ID   B3KWA8_HUMAN            Unreviewed;       919 AA.
AC   B3KWA8;
DT   02-SEP-2008, integrated into UniProtKB/TrEMBL.
DT   02-SEP-2008, sequence version 1.
DT   27-MAR-2024, entry version 123.
DE   RecName: Full=Adenylate cyclase type 5 {ECO:0000256|ARBA:ARBA00040910};
DE            EC=4.6.1.1 {ECO:0000256|ARBA:ARBA00012201};
DE   AltName: Full=ATP pyrophosphate-lyase 5 {ECO:0000256|ARBA:ARBA00042065};
DE   AltName: Full=Adenylate cyclase type V {ECO:0000256|ARBA:ARBA00042046};
DE   AltName: Full=Adenylyl cyclase 5 {ECO:0000256|ARBA:ARBA00041988};
GN   Name=ADCY5 {ECO:0000313|Ensembl:ENSP00000418537.1};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606 {ECO:0000313|EMBL:BAG54070.1};
RN   [1] {ECO:0000313|EMBL:BAG54070.1}
RP   NUCLEOTIDE SEQUENCE.
RC   TISSUE=Amygdala {ECO:0000313|EMBL:BAG54070.1};
RA   Oshima A., Takahashi-Fujii A., Tanase T., Imose N., Takeuchi K., Arita M.,
RA   Musashino K., Yuuki H., Hara H., Sugiyama T., Irie R., Otsuki T., Sato H.,
RA   Wakamatsu A., Ishii S., Yamamoto J., Isono Y., Kawai-Hio Y., Saito K.,
RA   Nishikawa T., Kimura K., Yamashita H., Matsuo K., Nakamura Y., Sekine M.,
RA   Kikuchi H., Kanda K., Wagatsuma M., Murakawa K., Kanehori K., Sugiyama A.,
RA   Kawakami B., Suzuki Y., Sugano S., Nagahari K., Masuho Y., Nagai K.,
RA   Isogai T.;
RT   "NEDO human cDNA sequencing project.";
RL   Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN   [2] {ECO:0000313|Ensembl:ENSP00000418537.1, ECO:0000313|Proteomes:UP000005640}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16641997; DOI=10.1038/nature04728;
RA   Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA   Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA   Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA   Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA   Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA   Sodergren E., Song X.Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA   Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA   Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA   Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA   Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA   Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA   Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA   Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.V., Okwuonu G.O.,
RA   Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA   Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA   Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA   Wang J., Wang Q., Williams G.A., Wong G.K., Yao Z., Zhang J., Zhang X.,
RA   Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA   Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT   "The DNA sequence, annotation and analysis of human chromosome 3.";
RL   Nature 440:1194-1198(2006).
RN   [3] {ECO:0000313|Ensembl:ENSP00000418537.1}
RP   IDENTIFICATION.
RG   Ensembl;
RL   Submitted (NOV-2023) to UniProtKB.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP = 3',5'-cyclic AMP + diphosphate; Xref=Rhea:RHEA:15389,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:58165; EC=4.6.1.1;
CC         Evidence={ECO:0000256|ARBA:ARBA00001593};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000256|PIRSR:PIRSR039050-51};
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000256|PIRSR:PIRSR039050-51};
CC       Note=Binds 2 magnesium ions per subunit. Is also active with manganese
CC       (in vitro). {ECO:0000256|PIRSR:PIRSR039050-51};
CC   -!- COFACTOR:
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000256|ARBA:ARBA00001936};
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000256|ARBA:ARBA00004651};
CC       Multi-pass membrane protein {ECO:0000256|ARBA:ARBA00004651}. Cell
CC       projection, cilium {ECO:0000256|ARBA:ARBA00004138}. Membrane
CC       {ECO:0000256|ARBA:ARBA00004141}; Multi-pass membrane protein
CC       {ECO:0000256|ARBA:ARBA00004141}.
CC   -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC       family. {ECO:0000256|RuleBase:RU000405}.
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DR   EMBL; AC025571; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC112503; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AK124691; BAG54070.1; -; mRNA.
DR   RefSeq; XP_006713546.1; XM_006713483.1.
DR   ProteomicsDB; 3785; -.
DR   Antibodypedia; 2807; 180 antibodies from 28 providers.
DR   DNASU; 111; -.
DR   Ensembl; ENST00000491190.5; ENSP00000418537.1; ENSG00000173175.16.
DR   GeneID; 111; -.
DR   UCSC; uc003egg.3; human.
DR   CTD; 111; -.
DR   HGNC; HGNC:236; ADCY5.
DR   VEuPathDB; HostDB:ENSG00000173175; -.
DR   GeneTree; ENSGT00940000158054; -.
DR   OrthoDB; 3686360at2759; -.
DR   BioGRID-ORCS; 111; 12 hits in 1149 CRISPR screens.
DR   ChiTaRS; ADCY5; human.
DR   GenomeRNAi; 111; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   Bgee; ENSG00000173175; Expressed in apex of heart and 127 other cell types or tissues.
DR   GO; GO:0005929; C:cilium; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0004016; F:adenylate cyclase activity; IEA:UniProtKB-EC.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0006171; P:cAMP biosynthetic process; IEA:UniProtKB-KW.
DR   GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR   CDD; cd07302; CHD; 1.
DR   CDD; cd07556; Nucleotidyl_cyc_III; 1.
DR   Gene3D; 3.30.70.1230; Nucleotide cyclase; 2.
DR   InterPro; IPR001054; A/G_cyclase.
DR   InterPro; IPR018297; A/G_cyclase_CS.
DR   InterPro; IPR032628; AC_N.
DR   InterPro; IPR030672; Adcy.
DR   InterPro; IPR009398; Adcy_conserved_dom.
DR   InterPro; IPR029787; Nucleotide_cyclase.
DR   PANTHER; PTHR45627; ADENYLATE CYCLASE TYPE 1; 1.
DR   PANTHER; PTHR45627:SF7; ADENYLATE CYCLASE TYPE 5; 1.
DR   Pfam; PF16214; AC_N; 1.
DR   Pfam; PF06327; Adcy_cons_dom; 1.
DR   Pfam; PF00211; Guanylate_cyc; 2.
DR   PIRSF; PIRSF039050; Ade_cyc; 1.
DR   SMART; SM00044; CYCc; 2.
DR   SUPFAM; SSF55073; Nucleotide cyclase; 2.
DR   PROSITE; PS00452; GUANYLATE_CYCLASE_1; 2.
DR   PROSITE; PS50125; GUANYLATE_CYCLASE_2; 2.
PE   1: Evidence at protein level;
KW   ATP-binding {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|PIRSR:PIRSR039050-
KW   50}; cAMP biosynthesis {ECO:0000256|ARBA:ARBA00022998};
KW   Cell membrane {ECO:0000256|ARBA:ARBA00022475};
KW   Cell projection {ECO:0000256|ARBA:ARBA00023273};
KW   Lyase {ECO:0000256|ARBA:ARBA00023239, ECO:0000256|RuleBase:RU000405};
KW   Magnesium {ECO:0000256|ARBA:ARBA00022842, ECO:0000256|PIRSR:PIRSR039050-
KW   51}; Manganese {ECO:0000256|PIRSR:PIRSR039050-51};
KW   Membrane {ECO:0000256|SAM:Phobius};
KW   Metal-binding {ECO:0000256|ARBA:ARBA00022723,
KW   ECO:0000256|PIRSR:PIRSR039050-51};
KW   Methylation {ECO:0000256|ARBA:ARBA00022481};
KW   Nucleotide-binding {ECO:0000256|PIRSR:PIRSR039050-50};
KW   Phosphoprotein {ECO:0000256|ARBA:ARBA00022553};
KW   Proteomics identification {ECO:0007829|MaxQB:B3KWA8,
KW   ECO:0007829|PeptideAtlas:B3KWA8};
KW   Reference proteome {ECO:0000313|Proteomes:UP000005640};
KW   Transmembrane {ECO:0000256|SAM:Phobius};
KW   Transmembrane helix {ECO:0000256|SAM:Phobius}.
FT   TRANSMEM        394..415
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|SAM:Phobius"
FT   TRANSMEM        421..446
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|SAM:Phobius"
FT   TRANSMEM        467..488
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|SAM:Phobius"
FT   TRANSMEM        542..560
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|SAM:Phobius"
FT   TRANSMEM        567..588
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|SAM:Phobius"
FT   TRANSMEM        642..661
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|SAM:Phobius"
FT   DOMAIN          102..229
FT                   /note="Guanylate cyclase"
FT                   /evidence="ECO:0000259|PROSITE:PS50125"
FT   DOMAIN          729..868
FT                   /note="Guanylate cyclase"
FT                   /evidence="ECO:0000259|PROSITE:PS50125"
FT   BINDING         107..112
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR039050-50"
FT   BINDING         107
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR039050-51"
FT   BINDING         107
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR039050-51"
FT   BINDING         108
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR039050-51"
FT   BINDING         149..151
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR039050-50"
FT   BINDING         151
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR039050-51"
FT   BINDING         151
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR039050-51"
FT   BINDING         195
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR039050-50"
FT   BINDING         781
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR039050-50"
FT   BINDING         855..857
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR039050-50"
FT   BINDING         862..866
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR039050-50"
FT   BINDING         902
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR039050-50"
SQ   SEQUENCE   919 AA;  103868 MW;  DC89BB6B6C4D9F6E CRC64;
     MAPSRFRTQL ELVSNVLIFS CTNIVGVCTH YPAEVSQRQA FQETRECIQA RLHSQRENQQ
     QERLLLSVLP RHVAMEMKAD INAKQEDMMF HKIYIQKHDN VSILFADIEG FTSLASQCTA
     QELVMTLNEL FARFDKLAAE NHCLRIKILG DCYYCVSGLP EARADHAHCC VEMGMDMIEA
     ISLVREVTGV NVNMRVGIHS GRVHCGVLGL RKWQFDVWSN DVTLANHMEA GGKAGRIHIT
     KATLNYLNGD YEVEPGCGGE RNAYLKEHSI ETFLILRCTQ KRKEEKAMIA KMNRQRTNSI
     GHNPPHWGAE RPFYNHLGGN QVSKEMKRMG FEDPKDKNAQ ESANPEDEVD EFLGRAIDAR
     SIDRLRSEHV RKFLLTFREP DLEKKYSKQV DDRFGAYVAC ASLVFLFICF VQITIVPHSI
     FMLSFYLTCS LLLTLVVFVS VIYSCVKLFP SPLQTLSRKI VRSKMNSTLV GVFTITLVFL
     AAFVNMFTCN SRDLLGCLAQ EHNISASQVN ACHVAESAVN YSLGDEQGFC GSPWPNCNFP
     EYFTYSVLLS LLACSVFLQI SCIGKLVLML AIELIYVLIV EVPGVTLFDN ADLLVTANAI
     DFFNNGTSQW SLCENLRHRR MEAGTYFPSG VKEQSPEHAT KVALKVVTPI IISVFVLALY
     LHAQQVESTA RLDFLWKLQA TEEKEEMEEL QAYNRRLLHN ILPKDVAAHF LARERRNDEL
     YYQSCECVAV MFASIANFSE FYVELEANNE GVECLRLLNE IIADFDEIIS EDRFRQLEKI
     KTIGSTYMAA SGLNDSTYDK VGKTHIKALA DFAMKLMDQM KYINEHSFNN FQMKIGLNIG
     PVVAGVIGAR KPQYDIWGNT VNVASRMDST GVPDRIQVTT DMYQVLAANT YQLECRGVVK
     VKGKGEMMTY FLNGGPPLS
//