1.F.3.1.6 A-Protein kinase ancoring protein of 2817 aas with 0 TMSs. Similarity of the sequence of this protein with other members of this family occur only at the C-terminus of the protein. A-kinase anchoring proteins (AKAPs) are key orchestrators of cAMP
signaling that act by recruiting protein kinase A (PKA) in proximity of
its substrates and regulators to specific subcellular compartments.
Modulation of AKAPs function offers the opportunity to achieve
compartment-restricted modulation of the cAMP/PKA axis, paving the way
to new targeted treatments. For instance, blocking the AKAP activity of
phosphoinositide 3-kinase γ (PI3Kγ) improves lung function by inducing
cAMP-mediated bronchorelaxation, ion transport, and antiinflammatory
responses. Here, we report the generation of a nonnatural peptide,
D-retroinverso (DRI)-Pep #20, optimized to disrupt the AKAP function of
PI3Kγ. DRI-Pep #20 mimicked the native interaction between the
N-terminal domain of PI3Kγ and PKA, demonstrating nanomolar affinity for
PKA, high resistance to protease degradation and high permeability to
the pulmonary mucus barrier (Della Sala et al. 2024).
|
Accession Number: | AAL11723.1 |
Protein Name: | AAL11723.1 A-kinase anchoring protein [Homo sapiens] |
Length: | 2818 |
Molecular Weight: | |
Species: | Homo sapiens [9606] |
Number of TMSs: | 1 |
Substrate |
protein |
---|
1: MKLNPQQAPL YGDCVVTVLL AEEDKAEDDV VFYLVFLGST LRHCTSTRKV SSDTLETIAP
61: GHDCCETVKV QLCASKEGLP VFVVAEEDFH FVQDEAYDAA QFLATSAGNQ QALNFTRFLD
121: QSGPPSGDVN SLDKKLVLAF RHLKLPTEWN VLGTDQSLHD AGPRETLMHF AVRLGLLRLT
181: WFLLQKPGGR GALSIHNQEG ATPVSLALER GYHKLHQLLT EENAGEPDSW SSLSYEIPYG
241: DCSVRHHREL DIYTLTSESD SHHEHPFPGD GCTGPIFKLM NIQQQLMKTN LKQMDSLMPL
301: MMTAQDPSSA PETDGQFLPC APEPTDPQRL SSSEETESTQ CCPGSPVAQT ESPCDLSSIV
361: EEENTDRSCR KKNKGVERKG EEVEPAPIVD SGTVSDQDSC LQSLPDCGVK GTEGLSSCGN
421: RNEETGTKSS GMPTDQESLS SGDAVLQRDL VMEPGTAQYS SGGELGGIST TNVSTPDTAG
481: EMEHGLMNPD ATVWKNVLQG GESTKERFEN SNIGTAGASD VHVTSKPVDK ISVPNCAPAA
541: SSLDGNKPAE SSLAFSNEET STEKTAETET SRSREESADA PVDQNSVVIP AAAKDKISDG
601: LEPYTLLAAG IGEAMSPSAL ALLVLEEDVM PHQNSETNSS HAQSQKGKSS PICSTTGDDK
661: LCADSACQQN TVTSSGDLVA KLCDNIVSES ESTTARQPSS QDPPDASHCE DPQAHTVTSD
721: PVRDTQERAD FCPFKVVDNK GQRKDVKLDK PLTNMLEVVS HPHPVVPKME KELVPDQAVI
781: SDSTFSLANS PGSESVTKDD ALSFVPSQKE KGTATPELHT ATDYRDGPDG NSNEPDTRPL
841: EDRAVGLSTS STAAELQHGM GNTSLTGLGG EHEGPAPPAI PEALNIKGNT DSSLQSMGKA
901: TLALDSVLTE EGKLLVVSES SAAQEQDKDK AVTCSSIKEN ALSSGTLQEE QRTPPPGQDT
961: QQFHEKSISA DCAKDKALQL SNSPGASSAF LKAETEHNKE VAPQVSLLTQ GGAAQSLVPP
1021: GASLATESRQ EALGAEHNSS ALLPCLLPDG SDGSDALNCS QPSPLDVGVK NTQSQGKTSA
1081: CEVSGDVTVD VTGVNALQGM AEPRRENISH NTQDILIPNV LLSQEKNAVL GLPVALQDKA
1141: VTDPQGVGTP EMIPLDWEKG KLEGADHSCT MGDAEEAQID DEAHPVLLQP VAKELPTDME
1201: LSAHDDGAPA GVREVMRAPP SGRERSTPSL PCMVSAQDAP LPKGADLIEE AASRIVDAVI
1261: EQVKAAGALL TEGEACHMSL SSPELGPLTK GLESAFTEKV STFPPGESLP MGSTPEEATG
1321: SLAGCFAGRE EPEKIILPVQ GPEPAAEMPD VKAEDEVDFR ASSISEEVAV GSIAATLKMK
1381: QGPMTQAINR ENWCTIEPCP DAASLLASKQ SPECENFLDV GLGRECTSKQ GVLKRESGSD
1441: SDLFHSPSDD MDSIIFPKPE EEHLACDITG SSSSTDDTAS LDRHSSHGSD VSLSQILKPN
1501: RSRDRQSLDG FYSHGMGAEG RESESEPADP GDVEEEEMDS ITEVPANCSV LRSSMRSLSP
1561: FRRHSWGPGK NAASDAEMNH RSMSWCPSGV QYSAGLSADF NYRSFSLEGL TGGAGVGNKP
1621: SSSLEVSSAN AEELRHPFSG EERVDSLVSL SEEDLESDQR EHRMFDQQIC HRSKQQGFNY
1681: CTSAISSPLT KSISLMTISH PGLDNSRPFH STFHNTSANL TESITEENYN FLPHSPSKKD
1741: SEWKSGTKVS RTFSYIKNKM SSSKKSKEKE KEKDKIKEKE KDSKDKEKDK KTVNGHTFSS
1801: IPVVGPISCS QCMKPFTNKD AYTCANCSAF VHKGCRESLA SCAKVKMKQP KGSLQAHDTS
1861: SLPTVIMRNK PSQPKERPRS AVLLVDETAT TPIFANRRSQ QSVSLSKSVS IQNITGVGND
1921: ENMSNTWKFL SHSTDSLNKI SKVNESTESL TDEGVGTDMN EGQLLGDFEI ESKQLEAESW
1981: SRIIDSKFLK QQKKDVVKRQ EVIYELMQTE FHHVRTLKIM SGVYSQGMMA DLLFEQQMVE
2041: KLFPCLDELI SIHSQFFQRI LERKKESLVD KSEKNFLIKR IGDVLVNQFS GENAERLKKT
2101: YGKFCGQHNQ SVNYFKDLYA KDKRFQAFVK KKMSSSVVRR LGIPECILLV TQRITKYPVL
2161: FQRILQCTKD NEVEQEDLAQ SLSLVKDVIG AVDSKVASYE KKVRLNEIYT KTDSKSIMRM
2221: KSGQMFAKED LKRKKLVRDG SVFLKNAAGR LKEVQAVLLT DILVFLQEKD QKYIFASLDQ
2281: KSTVISLKKL IVREVAHEEK GLFLISMGMT DPEMVEVHAS SKEERNSWIQ IIQDTINTLN
2341: RDEDEGIPSE NEEEKKMLDT RARELKEQLH QKDQKILLLL EEKEMIFRDM AECSTPLPED
2401: CSPTHSPRVL FRSNTEEALK GGPLMKSAIN EVEILQGLVS GNLGGTLGPT VSSPIEQDVV
2461: SPVSLPRRAE TFGGFDSHQM NASKGGEKEE GDDGQDLRRT ESDSGLKKGG NANLVFMLKR
2521: NSEQVVQSVV HLYELLSALQ GVVLQQDSYI EDQKLVLSER ALTRSLSRPS SLIEQEKQRS
2581: LEKQRQDLAN LQKQQAQYLE EKRRREREWE ARERELRERE ALLAQREEEV QQGQQDLEKE
2641: REELQQKKGT YQYDLERLRA AQKQLEREQE QLRREAERLS QRQTERDLCQ VSHPHTKLMR
2701: IPSFFPSPEE PPSPSAPSIA KSGSLDSELS VSPKRNSISR THKDKGPFHI LSSTSQTNKG
2761: PEGQSQAPAS TSASTRLFGL TKPKEKKEKK KKNKTSRSQP GDGPASEVSA EGEEIFC