AKA7A_HUMAN
ID AKA7A_HUMAN Reviewed; 104 AA.
AC O43687; A8K2K6; Q5TBR9; Q5TBS0; Q9HCZ8; Q9P0G4;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=A-kinase anchor protein 7 isoforms alpha and beta;
DE Short=AKAP-7 isoforms alpha and beta;
DE AltName: Full=A-kinase anchor protein 18 kDa;
DE Short=AKAP 18;
DE AltName: Full=Protein kinase A-anchoring protein 7 isoforms alpha/beta;
DE Short=PRKA7 isoforms alpha/beta;
GN Name=AKAP7; Synonyms=AKAP15, AKAP18;
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA), FUNCTION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, MYRISTOYLATION AT GLY-2, AND PALMITOYLATION AT CYS-5
RP AND CYS-6.
RC TISSUE=Brain;
RX PubMed=9545239; DOI=10.1093/emboj/17.8.2261;
RA Fraser I.D.C., Tavalin S.J., Lester L.B., Langeberg L.K., Westphal A.M.,
RA Dean R.A., Marrion N.V., Scott J.D.;
RT "A novel lipid-anchored A-kinase anchoring protein facilitates cAMP-
RT responsive membrane events.";
RL EMBO J. 17:2261-2272(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA), FUNCTION, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Lung;
RX PubMed=10613906; DOI=10.1083/jcb.147.7.1481;
RA Trotter K.W., Fraser I.D.C., Scott G.K., Stutts M.J., Scott J.D.,
RA Milgram S.L.;
RT "Alternative splicing regulates the subcellular localization of A-kinase
RT anchoring protein 18 isoforms.";
RL J. Cell Biol. 147:1481-1492(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA).
RC TISSUE=Colon;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA).
RC TISSUE=Adrenal cortex, Hippocampus, and Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, INTERACTION WITH PRKCA, AND MUTAGENESIS OF 2-GLY--CYS-6.
RX PubMed=17244820; DOI=10.1096/fj.06-6046com;
RA Bengrine A., Li J., Awayda M.S.;
RT "The A-kinase anchoring protein 15 regulates feedback inhibition of the
RT epithelial Na+ channel.";
RL FASEB J. 21:1189-1201(2007).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Targets the cAMP-dependent protein kinase (PKA) to the plasma
CC membrane, and permits functional coupling to the L-type calcium
CC channel. The membrane-associated form reduces epithelial sodium channel
CC (ENaC) activity, whereas the free cytoplasmic form may negatively
CC regulate ENaC channel feedback inhibition by intracellular sodium.
CC {ECO:0000269|PubMed:10613906, ECO:0000269|PubMed:17244820,
CC ECO:0000269|PubMed:9545239}.
CC -!- SUBUNIT: Binds cAMP-dependent protein kinase (PKA). Interacts with
CC PRKCA; only the cytoplasmic form is capable of interacting with PRKCA.
CC {ECO:0000269|PubMed:17244820}.
CC -!- INTERACTION:
CC O43687-2; Q8TAP6: CEP76; NbExp=6; IntAct=EBI-10185182, EBI-742887;
CC O43687-2; P10644: PRKAR1A; NbExp=3; IntAct=EBI-10185182, EBI-476431;
CC O43687-2; P31321: PRKAR1B; NbExp=5; IntAct=EBI-10185182, EBI-2805516;
CC O43687-2; P13861-2: PRKAR2A; NbExp=5; IntAct=EBI-10185182, EBI-11752137;
CC O43687-2; P31323: PRKAR2B; NbExp=8; IntAct=EBI-10185182, EBI-2930670;
CC O43687-2; Q6DHZ2: PRKAR2B; NbExp=4; IntAct=EBI-10185182, EBI-10185196;
CC O43687-2; Q9HAT0: ROPN1; NbExp=9; IntAct=EBI-10185182, EBI-1378139;
CC O43687-2; Q96C74: ROPN1L; NbExp=3; IntAct=EBI-10185182, EBI-9033237;
CC O43687-2; Q15506: SPA17; NbExp=6; IntAct=EBI-10185182, EBI-1377865;
CC -!- SUBCELLULAR LOCATION: [Isoform Alpha]: Lateral cell membrane; Lipid-
CC anchor. Note=Targeted predominantly to the lateral membrane.
CC -!- SUBCELLULAR LOCATION: [Isoform Beta]: Apical cell membrane; Lipid-
CC anchor. Note=Targeted predominantly to the apical membrane.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Additional isoforms seem to exist.;
CC Name=Beta;
CC IsoId=O43687-1; Sequence=Displayed;
CC Name=Alpha;
CC IsoId=O43687-2; Sequence=VSP_004101;
CC Name=Gamma;
CC IsoId=Q9P0M2-1; Sequence=External;
CC -!- TISSUE SPECIFICITY: Expressed in brain, heart, lung, pancreas and
CC skeletal muscle. {ECO:0000269|PubMed:9545239}.
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DR EMBL; AF047715; AAC39715.1; -; mRNA.
DR EMBL; AF161075; AAF26676.1; -; mRNA.
DR EMBL; AK290271; BAF82960.1; -; mRNA.
DR EMBL; AL136110; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL137063; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW48057.1; -; Genomic_DNA.
DR EMBL; BC016927; AAH16927.1; -; mRNA.
DR EMBL; BC073847; AAH73847.1; -; mRNA.
DR EMBL; BC094732; AAH94732.1; -; mRNA.
DR CCDS; CCDS5143.1; -. [O43687-2]
DR CCDS; CCDS5144.1; -. [O43687-1]
DR RefSeq; NP_004833.1; NM_004842.3. [O43687-2]
DR RefSeq; NP_619539.1; NM_138633.2. [O43687-1]
DR AlphaFoldDB; O43687; -.
DR SMR; O43687; -.
DR BioGRID; 114851; 42.
DR CORUM; O43687; -.
DR IntAct; O43687; 9.
DR iPTMnet; O43687; -.
DR SwissPalm; O43687; -.
DR BioMuta; AKAP7; -.
DR jPOST; O43687; -.
DR MassIVE; O43687; -.
DR PeptideAtlas; O43687; -.
DR PRIDE; O43687; -.
DR ProteomicsDB; 49115; -. [O43687-1]
DR ProteomicsDB; 49116; -. [O43687-2]
DR Antibodypedia; 19674; 297 antibodies from 28 providers.
DR DNASU; 9465; -.
DR Ensembl; ENST00000342266.4; ENSP00000345149.4; ENSG00000118507.18. [O43687-2]
DR Ensembl; ENST00000474850.2; ENSP00000418208.2; ENSG00000118507.18. [O43687-1]
DR GeneID; 9465; -.
DR UCSC; uc003qcm.3; human. [O43687-1]
DR CTD; 9465; -.
DR DisGeNET; 9465; -.
DR GeneCards; AKAP7; -.
DR HGNC; HGNC:377; AKAP7.
DR HPA; ENSG00000118507; Tissue enhanced (adrenal).
DR MIM; 604693; gene.
DR neXtProt; NX_O43687; -.
DR OpenTargets; ENSG00000118507; -.
DR PharmGKB; PA24671; -.
DR VEuPathDB; HostDB:ENSG00000118507; -.
DR GeneTree; ENSGT00390000012756; -.
DR HOGENOM; CLU_177905_0_0_1; -.
DR OrthoDB; 606751at2759; -.
DR PathwayCommons; O43687; -.
DR SignaLink; O43687; -.
DR BioGRID-ORCS; 9465; 11 hits in 1083 CRISPR screens.
DR ChiTaRS; AKAP7; human.
DR GeneWiki; AKAP7; -.
DR GenomeRNAi; 9465; -.
DR Pharos; O43687; Tbio.
DR Proteomes; UP000005640; Chromosome 6.
DR Bgee; ENSG00000118507; Expressed in adrenal tissue and 208 other tissues.
DR ExpressionAtlas; O43687; baseline and differential.
DR Genevisible; O43687; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0016328; C:lateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:UniProtKB.
DR GO; GO:0051018; F:protein kinase A binding; IDA:UniProtKB.
DR GO; GO:0001508; P:action potential; IC:BHF-UCL.
DR GO; GO:0071320; P:cellular response to cAMP; IDA:BHF-UCL.
DR GO; GO:0035556; P:intracellular signal transduction; TAS:UniProtKB.
DR GO; GO:0006811; P:ion transport; TAS:ProtInc.
DR GO; GO:1902261; P:positive regulation of delayed rectifier potassium channel activity; IDA:BHF-UCL.
DR GO; GO:1901381; P:positive regulation of potassium ion transmembrane transport; IDA:BHF-UCL.
DR GO; GO:0008104; P:protein localization; IC:UniProtKB.
DR GO; GO:0060306; P:regulation of membrane repolarization; IDA:BHF-UCL.
DR InterPro; IPR019511; AKAP7_RI-RII-bd_dom.
DR Pfam; PF10470; AKAP7_RIRII_bdg; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Lipoprotein; Membrane; Myristate;
KW Palmitate; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..104
FT /note="A-kinase anchor protein 7 isoforms alpha and beta"
FT /id="PRO_0000064522"
FT REGION 2..11
FT /note="Required for membrane localization"
FT REGION 18..40
FT /note="Required for apical membrane localization"
FT REGION 52..65
FT /note="RII-binding"
FT REGION 72..104
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 72..96
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:9545239"
FT LIPID 5
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:9545239"
FT LIPID 6
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:9545239"
FT VAR_SEQ 18..40
FT /note="Missing (in isoform Alpha)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9545239"
FT /id="VSP_004101"
FT MUTAGEN 2..6
FT /note="GQLCC->AQLAA: Abolishes membrane localization and
FT affects its ability to inhibit ENaC activity in a sodium-
FT dependent manner."
FT /evidence="ECO:0000269|PubMed:17244820"
SQ SEQUENCE 104 AA; 11465 MW; 6F84ED8E032AF954 CRC64;
MGQLCCFPFS RDEGKISELE SSSSAVLQRY SKDIPSWSSG EKNGGEPDDA ELVRLSKRLV
ENAVLKAVQQ YLEETQNKNK PGEGSSVKTE AADQNGNDNE NNRK
