ID   GSKIP_MACFA             Reviewed;         139 AA.
AC   Q4R812;
DT   20-JAN-2009, integrated into UniProtKB/Swiss-Prot.
DT   19-JUL-2005, sequence version 1.
DT   03-AUG-2022, entry version 54.
DE   RecName: Full=GSK3-beta interaction protein {ECO:0000250|UniProtKB:Q9P0R6};
DE            Short=GSKIP {ECO:0000250|UniProtKB:Q9P0R6};
GN   Name=GSKIP {ECO:0000250|UniProtKB:Q9P0R6}; ORFNames=QtsA-13786;
OS   Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC   Cercopithecidae; Cercopithecinae; Macaca.
OX   NCBI_TaxID=9541;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Testis;
RG   International consortium for macaque cDNA sequencing and analysis;
RT   "DNA sequences of macaque genes expressed in brain or testis and its
RT   evolutionary implications.";
RL   Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: A-kinase anchoring protein for GSK3B and PKA that regulates
CC       or facilitates their kinase activity towards their targets. The ternary
CC       complex enhances Wnt-induced signaling by facilitating the GSK3B- and
CC       PKA-induced phosphorylation of beta-catenin leading to beta-catenin
CC       degradation and stabilization respectively. Upon cAMP activation, the
CC       ternary complex contributes to neuroprotection against oxidative
CC       stress-induced apoptosis by facilitating the PKA-induced
CC       phosphorylation of DML1 and PKA-induced inactivation of GSK3B. During
CC       neurite outgrowth promotes neuron proliferation; while increases beta-
CC       catenin-induced transcriptional activity through GSK3B kinase activity
CC       inhibition, reduces N-cadherin level to promote cell cycle progression
CC       (By similarity). May play a role in cleft palate formation and is
CC       required for postnatal life through modulation of the activity of GSK3B
CC       during development (By similarity). {ECO:0000250|UniProtKB:Q8BGR8,
CC       ECO:0000250|UniProtKB:Q9P0R6}.
CC   -!- SUBUNIT: Forms a complex composed of PRKAR2A or PRKAR2B, GSK3B and
CC       GSKIP through GSKIP interaction; facilitates PKA-induced
CC       phosphorylation of GSK3B leading to GSK3B inactivation; recruits DNM1L
CC       through GSK3B for PKA-mediated phosphorylation of DNM1L; promotes beta-
CC       catenin degradation through GSK3B-induced phosphorylation of beta-
CC       catenin; stabilizes beta-catenin and enhances Wnt-induced signaling
CC       through PKA-induced phosphorylation of beta-catenin. Interacts with
CC       GSK3B; induces GSK3B-mediated phosphorylation of GSKIP and inhibits
CC       GSK3B kinase activity. {ECO:0000250|UniProtKB:Q9P0R6}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9P0R6}. Nucleus
CC       {ECO:0000250|UniProtKB:Q9P0R6}.
CC   -!- PTM: Phosphorylated by GSK3B. {ECO:0000250|UniProtKB:Q9P0R6}.
CC   -!- SIMILARITY: Belongs to the GSKIP family. {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; AB168649; BAE00760.1; -; mRNA.
DR   RefSeq; NP_001270488.1; NM_001283559.1.
DR   AlphaFoldDB; Q4R812; -.
DR   BMRB; Q4R812; -.
DR   SMR; Q4R812; -.
DR   STRING; 9541.XP_005562217.1; -.
DR   GeneID; 101865539; -.
DR   CTD; 51527; -.
DR   eggNOG; KOG3965; Eukaryota.
DR   Proteomes; UP000233100; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0004860; F:protein kinase inhibitor activity; ISS:UniProtKB.
DR   GO; GO:0008631; P:intrinsic apoptotic signaling pathway in response to oxidative stress; ISS:UniProtKB.
DR   GO; GO:0006469; P:negative regulation of protein kinase activity; ISS:UniProtKB.
DR   GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISS:UniProtKB.
DR   GO; GO:0030111; P:regulation of Wnt signaling pathway; ISS:UniProtKB.
DR   Gene3D; 3.30.2280.10; -; 1.
DR   InterPro; IPR037395; GSKIP.
DR   InterPro; IPR007967; GSKIP_dom.
DR   InterPro; IPR023231; GSKIP_dom_sf.
DR   PANTHER; PTHR12490; PTHR12490; 1.
DR   Pfam; PF05303; DUF727; 1.
DR   SUPFAM; SSF103107; SSF103107; 1.
PE   2: Evidence at transcript level;
KW   Cytoplasm; Nucleus; Reference proteome.
FT   CHAIN           1..139
FT                   /note="GSK3-beta interaction protein"
FT                   /id="PRO_0000359875"
FT   REGION          1..22
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          41..45
FT                   /note="Required for PRKAR2A interaction; contributes to a
FT                   protective effect against H(2)O(2)-induced apoptosis"
FT                   /evidence="ECO:0000250|UniProtKB:Q9P0R6"
FT   REGION          115..139
FT                   /note="Interaction with GSK3B and acts as GSK3B inhibitor"
FT                   /evidence="ECO:0000250|UniProtKB:Q9P0R6"
FT   SITE            130
FT                   /note="Required for GSK3B interaction; contributes to a
FT                   protective effect against H(2)O(2)-induced apoptosis"
FT                   /evidence="ECO:0000250|UniProtKB:Q9P0R6"
SQ   SEQUENCE   139 AA;  15692 MW;  A4050C290458B316 CRC64;
     METDCNPMEL SSMSGFEEGS ELNGFEGTDM KDMRLEAEAV VNDVLFAVNN MFVSKSLRCA
     DDVAYINVET KERNRYCLEL TEAGLKVVGY DFDQVDDHLQ TPYHETVYSL LDTLSPAYRE
     AFGNALLQRL EALKRDGQS