GSKIP_MOUSE
ID GSKIP_MOUSE Reviewed; 139 AA.
AC Q8BGR8; Q8CDW3; Q8K2G9;
DT 09-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=GSK3B-interacting protein {ECO:0000250|UniProtKB:Q9P0R6};
DE Short=GSKIP {ECO:0000250|UniProtKB:Q9P0R6};
GN Name=Gskip {ECO:0000312|MGI:MGI:1914037};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Cerebellum, Head, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Mammary tumor;
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 [3]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=26582204; DOI=10.1074/jbc.m115.701177;
RA Deak V.A., Skroblin P., Dittmayer C., Knobeloch K.P., Bachmann S.,
RA Klussmann E.;
RT "The A-kinase Anchoring Protein GSKIP Regulates GSK3beta Activity and
RT Controls Palatal Shelf Fusion in Mice.";
RL J. Biol. Chem. 291:681-690(2016).
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 (PubMed:26582204). {ECO:0000250|UniProtKB:Q9P0R6,
CC ECO:0000269|PubMed:26582204}.
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8BGR8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BGR8-2; Sequence=VSP_008199;
CC -!- PTM: Phosphorylated by GSK3B. {ECO:0000250|UniProtKB:Q9P0R6}.
CC -!- DISRUPTION PHENOTYPE: Knockout Gskip mice die at birth. At 18.5 dpc,
CC embryos are still alive but rapidly die within 5 to 30 min after
CC casarean section. Embryos obtained at 18.5 dpc are cyanotic, suffer
CC from respiratory distress, and fail to initiate breathing properly.
CC {ECO:0000269|PubMed:26582204}.
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; AK029484; BAC26470.1; -; mRNA.
DR EMBL; AK042664; BAC31325.1; -; mRNA.
DR EMBL; AK079775; BAC37748.1; -; mRNA.
DR EMBL; BC031494; AAH31494.1; -; mRNA.
DR CCDS; CCDS49161.1; -. [Q8BGR8-2]
DR RefSeq; NP_848728.2; NM_178613.3. [Q8BGR8-2]
DR AlphaFoldDB; Q8BGR8; -.
DR SMR; Q8BGR8; -.
DR BioGRID; 211719; 9.
DR STRING; 10090.ENSMUSP00000057939; -.
DR MaxQB; Q8BGR8; -.
DR PaxDb; Q8BGR8; -.
DR PRIDE; Q8BGR8; -.
DR ProteomicsDB; 271055; -. [Q8BGR8-1]
DR ProteomicsDB; 271056; -. [Q8BGR8-2]
DR Antibodypedia; 27335; 86 antibodies from 18 providers.
DR DNASU; 66787; -.
DR Ensembl; ENSMUST00000051934; ENSMUSP00000057939; ENSMUSG00000044715. [Q8BGR8-2]
DR GeneID; 66787; -.
DR KEGG; mmu:66787; -.
DR CTD; 51527; -.
DR MGI; MGI:1914037; Gskip.
DR VEuPathDB; HostDB:ENSMUSG00000044715; -.
DR eggNOG; KOG3965; Eukaryota.
DR GeneTree; ENSGT00390000009517; -.
DR HOGENOM; CLU_143747_0_0_1; -.
DR InParanoid; Q8BGR8; -.
DR OMA; FAVTEMH; -.
DR TreeFam; TF313906; -.
DR BioGRID-ORCS; 66787; 5 hits in 71 CRISPR screens.
DR ChiTaRS; Gskip; mouse.
DR PRO; PR:Q8BGR8; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q8BGR8; protein.
DR Bgee; ENSMUSG00000044715; Expressed in placenta labyrinth and 219 other tissues.
DR ExpressionAtlas; Q8BGR8; baseline and differential.
DR Genevisible; Q8BGR8; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:BHF-UCL.
DR GO; GO:0019207; F:kinase regulator activity; IBA:GO_Central.
DR GO; GO:0051018; F:protein kinase A binding; ISO:MGI.
DR GO; GO:0034237; F:protein kinase A regulatory subunit binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
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 Alternative splicing; Cytoplasm; Nucleus; Reference proteome.
FT CHAIN 1..139
FT /note="GSK3B-interacting protein"
FT /id="PRO_0000220952"
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"
FT VAR_SEQ 1
FT /note="M -> MGARRM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_008199"
FT CONFLICT 6
FT /note="N -> S (in Ref. 1; BAC26470)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 139 AA; 15642 MW; 78082F4AC59F7ECE CRC64;
METDYNPVEL SSMSGFEEGS ELNGFEGADM KDMQLEAEAV VNDVLFAVNH MFVSKSMPCA
DDVAYINVET KERNRYCLEL TEAGLRVVGY AFDQVEDHLQ TPYHETVYSL LDTLSPAYRE
AFGNALLQRL EALKRDGQS
