MAPKAP1
entrez
79109
canonical
uniprot
Q9BPZ7
canonical
ensembl
ENSG00000119487
resolver
ensp
ENSP00000265960
resolver
ensp
ENSP00000265961
resolver
ensp
ENSP00000362602
resolver
ensp
ENSP00000362610
resolver
ensp
ENSP00000377624
resolver
ensp
ENSP00000377627
resolver
genesymbol
MAPKAP1
resolver
genesymbol_syn
MIP1
resolver
genesymbol_syn
SIN1
resolver
hgnc
HGNC:18752
resolver
uniprot
A8K1Z5
resolver
uniprot
B1AMA4
resolver
uniprot
B7Z309
resolver
uniprot
Q00426
resolver
uniprot
Q5JSV5
resolver
uniprot
Q5JSV6
resolver
uniprot
Q5JSV9
resolver
uniprot
Q658R0
resolver
uniprot
Q699U1
resolver
uniprot
Q699U2
resolver
uniprot
Q699U3
resolver
uniprot
Q699U4
resolver
uniprot
Q6GVJ0
resolver
uniprot
Q6GVJ1
resolver
uniprot
Q6GVJ2
resolver
uniprot_entry
SIN1_HUMAN
resolver
uniprot_sec
A8K1Z5
resolver
uniprot_sec
B1AMA4
resolver
uniprot_sec
B7Z309
resolver
uniprot_sec
Q00426
resolver
uniprot_sec
Q5JSV5
resolver
uniprot_sec
Q5JSV6
resolver
uniprot_sec
Q5JSV9
resolver
uniprot_sec
Q658R0
resolver
uniprot_sec
Q699U1
resolver
uniprot_sec
Q699U2
resolver
uniprot_sec
Q699U3
resolver
uniprot_sec
Q699U4
resolver
uniprot_sec
Q6GVJ0
resolver
uniprot_sec
Q6GVJ1
resolver
uniprot_sec
Q6GVJ2
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:0000269|PubMed:26293922}.
uniprot
proteins
amino_acid_sequence
MAFLDNPTIILAHIRQSHVTSDDTGMCEMVLIDHDVDLEKIHPPSMPGDSGSEIQGSNGETQGYVYAQSVDITSSWDFGIRRRSNTAQRLERLRKERQNQIKCKNIQWKERNSKQSAQELKSLFEKKSLKEKPPISGKQSILSVRLEQCPLQLNNPFNEYSKFDGKGHVGTTATKKIDVYLPLHSSQDRLLPMTVVTMASARVQDLIGLICWQYTSEGREPKLNDNVSAYCLHIAEDDGEVDTDFPPLDSNEPIHKFGFSTLALVEKYSSPGLTSKESLFVRINAAHGFSLIQVDNTKVTMKEILLKAVKRRKGSQKVSGPQYRLEKQSEPNVAVDLDSTLESQSAWEFCLVRENSSRADGVFEEDSQIDIATVQDMLSSHHYKSFKVSMIHRLRFTTDVQLGISGDKVEIDPVTNQKASTKFWIKQKPISIDSDLLCACDLAEEKSPSHAIFKLTYLSNHDYKHLYFESDAATVNEIVLKVNYILESRASTARADYFAQKQRKLNRRTSFSFQKEKKSGQQ
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:15467718, PubMed:16919458, PubMed:16962653, PubMed:17043309, PubMed:21806543, PubMed:28264193, PubMed:28968999, PubMed:30837283, PubMed:35926713). 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 (PubMed:16919458, PubMed:16962653, PubMed:21806543, PubMed:28264193, PubMed:28968999, PubMed:30837283, PubMed:35926713). In contrast to mTORC1, mTORC2 is nutrient-insensitive (PubMed:16962653). 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:21806543, PubMed:28264193). 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:28264193, PubMed:35926713). mTORC2 catalyzes the phosphorylation of SGK1 at 'Ser-422' and of PRKCA on 'Ser-657' (PubMed:30837283, PubMed:35926713). The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1 (By similarity). mTORC2 acts upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors (PubMed:15467718). mTORC2 promotes the serum-induced formation of stress-fibers or F-actin (PubMed:15467718). MAPKAP1 inhibits MAP3K2 by preventing its dimerization and autophosphorylation (PubMed:15988011). Inhibits HRAS and KRAS independently of mTORC2 complex (PubMed:17303383, PubMed:34380736, PubMed:35522713). Enhances osmotic stress-induced phosphorylation of ATF2 and ATF2-mediated transcription (PubMed:17054722). Involved in ciliogenesis, regulates cilia length through its interaction with CCDC28B independently of mTORC2 complex (PubMed:23727834). {ECO:0000250|UniProtKB:Q8BKH7, ECO:0000269|PubMed:15467718, ECO:0000269|PubMed:15988011, ECO:0000269|PubMed:16919458, ECO:0000269|PubMed:16962653, ECO:0000269|PubMed:17043309, ECO:0000269|PubMed:17054722, ECO:0000269|PubMed:17303383, ECO:0000269|PubMed:21806543, ECO:0000269|PubMed:23727834, ECO:0000269|PubMed:28264193, ECO:0000269|PubMed:28968999, ECO:0000269|PubMed:30837283, ECO:0000269|PubMed:34380736, ECO:0000269|PubMed:35522713, ECO:0000269|PubMed:35926713}.; FUNCTION: [Isoform 4]: In contrast to isoform 1, isoform 2 and isoform 6, isoform 4 is not a component of the a mTORC2 complex. {ECO:0000269|PubMed:26263164}.
uniprot
proteins
mass_dalton
59123
uniprot
proteins
mutagenesis
MUTAGEN 83; /note="R->A: Specifically abolishes ability of the mTORC2 complex to catalyze phosphorylation of SGK1, without affecting AKT1."; /evidence="ECO:0000269|PubMed:35926713"; MUTAGEN 236..244; /note="EDDGEVDTD->QNNGQVNTN: Decreased ability of the mTORC2 complex to catalyze phosphorylation of AKT1."; /evidence="ECO:0000269|PubMed:28264193"; MUTAGEN 287; /note="H->A: Does not affect interaction with KRAS."; /evidence="ECO:0000269|PubMed:34380736"; MUTAGEN 291; /note="L->D: Decreased interaction with KRAS."; /evidence="ECO:0000269|PubMed:34380736"; MUTAGEN 311; /note="R->E: Does not affect interaction with KRAS."; /evidence="ECO:0000269|PubMed:34380736"; MUTAGEN 312; /note="R->E: Decreased interaction with KRAS."; /evidence="ECO:0000269|PubMed:34380736
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 (By similarity). Phosphorylated at Thr-86 by AKT1 or RPS6KB1 in the presence of growth factors; the effect of this phosphorylation is however unclear (By similarity). According to two studies, phosphorylation at Thr-86 by AKT1 is part of a positive feedback loop that increases mTORC2 activation (By similarity). According to another study, phosphorylation at Thr-86 and Thr-398 by RPS6KB1 promotes dissociation from the mTORC2 complex, leading to inhibit mTORC2 signaling (By similarity). {ECO:0000250|UniProtKB:Q8BKH7}.
uniprot
proteins
protein_family
SIN1 family
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15164053
uniprot
proteins
pubmed
15363842
uniprot
proteins
pubmed
15467718
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15988011
uniprot
proteins
pubmed
16919458
uniprot
proteins
pubmed
16962653
uniprot
proteins
pubmed
17043309
uniprot
proteins
pubmed
17054722
uniprot
proteins
pubmed
17303383
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
1849280
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
21806543
uniprot
proteins
pubmed
21867682
uniprot
proteins
pubmed
22505404
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23727834
uniprot
proteins
pubmed
23762398
uniprot
proteins
pubmed
24161930
uniprot
proteins
pubmed
26263164
uniprot
proteins
pubmed
26293922
uniprot
proteins
pubmed
28143890
uniprot
proteins
pubmed
28264193
uniprot
proteins
pubmed
28968999
uniprot
proteins
pubmed
29424687
uniprot
proteins
pubmed
29567957
uniprot
proteins
pubmed
30837283
uniprot
proteins
pubmed
31130364
uniprot
proteins
pubmed
33158864
uniprot
proteins
pubmed
33378666
uniprot
proteins
pubmed
34380736
uniprot
proteins
pubmed
34519268
uniprot
proteins
pubmed
35522713
uniprot
proteins
pubmed
35926713
uniprot
proteins
sequence_length
522
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17303383, ECO:0000269|PubMed:28143890}; Peripheral membrane protein {ECO:0000269|PubMed:17303383}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:21867682}; Peripheral membrane protein {ECO:0000269|PubMed:17303383}. Early endosome membrane {ECO:0000269|PubMed:28143890}; Peripheral membrane protein {ECO:0000269|PubMed:17303383}. Late endosome membrane {ECO:0000269|PubMed:28143890}; Peripheral membrane protein {ECO:0000269|PubMed:17303383}. Lysosome membrane {ECO:0000269|PubMed:31130364}; Peripheral membrane protein {ECO:0000269|PubMed:17303383}. Golgi apparatus membrane {ECO:0000269|PubMed:17303383}; Peripheral membrane protein {ECO:0000269|PubMed:17303383}. Mitochondrion outer membrane {ECO:0000269|PubMed:28143890}; Peripheral membrane protein {ECO:0000269|PubMed:17303383}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:30837283}. Nucleus {ECO:0000269|PubMed:26263164}. Note=The mTORC2 complex localizes to membranes: mTORC2 is active at the plasma membrane, endoplasmic reticulum membrane, lysosomes and perinuclear region (PubMed:17303383, PubMed:21867682, PubMed:30837283). In lysosomal membrane, mTORC2 is sensitive to lysosomal positioning in the cell (PubMed:31130364). Following phosphorylation by PKC, localizes to the perinuclear region, where the mTORC2 complex specifically phosphorylates SGK1, but not AKT (PubMed:30837283). {ECO:0000269|PubMed:17303383, ECO:0000269|PubMed:21867682, ECO:0000269|PubMed:30837283, ECO:0000269|PubMed:31130364}.; SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane {ECO:0000269|PubMed:26263164}. Nucleus {ECO:0000269|PubMed:26263164}.; SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane {ECO:0000269|PubMed:26263164}. Nucleus {ECO:0000269|PubMed:26263164}.; SUBCELLULAR LOCATION: [Isoform 4]: Cell membrane {ECO:0000269|PubMed:26263164}. Cytoplasm, cytosol {ECO:0000269|PubMed:26263164}.; SUBCELLULAR LOCATION: [Isoform 6]: Cytoplasm {ECO:0000269|PubMed:26263164}. Nucleus {ECO:0000269|PubMed:26263164}.
uniprot
proteins