AKAP4_HUMAN
ID AKAP4_HUMAN Reviewed; 854 AA.
AC Q5JQC9; A0AV85; O60904; O95246; Q5JQD1; Q5JQD2; Q5JQD3;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=A-kinase anchor protein 4;
DE Short=AKAP-4;
DE AltName: Full=A-kinase anchor protein 82 kDa;
DE Short=AKAP 82;
DE Short=hAKAP82;
DE AltName: Full=Major sperm fibrous sheath protein;
DE Short=HI;
DE AltName: Full=Protein kinase A-anchoring protein 4;
DE Short=PRKA4;
DE Flags: Precursor;
GN Name=AKAP4 {ECO:0000312|HGNC:HGNC:374}; Synonyms=AKAP82;
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] {ECO:0000305, ECO:0000312|EMBL:CAA75494.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RC TISSUE=Testis {ECO:0000312|EMBL:CAA75494.1};
RX PubMed=9514854; DOI=10.1006/bbrc.1998.8079;
RA Mohapatra B., Verma S., Shankar S., Suri A.;
RT "Molecular cloning of human testis mRNA specifically expressed in haploid
RT germ cells, having structural homology with the A-kinase anchoring
RT proteins.";
RL Biochem. Biophys. Res. Commun. 244:540-545(1998).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAC79433.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=9822690; DOI=10.1074/jbc.273.48.32135;
RA Turner R.M.O., Johnson L.R., Haig-Ladewig L., Gerton G.L., Moss S.B.;
RT "An X-linked gene encodes a major human sperm fibrous sheath protein,
RT hAKAP82. Genomic organization, protein kinase A-RII binding, and
RT distribution of the precursor in the sperm tail.";
RL J. Biol. Chem. 273:32135-32141(1998).
RN [3] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-300; TYR-303; SER-304;
RP SER-447 AND SER-450, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Sperm;
RX PubMed=12509440; DOI=10.1074/jbc.m202325200;
RA Ficarro S., Chertihin O., Westbrook V.A., White F., Jayes F., Kalab P.,
RA Marto J.A., Shabanowitz J., Herr J.C., Hunt D.F., Visconti P.E.;
RT "Phosphoproteome analysis of capacitated human sperm. Evidence of tyrosine
RT phosphorylation of a kinase-anchoring protein 3 and valosin-containing
RT protein/p97 during capacitation.";
RL J. Biol. Chem. 278:11579-11589(2003).
CC -!- FUNCTION: Major structural component of sperm fibrous sheath. Plays a
CC role in sperm motility. {ECO:0000269|PubMed:9822690}.
CC -!- SUBUNIT: Interacts with PRKAR1A and PRKAR2A. Interacts with ENO4.
CC {ECO:0000250|UniProtKB:Q60662}.
CC -!- INTERACTION:
CC Q5JQC9; P36873-2: PPP1CC; NbExp=4; IntAct=EBI-16628643, EBI-3964623;
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium, flagellum
CC {ECO:0000269|PubMed:9822690}. Note=Localizes to the principle piece of
CC the sperm flagellum.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:9514854};
CC IsoId=Q5JQC9-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:9822690};
CC IsoId=Q5JQC9-2; Sequence=VSP_052142;
CC -!- TISSUE SPECIFICITY: Testis specific; only expressed in round
CC spermatids. {ECO:0000269|PubMed:9514854}.
CC -!- DEVELOPMENTAL STAGE: Post-meiotic phase of spermatogenesis.
CC {ECO:0000269|PubMed:9514854}.
CC -!- DOMAIN: RI-alpha binding site, predicted to form an amphipathic helix,
CC could participate in protein-protein interactions with a complementary
CC surface on the R-subunit dimer. {ECO:0000250|UniProtKB:Q60662}.
CC -!- SIMILARITY: Belongs to the AKAP110 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA75494.1; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; Y15195; CAA75494.1; ALT_SEQ; mRNA.
DR EMBL; AF072756; AAC79433.1; -; mRNA.
DR EMBL; FO393402; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC126250; AAI26251.1; -; mRNA.
DR EMBL; BC126252; AAI26253.1; -; mRNA.
DR CCDS; CCDS14329.1; -. [Q5JQC9-1]
DR CCDS; CCDS14330.1; -. [Q5JQC9-2]
DR PIR; JC5986; JC5986.
DR RefSeq; NP_003877.2; NM_003886.2. [Q5JQC9-1]
DR RefSeq; NP_647450.1; NM_139289.1. [Q5JQC9-2]
DR AlphaFoldDB; Q5JQC9; -.
DR SMR; Q5JQC9; -.
DR BioGRID; 114377; 6.
DR IntAct; Q5JQC9; 1.
DR STRING; 9606.ENSP00000351327; -.
DR iPTMnet; Q5JQC9; -.
DR PhosphoSitePlus; Q5JQC9; -.
DR BioMuta; AKAP4; -.
DR DMDM; 74741729; -.
DR MassIVE; Q5JQC9; -.
DR MaxQB; Q5JQC9; -.
DR PaxDb; Q5JQC9; -.
DR PeptideAtlas; Q5JQC9; -.
DR PRIDE; Q5JQC9; -.
DR ProteomicsDB; 63039; -. [Q5JQC9-1]
DR ProteomicsDB; 63040; -. [Q5JQC9-2]
DR TopDownProteomics; Q5JQC9-2; -. [Q5JQC9-2]
DR Antibodypedia; 470; 151 antibodies from 29 providers.
DR DNASU; 8852; -.
DR Ensembl; ENST00000358526.7; ENSP00000351327.2; ENSG00000147081.15. [Q5JQC9-1]
DR Ensembl; ENST00000376064.7; ENSP00000365232.3; ENSG00000147081.15. [Q5JQC9-2]
DR GeneID; 8852; -.
DR KEGG; hsa:8852; -.
DR MANE-Select; ENST00000358526.7; ENSP00000351327.2; NM_003886.3; NP_003877.2.
DR UCSC; uc004dou.2; human. [Q5JQC9-1]
DR CTD; 8852; -.
DR DisGeNET; 8852; -.
DR GeneCards; AKAP4; -.
DR HGNC; HGNC:374; AKAP4.
DR HPA; ENSG00000147081; Tissue enriched (testis).
DR MIM; 300185; gene.
DR neXtProt; NX_Q5JQC9; -.
DR OpenTargets; ENSG00000147081; -.
DR PharmGKB; PA24668; -.
DR VEuPathDB; HostDB:ENSG00000147081; -.
DR eggNOG; ENOG502QQXJ; Eukaryota.
DR GeneTree; ENSGT00940000153313; -.
DR HOGENOM; CLU_016756_1_0_1; -.
DR InParanoid; Q5JQC9; -.
DR OMA; KCGSGQS; -.
DR OrthoDB; 221175at2759; -.
DR PhylomeDB; Q5JQC9; -.
DR TreeFam; TF105403; -.
DR PathwayCommons; Q5JQC9; -.
DR SignaLink; Q5JQC9; -.
DR BioGRID-ORCS; 8852; 21 hits in 698 CRISPR screens.
DR ChiTaRS; AKAP4; human.
DR GeneWiki; AKAP4; -.
DR GenomeRNAi; 8852; -.
DR Pharos; Q5JQC9; Tbio.
DR PRO; PR:Q5JQC9; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q5JQC9; protein.
DR Bgee; ENSG00000147081; Expressed in sperm and 70 other tissues.
DR ExpressionAtlas; Q5JQC9; baseline and differential.
DR Genevisible; Q5JQC9; HS.
DR GO; GO:0005952; C:cAMP-dependent protein kinase complex; NAS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; TAS:ProtInc.
DR GO; GO:0031514; C:motile cilium; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0097224; C:sperm connecting piece; IDA:UniProtKB.
DR GO; GO:0097229; C:sperm end piece; IDA:UniProtKB.
DR GO; GO:0035686; C:sperm fibrous sheath; IBA:GO_Central.
DR GO; GO:0097225; C:sperm midpiece; IDA:UniProtKB.
DR GO; GO:0097228; C:sperm principal piece; IDA:UniProtKB.
DR GO; GO:0030018; C:Z disc; IEA:Ensembl.
DR GO; GO:0051018; F:protein kinase A binding; ISS:UniProtKB.
DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl.
DR GO; GO:0045184; P:establishment of protein localization; IEA:Ensembl.
DR GO; GO:0030317; P:flagellated sperm motility; IMP:UniProtKB.
DR GO; GO:0008104; P:protein localization; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0007338; P:single fertilization; TAS:ProtInc.
DR GO; GO:0120316; P:sperm flagellum assembly; IEA:Ensembl.
DR GO; GO:0007178; P:transmembrane receptor protein serine/threonine kinase signaling pathway; IEA:Ensembl.
DR InterPro; IPR020799; AKAP_110.
DR InterPro; IPR018292; AKAP_110_C.
DR InterPro; IPR018459; RII-bd_1.
DR InterPro; IPR008382; SPHK1-interactor_AKAP_110.
DR PANTHER; PTHR10226; PTHR10226; 1.
DR Pfam; PF05716; AKAP_110; 3.
DR Pfam; PF10522; RII_binding_1; 1.
DR SMART; SM00807; AKAP_110; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; Cilium;
KW Cilium biogenesis/degradation; Flagellum; Phosphoprotein;
KW Reference proteome.
FT PROPEP 1..188
FT /evidence="ECO:0000255"
FT /id="PRO_0000248230"
FT CHAIN 189..854
FT /note="A-kinase anchor protein 4"
FT /evidence="ECO:0000250|UniProtKB:Q60662"
FT /id="PRO_0000248231"
FT REGION 184..207
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 219..232
FT /note="PKA-RI and PKA-RII subunit binding domain"
FT /evidence="ECO:0000250|UniProtKB:Q60662"
FT REGION 287..323
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 336..345
FT /note="PKA-RI-alpha subunit binding domain"
FT /evidence="ECO:0000250|UniProtKB:Q60662"
FT MOD_RES 96
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35774"
FT MOD_RES 130
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35774"
FT MOD_RES 190
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35774"
FT MOD_RES 213
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35774"
FT MOD_RES 226
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35774"
FT MOD_RES 272
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35774"
FT MOD_RES 300
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:12509440"
FT MOD_RES 303
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:12509440"
FT MOD_RES 304
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:12509440"
FT MOD_RES 307
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35774"
FT MOD_RES 342
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35774"
FT MOD_RES 432
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35774"
FT MOD_RES 443
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35774"
FT MOD_RES 445
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35774"
FT MOD_RES 447
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:12509440"
FT MOD_RES 450
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:12509440"
FT MOD_RES 464
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35774"
FT MOD_RES 492
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35774"
FT MOD_RES 506
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O35774"
FT MOD_RES 536
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35774"
FT MOD_RES 627
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35774"
FT MOD_RES 703
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35774"
FT VAR_SEQ 1..9
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9822690"
FT /id="VSP_052142"
FT VARIANT 233
FT /note="H -> R (in dbSNP:rs17174078)"
FT /id="VAR_048206"
FT VARIANT 673
FT /note="A -> G (in dbSNP:rs12012704)"
FT /id="VAR_027266"
FT CONFLICT 123
FT /note="L -> W (in Ref. 2; AAC79433)"
FT /evidence="ECO:0000305"
FT CONFLICT 128
FT /note="A -> E (in Ref. 2; AAC79433)"
FT /evidence="ECO:0000305"
FT CONFLICT 146
FT /note="E -> D (in Ref. 2; AAC79433)"
FT /evidence="ECO:0000305"
FT CONFLICT 369
FT /note="R -> W (in Ref. 1; CAA75494)"
FT /evidence="ECO:0000305"
FT CONFLICT 428..429
FT /note="KR -> IL (in Ref. 2; AAC79433)"
FT /evidence="ECO:0000305"
FT CONFLICT 517
FT /note="K -> M (in Ref. 2; AAC79433)"
FT /evidence="ECO:0000305"
FT CONFLICT 560
FT /note="T -> I (in Ref. 1; CAA75494)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 854 AA; 94477 MW; E440CBE8AB9394F4 CRC64;
MMAYSDTTMM SDDIDWLRSH RGVCKVDLYN PEGQQDQDRK VICFVDVSTL NVEDKDYKDA
ASSSSEGNLN LGSLEEKEII VIKDTEKKDQ SKTEGSVCLF KQAPSDPVSV LNWLLSDLQK
YALGFQHALS PSTSTCKHKV GDTEGEYHRA SSENCYSVYA DQVNIDYLMN RPQNLRLEMT
AAKNTNNNQS PSAPPAKPPS TQRAVISPDG ECSIDDLSFY VNRLSSLVIQ MAHKEIKEKL
EGKSKCLHHS ICPSPGNKER ISPRTPASKI ASEMAYEAVE LTAAEMRGTG EESREGGQKS
FLYSELSNKS KSGDKQMSQR ESKEFADSIS KGLMVYANQV ASDMMVSLMK TLKVHSSGKP
IPASVVLKRV LLRHTKEIVS DLIDSCMKNL HNITGVLMTD SDFVSAVKRN LFNQWKQNAT
DIMEAMLKRL VSALIGEEKE TKSQSLSYAS LKAGSHDPKC RNQSLEFSTM KAEMKERDKG
KMKSDPCKSL TSAEKVGEHI LKEGLTIWNQ KQGNSCKVAT KACSNKDEKG EKINASTDSL
AKDLIVSALK LIQYHLTQQT KGKDTCEEDC PGSTMGYMAQ STQYEKCGGG QSAKALSVKQ
LESHRAPGPS TCQKENQHLD SQKMDMSNIV LMLIQKLLNE NPFKCEDPCE GENKCSEPRA
SKAASMSNRS DKAEEQCQEH QELDCTSGMK QANGQFIDKL VESVMKLCLI MAKYSNDGAA
LAELEEQAAS ANKPNFRGTR CIHSGAMPQN YQDSLGHEVI VNNQCSTNSL QKQLQAVLQW
IAASQFNVPM LYFMGDKDGQ LEKLPQVSAK AAEKGYSVGG LLQEVMKFAK ERQPDEAVGK
VARKQLLDWL LANL
