Full text data of MAPKAP1
MAPKAP1
(MIP1, SIN1)
[Confidence: low (only semi-automatic identification from reviews)]
Target of rapamycin complex 2 subunit MAPKAP1; TORC2 subunit MAPKAP1 (Mitogen-activated protein kinase 2-associated protein 1; Stress-activated map kinase-interacting protein 1; SAPK-interacting protein 1; mSIN1)
Target of rapamycin complex 2 subunit MAPKAP1; TORC2 subunit MAPKAP1 (Mitogen-activated protein kinase 2-associated protein 1; Stress-activated map kinase-interacting protein 1; SAPK-interacting protein 1; mSIN1)
UniProt
Q9BPZ7
ID SIN1_HUMAN Reviewed; 522 AA.
AC Q9BPZ7; A8K1Z5; B1AMA4; B7Z309; Q00426; Q5JSV5; Q5JSV6; Q5JSV9;
read moreAC Q658R0; Q699U1; Q699U2; Q699U3; Q699U4; Q6GVJ0; Q6GVJ1; Q6GVJ2;
DT 14-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT 14-AUG-2001, sequence version 2.
DT 22-JAN-2014, entry version 108.
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;
DE Short=mSIN1;
GN Name=MAPKAP1; Synonyms=MIP1, SIN1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 5).
RX PubMed=15363842; DOI=10.1016/j.gene.2004.07.001;
RA Schroder W., Cloonan N., Bushell G., Sculley T.;
RT "Alternative polyadenylation and splicing of mRNAs transcribed from
RT the human Sin1 gene.";
RL Gene 339:17-23(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 6), TISSUE SPECIFICITY,
RP FUNCTION, AND INTERACTION WITH MAP3K2.
RX PubMed=15988011; DOI=10.1128/MCB.25.14.5955-5964.2005;
RA Cheng J., Zhang D., Kim K., Zhao Y., Zhao Y., Su B.;
RT "Mip1, an MEKK2-interacting protein, controls MEKK2 dimerization and
RT activation.";
RL Mol. Cell. Biol. 25:5955-5964(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4).
RC TISSUE=Corpus callosum, and Substantia nigra;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Stomach;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Lung;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 2-15 AND 257-267, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RA Bienvenut W.V., Waridel P., Quadroni M.;
RL Submitted (MAR-2009) to UniProtKB.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 76-502 (ISOFORM 1).
RC TISSUE=Glial cell;
RX PubMed=1849280; DOI=10.1073/pnas.88.7.2913;
RA Colicelli J., Nicolette C., Birchmeier C., Rodgers L., Riggs M.,
RA Wigler M.;
RT "Expression of three mammalian cDNAs that interfere with RAS function
RT in Saccharomyces cerevisiae.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:2913-2917(1991).
RN [10]
RP IDENTIFICATION IN THE TORC2 COMPLEX, FUNCTION, AND MASS SPECTROMETRY.
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.,
RA Huang Q., 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 [11]
RP IDENTIFICATION IN THE TORC2 COMPLEX.
RX PubMed=16919458; DOI=10.1016/j.cub.2006.08.001;
RA Frias M.A., Thoreen C.C., Jaffe J.D., Schroder W., Sculley T.,
RA Carr S.A., Sabatini D.M.;
RT "mSin1 is necessary for Akt/PKB phosphorylation, and its isoforms
RT define three distinct mTORC2s.";
RL Curr. Biol. 16:1865-1870(2006).
RN [12]
RP INTERACTION WITH ATF2 AND MAPK8, FUNCTION, AND SUBCELLULAR LOCATION.
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 [13]
RP FUNCTION.
RX PubMed=17043309; DOI=10.1101/gad.1461206;
RA Yang Q., Inoki K., Ikenoue T., Guan K.-L.;
RT "Identification of Sin1 as an essential TORC2 component required for
RT complex formation and kinase activity.";
RL Genes Dev. 20:2820-2832(2006).
RN [14]
RP INTERACTION WITH HRAS AND KRAS, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17303383; DOI=10.1016/j.cellsig.2007.01.013;
RA Schroder W.A., Buck M., Cloonan N., Hancock J.F., Suhrbier A.,
RA Sculley T., Bushell G.;
RT "Human Sin1 contains Ras-binding and pleckstrin homology domains and
RT suppresses Ras signalling.";
RL Cell. Signal. 19:1279-1289(2007).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-510, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [16]
RP INTERACTION WITH NBN.
RX PubMed=23762398; DOI=10.1371/journal.pone.0065586;
RA Wang J.Q., Chen J.H., Chen Y.C., Chen M.Y., Hsieh C.Y., Teng S.C.,
RA Wu K.J.;
RT "Interaction between NBS1 and the mTOR/Rictor/SIN1 complex through
RT specific domains.";
RL PLoS ONE 8:E65586-E65586(2013).
RN [17]
RP FUNCTION IN CILIOGENESIS, AND INTERACTION WITH CCDC28B.
RX PubMed=23727834; DOI=10.1093/hmg/ddt253;
RA Cardenas-Rodriguez M., Irigoin F., Osborn D.P., Gascue C.,
RA Katsanis N., Beales P.L., Badano J.L.;
RT "The Bardet-Biedl syndrome-related protein CCDC28B modulates mTORC2
RT function and interacts with SIN1 to control cilia length independently
RT of the mTOR complex.";
RL Hum. Mol. Genet. 22:4031-4042(2013).
CC -!- FUNCTION: Subunit of mTORC2, which regulates cell growth and
CC survival in response to hormonal signals. mTORC2 is activated by
CC growth factors, but, in contrast to mTORC1, seems to be nutrient-
CC insensitive. mTORC2 seems to function upstream of Rho GTPases to
CC regulate the actin cytoskeleton, probably by activating one or
CC more Rho-type guanine nucleotide exchange factors. mTORC2 promotes
CC the serum-induced formation of stress-fibers or F-actin. mTORC2
CC plays a critical role in AKT1 'Ser-473' phosphorylation, which may
CC facilitate the phosphorylation of the activation loop of AKT1 on
CC 'Thr-308' by PDK1 which is a prerequisite for full activation.
CC mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2
CC also modulates the phosphorylation of PRKCA on 'Ser-657'. Within
CC mTORC2, MAPKAP1 is required for complex formation and mTORC2
CC kinase activity. MAPKAP1 inhibits MAP3K2 by preventing its
CC dimerization and autophosphorylation. Inhibits HRAS and KRAS
CC signaling. Enhances osmotic stress-induced phosphorylation of ATF2
CC and ATF2-mediated transcription. Involved in ciliogenesis,
CC regulates cilia length through its interaction with CCDC28B
CC independently of mTORC2 complex.
CC -!- SUBUNIT: All isoforms except isoform 4 can be incorporated into
CC the mammalian target of rapamycin complex 2 (mTORC2) which
CC contains MTOR, MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR. Contrary
CC to mTORC1, mTORC2 does not bind to and is not sensitive to FKBP12-
CC rapamycin. Interacts with ATF2, MAP3K2 and MAPK8. Interacts with
CC GTP-bound HRAS and KRAS. Interacts with IFNAR2 and SGK1. Isoform 2
CC interacts with NBN. Isoform 1 interacts with CCDC28B.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein.
CC Cytoplasmic vesicle. Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1; Synonyms=beta, gamma;
CC IsoId=Q9BPZ7-1; Sequence=Displayed;
CC Name=2; Synonyms=alpha, beta;
CC IsoId=Q9BPZ7-2; Sequence=VSP_006098;
CC Name=3;
CC IsoId=Q9BPZ7-3; Sequence=VSP_033204;
CC Name=4;
CC IsoId=Q9BPZ7-4; Sequence=VSP_033202;
CC Note=Not involved in a TORC2 complex;
CC Name=5; Synonyms=alpha;
CC IsoId=Q9BPZ7-5; Sequence=VSP_033203, VSP_033207;
CC Name=6; Synonyms=gamma;
CC IsoId=Q9BPZ7-6; Sequence=VSP_033205, VSP_033206;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with highest levels in
CC heart and skeletal muscle.
CC -!- SIMILARITY: Belongs to the SIN1 family.
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DR EMBL; AY524429; AAS90839.1; -; mRNA.
DR EMBL; AY524430; AAS90840.1; -; mRNA.
DR EMBL; AY524431; AAS90841.1; -; mRNA.
DR EMBL; AY524432; AAS90842.1; -; mRNA.
DR EMBL; AY633624; AAT46478.1; -; mRNA.
DR EMBL; AY633625; AAT46479.1; -; mRNA.
DR EMBL; AY633626; AAT46480.1; -; mRNA.
DR EMBL; AK290060; BAF82749.1; -; mRNA.
DR EMBL; AK295364; BAH12045.1; -; mRNA.
DR EMBL; AK316149; BAH14520.1; -; mRNA.
DR EMBL; AL833042; CAH56311.1; -; mRNA.
DR EMBL; AL162584; CAI39500.1; -; Genomic_DNA.
DR EMBL; AL359632; CAI39500.1; JOINED; Genomic_DNA.
DR EMBL; AL162584; CAI39506.1; -; Genomic_DNA.
DR EMBL; AL359632; CAI39506.1; JOINED; Genomic_DNA.
DR EMBL; AL162584; CAI39507.1; -; Genomic_DNA.
DR EMBL; AL359632; CAI39507.1; JOINED; Genomic_DNA.
DR EMBL; AL359632; CAI39888.1; -; Genomic_DNA.
DR EMBL; AL162584; CAI39888.1; JOINED; Genomic_DNA.
DR EMBL; AL359632; CAI39891.1; -; Genomic_DNA.
DR EMBL; AL162584; CAI39891.1; JOINED; Genomic_DNA.
DR EMBL; AL359632; CAI39892.1; -; Genomic_DNA.
DR EMBL; AL162584; CAI39892.1; JOINED; Genomic_DNA.
DR EMBL; CH471090; EAW87630.1; -; Genomic_DNA.
DR EMBL; CH471090; EAW87631.1; -; Genomic_DNA.
DR EMBL; CH471090; EAW87632.1; -; Genomic_DNA.
DR EMBL; BC003044; AAH03044.1; -; mRNA.
DR EMBL; BC002326; AAH02326.1; -; mRNA.
DR EMBL; M37191; AAA36551.1; -; mRNA.
DR PIR; C38637; C38637.
DR RefSeq; NP_001006618.1; NM_001006617.1.
DR RefSeq; NP_001006619.1; NM_001006618.1.
DR RefSeq; NP_001006620.1; NM_001006619.1.
DR RefSeq; NP_001006621.1; NM_001006620.1.
DR RefSeq; NP_001006622.1; NM_001006621.1.
DR RefSeq; NP_077022.1; NM_024117.3.
DR RefSeq; XP_005252261.1; XM_005252204.1.
DR UniGene; Hs.495138; -.
DR PDB; 3VOQ; X-ray; 2.00 A; A/B=372-493.
DR PDBsum; 3VOQ; -.
DR ProteinModelPortal; Q9BPZ7; -.
DR SMR; Q9BPZ7; 371-490.
DR IntAct; Q9BPZ7; 17.
DR MINT; MINT-1454116; -.
DR PhosphoSite; Q9BPZ7; -.
DR DMDM; 15214282; -.
DR PaxDb; Q9BPZ7; -.
DR PRIDE; Q9BPZ7; -.
DR DNASU; 79109; -.
DR Ensembl; ENST00000265960; ENSP00000265960; ENSG00000119487.
DR Ensembl; ENST00000350766; ENSP00000265961; ENSG00000119487.
DR Ensembl; ENST00000373498; ENSP00000362597; ENSG00000119487.
DR Ensembl; ENST00000373503; ENSP00000362602; ENSG00000119487.
DR Ensembl; ENST00000373511; ENSP00000362610; ENSG00000119487.
DR Ensembl; ENST00000394060; ENSP00000377624; ENSG00000119487.
DR Ensembl; ENST00000394063; ENSP00000377627; ENSG00000119487.
DR GeneID; 79109; -.
DR KEGG; hsa:79109; -.
DR UCSC; uc004bpv.3; human.
DR CTD; 79109; -.
DR GeneCards; GC09M128199; -.
DR HGNC; HGNC:18752; MAPKAP1.
DR HPA; HPA029091; -.
DR HPA; HPA029092; -.
DR MIM; 610558; gene.
DR neXtProt; NX_Q9BPZ7; -.
DR PharmGKB; PA38674; -.
DR eggNOG; NOG303753; -.
DR HOVERGEN; HBG023148; -.
DR InParanoid; Q9BPZ7; -.
DR OMA; LCACDLV; -.
DR OrthoDB; EOG7GXPBF; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_6900; Immune System.
DR GeneWiki; MAPKAP1; -.
DR GenomeRNAi; 79109; -.
DR NextBio; 67979; -.
DR PRO; PR:Q9BPZ7; -.
DR ArrayExpress; Q9BPZ7; -.
DR Bgee; Q9BPZ7; -.
DR Genevestigator; Q9BPZ7; -.
DR GO; GO:0016023; C:cytoplasmic membrane-bounded vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0070300; F:phosphatidic acid binding; IDA:UniProtKB.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:UniProtKB.
DR GO; GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; IDA:UniProtKB.
DR GO; GO:0080025; F:phosphatidylinositol-3,5-bisphosphate binding; IDA:UniProtKB.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:UniProtKB.
DR GO; GO:0017016; F:Ras GTPase binding; IDA:UniProtKB.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; IMP:UniProtKB.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
DR GO; GO:0031295; P:T cell costimulation; TAS:Reactome.
DR InterPro; IPR008828; SIN1.
DR PANTHER; PTHR13335; PTHR13335; 1.
DR Pfam; PF05422; SIN1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell membrane;
KW Complete proteome; Cytoplasmic vesicle; Direct protein sequencing;
KW Membrane; Nucleus; Phosphoprotein; Reference proteome;
KW Stress response.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 522 Target of rapamycin complex 2 subunit
FT MAPKAP1.
FT /FTId=PRO_0000218768.
FT REGION 2 267 Interaction with NBN.
FT REGION 2 184 Interaction with MAP3K2.
FT REGION 468 522 Interaction with ATF2.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 510 510 Phosphoserine.
FT VAR_SEQ 1 192 Missing (in isoform 4).
FT /FTId=VSP_033202.
FT VAR_SEQ 321 438 Missing (in isoform 5).
FT /FTId=VSP_033203.
FT VAR_SEQ 321 356 Missing (in isoform 2).
FT /FTId=VSP_006098.
FT VAR_SEQ 357 403 Missing (in isoform 3).
FT /FTId=VSP_033204.
FT VAR_SEQ 357 372 SRADGVFEEDSQIDIA -> TLAASLHARFVRCKLA (in
FT isoform 6).
FT /FTId=VSP_033205.
FT VAR_SEQ 373 522 Missing (in isoform 6).
FT /FTId=VSP_033206.
FT VAR_SEQ 442 522 Missing (in isoform 5).
FT /FTId=VSP_033207.
FT CONFLICT 76 86 WDFGIRRRSNT -> ADPARSVEAAS (in Ref. 9;
FT AAA36551).
FT CONFLICT 178 178 D -> N (in Ref. 2; AAT46480/AAT46478/
FT AAT46479).
FT CONFLICT 305 305 L -> F (in Ref. 3; BAF82749).
FT CONFLICT 478 478 I -> T (in Ref. 4; CAH56311).
FT CONFLICT 491 491 S -> N (in Ref. 2; AAT46478/AAT46479).
FT CONFLICT 502 502 Q -> K (in Ref. 9; AAA36551).
FT HELIX 372 378
FT TURN 379 381
FT STRAND 384 392
FT TURN 393 395
FT STRAND 396 404
FT STRAND 406 413
FT STRAND 430 433
FT HELIX 434 436
FT STRAND 437 445
FT STRAND 447 449
FT STRAND 451 459
FT STRAND 462 470
FT HELIX 472 487
SQ SEQUENCE 522 AA; 59123 MW; E3B808C6E58F7C48 CRC64;
MAFLDNPTII LAHIRQSHVT SDDTGMCEMV LIDHDVDLEK IHPPSMPGDS GSEIQGSNGE
TQGYVYAQSV DITSSWDFGI RRRSNTAQRL ERLRKERQNQ IKCKNIQWKE RNSKQSAQEL
KSLFEKKSLK EKPPISGKQS ILSVRLEQCP LQLNNPFNEY SKFDGKGHVG TTATKKIDVY
LPLHSSQDRL LPMTVVTMAS ARVQDLIGLI CWQYTSEGRE PKLNDNVSAY CLHIAEDDGE
VDTDFPPLDS NEPIHKFGFS TLALVEKYSS PGLTSKESLF VRINAAHGFS LIQVDNTKVT
MKEILLKAVK RRKGSQKVSG PQYRLEKQSE PNVAVDLDST LESQSAWEFC LVRENSSRAD
GVFEEDSQID IATVQDMLSS HHYKSFKVSM IHRLRFTTDV QLGISGDKVE IDPVTNQKAS
TKFWIKQKPI SIDSDLLCAC DLAEEKSPSH AIFKLTYLSN HDYKHLYFES DAATVNEIVL
KVNYILESRA STARADYFAQ KQRKLNRRTS FSFQKEKKSG QQ
//
ID SIN1_HUMAN Reviewed; 522 AA.
AC Q9BPZ7; A8K1Z5; B1AMA4; B7Z309; Q00426; Q5JSV5; Q5JSV6; Q5JSV9;
read moreAC Q658R0; Q699U1; Q699U2; Q699U3; Q699U4; Q6GVJ0; Q6GVJ1; Q6GVJ2;
DT 14-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT 14-AUG-2001, sequence version 2.
DT 22-JAN-2014, entry version 108.
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;
DE Short=mSIN1;
GN Name=MAPKAP1; Synonyms=MIP1, SIN1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 5).
RX PubMed=15363842; DOI=10.1016/j.gene.2004.07.001;
RA Schroder W., Cloonan N., Bushell G., Sculley T.;
RT "Alternative polyadenylation and splicing of mRNAs transcribed from
RT the human Sin1 gene.";
RL Gene 339:17-23(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 6), TISSUE SPECIFICITY,
RP FUNCTION, AND INTERACTION WITH MAP3K2.
RX PubMed=15988011; DOI=10.1128/MCB.25.14.5955-5964.2005;
RA Cheng J., Zhang D., Kim K., Zhao Y., Zhao Y., Su B.;
RT "Mip1, an MEKK2-interacting protein, controls MEKK2 dimerization and
RT activation.";
RL Mol. Cell. Biol. 25:5955-5964(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4).
RC TISSUE=Corpus callosum, and Substantia nigra;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Stomach;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Lung;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 2-15 AND 257-267, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RA Bienvenut W.V., Waridel P., Quadroni M.;
RL Submitted (MAR-2009) to UniProtKB.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 76-502 (ISOFORM 1).
RC TISSUE=Glial cell;
RX PubMed=1849280; DOI=10.1073/pnas.88.7.2913;
RA Colicelli J., Nicolette C., Birchmeier C., Rodgers L., Riggs M.,
RA Wigler M.;
RT "Expression of three mammalian cDNAs that interfere with RAS function
RT in Saccharomyces cerevisiae.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:2913-2917(1991).
RN [10]
RP IDENTIFICATION IN THE TORC2 COMPLEX, FUNCTION, AND MASS SPECTROMETRY.
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.,
RA Huang Q., 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 [11]
RP IDENTIFICATION IN THE TORC2 COMPLEX.
RX PubMed=16919458; DOI=10.1016/j.cub.2006.08.001;
RA Frias M.A., Thoreen C.C., Jaffe J.D., Schroder W., Sculley T.,
RA Carr S.A., Sabatini D.M.;
RT "mSin1 is necessary for Akt/PKB phosphorylation, and its isoforms
RT define three distinct mTORC2s.";
RL Curr. Biol. 16:1865-1870(2006).
RN [12]
RP INTERACTION WITH ATF2 AND MAPK8, FUNCTION, AND SUBCELLULAR LOCATION.
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 [13]
RP FUNCTION.
RX PubMed=17043309; DOI=10.1101/gad.1461206;
RA Yang Q., Inoki K., Ikenoue T., Guan K.-L.;
RT "Identification of Sin1 as an essential TORC2 component required for
RT complex formation and kinase activity.";
RL Genes Dev. 20:2820-2832(2006).
RN [14]
RP INTERACTION WITH HRAS AND KRAS, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17303383; DOI=10.1016/j.cellsig.2007.01.013;
RA Schroder W.A., Buck M., Cloonan N., Hancock J.F., Suhrbier A.,
RA Sculley T., Bushell G.;
RT "Human Sin1 contains Ras-binding and pleckstrin homology domains and
RT suppresses Ras signalling.";
RL Cell. Signal. 19:1279-1289(2007).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-510, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [16]
RP INTERACTION WITH NBN.
RX PubMed=23762398; DOI=10.1371/journal.pone.0065586;
RA Wang J.Q., Chen J.H., Chen Y.C., Chen M.Y., Hsieh C.Y., Teng S.C.,
RA Wu K.J.;
RT "Interaction between NBS1 and the mTOR/Rictor/SIN1 complex through
RT specific domains.";
RL PLoS ONE 8:E65586-E65586(2013).
RN [17]
RP FUNCTION IN CILIOGENESIS, AND INTERACTION WITH CCDC28B.
RX PubMed=23727834; DOI=10.1093/hmg/ddt253;
RA Cardenas-Rodriguez M., Irigoin F., Osborn D.P., Gascue C.,
RA Katsanis N., Beales P.L., Badano J.L.;
RT "The Bardet-Biedl syndrome-related protein CCDC28B modulates mTORC2
RT function and interacts with SIN1 to control cilia length independently
RT of the mTOR complex.";
RL Hum. Mol. Genet. 22:4031-4042(2013).
CC -!- FUNCTION: Subunit of mTORC2, which regulates cell growth and
CC survival in response to hormonal signals. mTORC2 is activated by
CC growth factors, but, in contrast to mTORC1, seems to be nutrient-
CC insensitive. mTORC2 seems to function upstream of Rho GTPases to
CC regulate the actin cytoskeleton, probably by activating one or
CC more Rho-type guanine nucleotide exchange factors. mTORC2 promotes
CC the serum-induced formation of stress-fibers or F-actin. mTORC2
CC plays a critical role in AKT1 'Ser-473' phosphorylation, which may
CC facilitate the phosphorylation of the activation loop of AKT1 on
CC 'Thr-308' by PDK1 which is a prerequisite for full activation.
CC mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2
CC also modulates the phosphorylation of PRKCA on 'Ser-657'. Within
CC mTORC2, MAPKAP1 is required for complex formation and mTORC2
CC kinase activity. MAPKAP1 inhibits MAP3K2 by preventing its
CC dimerization and autophosphorylation. Inhibits HRAS and KRAS
CC signaling. Enhances osmotic stress-induced phosphorylation of ATF2
CC and ATF2-mediated transcription. Involved in ciliogenesis,
CC regulates cilia length through its interaction with CCDC28B
CC independently of mTORC2 complex.
CC -!- SUBUNIT: All isoforms except isoform 4 can be incorporated into
CC the mammalian target of rapamycin complex 2 (mTORC2) which
CC contains MTOR, MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR. Contrary
CC to mTORC1, mTORC2 does not bind to and is not sensitive to FKBP12-
CC rapamycin. Interacts with ATF2, MAP3K2 and MAPK8. Interacts with
CC GTP-bound HRAS and KRAS. Interacts with IFNAR2 and SGK1. Isoform 2
CC interacts with NBN. Isoform 1 interacts with CCDC28B.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein.
CC Cytoplasmic vesicle. Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1; Synonyms=beta, gamma;
CC IsoId=Q9BPZ7-1; Sequence=Displayed;
CC Name=2; Synonyms=alpha, beta;
CC IsoId=Q9BPZ7-2; Sequence=VSP_006098;
CC Name=3;
CC IsoId=Q9BPZ7-3; Sequence=VSP_033204;
CC Name=4;
CC IsoId=Q9BPZ7-4; Sequence=VSP_033202;
CC Note=Not involved in a TORC2 complex;
CC Name=5; Synonyms=alpha;
CC IsoId=Q9BPZ7-5; Sequence=VSP_033203, VSP_033207;
CC Name=6; Synonyms=gamma;
CC IsoId=Q9BPZ7-6; Sequence=VSP_033205, VSP_033206;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with highest levels in
CC heart and skeletal muscle.
CC -!- SIMILARITY: Belongs to the SIN1 family.
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DR EMBL; AY524429; AAS90839.1; -; mRNA.
DR EMBL; AY524430; AAS90840.1; -; mRNA.
DR EMBL; AY524431; AAS90841.1; -; mRNA.
DR EMBL; AY524432; AAS90842.1; -; mRNA.
DR EMBL; AY633624; AAT46478.1; -; mRNA.
DR EMBL; AY633625; AAT46479.1; -; mRNA.
DR EMBL; AY633626; AAT46480.1; -; mRNA.
DR EMBL; AK290060; BAF82749.1; -; mRNA.
DR EMBL; AK295364; BAH12045.1; -; mRNA.
DR EMBL; AK316149; BAH14520.1; -; mRNA.
DR EMBL; AL833042; CAH56311.1; -; mRNA.
DR EMBL; AL162584; CAI39500.1; -; Genomic_DNA.
DR EMBL; AL359632; CAI39500.1; JOINED; Genomic_DNA.
DR EMBL; AL162584; CAI39506.1; -; Genomic_DNA.
DR EMBL; AL359632; CAI39506.1; JOINED; Genomic_DNA.
DR EMBL; AL162584; CAI39507.1; -; Genomic_DNA.
DR EMBL; AL359632; CAI39507.1; JOINED; Genomic_DNA.
DR EMBL; AL359632; CAI39888.1; -; Genomic_DNA.
DR EMBL; AL162584; CAI39888.1; JOINED; Genomic_DNA.
DR EMBL; AL359632; CAI39891.1; -; Genomic_DNA.
DR EMBL; AL162584; CAI39891.1; JOINED; Genomic_DNA.
DR EMBL; AL359632; CAI39892.1; -; Genomic_DNA.
DR EMBL; AL162584; CAI39892.1; JOINED; Genomic_DNA.
DR EMBL; CH471090; EAW87630.1; -; Genomic_DNA.
DR EMBL; CH471090; EAW87631.1; -; Genomic_DNA.
DR EMBL; CH471090; EAW87632.1; -; Genomic_DNA.
DR EMBL; BC003044; AAH03044.1; -; mRNA.
DR EMBL; BC002326; AAH02326.1; -; mRNA.
DR EMBL; M37191; AAA36551.1; -; mRNA.
DR PIR; C38637; C38637.
DR RefSeq; NP_001006618.1; NM_001006617.1.
DR RefSeq; NP_001006619.1; NM_001006618.1.
DR RefSeq; NP_001006620.1; NM_001006619.1.
DR RefSeq; NP_001006621.1; NM_001006620.1.
DR RefSeq; NP_001006622.1; NM_001006621.1.
DR RefSeq; NP_077022.1; NM_024117.3.
DR RefSeq; XP_005252261.1; XM_005252204.1.
DR UniGene; Hs.495138; -.
DR PDB; 3VOQ; X-ray; 2.00 A; A/B=372-493.
DR PDBsum; 3VOQ; -.
DR ProteinModelPortal; Q9BPZ7; -.
DR SMR; Q9BPZ7; 371-490.
DR IntAct; Q9BPZ7; 17.
DR MINT; MINT-1454116; -.
DR PhosphoSite; Q9BPZ7; -.
DR DMDM; 15214282; -.
DR PaxDb; Q9BPZ7; -.
DR PRIDE; Q9BPZ7; -.
DR DNASU; 79109; -.
DR Ensembl; ENST00000265960; ENSP00000265960; ENSG00000119487.
DR Ensembl; ENST00000350766; ENSP00000265961; ENSG00000119487.
DR Ensembl; ENST00000373498; ENSP00000362597; ENSG00000119487.
DR Ensembl; ENST00000373503; ENSP00000362602; ENSG00000119487.
DR Ensembl; ENST00000373511; ENSP00000362610; ENSG00000119487.
DR Ensembl; ENST00000394060; ENSP00000377624; ENSG00000119487.
DR Ensembl; ENST00000394063; ENSP00000377627; ENSG00000119487.
DR GeneID; 79109; -.
DR KEGG; hsa:79109; -.
DR UCSC; uc004bpv.3; human.
DR CTD; 79109; -.
DR GeneCards; GC09M128199; -.
DR HGNC; HGNC:18752; MAPKAP1.
DR HPA; HPA029091; -.
DR HPA; HPA029092; -.
DR MIM; 610558; gene.
DR neXtProt; NX_Q9BPZ7; -.
DR PharmGKB; PA38674; -.
DR eggNOG; NOG303753; -.
DR HOVERGEN; HBG023148; -.
DR InParanoid; Q9BPZ7; -.
DR OMA; LCACDLV; -.
DR OrthoDB; EOG7GXPBF; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_6900; Immune System.
DR GeneWiki; MAPKAP1; -.
DR GenomeRNAi; 79109; -.
DR NextBio; 67979; -.
DR PRO; PR:Q9BPZ7; -.
DR ArrayExpress; Q9BPZ7; -.
DR Bgee; Q9BPZ7; -.
DR Genevestigator; Q9BPZ7; -.
DR GO; GO:0016023; C:cytoplasmic membrane-bounded vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0070300; F:phosphatidic acid binding; IDA:UniProtKB.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:UniProtKB.
DR GO; GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; IDA:UniProtKB.
DR GO; GO:0080025; F:phosphatidylinositol-3,5-bisphosphate binding; IDA:UniProtKB.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:UniProtKB.
DR GO; GO:0017016; F:Ras GTPase binding; IDA:UniProtKB.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; IMP:UniProtKB.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
DR GO; GO:0031295; P:T cell costimulation; TAS:Reactome.
DR InterPro; IPR008828; SIN1.
DR PANTHER; PTHR13335; PTHR13335; 1.
DR Pfam; PF05422; SIN1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell membrane;
KW Complete proteome; Cytoplasmic vesicle; Direct protein sequencing;
KW Membrane; Nucleus; Phosphoprotein; Reference proteome;
KW Stress response.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 522 Target of rapamycin complex 2 subunit
FT MAPKAP1.
FT /FTId=PRO_0000218768.
FT REGION 2 267 Interaction with NBN.
FT REGION 2 184 Interaction with MAP3K2.
FT REGION 468 522 Interaction with ATF2.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 510 510 Phosphoserine.
FT VAR_SEQ 1 192 Missing (in isoform 4).
FT /FTId=VSP_033202.
FT VAR_SEQ 321 438 Missing (in isoform 5).
FT /FTId=VSP_033203.
FT VAR_SEQ 321 356 Missing (in isoform 2).
FT /FTId=VSP_006098.
FT VAR_SEQ 357 403 Missing (in isoform 3).
FT /FTId=VSP_033204.
FT VAR_SEQ 357 372 SRADGVFEEDSQIDIA -> TLAASLHARFVRCKLA (in
FT isoform 6).
FT /FTId=VSP_033205.
FT VAR_SEQ 373 522 Missing (in isoform 6).
FT /FTId=VSP_033206.
FT VAR_SEQ 442 522 Missing (in isoform 5).
FT /FTId=VSP_033207.
FT CONFLICT 76 86 WDFGIRRRSNT -> ADPARSVEAAS (in Ref. 9;
FT AAA36551).
FT CONFLICT 178 178 D -> N (in Ref. 2; AAT46480/AAT46478/
FT AAT46479).
FT CONFLICT 305 305 L -> F (in Ref. 3; BAF82749).
FT CONFLICT 478 478 I -> T (in Ref. 4; CAH56311).
FT CONFLICT 491 491 S -> N (in Ref. 2; AAT46478/AAT46479).
FT CONFLICT 502 502 Q -> K (in Ref. 9; AAA36551).
FT HELIX 372 378
FT TURN 379 381
FT STRAND 384 392
FT TURN 393 395
FT STRAND 396 404
FT STRAND 406 413
FT STRAND 430 433
FT HELIX 434 436
FT STRAND 437 445
FT STRAND 447 449
FT STRAND 451 459
FT STRAND 462 470
FT HELIX 472 487
SQ SEQUENCE 522 AA; 59123 MW; E3B808C6E58F7C48 CRC64;
MAFLDNPTII LAHIRQSHVT SDDTGMCEMV LIDHDVDLEK IHPPSMPGDS GSEIQGSNGE
TQGYVYAQSV DITSSWDFGI RRRSNTAQRL ERLRKERQNQ IKCKNIQWKE RNSKQSAQEL
KSLFEKKSLK EKPPISGKQS ILSVRLEQCP LQLNNPFNEY SKFDGKGHVG TTATKKIDVY
LPLHSSQDRL LPMTVVTMAS ARVQDLIGLI CWQYTSEGRE PKLNDNVSAY CLHIAEDDGE
VDTDFPPLDS NEPIHKFGFS TLALVEKYSS PGLTSKESLF VRINAAHGFS LIQVDNTKVT
MKEILLKAVK RRKGSQKVSG PQYRLEKQSE PNVAVDLDST LESQSAWEFC LVRENSSRAD
GVFEEDSQID IATVQDMLSS HHYKSFKVSM IHRLRFTTDV QLGISGDKVE IDPVTNQKAS
TKFWIKQKPI SIDSDLLCAC DLAEEKSPSH AIFKLTYLSN HDYKHLYFES DAATVNEIVL
KVNYILESRA STARADYFAQ KQRKLNRRTS FSFQKEKKSG QQ
//
MIM
610558
*RECORD*
*FIELD* NO
610558
*FIELD* TI
*610558 MITOGEN-ACTIVATED PROTEIN KINASE-ASSOCIATED PROTEIN 1; MAPKAP1
;;SAPK-INTERACTING PROTEIN 1; SIN1;;
read moreMEKK2-INTERACTING PROTEIN 1; MIP1;;
JC310
*FIELD* TX
DESCRIPTION
SIN1, MTOR (FRAP1; 601231), RICTOR (609022), and LST8 (GBL; 612190) are
components of TORC2, a protein kinase complex involved in AKT (164730)
phosphorylation and cell signaling (Yang et al., 2006).
CLONING
By screening an expression library for cDNAs that suppressed the heat
shock-sensitive phenotype of yeast with an activated Ras2 gene (see
HRAS; 190020), Colicelli et al. (1991) obtained a partial cDNA encoding
MAPKAP1, which they called JC310.
By searching an EST database with the partial JC310 sequence, followed
by RT-PCR, Schroder et al. (2004) obtained a full-length cDNA encoding
MAPKAP1, which they called SIN1. The deduced 522-amino acid protein has
a nuclear localization signal, 2 bipartite nuclear localization signals,
a peroxisomal targeting signal, and a PEST motif for rapid protein
degradation. Comparison of SIN1 with homologs from various species
revealed a short, highly conserved region, designated Box1, located
within a larger conserved domain, designated CRIM (conserved region in
middle). Schroder et al. (2004) also identified several SIN1 splice
variants, including SIN1-alpha, which encodes a 323-amino acid
C-terminally truncated protein, and SIN1-beta and SIN1-gamma, which
encode 487- and 475-amino acid proteins, respectively, with internal
deletions. Two other variants, SIN1-delta and SIN1-epsilon, lack the
first coding exon and the first 2 coding exons of SIN1, respectively.
Northern blot analysis detected SIN1 transcripts of 3.8 and 2.6 kb in
all tissues examined, with highest levels in skeletal muscle and heart.
GENE FUNCTION
Yang et al. (2006) identified SIN1 as an essential component of TORC2,
but not TORC1. SIN1 specifically interacted with MTOR and RICTOR, but
not RAPTOR (607130), the defining component of the TORC1 complex.
Knockdown of SIN1 resulted in decreased RICTOR phosphorylation and
protein levels, as well as disruption of binding between RICTOR and
MTOR. RICTOR knockdown dramatically decreased SIN1 protein levels.
Knockdown of SIN1 in both Drosophila and human cells diminished AKT
phosphorylation, and SIN1-knockdown cells displayed less phosphorylation
of AKT substrates and more sensitivity to apoptosis.
Independently, Jacinto et al. (2006) identified SIN1 as an essential
TORC2 subunit in human cells. Phosphorylation of Akt at ser473 was lost
in Sin1 -/- mouse embryonic fibroblasts (MEFs), whereas phosphorylation
of thr308 was unaffected. Defective ser473 phosphorylation affected only
a subset of Akt targets in vivo, including Foxo1 (136533) and Foxo3a
(602681). Sin1 -/- MEFs were more sensitive to stress-induced apoptosis,
suggesting that phosphorylation of AKT at ser473 plays an important role
in cell survival.
GENE STRUCTURE
Schroder et al. (2004) determined that the MAPKAP1 gene contains 13
exons, the first of which is noncoding. The 5-prime region contains 2
short open reading frames of 9 and 5 codons, and the 3-prime region
contains 2 polyadenylation sites.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the MAPKAP1
gene to chromosome 9 (TMAP RH41772).
ANIMAL MODEL
Jacinto et al. (2006) found that Sin1 deletion was embryonic lethal in
mice due to early developmental problems.
*FIELD* RF
1. Colicelli, J.; Nicolette, C.; Birchmeier, C.; Rodgers, L.; Riggs,
M.; Wigler, M.: Expression of three mammalian cDNAs that interfere
with RAS function in Saccharomyces cerevisiae. Proc. Nat. Acad. Sci. 88:
2913-2917, 1991.
2. Jacinto, E.; Facchinetti, V.; Liu, D.; Soto, N.; Wei, S.; Jung,
S. Y.; Huang, Q.; Qin, J.; Su, B.: SIN1/MIP1 maintains rictor-mTOR
complex integrity and regulates Akt phosphorylation and substrate
specificity. Cell 127: 125-137, 2006.
3. Schroder, W.; Cloonan, N.; Bushell, G.; Sculley, T.: Alternative
polyadenylation and splicing of mRNAs transcribed from the human Sin1
gene. Gene 339: 17-23, 2004.
4. Yang, Q.; Inoki, K.; Ikenoue, T.; Guan, K.-L.: Identification
of Sin1 as an essential TORC2 component required for complex formation
and kinase activity. Genes Dev. 20: 2820-2832, 2006.
*FIELD* CN
Matthew B. Gross - updated: 5/7/2009
*FIELD* CD
Patricia A. Hartz: 11/9/2006
*FIELD* ED
wwang: 05/11/2009
mgross: 5/7/2009
mgross: 7/22/2008
mgross: 11/9/2006
*RECORD*
*FIELD* NO
610558
*FIELD* TI
*610558 MITOGEN-ACTIVATED PROTEIN KINASE-ASSOCIATED PROTEIN 1; MAPKAP1
;;SAPK-INTERACTING PROTEIN 1; SIN1;;
read moreMEKK2-INTERACTING PROTEIN 1; MIP1;;
JC310
*FIELD* TX
DESCRIPTION
SIN1, MTOR (FRAP1; 601231), RICTOR (609022), and LST8 (GBL; 612190) are
components of TORC2, a protein kinase complex involved in AKT (164730)
phosphorylation and cell signaling (Yang et al., 2006).
CLONING
By screening an expression library for cDNAs that suppressed the heat
shock-sensitive phenotype of yeast with an activated Ras2 gene (see
HRAS; 190020), Colicelli et al. (1991) obtained a partial cDNA encoding
MAPKAP1, which they called JC310.
By searching an EST database with the partial JC310 sequence, followed
by RT-PCR, Schroder et al. (2004) obtained a full-length cDNA encoding
MAPKAP1, which they called SIN1. The deduced 522-amino acid protein has
a nuclear localization signal, 2 bipartite nuclear localization signals,
a peroxisomal targeting signal, and a PEST motif for rapid protein
degradation. Comparison of SIN1 with homologs from various species
revealed a short, highly conserved region, designated Box1, located
within a larger conserved domain, designated CRIM (conserved region in
middle). Schroder et al. (2004) also identified several SIN1 splice
variants, including SIN1-alpha, which encodes a 323-amino acid
C-terminally truncated protein, and SIN1-beta and SIN1-gamma, which
encode 487- and 475-amino acid proteins, respectively, with internal
deletions. Two other variants, SIN1-delta and SIN1-epsilon, lack the
first coding exon and the first 2 coding exons of SIN1, respectively.
Northern blot analysis detected SIN1 transcripts of 3.8 and 2.6 kb in
all tissues examined, with highest levels in skeletal muscle and heart.
GENE FUNCTION
Yang et al. (2006) identified SIN1 as an essential component of TORC2,
but not TORC1. SIN1 specifically interacted with MTOR and RICTOR, but
not RAPTOR (607130), the defining component of the TORC1 complex.
Knockdown of SIN1 resulted in decreased RICTOR phosphorylation and
protein levels, as well as disruption of binding between RICTOR and
MTOR. RICTOR knockdown dramatically decreased SIN1 protein levels.
Knockdown of SIN1 in both Drosophila and human cells diminished AKT
phosphorylation, and SIN1-knockdown cells displayed less phosphorylation
of AKT substrates and more sensitivity to apoptosis.
Independently, Jacinto et al. (2006) identified SIN1 as an essential
TORC2 subunit in human cells. Phosphorylation of Akt at ser473 was lost
in Sin1 -/- mouse embryonic fibroblasts (MEFs), whereas phosphorylation
of thr308 was unaffected. Defective ser473 phosphorylation affected only
a subset of Akt targets in vivo, including Foxo1 (136533) and Foxo3a
(602681). Sin1 -/- MEFs were more sensitive to stress-induced apoptosis,
suggesting that phosphorylation of AKT at ser473 plays an important role
in cell survival.
GENE STRUCTURE
Schroder et al. (2004) determined that the MAPKAP1 gene contains 13
exons, the first of which is noncoding. The 5-prime region contains 2
short open reading frames of 9 and 5 codons, and the 3-prime region
contains 2 polyadenylation sites.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the MAPKAP1
gene to chromosome 9 (TMAP RH41772).
ANIMAL MODEL
Jacinto et al. (2006) found that Sin1 deletion was embryonic lethal in
mice due to early developmental problems.
*FIELD* RF
1. Colicelli, J.; Nicolette, C.; Birchmeier, C.; Rodgers, L.; Riggs,
M.; Wigler, M.: Expression of three mammalian cDNAs that interfere
with RAS function in Saccharomyces cerevisiae. Proc. Nat. Acad. Sci. 88:
2913-2917, 1991.
2. Jacinto, E.; Facchinetti, V.; Liu, D.; Soto, N.; Wei, S.; Jung,
S. Y.; Huang, Q.; Qin, J.; Su, B.: SIN1/MIP1 maintains rictor-mTOR
complex integrity and regulates Akt phosphorylation and substrate
specificity. Cell 127: 125-137, 2006.
3. Schroder, W.; Cloonan, N.; Bushell, G.; Sculley, T.: Alternative
polyadenylation and splicing of mRNAs transcribed from the human Sin1
gene. Gene 339: 17-23, 2004.
4. Yang, Q.; Inoki, K.; Ikenoue, T.; Guan, K.-L.: Identification
of Sin1 as an essential TORC2 component required for complex formation
and kinase activity. Genes Dev. 20: 2820-2832, 2006.
*FIELD* CN
Matthew B. Gross - updated: 5/7/2009
*FIELD* CD
Patricia A. Hartz: 11/9/2006
*FIELD* ED
wwang: 05/11/2009
mgross: 5/7/2009
mgross: 7/22/2008
mgross: 11/9/2006