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Protein

Adenylate cyclase type 7

Gene

ADCY7

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

Functioni

Catalyzes the formation of cAMP in response to activation of G protein-coupled receptors (Probable). Functions in signaling cascades activated namely by thrombin and sphingosine 1-phosphate and mediates regulation of cAMP synthesis through synergistic action of the stimulatory G alpha protein with GNA13 (PubMed:23229509, PubMed:18541530). Also, during inflammation, mediates zymosan-induced increase intracellular cAMP, leading to protein kinase A pathway activation in order to modulate innate immune responses through heterotrimeric G proteins G(12/13) (By similarity). Functions in signaling cascades activated namely by dopamine and C5 alpha chain and mediates regulation of cAMP synthesis through synergistic action of the stimulatory G protein with G beta:gamma complex (PubMed:23842570, PubMed:23229509). Functions, through cAMP response regulation, to keep inflammation under control during bacterial infection by sensing the presence of serum factors, such as the bioactive lysophospholipid (LPA) that regulate LPS-induced TNF-alpha production. However, it is also required for the optimal functions of B and T cells during adaptive immune responses by regulating cAMP synthesis in both B and T cells (By similarity).By similarity2 Publications3 Publications

Catalytic activityi

ATP = 3',5'-cyclic AMP + diphosphate.2 Publications

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 the G protein alpha subunit (PubMed:18541530). Activated by the G protein beta and gamma subunit complex (PubMed:23229509). Activated by GNA13 and GNA12 (PubMed:18541530). Ethanol and phorbol 12,13-dibutanoate significantly potentiate adenylate cyclase activity generated in response to the activation of the prostanoid receptor by the agonist prostaglandin E11- in a PKC-dependent manner (PubMed:12454008). Inhibited by lithium (By similarity).By similarity3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi284Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi284Magnesium 2; catalyticPROSITE-ProRule annotation1
Metal bindingi285Magnesium 2; via carbonyl oxygen; catalyticPROSITE-ProRule annotation1
Metal bindingi328Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi328Magnesium 2; catalyticPROSITE-ProRule annotation1
Binding sitei372ATPBy similarity1
Binding sitei931ATPBy similarity1
Binding sitei1057ATPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi284 – 289ATPBy similarity6
Nucleotide bindingi326 – 328ATPBy similarity3
Nucleotide bindingi1010 – 1012ATPBy similarity3
Nucleotide bindingi1017 – 1021ATPBy similarity5

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

Molecular functionLyase
Biological processcAMP biosynthesis
LigandATP-binding, Magnesium, Manganese, 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
SIGNORiP51828

Names & Taxonomyi

Protein namesi
Recommended name:
Adenylate cyclase type 7Curated (EC:4.6.1.12 Publications)
Alternative name(s):
ATP pyrophosphate-lyase 7
Adenylate cyclase type VII
Adenylyl cyclase 7
Gene namesi
Name:ADCY7Imported
Synonyms:KIAA00371 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000121281.12
HGNCiHGNC:238 ADCY7
MIMi600385 gene
neXtProtiNX_P51828

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 – 33CytoplasmicSequence analysisAdd BLAST33
Transmembranei34 – 54HelicalSequence analysisAdd BLAST21
Transmembranei63 – 83HelicalSequence analysisAdd BLAST21
Transmembranei95 – 117HelicalSequence analysisAdd BLAST23
Transmembranei122 – 142HelicalSequence analysisAdd BLAST21
Transmembranei147 – 167HelicalSequence analysisAdd BLAST21
Transmembranei176 – 196HelicalSequence analysisAdd BLAST21
Topological domaini197 – 594CytoplasmicSequence analysisAdd BLAST398
Transmembranei595 – 615HelicalSequence analysisAdd BLAST21
Transmembranei620 – 640HelicalSequence analysisAdd BLAST21
Transmembranei669 – 688HelicalSequence analysisAdd BLAST20
Transmembranei718 – 737HelicalSequence analysisAdd BLAST20
Transmembranei746 – 773HelicalSequence analysisAdd BLAST28
Transmembranei794 – 814HelicalSequence analysisAdd BLAST21
Topological domaini815 – 1080CytoplasmicSequence analysisAdd BLAST266

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi477 – 482KMRASV → NAAIRS: Does not affect cAMP biosynthetic process in response to sphingosine 1-phosphate stimulation. Reduces by 40% cAMP biosynthetic process in response to C5 alpha chain stimulation. 1 Publication6
Mutagenesisi485 – 489TRYLE → NAAIR: Reduces cAMP biosynthetic process in response to C5 alpha chain stimulation and more severely in response to sphingosine 1-phosphate stimulation. 1 Publication5
Mutagenesisi491 – 496WGAARP → NAAIRS: Does not affect cAMP biosynthetic process in response to C5 alpha chain stimulation. Reduces by 40?60% cAMP biosynthetic process in response to sphingosine 1-phosphate stimulation. 1 Publication6
Mutagenesisi494 – 499ARPFAH → NAAIRS: Does not affect cAMP biosynthetic process in response to C5 alpha chain stimulation. Reduces by 40?60% cAMP biosynthetic process in response to sphingosine 1-phosphate stimulation. 1 Publication6
Mutagenesisi564 – 569SKSDDF → NAAIRS: Reduces cAMP biosynthetic process in response to C5 alpha chain stimulation and more severely in response to sphingosine 1-phosphate stimulation. 1 Publication6

Organism-specific databases

DisGeNETi113
OpenTargetsiENSG00000121281
PharmGKBiPA28

Chemistry databases

ChEMBLiCHEMBL2097167

Polymorphism and mutation databases

BioMutaiADCY7
DMDMi1706218

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001957031 – 1080Adenylate cyclase type 7Add BLAST1080

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi701N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi776N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi781N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Phosphorylated by PRKCD.1 Publication

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiP51828
MaxQBiP51828
PaxDbiP51828
PeptideAtlasiP51828
PRIDEiP51828
ProteomicsDBi56430

PTM databases

iPTMnetiP51828
PhosphoSitePlusiP51828
SwissPalmiP51828

Expressioni

Gene expression databases

BgeeiENSG00000121281 Expressed in 215 organ(s), highest expression level in leukocyte
CleanExiHS_ADCY7
ExpressionAtlasiP51828 baseline and differential
GenevisibleiP51828 HS

Organism-specific databases

HPAiHPA041218
HPA048241

Interactioni

Protein-protein interaction databases

BioGridi106626, 3 interactors
IntActiP51828, 3 interactors
STRINGi9606.ENSP00000254235

Structurei

3D structure databases

ProteinModelPortaliP51828
SMRiP51828
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini279 – 406Guanylate cyclase 1PROSITE-ProRule annotationAdd BLAST128
Domaini879 – 1023Guanylate cyclase 2PROSITE-ProRule annotationAdd BLAST145

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni477 – 482Mediates regulation of adenylate cyclase activity by C5 alpha-induced G- beta and gamma pathway1 Publication6
Regioni491 – 499Mediates regulation of adenylate cyclase activity by sphingosine 1-phosphate-induced G alpha 13 pathway1 Publication9
Regioni506 – 584Modulates adenylate cyclase activity by modulating the binding of G(s)alpha to the high-affinity G(s)alpha binding site in 7C1a/7C21 PublicationAdd BLAST79

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

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3619 Eukaryota
COG2114 LUCA
GeneTreeiENSGT00760000119042
HOGENOMiHOG000006941
HOVERGENiHBG050458
InParanoidiP51828
KOiK08047
OMAiTNFYLVL
OrthoDBiEOG091G05JR
PhylomeDBiP51828
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, 1 hit
PS50125 GUANYLATE_CYCLASE_2, 2 hits

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 6 potential isoforms that are computationally mapped.Show allAlign All

P51828-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MPAKGRYFLN EGEEGPDQDA LYEKYQLTSQ HGPLLLTLLL VAATACVALI
60 70 80 90 100
IIAFSQGDPS RHQAILGMAF LVLAVFAALS VLMYVECLLR RWLRALALLT
110 120 130 140 150
WACLVALGYV LVFDAWTKAA CAWEQVPFFL FIVFVVYTLL PFSMRGAVAV
160 170 180 190 200
GAVSTASHLL VLGSLMGGFT TPSVRVGLQL LANAVIFLCG NLTGAFHKHQ
210 220 230 240 250
MQDASRDLFT YTVKCIQIRR KLRIEKRQQE NLLLSVLPAH ISMGMKLAII
260 270 280 290 300
ERLKEHGDRR CMPDNNFHSL YVKRHQNVSI LYADIVGFTQ LASDCSPKEL
310 320 330 340 350
VVVLNELFGK FDQIAKANEC MRIKILGDCY YCVSGLPVSL PTHARNCVKM
360 370 380 390 400
GLDMCQAIKQ VREATGVDIN MRVGIHSGNV LCGVIGLRKW QYDVWSHDVS
410 420 430 440 450
LANRMEAAGV PGRVHITEAT LKHLDKAYEV EDGHGQQRDP YLKEMNIRTY
460 470 480 490 500
LVIDPRSQQP PPPSQHLPRP KGDAALKMRA SVRMTRYLES WGAARPFAHL
510 520 530 540 550
NHRESVSSGE THVPNGRRPK SVPQRHRRTP DRSMSPKGRS EDDSYDDEML
560 570 580 590 600
SAIEGLSSTR PCCSKSDDFY TFGSIFLEKG FEREYRLAPI PRARHDFACA
610 620 630 640 650
SLIFVCILLV HVLLMPRTAA LGVSFGLVAC VLGLVLGLCF ATKFSRCCPA
660 670 680 690 700
RGTLCTISER VETQPLLRLT LAVLTIGSLL TVAIINLPLM PFQVPELPVG
710 720 730 740 750
NETGLLAASS KTRALCEPLP YYTCSCVLGF IACSVFLRMS LEPKVVLLTV
760 770 780 790 800
ALVAYLVLFN LSPCWQWDCC GQGLGNLTKP NGTTSGTPSC SWKDLKTMTN
810 820 830 840 850
FYLVLFYITL LTLSRQIDYY CRLDCLWKKK FKKEHEEFET MENVNRLLLE
860 870 880 890 900
NVLPAHVAAH FIGDKLNEDW YHQSYDCVCV MFASVPDFKV FYTECDVNKE
910 920 930 940 950
GLECLRLLNE IIADFDELLL KPKFSGVEKI KTIGSTYMAA AGLSVASGHE
960 970 980 990 1000
NQELERQHAH IGVMVEFSIA LMSKLDGINR HSFNSFRLRV GINHGPVIAG
1010 1020 1030 1040 1050
VIGARKPQYD IWGNTVNVAS RMESTGELGK IQVTEETCTI LQGLGYSCEC
1060 1070 1080
RGLINVKGKG ELRTYFVCTD TAKFQGLGLN
Length:1,080
Mass (Da):120,308
Last modified:October 1, 1996 - v1
Checksum:iE33951621E281242
GO

Computationally mapped potential isoform sequencesi

There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F5H4D1F5H4D1_HUMAN
Adenylate cyclase type 7
ADCY7
734Annotation score:
H3BQ93H3BQ93_HUMAN
Adenylate cyclase type 7
ADCY7
530Annotation score:
F5H699F5H699_HUMAN
Adenylate cyclase type 7
ADCY7
433Annotation score:
I3L3Q5I3L3Q5_HUMAN
Adenylate cyclase type 7
ADCY7
81Annotation score:
H3BMA5H3BMA5_HUMAN
Adenylate cyclase type 7
ADCY7
108Annotation score:
I3L2Y1I3L2Y1_HUMAN
Adenylate cyclase type 7
ADCY7
17Annotation score:

Sequence cautioni

The sequence BAA05021 differs from that shown. Reason: Erroneous initiation.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D25538 mRNA Translation: BAA05021.2 Different initiation.
AC007597 Genomic DNA No translation available.
BC126271 mRNA Translation: AAI26272.1
CCDSiCCDS10741.1
PIRiPN0453
RefSeqiNP_001105.1, NM_001114.4
XP_016878384.1, XM_017022895.1
UniGeneiHs.513578

Genome annotation databases

EnsembliENST00000254235; ENSP00000254235; ENSG00000121281
ENST00000394697; ENSP00000378187; ENSG00000121281
GeneIDi113
KEGGihsa:113
UCSCiuc002egd.3 human

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D25538 mRNA Translation: BAA05021.2 Different initiation.
AC007597 Genomic DNA No translation available.
BC126271 mRNA Translation: AAI26272.1
CCDSiCCDS10741.1
PIRiPN0453
RefSeqiNP_001105.1, NM_001114.4
XP_016878384.1, XM_017022895.1
UniGeneiHs.513578

3D structure databases

ProteinModelPortaliP51828
SMRiP51828
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106626, 3 interactors
IntActiP51828, 3 interactors
STRINGi9606.ENSP00000254235

Chemistry databases

ChEMBLiCHEMBL2097167

PTM databases

iPTMnetiP51828
PhosphoSitePlusiP51828
SwissPalmiP51828

Polymorphism and mutation databases

BioMutaiADCY7
DMDMi1706218

Proteomic databases

EPDiP51828
MaxQBiP51828
PaxDbiP51828
PeptideAtlasiP51828
PRIDEiP51828
ProteomicsDBi56430

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000254235; ENSP00000254235; ENSG00000121281
ENST00000394697; ENSP00000378187; ENSG00000121281
GeneIDi113
KEGGihsa:113
UCSCiuc002egd.3 human

Organism-specific databases

CTDi113
DisGeNETi113
EuPathDBiHostDB:ENSG00000121281.12
GeneCardsiADCY7
HGNCiHGNC:238 ADCY7
HPAiHPA041218
HPA048241
MIMi600385 gene
neXtProtiNX_P51828
OpenTargetsiENSG00000121281
PharmGKBiPA28
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3619 Eukaryota
COG2114 LUCA
GeneTreeiENSGT00760000119042
HOGENOMiHOG000006941
HOVERGENiHBG050458
InParanoidiP51828
KOiK08047
OMAiTNFYLVL
OrthoDBiEOG091G05JR
PhylomeDBiP51828
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
SIGNORiP51828

Miscellaneous databases

ChiTaRSiADCY7 human
GeneWikiiADCY7
GenomeRNAii113
PROiPR:P51828
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000121281 Expressed in 215 organ(s), highest expression level in leukocyte
CleanExiHS_ADCY7
ExpressionAtlasiP51828 baseline and differential
GenevisibleiP51828 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, 1 hit
PS50125 GUANYLATE_CYCLASE_2, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiADCY7_HUMAN
AccessioniPrimary (citable) accession number: P51828
Secondary accession number(s): A0AVA6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 7, 2018
This is version 159 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. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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