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Protein

Adenylate cyclase type 4

Gene

ADCY4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Activity 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

  • adenylate cyclase activity Source: BHF-UCL
  • ATP binding Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW
  • protein kinase C binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionLyase
Biological processcAMP biosynthesis
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000129467.13
HGNCiHGNC:235 ADCY4
MIMi600292 gene
neXtProtiNX_Q8NFM4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

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...) asparagineSequence analysis1
Glycosylationi704N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ8NFM4
MaxQBiQ8NFM4
PaxDbiQ8NFM4
PeptideAtlasiQ8NFM4
PRIDEiQ8NFM4
ProteomicsDBi73323

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 Expressed in 163 organ(s), highest expression level in left lobe of thyroid gland
CleanExiHS_ADCY4
ExpressionAtlasiQ8NFM4 baseline and differential
GenevisibleiQ8NFM4 HS

Organism-specific databases

HPAiCAB005070
HPA048344

Interactioni

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi128229, 1 interactor
IntActiQ8NFM4, 9 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

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

Gene3Di3.30.70.1230, 2 hits
InterProiView protein in InterPro
IPR001054 A/G_cyclase
IPR018297 A/G_cyclase_CS
IPR032628 AC_N
IPR030672 Adcy
IPR009398 Adcy_conserved_dom
IPR029787 Nucleotide_cyclase
PfamiView protein in Pfam
PF16214 AC_N, 1 hit
PF06327 DUF1053, 1 hit
PF00211 Guanylate_cyc, 2 hits
PIRSFiPIRSF039050 Ade_cyc, 1 hit
SMARTiView protein in SMART
SM00044 CYCc, 2 hits
SUPFAMiSSF55073 SSF55073, 2 hits
PROSITEiView protein in PROSITE
PS00452 GUANYLATE_CYCLASE_1, 2 hits
PS50125 GUANYLATE_CYCLASE_2, 2 hits

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
G3V258G3V258_HUMAN
Adenylate cyclase type 4
ADCY4
449Annotation score:
G3V262G3V262_HUMAN
Adenylate cyclase type 4
ADCY4
216Annotation score:
H0YJ57H0YJ57_HUMAN
Adenylate cyclase type 4
ADCY4
137Annotation score:
H0YN72H0YN72_HUMAN
Adenylate cyclase type 4
ADCY4
115Annotation score:
H0YLM0H0YLM0_HUMAN
Adenylate cyclase type 4
ADCY4
36Annotation score:

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]
ENST00000642645; ENSP00000495316; ENSG00000284814 [Q8NFM4-1]
ENST00000644961; ENSP00000494454; ENSG00000284814 [Q8NFM4-1]
ENST00000646612; ENSP00000494977; ENSG00000284814 [Q8NFM4-1]
GeneIDi196883
KEGGihsa:196883
UCSCiuc001wow.4 human [Q8NFM4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

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, 9 interactors
STRINGi9606.ENSP00000312126

Chemistry databases

ChEMBLiCHEMBL2097167

PTM databases

iPTMnetiQ8NFM4
PhosphoSitePlusiQ8NFM4

Polymorphism and mutation databases

BioMutaiADCY4
DMDMi25008336

Proteomic databases

EPDiQ8NFM4
MaxQBiQ8NFM4
PaxDbiQ8NFM4
PeptideAtlasiQ8NFM4
PRIDEiQ8NFM4
ProteomicsDBi73323

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]
ENST00000642645; ENSP00000495316; ENSG00000284814 [Q8NFM4-1]
ENST00000644961; ENSP00000494454; ENSG00000284814 [Q8NFM4-1]
ENST00000646612; ENSP00000494977; ENSG00000284814 [Q8NFM4-1]
GeneIDi196883
KEGGihsa:196883
UCSCiuc001wow.4 human [Q8NFM4-1]

Organism-specific databases

CTDi196883
EuPathDBiHostDB:ENSG00000129467.13
GeneCardsiADCY4
HGNCiHGNC:235 ADCY4
HPAiCAB005070
HPA048344
MIMi600292 gene
neXtProtiNX_Q8NFM4
OpenTargetsiENSG00000129467
PharmGKBiPA24562
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

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

ChiTaRSiADCY4 human
GeneWikiiADCY4
GenomeRNAii196883
PROiPR:Q8NFM4
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000129467 Expressed in 163 organ(s), highest expression level in left lobe of thyroid gland
CleanExiHS_ADCY4
ExpressionAtlasiQ8NFM4 baseline and differential
GenevisibleiQ8NFM4 HS

Family and domain databases

Gene3Di3.30.70.1230, 2 hits
InterProiView protein in InterPro
IPR001054 A/G_cyclase
IPR018297 A/G_cyclase_CS
IPR032628 AC_N
IPR030672 Adcy
IPR009398 Adcy_conserved_dom
IPR029787 Nucleotide_cyclase
PfamiView protein in Pfam
PF16214 AC_N, 1 hit
PF06327 DUF1053, 1 hit
PF00211 Guanylate_cyc, 2 hits
PIRSFiPIRSF039050 Ade_cyc, 1 hit
SMARTiView protein in SMART
SM00044 CYCc, 2 hits
SUPFAMiSSF55073 SSF55073, 2 hits
PROSITEiView protein in PROSITE
PS00452 GUANYLATE_CYCLASE_1, 2 hits
PS50125 GUANYLATE_CYCLASE_2, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiADCY4_HUMAN
AccessioniPrimary (citable) accession number: Q8NFM4
Secondary accession number(s): B3KV74
, D3DS75, Q17R40, Q6ZTM6, Q96ML7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 8, 2002
Last sequence update: October 1, 2002
Last modified: November 7, 2018
This is version 152 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
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