SIN1_MOUSE
ID SIN1_MOUSE Reviewed; 522 AA.
AC Q8BKH7; A2AN72; A2AN74; A2AR13; A2AR16; Q80UY4; Q8BMV5; Q8R2N9;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Target of rapamycin complex 2 subunit MAPKAP1;
DE Short=TORC2 subunit MAPKAP1;
DE AltName: Full=Mitogen-activated protein kinase 2-associated protein 1;
DE AltName: Full=Stress-activated map kinase-interacting protein 1;
DE Short=SAPK-interacting protein 1;
GN Name=Mapkap1; Synonyms=Mip1, Sin1;
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=Embryo, Eye, and Placenta;
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 GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J, and FVB/N;
RC TISSUE=Brain, Mammary tumor, and Olfactory epithelium;
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 [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16962653; DOI=10.1016/j.cell.2006.08.033;
RA Jacinto E., Facchinetti V., Liu D., Soto N., Wei S., Jung S.Y., Huang Q.,
RA Qin J., Su B.;
RT "SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt
RT phosphorylation and substrate specificity.";
RL Cell 127:125-137(2006).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=17054722; DOI=10.1111/j.1365-2443.2006.01016.x;
RA Makino C., Sano Y., Shinagawa T., Millar J.B., Ishii S.;
RT "Sin1 binds to both ATF-2 and p38 and enhances ATF-2-dependent
RT transcription in an SAPK signaling pathway.";
RL Genes Cells 11:1239-1251(2006).
RN [6]
RP INTERACTION WITH SGK1.
RX PubMed=21757730; DOI=10.1074/jbc.m111.257592;
RA Lu M., Wang J., Ives H.E., Pearce D.;
RT "mSIN1 protein mediates SGK1 protein interaction with mTORC2 protein
RT complex and is required for selective activation of the epithelial sodium
RT channel.";
RL J. Biol. Chem. 286:30647-30654(2011).
CC -!- FUNCTION: Subunit of mTORC2, which regulates cell growth and survival
CC in response to hormonal signals. mTORC2 is activated by growth factors,
CC but, in contrast to mTORC1, seems to be nutrient-insensitive. mTORC2
CC seems to function upstream of Rho GTPases to regulate the actin
CC cytoskeleton, probably by activating one or more Rho-type guanine
CC nucleotide exchange factors. mTORC2 promotes the serum-induced
CC formation of stress-fibers or F-actin. mTORC2 plays a critical role in
CC AKT1 'Ser-473' phosphorylation, which may facilitate the
CC phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1
CC which is a prerequisite for full activation. mTORC2 regulates the
CC phosphorylation of SGK1 at 'Ser-422'. mTORC2 also modulates the
CC phosphorylation of PRKCA on 'Ser-657'. Within mTORC2, MAPKAP1 is
CC required for complex formation and mTORC2 kinase activity. MAPKAP1
CC inhibits MAP3K2 by preventing its dimerization and autophosphorylation.
CC Inhibits HRAS and KRAS signaling. Enhances osmotic stress-induced
CC phosphorylation of ATF2 and ATF2-mediated transcription. Isoform 1 is
CC involved in ciliogenesis, regulates cilia length through its
CC interaction with CCDC28B independently of mTORC2 complex.
CC {ECO:0000269|PubMed:16962653}.
CC -!- SUBUNIT: All isoforms except isoform 4 can be incorporated into the
CC mammalian target of rapamycin complex 2 (mTORC2) which contains MTOR,
CC MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR. Contrary to mTORC1, mTORC2
CC does not bind to and is not sensitive to FKBP12-rapamycin. Interacts
CC with ATF2, MAP3K2 and MAPK8. Interacts with GTP-bound HRAS and KRAS.
CC Interacts with IFNAR2 and SGK1. Isoform 2 interacts with NBN. Isoform 1
CC interacts with CCDC28B. {ECO:0000250|UniProtKB:Q9BPZ7,
CC ECO:0000269|PubMed:21757730}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Peripheral membrane
CC protein {ECO:0000250}. Cytoplasmic vesicle {ECO:0000250}. Nucleus
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8BKH7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BKH7-2; Sequence=VSP_033209;
CC Name=3;
CC IsoId=Q8BKH7-3; Sequence=VSP_033208;
CC -!- TISSUE SPECIFICITY: Uniquitously expresseed, with highest levels in
CC testis, kidney and liver. Present in renal tubule cells (at protein
CC level). {ECO:0000269|PubMed:17054722}.
CC -!- DISRUPTION PHENOTYPE: Death during early embryonic stages.
CC {ECO:0000269|PubMed:16962653}.
CC -!- SIMILARITY: Belongs to the SIN1 family. {ECO:0000305}.
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DR EMBL; AK027932; BAC25671.1; -; mRNA.
DR EMBL; AK052045; BAC34838.1; -; mRNA.
DR EMBL; AK132263; BAE21066.1; -; mRNA.
DR EMBL; AL808102; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL845262; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC027377; AAH27377.1; -; mRNA.
DR EMBL; BC031579; AAH31579.1; -; mRNA.
DR EMBL; BC043296; AAH43296.1; -; mRNA.
DR EMBL; BC090644; AAH90644.1; -; mRNA.
DR EMBL; BC096618; AAH96618.1; -; mRNA.
DR CCDS; CCDS15948.1; -. [Q8BKH7-1]
DR CCDS; CCDS71035.1; -. [Q8BKH7-3]
DR CCDS; CCDS89477.1; -. [Q8BKH7-2]
DR RefSeq; NP_001277554.1; NM_001290625.1. [Q8BKH7-1]
DR RefSeq; NP_001277555.1; NM_001290626.1. [Q8BKH7-3]
DR RefSeq; NP_796319.1; NM_177345.4. [Q8BKH7-1]
DR RefSeq; XP_006498038.1; XM_006497975.2. [Q8BKH7-1]
DR RefSeq; XP_006498041.1; XM_006497978.3. [Q8BKH7-2]
DR RefSeq; XP_006498045.1; XM_006497982.2.
DR RefSeq; XP_006498046.1; XM_006497983.2. [Q8BKH7-3]
DR RefSeq; XP_011237384.1; XM_011239082.2.
DR RefSeq; XP_011237385.1; XM_011239083.2. [Q8BKH7-1]
DR RefSeq; XP_011237386.1; XM_011239084.2. [Q8BKH7-1]
DR RefSeq; XP_011237387.1; XM_011239085.2.
DR RefSeq; XP_017172932.1; XM_017317443.1.
DR AlphaFoldDB; Q8BKH7; -.
DR SMR; Q8BKH7; -.
DR BioGRID; 230681; 3.
DR ComplexPortal; CPX-4472; mTORC2 complex.
DR DIP; DIP-57240N; -.
DR IntAct; Q8BKH7; 7.
DR MINT; Q8BKH7; -.
DR STRING; 10090.ENSMUSP00000116494; -.
DR iPTMnet; Q8BKH7; -.
DR PhosphoSitePlus; Q8BKH7; -.
DR SwissPalm; Q8BKH7; -.
DR EPD; Q8BKH7; -.
DR jPOST; Q8BKH7; -.
DR MaxQB; Q8BKH7; -.
DR PaxDb; Q8BKH7; -.
DR PeptideAtlas; Q8BKH7; -.
DR PRIDE; Q8BKH7; -.
DR ProteomicsDB; 261365; -. [Q8BKH7-1]
DR ProteomicsDB; 261366; -. [Q8BKH7-2]
DR ProteomicsDB; 261367; -. [Q8BKH7-3]
DR Antibodypedia; 30572; 326 antibodies from 39 providers.
DR DNASU; 227743; -.
DR Ensembl; ENSMUST00000113123; ENSMUSP00000108748; ENSMUSG00000038696. [Q8BKH7-3]
DR Ensembl; ENSMUST00000113124; ENSMUSP00000108749; ENSMUSG00000038696. [Q8BKH7-2]
DR Ensembl; ENSMUST00000113126; ENSMUSP00000108751; ENSMUSG00000038696. [Q8BKH7-1]
DR Ensembl; ENSMUST00000147337; ENSMUSP00000116494; ENSMUSG00000038696. [Q8BKH7-1]
DR GeneID; 227743; -.
DR KEGG; mmu:227743; -.
DR UCSC; uc008jil.2; mouse. [Q8BKH7-1]
DR CTD; 79109; -.
DR MGI; MGI:2444554; Mapkap1.
DR VEuPathDB; HostDB:ENSMUSG00000038696; -.
DR eggNOG; KOG3739; Eukaryota.
DR GeneTree; ENSGT00390000000642; -.
DR HOGENOM; CLU_514767_0_0_1; -.
DR InParanoid; Q8BKH7; -.
DR OMA; NAKFWPQ; -.
DR OrthoDB; 1492466at2759; -.
DR PhylomeDB; Q8BKH7; -.
DR TreeFam; TF315174; -.
DR Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
DR Reactome; R-MMU-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-MMU-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-MMU-6804757; Regulation of TP53 Degradation.
DR BioGRID-ORCS; 227743; 5 hits in 73 CRISPR screens.
DR ChiTaRS; Mapkap1; mouse.
DR PRO; PR:Q8BKH7; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q8BKH7; protein.
DR Bgee; ENSMUSG00000038696; Expressed in animal zygote and 254 other tissues.
DR ExpressionAtlas; Q8BKH7; baseline and differential.
DR Genevisible; Q8BKH7; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0031932; C:TORC2 complex; IDA:UniProtKB.
DR GO; GO:0070300; F:phosphatidic acid binding; ISO:MGI.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; ISO:MGI.
DR GO; GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; ISO:MGI.
DR GO; GO:0080025; F:phosphatidylinositol-3,5-bisphosphate binding; ISO:MGI.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISS:ParkinsonsUK-UCL.
DR GO; GO:0031267; F:small GTPase binding; ISO:MGI.
DR GO; GO:0031669; P:cellular response to nutrient levels; IC:ComplexPortal.
DR GO; GO:0007010; P:cytoskeleton organization; IC:ComplexPortal.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IC:ComplexPortal.
DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; ISO:MGI.
DR GO; GO:0016310; P:phosphorylation; ISO:MGI.
DR GO; GO:0030307; P:positive regulation of cell growth; IC:ComplexPortal.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IMP:UniProtKB.
DR GO; GO:1900407; P:regulation of cellular response to oxidative stress; IMP:UniProtKB.
DR GO; GO:0038203; P:TORC2 signaling; IBA:GO_Central.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR031567; CRIM_dom.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR008828; Sin1/Avo1.
DR InterPro; IPR032679; Sin1_N.
DR InterPro; IPR031313; Sin1_PH_dom.
DR PANTHER; PTHR13335; PTHR13335; 1.
DR Pfam; PF16978; CRIM; 1.
DR Pfam; PF05422; SIN1; 1.
DR Pfam; PF16979; SIN1_PH; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cell membrane; Cytoplasmic vesicle;
KW Membrane; Nucleus; Phosphoprotein; Reference proteome; Stress response.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9BPZ7"
FT CHAIN 2..522
FT /note="Target of rapamycin complex 2 subunit MAPKAP1"
FT /id="PRO_0000328033"
FT REGION 2..267
FT /note="Interaction with NBN"
FT /evidence="ECO:0000250"
FT REGION 2..184
FT /note="Interaction with MAP3K2"
FT /evidence="ECO:0000250"
FT REGION 38..59
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 468..522
FT /note="Interaction with ATF2"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q9BPZ7"
FT MOD_RES 186
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BPZ7"
FT MOD_RES 510
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BPZ7"
FT VAR_SEQ 1..192
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_033208"
FT VAR_SEQ 321..356
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_033209"
FT CONFLICT 516
FT /note="E -> K (in Ref. 3; AAH43296)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 522 AA; 59009 MW; 994C669D04065926 CRC64;
MAFLDNPTII LAHIRQSHVT SDDTGMCEMV LIDHDVDLEK THPPSVPGDS GSEVQGSSGE
TQGYIYAQSV DITSSWDFGI RRRSNTAQRL ERLRKERQNQ IKCKNIQWKE RNSKQSAQEL
KSLFEKKSLK EKPPSSGKQS ILSVRLEQCP LQLNNPFNEY SKFDGKGHVG TTATKKIDVY
LPLHSSQDRL LPMTVVTMAS ARVQDLIGLI CWQYTSEGRE PKLNDNVSAY CLHIAEDDGE
VDTDFPPLDS NEPIHKFGFS TLALVEKYSS PGLTSKESLF VRINAAHGFS LIQVDNTKVT
MKEILLKAVK RRKGSQKISG PQYRLEKQSE PNIAVDLEST LESQNAWEFC LVRENSSRAD
GVFEEDSQID IATVQDMLSS HHYKSFKVSM IHRLRFTTDV QLGISGDKVE IDPVTNQKAS
TKFWIKQKPI SIDCDLLCAC DLAEEKSPSH AVFKLTYLSS HDYKHLYFES DAATVSEIVL
KVNYILESRA STARADYLAQ KQRKLNRRTS FSFQKEKKSG QQ
