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Q8BKH7

- SIN1_MOUSE

UniProt

Q8BKH7 - SIN1_MOUSE

Protein

Target of rapamycin complex 2 subunit MAPKAP1

Gene

Mapkap1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 95 (01 Oct 2014)
      Sequence version 1 (01 Mar 2003)
      Previous versions | rss
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    Functioni

    Subunit of mTORC2, which regulates cell growth and survival in response to hormonal signals. mTORC2 is activated by growth factors, but, in contrast to mTORC1, seems to be nutrient-insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin. mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657'. Within mTORC2, MAPKAP1 is required for complex formation and mTORC2 kinase activity. MAPKAP1 inhibits MAP3K2 by preventing its dimerization and autophosphorylation. Inhibits HRAS and KRAS signaling. Enhances osmotic stress-induced phosphorylation of ATF2 and ATF2-mediated transcription. Isoform 1 is involved in ciliogenesis, regulates cilia length through its interaction with CCDC28B independently of mTORC2 complex.1 Publication

    GO - Molecular functioni

    1. phosphatidic acid binding Source: Ensembl
    2. phosphatidylinositol-3,4,5-trisphosphate binding Source: Ensembl
    3. phosphatidylinositol-3,4-bisphosphate binding Source: Ensembl
    4. phosphatidylinositol-3,5-bisphosphate binding Source: Ensembl
    5. phosphatidylinositol-4,5-bisphosphate binding Source: Ensembl
    6. protein binding Source: UniProtKB

    GO - Biological processi

    1. negative regulation of Ras protein signal transduction Source: Ensembl
    2. response to stress Source: UniProtKB-KW

    Keywords - Biological processi

    Stress response

    Enzyme and pathway databases

    ReactomeiREACT_196588. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_226151. CD28 dependent PI3K/Akt signaling.
    REACT_226341. PIP3 activates AKT signaling.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Target of rapamycin complex 2 subunit MAPKAP1
    Short name:
    TORC2 subunit MAPKAP1
    Alternative name(s):
    Mitogen-activated protein kinase 2-associated protein 1
    Stress-activated map kinase-interacting protein 1
    Short name:
    SAPK-interacting protein 1
    Gene namesi
    Name:Mapkap1
    Synonyms:Mip1, Sin1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 2

    Organism-specific databases

    MGIiMGI:2444554. Mapkap1.

    Subcellular locationi

    Cell membrane By similarity; Peripheral membrane protein By similarity. Cytoplasmic vesicle By similarity. Nucleus By similarity

    GO - Cellular componenti

    1. cytoplasmic membrane-bounded vesicle Source: UniProtKB-SubCell
    2. Golgi apparatus Source: Ensembl
    3. nucleus Source: UniProtKB-SubCell
    4. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Cytoplasmic vesicle, Membrane, Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    Death during early embryonic stages.1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 522521Target of rapamycin complex 2 subunit MAPKAP1PRO_0000328033Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanineBy similarity
    Modified residuei510 – 5101PhosphoserineBy similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    PRIDEiQ8BKH7.

    PTM databases

    PhosphoSiteiQ8BKH7.

    Expressioni

    Tissue specificityi

    Uniquitously expresseed, with highest levels in testis, kidney and liver. Present in renal tubule cells (at protein level).1 Publication

    Gene expression databases

    ArrayExpressiQ8BKH7.
    BgeeiQ8BKH7.
    GenevestigatoriQ8BKH7.

    Interactioni

    Subunit structurei

    All isoforms except isoform 4 can be incorporated into the mammalian target of rapamycin complex 2 (mTORC2) which contains MTOR, MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR. Contrary to mTORC1, mTORC2 does not bind to and is not sensitive to FKBP12-rapamycin. Interacts with ATF2, MAP3K2 and MAPK8. Interacts with GTP-bound HRAS and KRAS. Interacts with IFNAR2 and SGK1. Isoform 2 interacts with NBN. Isoform 1 interacts with CCDC28B.1 Publication

    Protein-protein interaction databases

    DIPiDIP-57240N.
    IntActiQ8BKH7. 7 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8BKH7.
    SMRiQ8BKH7. Positions 371-490.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni2 – 267266Interaction with NBNBy similarityAdd
    BLAST
    Regioni2 – 184183Interaction with MAP3K2By similarityAdd
    BLAST
    Regioni468 – 52255Interaction with ATF2By similarityAdd
    BLAST

    Sequence similaritiesi

    Belongs to the SIN1 family.Curated

    Phylogenomic databases

    eggNOGiNOG303753.
    GeneTreeiENSGT00390000000642.
    HOVERGENiHBG023148.
    InParanoidiQ8BKH7.
    OMAiLCACDLV.
    PhylomeDBiQ8BKH7.
    TreeFamiTF315174.

    Family and domain databases

    InterProiIPR008828. SIN1.
    [Graphical view]
    PANTHERiPTHR13335. PTHR13335. 1 hit.
    PfamiPF05422. SIN1. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q8BKH7-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MAFLDNPTII LAHIRQSHVT SDDTGMCEMV LIDHDVDLEK THPPSVPGDS    50
    GSEVQGSSGE TQGYIYAQSV DITSSWDFGI RRRSNTAQRL ERLRKERQNQ 100
    IKCKNIQWKE RNSKQSAQEL KSLFEKKSLK EKPPSSGKQS ILSVRLEQCP 150
    LQLNNPFNEY SKFDGKGHVG TTATKKIDVY LPLHSSQDRL LPMTVVTMAS 200
    ARVQDLIGLI CWQYTSEGRE PKLNDNVSAY CLHIAEDDGE VDTDFPPLDS 250
    NEPIHKFGFS TLALVEKYSS PGLTSKESLF VRINAAHGFS LIQVDNTKVT 300
    MKEILLKAVK RRKGSQKISG PQYRLEKQSE PNIAVDLEST LESQNAWEFC 350
    LVRENSSRAD GVFEEDSQID IATVQDMLSS HHYKSFKVSM IHRLRFTTDV 400
    QLGISGDKVE IDPVTNQKAS TKFWIKQKPI SIDCDLLCAC DLAEEKSPSH 450
    AVFKLTYLSS HDYKHLYFES DAATVSEIVL KVNYILESRA STARADYLAQ 500
    KQRKLNRRTS FSFQKEKKSG QQ 522
    Length:522
    Mass (Da):59,009
    Last modified:March 1, 2003 - v1
    Checksum:i994C669D04065926
    GO
    Isoform 2 (identifier: Q8BKH7-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         321-356: Missing.

    Show »
    Length:486
    Mass (Da):54,802
    Checksum:iF42F6C1899858727
    GO
    Isoform 3 (identifier: Q8BKH7-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         2-192: Missing.

    Show »
    Length:331
    Mass (Da):37,434
    Checksum:iCB7495E7C17E147F
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti516 – 5161E → K in AAH43296. (PubMed:15489334)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei2 – 192191Missing in isoform 3. CuratedVSP_033208Add
    BLAST
    Alternative sequencei321 – 35636Missing in isoform 2. CuratedVSP_033209Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AK027932 mRNA. Translation: BAC25671.1.
    AK052045 mRNA. Translation: BAC34838.1.
    AK132263 mRNA. Translation: BAE21066.1.
    AL845262, AL808102 Genomic DNA. Translation: CAM15450.1.
    AL845262, AL808102 Genomic DNA. Translation: CAM15451.1.
    AL845262, AL808102 Genomic DNA. Translation: CAM15454.1.
    AL808102, AL845262 Genomic DNA. Translation: CAM17090.1.
    AL808102, AL845262 Genomic DNA. Translation: CAM17091.1.
    AL808102, AL845262 Genomic DNA. Translation: CAM17094.1.
    BC027377 mRNA. Translation: AAH27377.1.
    BC031579 mRNA. Translation: AAH31579.1.
    BC043296 mRNA. Translation: AAH43296.1.
    BC090644 mRNA. Translation: AAH90644.1.
    BC096618 mRNA. Translation: AAH96618.1.
    CCDSiCCDS15948.1. [Q8BKH7-1]
    RefSeqiNP_001277554.1. NM_001290625.1. [Q8BKH7-1]
    NP_001277555.1. NM_001290626.1.
    NP_796319.1. NM_177345.4. [Q8BKH7-1]
    XP_006498036.1. XM_006497973.1. [Q8BKH7-1]
    XP_006498038.1. XM_006497975.1. [Q8BKH7-1]
    XP_006498039.1. XM_006497976.1. [Q8BKH7-1]
    XP_006498041.1. XM_006497978.1. [Q8BKH7-2]
    UniGeneiMm.270866.
    Mm.487284.

    Genome annotation databases

    EnsembliENSMUST00000113124; ENSMUSP00000108749; ENSMUSG00000038696. [Q8BKH7-2]
    ENSMUST00000113126; ENSMUSP00000108751; ENSMUSG00000038696. [Q8BKH7-1]
    ENSMUST00000147337; ENSMUSP00000116494; ENSMUSG00000038696. [Q8BKH7-1]
    GeneIDi227743.
    KEGGimmu:227743.
    UCSCiuc008jil.1. mouse. [Q8BKH7-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AK027932 mRNA. Translation: BAC25671.1 .
    AK052045 mRNA. Translation: BAC34838.1 .
    AK132263 mRNA. Translation: BAE21066.1 .
    AL845262 , AL808102 Genomic DNA. Translation: CAM15450.1 .
    AL845262 , AL808102 Genomic DNA. Translation: CAM15451.1 .
    AL845262 , AL808102 Genomic DNA. Translation: CAM15454.1 .
    AL808102 , AL845262 Genomic DNA. Translation: CAM17090.1 .
    AL808102 , AL845262 Genomic DNA. Translation: CAM17091.1 .
    AL808102 , AL845262 Genomic DNA. Translation: CAM17094.1 .
    BC027377 mRNA. Translation: AAH27377.1 .
    BC031579 mRNA. Translation: AAH31579.1 .
    BC043296 mRNA. Translation: AAH43296.1 .
    BC090644 mRNA. Translation: AAH90644.1 .
    BC096618 mRNA. Translation: AAH96618.1 .
    CCDSi CCDS15948.1. [Q8BKH7-1 ]
    RefSeqi NP_001277554.1. NM_001290625.1. [Q8BKH7-1 ]
    NP_001277555.1. NM_001290626.1.
    NP_796319.1. NM_177345.4. [Q8BKH7-1 ]
    XP_006498036.1. XM_006497973.1. [Q8BKH7-1 ]
    XP_006498038.1. XM_006497975.1. [Q8BKH7-1 ]
    XP_006498039.1. XM_006497976.1. [Q8BKH7-1 ]
    XP_006498041.1. XM_006497978.1. [Q8BKH7-2 ]
    UniGenei Mm.270866.
    Mm.487284.

    3D structure databases

    ProteinModelPortali Q8BKH7.
    SMRi Q8BKH7. Positions 371-490.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-57240N.
    IntActi Q8BKH7. 7 interactions.

    PTM databases

    PhosphoSitei Q8BKH7.

    Proteomic databases

    PRIDEi Q8BKH7.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000113124 ; ENSMUSP00000108749 ; ENSMUSG00000038696 . [Q8BKH7-2 ]
    ENSMUST00000113126 ; ENSMUSP00000108751 ; ENSMUSG00000038696 . [Q8BKH7-1 ]
    ENSMUST00000147337 ; ENSMUSP00000116494 ; ENSMUSG00000038696 . [Q8BKH7-1 ]
    GeneIDi 227743.
    KEGGi mmu:227743.
    UCSCi uc008jil.1. mouse. [Q8BKH7-1 ]

    Organism-specific databases

    CTDi 79109.
    MGIi MGI:2444554. Mapkap1.

    Phylogenomic databases

    eggNOGi NOG303753.
    GeneTreei ENSGT00390000000642.
    HOVERGENi HBG023148.
    InParanoidi Q8BKH7.
    OMAi LCACDLV.
    PhylomeDBi Q8BKH7.
    TreeFami TF315174.

    Enzyme and pathway databases

    Reactomei REACT_196588. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_226151. CD28 dependent PI3K/Akt signaling.
    REACT_226341. PIP3 activates AKT signaling.

    Miscellaneous databases

    ChiTaRSi MAPKAP1. mouse.
    NextBioi 378816.
    PROi Q8BKH7.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q8BKH7.
    Bgeei Q8BKH7.
    Genevestigatori Q8BKH7.

    Family and domain databases

    InterProi IPR008828. SIN1.
    [Graphical view ]
    PANTHERi PTHR13335. PTHR13335. 1 hit.
    Pfami PF05422. SIN1. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Strain: C57BL/6J.
      Tissue: Embryo, Eye and Placenta.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Strain: C57BL/6 and FVB/N.
      Tissue: Brain, Mammary tumor and Olfactory epithelium.
    4. "SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity."
      Jacinto E., Facchinetti V., Liu D., Soto N., Wei S., Jung S.Y., Huang Q., Qin J., Su B.
      Cell 127:125-137(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DISRUPTION PHENOTYPE.
    5. "Sin1 binds to both ATF-2 and p38 and enhances ATF-2-dependent transcription in an SAPK signaling pathway."
      Makino C., Sano Y., Shinagawa T., Millar J.B., Ishii S.
      Genes Cells 11:1239-1251(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    6. "mSIN1 protein mediates SGK1 protein interaction with mTORC2 protein complex and is required for selective activation of the epithelial sodium channel."
      Lu M., Wang J., Ives H.E., Pearce D.
      J. Biol. Chem. 286:30647-30654(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SGK1.

    Entry informationi

    Entry nameiSIN1_MOUSE
    AccessioniPrimary (citable) accession number: Q8BKH7
    Secondary accession number(s): A2AN72
    , A2AN74, A2AR13, A2AR16, Q80UY4, Q8BMV5, Q8R2N9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 8, 2008
    Last sequence update: March 1, 2003
    Last modified: October 1, 2014
    This is version 95 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3