. XM_005268605.1. [O43306-1 ]
XP_006719273.1. XM_006719210.1. [O43306-1 ]
UniGenei Hs.525401.
Hs.694408.

3D structure databases

ProteinModelPortali O43306.
SMRi O43306. Positions 364-553, 970-1145.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 106625. 9 interactions.
IntActi O43306. 1 interaction.
MINTi MINT-2856766.
STRINGi 9606.ENSP00000311405.

Chemistry

BindingDBi O43306.
ChEMBLi CHEMBL2097167.

PTM databases

PhosphoSitei O43306.

Proteomic databases

MaxQBi O43306.
PaxDbi O43306.
PRIDEi O43306.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000307885 ; ENSP00000311405 ; ENSG00000174233 . [O43306-1 ]
ENST00000357869 ; ENSP00000350536 ; ENSG00000174233 . [O43306-2 ]
ENST00000550422 ; ENSP00000446730 ; ENSG00000174233 . [O43306-2 ]
GeneIDi 112.
KEGGi hsa:112.
UCSCi uc001rsh.4. human. [O43306-1 ]
uc001rsi.4. human. [O43306-2 ]

Organism-specific databases

CTDi 112.
GeneCardsi GC12M049159.
HGNCi HGNC:237. ADCY6.
HPAi CAB018365.
MIMi 600294. gene.
neXtProti NX_O43306.
Orphaneti 2680. Hypomyelination neuropathy - arthrogryposis.
PharmGKBi PA27.
HUGEi Search...
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG2114.
GeneTreei ENSGT00760000119042.
HOGENOMi HOG000006941.
HOVERGENi HBG050458.
InParanoidi O43306.
KOi K08046.
OMAi RSCWRRL.
OrthoDBi EOG7B8S30.
PhylomeDBi O43306.
TreeFami TF313845.

Enzyme and pathway databases

BRENDAi 4.6.1.1. 2681.
Reactomei REACT_15312. Adenylate cyclase activating pathway.
REACT_15333. Adenylate cyclase inhibitory pathway.
REACT_15530. PKA activation.
REACT_1665. Glucagon signaling in metabolic regulation.
REACT_18274. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
REACT_18339. Adrenaline,noradrenaline inhibits insulin secretion.
REACT_19231. G alpha (i) signalling events.
REACT_19327. G alpha (s) signalling events.
REACT_19333. G alpha (z) signalling events.
REACT_1946. PKA activation in glucagon signalling.
REACT_24023. Regulation of water balance by renal Aquaporins.

Miscellaneous databases

GeneWikii ADCY6.
GenomeRNAii 112.
NextBioi 431.
PROi O43306.
SOURCEi Search...

Gene expression databases

Bgeei O43306.
CleanExi HS_ADCY6.
ExpressionAtlasi O43306. baseline and differential.
Genevestigatori O43306.

Family and domain databases

Gene3Di 3.30.70.1230. 2 hits.
InterProi IPR001054. A/G_cyclase.
IPR018297. A/G_cyclase_CS.
IPR009398. Adenylate_cyclase-like.
IPR029787. Nucleotide_cyclase.
[Graphical view ]
Pfami PF06327. DUF1053. 1 hit.
PF00211. Guanylate_cyc. 2 hits.
[Graphical view ]
SMARTi SM00044. CYCc. 2 hits.
[Graphical view ]
SUPFAMi SSF55073. SSF55073. 2 hits.
PROSITEi PS00452. GUANYLATE_CYCLASE_1. 2 hits.
PS50125. GUANYLATE_CYCLASE_2. 2 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and expression of human adenylyl cyclase type VI in normal thyroid tissues."
    Wicker R., Catalan A.G., Cailleux A.-F., Starenki D., Stengel D., Sarasin A., Suarez H.G.
    Biochim. Biophys. Acta 1493:279-283(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Thyroid.
  2. "Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro."
    Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
    DNA Res. 4:307-313(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Brain.
  3. "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones."
    Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.
    DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: SEQUENCE REVISION.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Retina.
  5. "A novel adenylyl cyclase sequence cloned from the human erythroleukemia cell line."
    Hellevuo K., Yoshimura M., Kao M., Hoffman P.L., Cooper D.M.F., Tabakoff B.
    Biochem. Biophys. Res. Commun. 192:311-318(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1040-1103.
  6. "Raf kinase activation of adenylyl cyclases: isoform-selective regulation."
    Ding Q., Gros R., Gray I.D., Taussig R., Ferguson S.S., Feldman R.D.
    Mol. Pharmacol. 66:921-928(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION BY RAF1, INTERACTION WITH RAF1, ENZYME REGULATION.
  7. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-576, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Platelet.
  8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.

Entry informationi

Entry nameiADCY6_HUMAN
AccessioniPrimary (citable) accession number: O43306
Secondary accession number(s): Q9NR75, Q9UDB0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 11, 2001
Last modified: October 29, 2014
This is version 146 of the entry and version 2 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 12
    Human chromosome 12: 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

External Data

Dasty 3