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Q08828

- ADCY1_HUMAN

UniProt

Q08828 - ADCY1_HUMAN

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Protein

Adenylate cyclase type 1

Gene

ADCY1

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

Functioni

This is a calmodulin-sensitive adenylyl cyclase. May be involved in regulatory processes in the central nervous system. It may play a role in memory acquisition and learning. Plays a role in the regulation of the circadian rhythm of daytime contrast sensitivity probably by modulating the rhythmic synthesis of cyclic AMP in the retina By similarity.By similarity

Catalytic activityi

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

Cofactori

Binds 2 magnesium ions per subunit.By similarity

Enzyme regulationi

Activated by calcium/calmodulin. Inhibited by the G protein beta and gamma subunit complex.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi308 – 3081Magnesium 1PROSITE-ProRule annotation
Metal bindingi308 – 3081Magnesium 2PROSITE-ProRule annotation
Metal bindingi309 – 3091Magnesium 2; via carbonyl oxygenPROSITE-ProRule annotation
Metal bindingi352 – 3521Magnesium 1PROSITE-ProRule annotation
Metal bindingi352 – 3521Magnesium 2PROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. calcium- and calmodulin-responsive adenylate cyclase activity Source: UniProtKB
  3. metal ion binding Source: UniProtKB-KW

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. axonogenesis Source: Ensembl
  6. cellular response to glucagon stimulus Source: Reactome
  7. circadian rhythm Source: Ensembl
  8. energy reserve metabolic process Source: Reactome
  9. epidermal growth factor receptor signaling pathway Source: Reactome
  10. fibroblast growth factor receptor signaling pathway Source: Reactome
  11. innate immune response Source: Reactome
  12. intracellular signal transduction Source: InterPro
  13. long-term memory Source: Ensembl
  14. neurotrophin TRK receptor signaling pathway Source: Reactome
  15. regulation of circadian rhythm Source: UniProtKB
  16. response to drug Source: Ensembl
  17. response to lithium ion Source: Ensembl
  18. signal transduction Source: Reactome
  19. small molecule metabolic process Source: Reactome
  20. synaptic transmission Source: Reactome
  21. transmembrane transport Source: Reactome
  22. water transport Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Biological processi

Biological rhythms, cAMP biosynthesis

Keywords - Ligandi

ATP-binding, Calmodulin-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_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_20625. CREB phosphorylation through the activation of Adenylate Cyclase.
REACT_24023. Regulation of water balance by renal Aquaporins.

Names & Taxonomyi

Protein namesi
Recommended name:
Adenylate cyclase type 1 (EC:4.6.1.1)
Alternative name(s):
ATP pyrophosphate-lyase 1
Adenylate cyclase type I
Adenylyl cyclase 1
Ca(2+)/calmodulin-activated adenylyl cyclase
Gene namesi
Name:ADCY1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 7

Organism-specific databases

HGNCiHGNC:232. ADCY1.

Subcellular locationi

Membrane; Multi-pass membrane protein. Cytoplasm By similarity
Note: Expressed in the cytoplasm of supporting cells and hair cells of the cochlea vestibule, as well as to the cochlear hair cell nuclei and stereocilia.By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. extracellular vesicular exosome Source: UniProt
  3. integral component of membrane Source: UniProtKB-KW
  4. nucleus Source: Ensembl
  5. plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

Deafness, autosomal recessive, 44 (DFNB44) [MIM:610154]: A form of non-syndromic deafness characterized by prelingual profound hearing loss affecting all frequencies.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.

Keywords - Diseasei

Deafness, Non-syndromic deafness

Organism-specific databases

MIMi610154. phenotype.
Orphaneti90636. Autosomal recessive non-syndromic sensorineural deafness type DFNB.
PharmGKBiPA24560.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11191119Adenylate cyclase type 1PRO_0000195682Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi704 – 7041N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ08828.
PRIDEiQ08828.

PTM databases

PhosphoSiteiQ08828.

Expressioni

Tissue specificityi

Brain, retina and adrenal medulla.

Gene expression databases

BgeeiQ08828.
CleanExiHS_ADCY1.
ExpressionAtlasiQ08828. baseline and differential.
GenevestigatoriQ08828.

Organism-specific databases

HPAiCAB018364.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000297323.

Structurei

3D structure databases

ProteinModelPortaliQ08828.
SMRiQ08828. Positions 290-477, 860-1054.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 6363CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini235 – 610376CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini795 – 1119325CytoplasmicSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei64 – 8421HelicalSequence AnalysisAdd
BLAST
Transmembranei88 – 10821HelicalSequence AnalysisAdd
BLAST
Transmembranei125 – 14521HelicalSequence AnalysisAdd
BLAST
Transmembranei158 – 17821HelicalSequence AnalysisAdd
BLAST
Transmembranei183 – 20321HelicalSequence AnalysisAdd
BLAST
Transmembranei214 – 23421HelicalSequence AnalysisAdd
BLAST
Transmembranei611 – 63121HelicalSequence AnalysisAdd
BLAST
Transmembranei635 – 65521HelicalSequence AnalysisAdd
BLAST
Transmembranei674 – 69421HelicalSequence AnalysisAdd
BLAST
Transmembranei725 – 74521HelicalSequence AnalysisAdd
BLAST
Transmembranei753 – 77321HelicalSequence AnalysisAdd
BLAST
Transmembranei775 – 79420HelicalSequence AnalysisAdd
BLAST

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni493 – 52028Interaction with calmodulinBy similarityAdd
BLAST
Regioni1024 – 104724Interaction with calmodulinBy similarityAdd
BLAST

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.
InParanoidiQ08828.
KOiK08041.
OMAiCLPWAWS.
OrthoDBiEOG7B8S30.
PhylomeDBiQ08828.
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.

Q08828-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MAGAPRGGGG GGGGAGEPGG AERAAGTSRR RGLRACDEEF ACPELEALFR
60 70 80 90 100
GYTLRLEQAA TLKALAVLSL LAGALALAEL LGAPGPAPGL AKGSHPVHCV
110 120 130 140 150
LFLALLVVTN VRSLQVPQLQ QVGQLALLFS LTFALLCCPF ALGGPARGSA
160 170 180 190 200
GAAGGPATAE QGVWQLLLVT FVSYALLPVR SLLAIGFGLV VAASHLLVTA
210 220 230 240 250
TLVPAKRPRL WRTLGANALL FVGVNMYGVF VRILTERSQR KAFLQARSCI
260 270 280 290 300
EDRLRLEDEN EKQERLLMSL LPRNVAMEMK EDFLKPPERI FHKIYIQRHD
310 320 330 340 350
NVSILFADIV GFTGLASQCT AQELVKLLNE LFGKFDELAT ENHCRRIKIL
360 370 380 390 400
GDCYYCVSGL TQPKTDHAHC CVEMGLDMID TITSVAEATE VDLNMRVGLH
410 420 430 440 450
TGRVLCGVLG LRKWQYDVWS NDVTLANVME AAGLPGKVHI TKTTLACLNG
460 470 480 490 500
DYEVEPGYGH ERNSFLKTHN IETFFIVPSH RRKIFPGLIL SDIKPAKRMK
510 520 530 540 550
FKTVCYLLVQ LMHCRKMFKA EIPFSNVMTC EDDDKRRALR TASEKLRNRS
560 570 580 590 600
SFSTNVVYTT PGTRVNRYIS RLLEARQTEL EMADLNFFTL KYKHVEREQK
610 620 630 640 650
YHQLQDEYFT SAVVLTLILA ALFGLVYLLI FPQSVVVLLL LVFCICFLVA
660 670 680 690 700
CVLYLHITRV QCFPGCLTIQ IRTVLCIFIV VLIYSVAQGC VVGCLPWAWS
710 720 730 740 750
SKPNSSLVVL SSGGQRTALP TLPCESTHHA LLCCLVGTLP LAIFFRVSSL
760 770 780 790 800
PKMILLSGLT TSYILVLELS GYTRTGGGAV SGRSYEPIVA ILLFSCALAL
810 820 830 840 850
HARQVDIRLR LDYLWAAQAE EEREDMEKVK LDNRRILFNL LPAHVAQHFL
860 870 880 890 900
MSNPRNMDLY YQSYSQVGVM FASIPNFNDF YIELDGNNMG VECLRLLNEI
910 920 930 940 950
IADFDELMEK DFYKDIEKIK TIGSTYMAAV GLAPTSGTKA KKSISSHLST
960 970 980 990 1000
LADFAIEMFD VLDEINYQSY NDFVLRVGIN VGPVVAGVIG ARRPQYDIWG
1010 1020 1030 1040 1050
NTVNVASRMD STGVQGRIQV TEEVHRLLRR CPYHFVCRGK VSVKGKGEML
1060 1070 1080 1090 1100
TYFLEGRTDG NGSQIRSLGL DRKMCPFGRA GLQGRRPPVC PMPGVSVRAG
1110
LPPHSPGQYL PSAAAGKEA
Length:1,119
Mass (Da):123,440
Last modified:April 12, 2005 - v2
Checksum:iE8DDC8FCB58743D7
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti456 – 4561P → L.
Corresponds to variant rs12721473 [ dbSNP | Ensembl ].
VAR_029186
Natural varianti940 – 9401A → T.
Corresponds to variant rs45444695 [ dbSNP | Ensembl ].
VAR_029187
Natural varianti984 – 9841V → M.
Corresponds to variant rs2293106 [ dbSNP | Ensembl ].
VAR_048246

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AC069008 Genomic DNA. Translation: AAS07467.1.
AC091439 Genomic DNA. No translation available.
CH236960 Genomic DNA. Translation: EAL23741.1.
L05500 mRNA. Translation: AAA02907.1.
CCDSiCCDS34631.1.
PIRiA47007.
RefSeqiNP_066939.1. NM_021116.2.
UniGeneiHs.192215.

Genome annotation databases

EnsembliENST00000297323; ENSP00000297323; ENSG00000164742.
GeneIDi107.
KEGGihsa:107.
UCSCiuc003tne.4. human.

Polymorphism databases

DMDMi62512172.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AC069008 Genomic DNA. Translation: AAS07467.1 .
AC091439 Genomic DNA. No translation available.
CH236960 Genomic DNA. Translation: EAL23741.1 .
L05500 mRNA. Translation: AAA02907.1 .
CCDSi CCDS34631.1.
PIRi A47007.
RefSeqi NP_066939.1. NM_021116.2.
UniGenei Hs.192215.

3D structure databases

ProteinModelPortali Q08828.
SMRi Q08828. Positions 290-477, 860-1054.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9606.ENSP00000297323.

Chemistry

BindingDBi Q08828.
ChEMBLi CHEMBL2899.
DrugBanki DB00131. Adenosine monophosphate.
DB00171. Adenosine triphosphate.

PTM databases

PhosphoSitei Q08828.

Polymorphism databases

DMDMi 62512172.

Proteomic databases

PaxDbi Q08828.
PRIDEi Q08828.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000297323 ; ENSP00000297323 ; ENSG00000164742 .
GeneIDi 107.
KEGGi hsa:107.
UCSCi uc003tne.4. human.

Organism-specific databases

CTDi 107.
GeneCardsi GC07P045580.
H-InvDB HIX0033533.
HGNCi HGNC:232. ADCY1.
HPAi CAB018364.
MIMi 103072. gene.
610154. phenotype.
neXtProti NX_Q08828.
Orphaneti 90636. Autosomal recessive non-syndromic sensorineural deafness type DFNB.
PharmGKBi PA24560.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG2114.
GeneTreei ENSGT00760000119042.
HOGENOMi HOG000006941.
HOVERGENi HBG050458.
InParanoidi Q08828.
KOi K08041.
OMAi CLPWAWS.
OrthoDBi EOG7B8S30.
PhylomeDBi Q08828.
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_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_20625. CREB phosphorylation through the activation of Adenylate Cyclase.
REACT_24023. Regulation of water balance by renal Aquaporins.

Miscellaneous databases

ChiTaRSi ADCY1. human.
GeneWikii ADCY1.
GenomeRNAii 107.
NextBioi 415.
PROi Q08828.
SOURCEi Search...

Gene expression databases

Bgeei Q08828.
CleanExi HS_ADCY1.
ExpressionAtlasi Q08828. baseline and differential.
Genevestigatori Q08828.

Family and domain databases

Gene3Di 3.30.70.1230. 2 hits.
InterProi IPR001054. A/G_cyclase.
IPR018297. A/G_cyclase_CS.
IPR029787. Nucleotide_cyclase.
[Graphical view ]
Pfami 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. "The DNA sequence of human chromosome 7."
    Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L.
    , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
    Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  2. "Human chromosome 7: DNA sequence and biology."
    Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S.
    , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
    Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "Cloning, chromosomal mapping, and expression of human fetal brain type I adenylyl cyclase."
    Villacres E.C., Xia Z., Bookbinder L.H., Edelhoff S., Disteche C.M., Storm D.R.
    Genomics 16:473-478(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 281-1119.
    Tissue: Fetal brain.
  4. "Adenylate cyclase 1 (ADCY1) mutations cause recessive hearing impairment in humans and defects in hair cell function and hearing in zebrafish."
    Santos-Cortez R.L., Lee K., Giese A.P., Ansar M., Amin-Ud-Din M., Rehn K., Wang X., Aziz A., Chiu I., Hussain Ali R., Smith J.D., Shendure J., Bamshad M., Nickerson D.A., Ahmed Z.M., Ahmad W., Riazuddin S., Leal S.M.
    Hum. Mol. Genet. 23:3289-3298(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN DFNB44.

Entry informationi

Entry nameiADCY1_HUMAN
AccessioniPrimary (citable) accession number: Q08828
Secondary accession number(s): A4D2L8, Q75MI1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: April 12, 2005
Last modified: October 29, 2014
This is version 136 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 7
    Human chromosome 7: 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