Mapkap1
entrez
227743
canonical
uniprot
Q8BKH7
canonical
ensembl
ENSMUSG00000038696
resolver
ensp
ENSMUSP00000108751
resolver
ensp
ENSMUSP00000116494
resolver
ensp
ENSMUSP00000123301
resolver
ensp
ENSMUSP00000234617
resolver
ensp
ENSMUSP00000234620
resolver
ensp
ENSMUSP00000234621
resolver
ensp
ENSMUSP00000234622
resolver
ensp
ENSMUSP00000234624
resolver
ensp
ENSMUSP00000234625
resolver
ensp
ENSMUSP00000234631
resolver
ensp
ENSMUSP00000234638
resolver
ensp
ENSMUSP00000234646
resolver
genesymbol
Mapkap1
resolver
genesymbol_syn
Mip1
resolver
genesymbol_syn
Sin1
resolver
uniprot
A2AN72
resolver
uniprot
A2AN74
resolver
uniprot
A2AR13
resolver
uniprot
A2AR16
resolver
uniprot
Q80UY4
resolver
uniprot
Q8BMV5
resolver
uniprot
Q8R2N9
resolver
uniprot_entry
SIN1_MOUSE
resolver
uniprot_sec
A2AN72
resolver
uniprot_sec
A2AN74
resolver
uniprot_sec
A2AR13
resolver
uniprot_sec
A2AR16
resolver
uniprot_sec
Q80UY4
resolver
uniprot_sec
Q8BMV5
resolver
uniprot_sec
Q8R2N9
resolver
activity_regulation
ACTIVITY REGULATION: Phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) promotes MTOR activation by relieving MAPKAP1/SIN1-mediated inhibition of MTOR that takes place in absence of PI(3,4,5)P3. {ECO:0000250|UniProtKB:Q9BPZ7}.
uniprot
proteins
amino_acid_sequence
MAFLDNPTIILAHIRQSHVTSDDTGMCEMVLIDHDVDLEKTHPPSVPGDSGSEVQGSSGETQGYIYAQSVDITSSWDFGIRRRSNTAQRLERLRKERQNQIKCKNIQWKERNSKQSAQELKSLFEKKSLKEKPPSSGKQSILSVRLEQCPLQLNNPFNEYSKFDGKGHVGTTATKKIDVYLPLHSSQDRLLPMTVVTMASARVQDLIGLICWQYTSEGREPKLNDNVSAYCLHIAEDDGEVDTDFPPLDSNEPIHKFGFSTLALVEKYSSPGLTSKESLFVRINAAHGFSLIQVDNTKVTMKEILLKAVKRRKGSQKISGPQYRLEKQSEPNIAVDLESTLESQNAWEFCLVRENSSRADGVFEEDSQIDIATVQDMLSSHHYKSFKVSMIHRLRFTTDVQLGISGDKVEIDPVTNQKASTKFWIKQKPISIDCDLLCACDLAEEKSPSHAVFKLTYLSSHDYKHLYFESDAATVSEIVLKVNYILESRASTARADYLAQKQRKLNRRTSFSFQKEKKSGQQ
uniprot
proteins
function
FUNCTION: Component of the mechanistic target of rapamycin complex 2 (mTORC2), which transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output (PubMed:16962653, PubMed:21757730, PubMed:24161930, PubMed:30837283, PubMed:33850054). In response to growth factors, mTORC2 phosphorylates and activates AGC protein kinase family members, including AKT (AKT1, AKT2 and AKT3), PKC (PRKCA, PRKCB and PRKCE) and SGK1 (By similarity). In contrast to mTORC1, mTORC2 is nutrient-insensitive (By similarity). Within the mTORC2 complex, MAPKAP1/SIN1 acts as a substrate adapter which recognizes and binds AGC protein kinase family members for phosphorylation by MTOR (PubMed:33850054). mTORC2 plays a critical role in AKT1 activation by mediating phosphorylation of different sites depending on the context, such as 'Thr-450', 'Ser-473', 'Ser-477' or 'Thr-479', facilitating the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDPK1/PDK1 which is a prerequisite for full activation (PubMed:33850054). mTORC2 catalyzes the phosphorylation of SGK1 at 'Ser-422' and of PRKCA on 'Ser-657' (PubMed:21757730, PubMed:30837283). The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1 (PubMed:23142081, PubMed:23388827). mTORC2 acts upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors (By similarity). mTORC2 promotes the serum-induced formation of stress-fibers or F-actin (By similarity). MAPKAP1 inhibits MAP3K2 by preventing its dimerization and autophosphorylation (By similarity). Inhibits HRAS and KRAS independently of mTORC2 complex (By similarity). Enhances osmotic stress-induced phosphorylation of ATF2 and ATF2-mediated transcription (By similarity). Involved in ciliogenesis, regulates cilia length through its interaction with CCDC28B independently of mTORC2 complex (By similarity). {ECO:0000250|UniProtKB:Q9BPZ7, ECO:0000269|PubMed:16962653, ECO:0000269|PubMed:21757730, ECO:0000269|PubMed:23142081, ECO:0000269|PubMed:23388827, ECO:0000269|PubMed:24161930, ECO:0000269|PubMed:30837283, ECO:0000269|PubMed:33850054}.
uniprot
proteins
mass_dalton
59009
uniprot
proteins
mutagenesis
MUTAGEN 86; /note="T->A: Abolished phosphorylation by AKT1. Abolished phosphorylation by RPS6KB1; when associated with A-398."; /evidence="ECO:0000269|PubMed:23684622, ECO:0000269|PubMed:24161930"; MUTAGEN 86; /note="T->E: Mimics phosphorylation."; /evidence="ECO:0000269|PubMed:23684622"; MUTAGEN 128; /note="S->A: Abolished phosphorylation by PKC, leading to decreased ability of the mTORC2 complex to phosphorylate SGK1."; /evidence="ECO:0000269|PubMed:30837283"; MUTAGEN 398; /note="T->A: Abolished phosphorylation by RPS6KB1; when associated with A-86."; /evidence="ECO:0000269|PubMed:23684622, ECO:0000269|PubMed:24161930
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-128 by PKC promotes relocalization to the perinuclear region, where the mTORC2 complex specifically mediates phosphorylation of SGK1 (PubMed:30837283). Phosphorylated at Thr-86 by AKT1 or RPS6KB1 in the presence of growth factors; the effect of this phosphorylation is however unclear (PubMed:23684622, PubMed:24161930, PubMed:26235620). According to two studies, phosphorylation at Thr-86 by AKT1 is part of a positive feedback loop that increases mTORC2 activation (PubMed:23684622, PubMed:26235620). According to another study, phosphorylation at Thr-86 and Thr-398 by RPS6KB1 promotes dissociation from the mTORC2 complex, leading to inhibit mTORC2 signaling (PubMed:24161930). {ECO:0000269|PubMed:23684622, ECO:0000269|PubMed:24161930, ECO:0000269|PubMed:26235620, ECO:0000269|PubMed:30837283}.
uniprot
proteins
protein_family
SIN1 family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
16962653
uniprot
proteins
pubmed
17054722
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
21757730
uniprot
proteins
pubmed
23142081
uniprot
proteins
pubmed
23388827
uniprot
proteins
pubmed
23684622
uniprot
proteins
pubmed
24161930
uniprot
proteins
pubmed
26235620
uniprot
proteins
pubmed
30837283
uniprot
proteins
pubmed
33850054
uniprot
proteins
sequence_length
522
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9BPZ7}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q9BPZ7}. Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q9BPZ7}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q9BPZ7}. Early endosome membrane {ECO:0000250|UniProtKB:Q9BPZ7}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q9BPZ7}. Late endosome membrane {ECO:0000250|UniProtKB:Q9BPZ7}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q9BPZ7}. Lysosome membrane {ECO:0000250|UniProtKB:Q9BPZ7}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q9BPZ7}. Golgi apparatus membrane {ECO:0000250|UniProtKB:Q9BPZ7}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q9BPZ7}. Mitochondrion outer membrane {ECO:0000250|UniProtKB:Q9BPZ7}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q9BPZ7}. Cytoplasm, perinuclear region {ECO:0000305|PubMed:30837283}. Nucleus {ECO:0000250|UniProtKB:Q9BPZ7}. Note=The mTORC2 complex localizes to membranes: mTORC2 is active at the plasma membrane, endoplasmic reticulum membrane, lysosomes and perinuclear region (By similarity). In lysosomal membrane, mTORC2 is sensitive to lysosomal positioning in the cell (By similarity). Following phosphorylation by PKC, localizes to the perinuclear region, where the mTORC2 complex specifically phosphorylates SGK1, but not AKT (PubMed:30837283). {ECO:0000250|UniProtKB:Q9BPZ7, ECO:0000269|PubMed:30837283}.
uniprot
proteins