GSKIP_RAT
ID GSKIP_RAT Reviewed; 139 AA.
AC Q5PPI3;
DT 20-JAN-2009, integrated into UniProtKB/Swiss-Prot.
DT 04-JAN-2005, sequence version 1.
DT 25-MAY-2022, entry version 89.
DE RecName: Full=GSK3B-interacting protein {ECO:0000250|UniProtKB:Q9P0R6};
DE Short=GSKIP {ECO:0000250|UniProtKB:Q9P0R6};
GN Name=Gskip {ECO:0000312|RGD:1308470};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [2]
RP INTERACTION WITH PRKAR2A.
RX PubMed=20007971; DOI=10.1074/jbc.m109.047944;
RA Hundsrucker C., Skroblin P., Christian F., Zenn H.M., Popara V., Joshi M.,
RA Eichhorst J., Wiesner B., Herberg F.W., Reif B., Rosenthal W.,
RA Klussmann E.;
RT "Glycogen synthase kinase 3beta interaction protein functions as an A-
RT kinase anchoring protein.";
RL J. Biol. Chem. 285:5507-5521(2010).
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 (PubMed:20007971).
CC Interacts with GSK3B; induces GSK3B-mediated phosphorylation of GSKIP
CC and inhibits GSK3B kinase activity (By similarity).
CC {ECO:0000250|UniProtKB:Q9P0R6, ECO:0000269|PubMed:20007971}.
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}.
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DR EMBL; BC087681; AAH87681.1; -; mRNA.
DR RefSeq; NP_001014220.2; NM_001014198.2.
DR RefSeq; XP_006240589.1; XM_006240527.3.
DR AlphaFoldDB; Q5PPI3; -.
DR SMR; Q5PPI3; -.
DR STRING; 10116.ENSRNOP00000006307; -.
DR PaxDb; Q5PPI3; -.
DR GeneID; 362778; -.
DR KEGG; rno:362778; -.
DR UCSC; RGD:1308470; rat.
DR CTD; 51527; -.
DR RGD; 1308470; Gskip.
DR eggNOG; KOG3965; Eukaryota.
DR HOGENOM; CLU_143747_0_0_1; -.
DR InParanoid; Q5PPI3; -.
DR OrthoDB; 1508955at2759; -.
DR PhylomeDB; Q5PPI3; -.
DR PRO; PR:Q5PPI3; -.
DR Proteomes; UP000002494; Unplaced.
DR Genevisible; Q5PPI3; RN.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0019207; F:kinase regulator activity; IBA:GO_Central.
DR GO; GO:0051018; F:protein kinase A binding; ISO:RGD.
DR GO; GO:0034237; F:protein kinase A regulatory subunit binding; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
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 1: Evidence at protein level;
KW Cytoplasm; Nucleus; Reference proteome.
FT CHAIN 1..139
FT /note="GSK3B-interacting protein"
FT /id="PRO_0000359876"
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; 15557 MW; 3E09486313D001B0 CRC64;
METDCNPVDL SSMSGFEEGS ELNGFEGTDM KDMQLEAEAV VNDVLFAVNN MFVSKSLPCA
DDVAYINVET KERNRYCLEL TEAGLRVVGY AFDQVEDHLQ TPYHETVYSL LDTLSPAYRE
AFGNALLQRL EALKRDGQS
