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Protein

Adenylate cyclase type 4

Gene

ADCY4

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.By similarity

Catalytic activityi

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

Cofactori

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

Enzyme regulationi

Activated by forskolin. Insensitive to calcium/calmodulin. Stimulated by GNAS and by the G-protein beta and gamma subunit complex.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi278Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi278Magnesium 2; catalyticPROSITE-ProRule annotation1
Metal bindingi279Magnesium 2; via carbonyl oxygen; catalyticPROSITE-ProRule annotation1
Metal bindingi322Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi322Magnesium 2; catalyticPROSITE-ProRule annotation1
Binding sitei366ATPBy similarity1
Binding sitei925ATPBy similarity1
Binding sitei1052ATPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi278 – 283ATPBy similarity6
Nucleotide bindingi320 – 322ATPBy similarity3
Nucleotide bindingi1005 – 1007ATPBy similarity3
Nucleotide bindingi1012 – 1016ATPBy 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:HS05281-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.
SIGNORiQ8NFM4.

Names & Taxonomyi

Protein namesi
Recommended name:
Adenylate cyclase type 4 (EC:4.6.1.1By similarity)
Alternative name(s):
ATP pyrophosphate-lyase 4
Adenylate cyclase type IV
Adenylyl cyclase 4
Gene namesi
Name:ADCY4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:235. ADCY4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 28CytoplasmicSequence analysisAdd BLAST28
Transmembranei29 – 50HelicalSequence analysisAdd BLAST22
Transmembranei61 – 80HelicalSequence analysisAdd BLAST20
Transmembranei94 – 117HelicalSequence analysisAdd BLAST24
Transmembranei120 – 138HelicalSequence analysisAdd BLAST19
Transmembranei141 – 162HelicalSequence analysisAdd BLAST22
Transmembranei170 – 190HelicalSequence analysisAdd BLAST21
Topological domaini191 – 585CytoplasmicSequence analysisAdd BLAST395
Transmembranei586 – 607HelicalSequence analysisAdd BLAST22
Transmembranei611 – 633HelicalSequence analysisAdd BLAST23
Transmembranei664 – 687HelicalSequence analysisAdd BLAST24
Topological domaini688 – 714ExtracellularSequence analysisAdd BLAST27
Transmembranei715 – 736HelicalSequence analysisAdd BLAST22
Transmembranei744 – 764HelicalSequence analysisAdd BLAST21
Transmembranei791 – 807HelicalSequence analysisAdd BLAST17
Topological domaini808 – 1077CytoplasmicSequence analysisAdd BLAST270

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • dendrite Source: Ensembl
  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: BHF-UCL
  • plasma membrane Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Organism-specific databases

OpenTargetsiENSG00000129467.
PharmGKBiPA24562.

Chemistry databases

ChEMBLiCHEMBL2097167.

Polymorphism and mutation databases

BioMutaiADCY4.
DMDMi25008336.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001956901 – 1077Adenylate cyclase type 4Add BLAST1077

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei520PhosphoserineBy similarity1
Modified residuei536PhosphothreonineBy similarity1
Glycosylationi697N-linked (GlcNAc...)Sequence analysis1
Glycosylationi704N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ8NFM4.
PaxDbiQ8NFM4.
PeptideAtlasiQ8NFM4.
PRIDEiQ8NFM4.

PTM databases

iPTMnetiQ8NFM4.
PhosphoSitePlusiQ8NFM4.

Expressioni

Tissue specificityi

Detected in the zona glomerulosa and the zona fasciculata in the adrenal gland (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000129467.
CleanExiHS_ADCY4.
ExpressionAtlasiQ8NFM4. baseline and differential.
GenevisibleiQ8NFM4. HS.

Organism-specific databases

HPAiCAB005070.
HPA048344.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
TRIM54Q9BYV23EBI-2838710,EBI-2130429

Protein-protein interaction databases

BioGridi128229. 1 interactor.
IntActiQ8NFM4. 6 interactors.
STRINGi9606.ENSP00000312126.

Structurei

3D structure databases

ProteinModelPortaliQ8NFM4.
SMRiQ8NFM4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal modules have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two modules.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.
HOGENOMiHOG000143645.
HOVERGENiHBG050458.
InParanoidiQ8NFM4.
KOiK08044.
OMAiRRNEETH.
OrthoDBiEOG091G05JR.
PhylomeDBiQ8NFM4.
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: Q8NFM4-1) [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
MARLFSPRPP PSEDLFYETY YSLSQQYPLL LLLLGIVLCA LAALLAVAWA
60 70 80 90 100
SGRELTSDPS FLTTVLCALG GFSLLLGLAS REQRLQRWTR PLSGLVWVAL
110 120 130 140 150
LALGHAFLFT GGVVSAWDQV SYFLFVIFTA YAMLPLGMRD AAVAGLASSL
160 170 180 190 200
SHLLVLGLYL GPQPDSRPAL LPQLAANAVL FLCGNVAGVY HKALMERALR
210 220 230 240 250
ATFREALSSL HSRRRLDTEK KHQEHLLLSI LPAYLAREMK AEIMARLQAG
260 270 280 290 300
QGSRPESTNN FHSLYVKRHQ GVSVLYADIV GFTRLASECS PKELVLMLNE
310 320 330 340 350
LFGKFDQIAK EHECMRIKIL GDCYYCVSGL PLSLPDHAIN CVRMGLDMCR
360 370 380 390 400
AIRKLRAATG VDINMRVGVH SGSVLCGVIG LQKWQYDVWS HDVTLANHME
410 420 430 440 450
AGGVPGRVHI TGATLALLAG AYAVEDAGME HRDPYLRELG EPTYLVIDPR
460 470 480 490 500
AEEEDEKGTA GGLLSSLEGL KMRPSLLMTR YLESWGAAKP FAHLSHGDSP
510 520 530 540 550
VSTSTPLPEK TLASFSTQWS LDRSRTPRGL DDELDTGDAK FFQVIEQLNS
560 570 580 590 600
QKQWKQSKDF NPLTLYFREK EMEKEYRLSA IPAFKYYEAC TFLVFLSNFI
610 620 630 640 650
IQMLVTNRPP ALAITYSITF LLFLLILFVC FSEDLMRCVL KGPKMLHWLP
660 670 680 690 700
ALSGLVATRP GLRIALGTAT ILLVFAMAIT SLFFFPTSSD CPFQAPNVSS
710 720 730 740 750
MISNLSWELP GSLPLISVPY SMHCCTLGFL SCSLFLHMSF ELKLLLLLLW
760 770 780 790 800
LAASCSLFLH SHAWLSECLI VRLYLGPLDS RPGVLKEPKL MGAISFFIFF
810 820 830 840 850
FTLLVLARQN EYYCRLDFLW KKKLRQEREE TETMENLTRL LLENVLPAHV
860 870 880 890 900
APQFIGQNRR NEDLYHQSYE CVCVLFASVP DFKEFYSESN INHEGLECLR
910 920 930 940 950
LLNEIIADFD ELLSKPKFSG VEKIKTIGST YMAATGLNAT SGQDAQQDAE
960 970 980 990 1000
RSCSHLGTMV EFAVALGSKL DVINKHSFNN FRLRVGLNHG PVVAGVIGAQ
1010 1020 1030 1040 1050
KPQYDIWGNT VNVASRMEST GVLGKIQVTE ETAWALQSLG YTCYSRGVIK
1060 1070
VKGKGQLCTY FLNTDLTRTG PPSATLG
Length:1,077
Mass (Da):119,794
Last modified:October 1, 2002 - v1
Checksum:i24C0D5AE495CFD50
GO
Isoform 2 (identifier: Q8NFM4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-45: MARLFSPRPP...IVLCALAALL → MSRGTRESAC...SSLASSTRLP
     46-352: Missing.
     720-726: YSMHCCT → VSVPTCP
     727-1077: Missing.

Note: No experimental confirmation available.
Show »
Length:419
Mass (Da):46,245
Checksum:iCDBC2C78773CD634
GO

Sequence cautioni

The sequence BAB71270 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti571E → G in BAB71270 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0558161 – 45MARLF…LAALL → MSRGTRESACCMLTSWASRG WPASVPLRSWCSCSMSSLAS STRLP in isoform 2. 1 PublicationAdd BLAST45
Alternative sequenceiVSP_05581746 – 352Missing in isoform 2. 1 PublicationAdd BLAST307
Alternative sequenceiVSP_055818720 – 726YSMHCCT → VSVPTCP in isoform 2. 1 Publication7
Alternative sequenceiVSP_055819727 – 1077Missing in isoform 2. 1 PublicationAdd BLAST351

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF497516 mRNA. Translation: AAM94373.1.
AK056745 mRNA. Translation: BAB71270.1. Different initiation.
AK122714 mRNA. Translation: BAG53686.1.
AK126468 mRNA. Translation: BAC86560.1.
AL096870 Genomic DNA. No translation available.
CH471078 Genomic DNA. Translation: EAW66023.1.
CH471078 Genomic DNA. Translation: EAW66026.1.
CH471078 Genomic DNA. Translation: EAW66027.1.
CH471078 Genomic DNA. Translation: EAW66028.1.
BC117473 mRNA. Translation: AAI17474.1.
BC117475 mRNA. Translation: AAI17476.1.
CCDSiCCDS9627.1. [Q8NFM4-1]
RefSeqiNP_001185497.1. NM_001198568.1. [Q8NFM4-1]
NP_001185521.1. NM_001198592.1. [Q8NFM4-1]
NP_640340.2. NM_139247.3. [Q8NFM4-1]
UniGeneiHs.443428.

Genome annotation databases

EnsembliENST00000310677; ENSP00000312126; ENSG00000129467. [Q8NFM4-1]
ENST00000418030; ENSP00000393177; ENSG00000129467. [Q8NFM4-1]
ENST00000554068; ENSP00000452250; ENSG00000129467. [Q8NFM4-1]
GeneIDi196883.
KEGGihsa:196883.
UCSCiuc001wow.4. human. [Q8NFM4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF497516 mRNA. Translation: AAM94373.1.
AK056745 mRNA. Translation: BAB71270.1. Different initiation.
AK122714 mRNA. Translation: BAG53686.1.
AK126468 mRNA. Translation: BAC86560.1.
AL096870 Genomic DNA. No translation available.
CH471078 Genomic DNA. Translation: EAW66023.1.
CH471078 Genomic DNA. Translation: EAW66026.1.
CH471078 Genomic DNA. Translation: EAW66027.1.
CH471078 Genomic DNA. Translation: EAW66028.1.
BC117473 mRNA. Translation: AAI17474.1.
BC117475 mRNA. Translation: AAI17476.1.
CCDSiCCDS9627.1. [Q8NFM4-1]
RefSeqiNP_001185497.1. NM_001198568.1. [Q8NFM4-1]
NP_001185521.1. NM_001198592.1. [Q8NFM4-1]
NP_640340.2. NM_139247.3. [Q8NFM4-1]
UniGeneiHs.443428.

3D structure databases

ProteinModelPortaliQ8NFM4.
SMRiQ8NFM4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi128229. 1 interactor.
IntActiQ8NFM4. 6 interactors.
STRINGi9606.ENSP00000312126.

Chemistry databases

ChEMBLiCHEMBL2097167.

PTM databases

iPTMnetiQ8NFM4.
PhosphoSitePlusiQ8NFM4.

Polymorphism and mutation databases

BioMutaiADCY4.
DMDMi25008336.

Proteomic databases

MaxQBiQ8NFM4.
PaxDbiQ8NFM4.
PeptideAtlasiQ8NFM4.
PRIDEiQ8NFM4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000310677; ENSP00000312126; ENSG00000129467. [Q8NFM4-1]
ENST00000418030; ENSP00000393177; ENSG00000129467. [Q8NFM4-1]
ENST00000554068; ENSP00000452250; ENSG00000129467. [Q8NFM4-1]
GeneIDi196883.
KEGGihsa:196883.
UCSCiuc001wow.4. human. [Q8NFM4-1]

Organism-specific databases

CTDi196883.
GeneCardsiADCY4.
HGNCiHGNC:235. ADCY4.
HPAiCAB005070.
HPA048344.
MIMi600292. gene.
neXtProtiNX_Q8NFM4.
OpenTargetsiENSG00000129467.
PharmGKBiPA24562.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3619. Eukaryota.
COG2114. LUCA.
GeneTreeiENSGT00760000119042.
HOGENOMiHOG000143645.
HOVERGENiHBG050458.
InParanoidiQ8NFM4.
KOiK08044.
OMAiRRNEETH.
OrthoDBiEOG091G05JR.
PhylomeDBiQ8NFM4.
TreeFamiTF313845.

Enzyme and pathway databases

BioCyciZFISH:HS05281-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.
SIGNORiQ8NFM4.

Miscellaneous databases

GeneWikiiADCY4.
GenomeRNAii196883.
PROiQ8NFM4.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000129467.
CleanExiHS_ADCY4.
ExpressionAtlasiQ8NFM4. baseline and differential.
GenevisibleiQ8NFM4. 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 nameiADCY4_HUMAN
AccessioniPrimary (citable) accession number: Q8NFM4
Secondary accession number(s): B3KV74
, D3DS75, Q17R40, Q6ZTM6, Q96ML7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 8, 2002
Last sequence update: October 1, 2002
Last modified: November 30, 2016
This is version 138 of the entry and version 1 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 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. 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.