AKT1_XENLA
ID AKT1_XENLA Reviewed; 481 AA.
AC Q98TY9;
DT 21-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=RAC-alpha serine/threonine-protein kinase;
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:P31750};
DE AltName: Full=Protein kinase Akt-1;
DE Short=xAkt;
DE AltName: Full=Protein kinase B, alpha;
DE Short=PKB alpha;
DE AltName: Full=RAC-PK-alpha;
GN Name=akt1 {ECO:0000250|UniProtKB:P31750};
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAG59601.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ACTIVITY REGULATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Oocyte {ECO:0000269|PubMed:12374568};
RX PubMed=12374568; DOI=10.1042/bj20021243;
RA Andersen C.B., Sakaue H., Nedachi T., Kovacina K.S., Clayberger C.,
RA Conti M., Roth R.A.;
RT "Protein kinase B/Akt is essential for the insulin- but not progesterone-
RT stimulated resumption of meiosis in Xenopus oocytes.";
RL Biochem. J. 369:227-238(2003).
CC -!- FUNCTION: AKT1 is one of several closely related serine/threonine-
CC protein kinases known as the AKT kinase, and which regulate many
CC processes including metabolism, proliferation, cell survival, growth
CC and angiogenesis. This is mediated through serine and/or threonine
CC phosphorylation of a range of downstream substrates. Over 100 substrate
CC candidates have been reported so far, but for most of them, no isoform
CC specificity has been reported. Signals downstream of
CC phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of
CC various growth factors such as platelet-derived growth factor (PDGF),
CC epidermal growth factor (EGF), insulin and insulin-like growth factor I
CC (IGF-I). Plays a role as a key modulator of the AKT-mTOR signaling
CC pathway controlling the tempo of the process of newborn neurons
CC integration during adult neurogenesis, including correct neuron
CC positioning, dendritic development and synapse formation. Plays a role
CC in glucose transport by mediating insulin-induced translocation of the
CC GLUT4 glucose transporter to the cell surface. Mediates the
CC antiapoptotic effects of IGF-I. Mediates insulin-stimulated protein
CC synthesis, partly by playing a role in both insulin-induced
CC phosphorylation of 4E-BP1 and in insulin-induced activation of p70 S6
CC kinase. Promotes glycogen synthesis by mediating the insulin-induced
CC activation of glycogen synthase (By similarity). Required for insulin-
CC stimulated meiotic reinitiation during oocyte maturation.
CC {ECO:0000250|UniProtKB:P31749, ECO:0000250|UniProtKB:P31750,
CC ECO:0000269|PubMed:12374568}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:P31750};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:P31750};
CC -!- ACTIVITY REGULATION: Activated in response to insulin. Three specific
CC sites, one in the kinase domain (Thr-309) and the two other ones in the
CC C-terminal regulatory region (Ser-474 and Tyr-475), need to be
CC phosphorylated for its full activation. {ECO:0000269|PubMed:12374568}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P31750}. Nucleus
CC {ECO:0000250|UniProtKB:P31750}. Note=Nucleus after activation by
CC integrin-linked protein kinase 1 (ILK1).
CC {ECO:0000250|UniProtKB:P31750}.
CC -!- TISSUE SPECIFICITY: Expressed in the oocyte.
CC {ECO:0000269|PubMed:12374568}.
CC -!- DOMAIN: Binding of the PH domain to phosphatidylinositol 3,4,5-
CC trisphosphate (PI(3,4,5)P3) following phosphatidylinositol 3-kinase
CC alpha (PIK3CA) activity results in its targeting to the plasma
CC membrane. {ECO:0000250|UniProtKB:P31749}.
CC -!- PTM: Cleavage by caspase-3/CASP3 (By similarity). Cleaved at the
CC caspase-3 consensus site Asp-463 during apoptosis, resulting in down-
CC regulation of the AKT signaling pathway and decreased cell survival (By
CC similarity). {ECO:0000250|UniProtKB:P31749,
CC ECO:0000250|UniProtKB:P31750}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. RAC subfamily. {ECO:0000305}.
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DR EMBL; AF317656; AAG59601.1; -; mRNA.
DR RefSeq; NP_001083878.1; NM_001090409.2.
DR AlphaFoldDB; Q98TY9; -.
DR SMR; Q98TY9; -.
DR BioGRID; 100495; 1.
DR GeneID; 399170; -.
DR KEGG; xla:399170; -.
DR CTD; 399170; -.
DR Xenbase; XB-GENE-484957; akt1.S.
DR Proteomes; UP000186698; Chromosome 8S.
DR Bgee; 399170; Expressed in blastula and 19 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0099104; F:potassium channel activator activity; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0008643; P:carbohydrate transport; IEA:UniProtKB-KW.
DR GO; GO:0006006; P:glucose metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0005978; P:glycogen biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0008286; P:insulin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; ISS:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:UniProtKB.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0046889; P:positive regulation of lipid biosynthetic process; ISS:UniProtKB.
DR GO; GO:2000010; P:positive regulation of protein localization to cell surface; ISS:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; IEA:InterPro.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0010975; P:regulation of neuron projection development; ISS:UniProtKB.
DR GO; GO:0070848; P:response to growth factor; ISS:UniProtKB.
DR CDD; cd01241; PH_PKB; 1.
DR CDD; cd05594; STKc_PKB_alpha; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR034676; Akt1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR039026; PH_PKB.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR039027; RAC_alpha.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR24351:SF200; PTHR24351:SF200; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Carbohydrate metabolism; Cytoplasm; Glucose metabolism;
KW Glycogen biosynthesis; Glycoprotein; Kinase; Neurogenesis;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Sugar transport; Transferase; Transport.
FT CHAIN 1..481
FT /note="RAC-alpha serine/threonine-protein kinase"
FT /evidence="ECO:0000305"
FT /id="PRO_0000223507"
FT DOMAIN 5..108
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 151..409
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 410..481
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 120..141
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 275
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 157..165
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 180
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 463
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000250|UniProtKB:P31750"
FT MOD_RES 309
FT /note="Phosphothreonine; by PDPK1"
FT /evidence="ECO:0000250|UniProtKB:P31749"
FT MOD_RES 474
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P31749"
FT MOD_RES 475
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P31749"
FT CARBOHYD 127
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000250|UniProtKB:P31749"
FT CARBOHYD 130
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000250|UniProtKB:P31749"
FT CARBOHYD 306
FT /note="O-linked (GlcNAc) threonine"
FT /evidence="ECO:0000250|UniProtKB:P31749"
FT CARBOHYD 313
FT /note="O-linked (GlcNAc) threonine"
FT /evidence="ECO:0000250|UniProtKB:P31749"
FT CARBOHYD 474
FT /note="O-linked (GlcNAc) serine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P31750"
SQ SEQUENCE 481 AA; 56042 MW; FF56CFB9A6454303 CRC64;
MNEVAIVKEG WLHKRGEYIK TWRPRYFLLK SDGTFIGYKE RPQDVDQLET PLNNFSVAKC
QLMKTERPKP NTFIIRCLQW TTVIERTFHV DSPEEREEWI QVIQHVADNL KKQEEEMMEV
RSGDSPSDNS GAEEMEVSHS KPKHKVTMNE FEYLKLLGKG TFGKVILVKE KATGRYYAMK
ILKKEVIVAK DEVAHTLTEN RVLQNSRHPF LTALKYSFQT HDRLCFVMEY ANGGELFFHL
SRERIFSEDR ARFYGAEIVS ALDYLHSEKN VVYRDLKLEN LMLDKDGHIK ITDFGLCKEG
IKDGATMKTF CGTPEYLAPE VLEDNDYGRA VDWWGLGVVM YEMMCGRLPF YNQDHEKLFE
LILMEEIRFP RTLLPEAKSL LSGLLKKDPK QRLGGGPDDA KEIMQHKFFA GIVWQDVYEK
KLVPPFKPQV TSETDTRYFD EEFTAQMITI TPPDQDDNFE FVDNERRPHF PQFSYSASGN
A
