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SGK1_MACFA
ID   SGK1_MACFA              Reviewed;         431 AA.
AC   Q4R633;
DT   28-JUL-2009, integrated into UniProtKB/Swiss-Prot.
DT   19-JUL-2005, sequence version 1.
DT   03-AUG-2022, entry version 67.
DE   RecName: Full=Serine/threonine-protein kinase Sgk1;
DE            EC=2.7.11.1;
DE   AltName: Full=Serum/glucocorticoid-regulated kinase 1;
GN   Name=SGK1; ORFNames=QtsA-19250;
OS   Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC   Cercopithecidae; Cercopithecinae; Macaca.
OX   NCBI_TaxID=9541;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Testis;
RG   International consortium for macaque cDNA sequencing and analysis;
RT   "DNA sequences of macaque genes expressed in brain or testis and its
RT   evolutionary implications.";
RL   Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Serine/threonine-protein kinase which is involved in the
CC       regulation of a wide variety of ion channels, membrane transporters,
CC       cellular enzymes, transcription factors, neuronal excitability, cell
CC       growth, proliferation, survival, migration and apoptosis. Plays an
CC       important role in cellular stress response. Contributes to regulation
CC       of renal Na(+) retention, renal K(+) elimination, salt appetite,
CC       gastric acid secretion, intestinal Na(+)/H(+) exchange and nutrient
CC       transport, insulin-dependent salt sensitivity of blood pressure, salt
CC       sensitivity of peripheral glucose uptake, cardiac repolarization and
CC       memory consolidation. Up-regulates Na(+) channels: SCNN1A/ENAC, SCN5A
CC       and ASIC1/ACCN2, K(+) channels: KCNJ1/ROMK1, KCNA1-5, KCNQ1-5 and
CC       KCNE1, epithelial Ca(2+) channels: TRPV5 and TRPV6, chloride channels:
CC       BSND, CLCN2 and CFTR, glutamate transporters: SLC1A3/EAAT1, SLC1A2
CC       /EAAT2, SLC1A1/EAAT3, SLC1A6/EAAT4 and SLC1A7/EAAT5, amino acid
CC       transporters: SLC1A5/ASCT2, SLC38A1/SN1 and SLC6A19, creatine
CC       transporter: SLC6A8, Na(+)/dicarboxylate cotransporter: SLC13A2/NADC1,
CC       Na(+)-dependent phosphate cotransporter: SLC34A2/NAPI-2B, glutamate
CC       receptor: GRIK2/GLUR6. Up-regulates carriers: SLC9A3/NHE3,
CC       SLC12A1/NKCC2, SLC12A3/NCC, SLC5A3/SMIT, SLC2A1/GLUT1, SLC5A1/SGLT1 and
CC       SLC15A2/PEPT2. Regulates enzymes: GSK3A/B, PMM2 and Na(+)/K(+) ATPase,
CC       and transcription factors: CTNNB1 and nuclear factor NF-kappa-B.
CC       Stimulates sodium transport into epithelial cells by enhancing the
CC       stability and expression of SCNN1A/ENAC. This is achieved by
CC       phosphorylating the NEDD4L ubiquitin E3 ligase, promoting its
CC       interaction with 14-3-3 proteins, thereby preventing it from binding to
CC       SCNN1A/ENAC and targeting it for degradation. Regulates store-operated
CC       Ca(+2) entry (SOCE) by stimulating ORAI1 and STIM1. Regulates
CC       KCNJ1/ROMK1 directly via its phosphorylation or indirectly via
CC       increased interaction with SLC9A3R2/NHERF2. Phosphorylates MDM2 and
CC       activates MDM2-dependent ubiquitination of p53/TP53. Phosphorylates
CC       MAPT/TAU and mediates microtubule depolymerization and neurite
CC       formation in hippocampal neurons. Phosphorylates SLC2A4/GLUT4 and up-
CC       regulates its activity. Phosphorylates APBB1/FE65 and promotes its
CC       localization to the nucleus. Phosphorylates MAPK1/ERK2 and activates it
CC       by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2.
CC       Phosphorylates FBXW7 and plays an inhibitory role in the NOTCH1
CC       signaling. Phosphorylates FOXO1 resulting in its relocalization from
CC       the nucleus to the cytoplasm. Phosphorylates FOXO3, promoting its exit
CC       from the nucleus and interference with FOXO3-dependent transcription.
CC       Phosphorylates BRAF and MAP3K3/MEKK3 and inhibits their activity.
CC       Phosphorylates SLC9A3/NHE3 in response to dexamethasone, resulting in
CC       its activation and increased localization at the cell membrane.
CC       Phosphorylates CREB1. Necessary for vascular remodeling during
CC       angiogenesis (By similarity). {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC         [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC         COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC         threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC         Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC         EC=2.7.11.1;
CC   -!- ACTIVITY REGULATION: Two specific sites, one in the kinase domain (Thr-
CC       256) and the other in the C-terminal regulatory region (Ser-422), need
CC       to be phosphorylated for its full activation. Phosphorylation at Ser-
CC       397 and Ser-401 are also essential for its activity. Activated by WNK1,
CC       WNK2, WNK3 and WNK4 (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Homodimer; disulfide-linked. Forms a trimeric complex with
CC       FBXW7 and NOTCH1. Interacts with MAPK3/ERK1, MAPK1/ERK2, MAP2K1/MEK1,
CC       MAP2K2/MEK2, NEDD4, NEDD4L, MAPT/TAU, MAPK7, CREB1, SLC9A3R2/NHERF2 and
CC       KCNJ1/ROMK1. Associates with the mammalian target of rapamycin complex
CC       2 (mTORC2) via an interaction with MAPKAP1/SIN1 (By similarity).
CC       {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC       Endoplasmic reticulum membrane {ECO:0000250}. Cell membrane
CC       {ECO:0000250}. Mitochondrion {ECO:0000250}. Note=The subcellular
CC       localization is controlled by the cell cycle, as well as by exposure to
CC       specific hormones and environmental stress stimuli. In proliferating
CC       cells, it shuttles between the nucleus and cytoplasm in synchrony with
CC       the cell cycle, and in serum/growth factor-stimulated cells it resides
CC       in the nucleus. In contrast, after exposure to environmental stress or
CC       treatment with glucocorticoids, it is detected in the cytoplasm and
CC       with certain stress conditions is associated with the mitochondria. In
CC       osmoregulation through the epithelial sodium channel, it can be
CC       localized to the cytoplasmic surface of the cell membrane. Nuclear,
CC       upon phosphorylation (By similarity). {ECO:0000250}.
CC   -!- PTM: Regulated by phosphorylation. Activated by phosphorylation on Ser-
CC       422 by mTORC2, transforming it into a substrate for PDPK1 which
CC       phosphorylates it on Thr-256. Phosphorylation on Ser-397 and Ser-401
CC       are also essential for its activity. Phosphorylation on Ser-78 by MAPK7
CC       is required for growth factor-induced cell cycle progression (By
CC       similarity). {ECO:0000250}.
CC   -!- PTM: Ubiquitinated by NEDD4L; which promotes proteasomal degradation.
CC       Ubiquitinated by SYVN1 at the endoplasmic reticulum; which promotes
CC       rapid proteasomal degradation and maintains a high turnover rate in
CC       resting cells (By similarity). {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC       protein kinase family. {ECO:0000305}.
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DR   EMBL; AB169357; BAE01442.1; -; mRNA.
DR   AlphaFoldDB; Q4R633; -.
DR   SMR; Q4R633; -.
DR   STRING; 9541.XP_005551948.1; -.
DR   eggNOG; KOG0598; Eukaryota.
DR   Proteomes; UP000233100; Unplaced.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR   GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR   GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR   InterPro; IPR000961; AGC-kinase_C.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR017892; Pkinase_C.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   Pfam; PF00069; Pkinase; 1.
DR   Pfam; PF00433; Pkinase_C; 1.
DR   SMART; SM00133; S_TK_X; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; SSF56112; 1.
DR   PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE   2: Evidence at transcript level;
KW   Apoptosis; ATP-binding; Cell membrane; Cytoplasm; Disulfide bond;
KW   Endoplasmic reticulum; Kinase; Membrane; Mitochondrion; Nucleotide-binding;
KW   Nucleus; Phosphoprotein; Reference proteome;
KW   Serine/threonine-protein kinase; Stress response; Transferase;
KW   Ubl conjugation.
FT   CHAIN           1..431
FT                   /note="Serine/threonine-protein kinase Sgk1"
FT                   /id="PRO_0000380129"
FT   DOMAIN          98..355
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   DOMAIN          356..431
FT                   /note="AGC-kinase C-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT   REGION          1..60
FT                   /note="Necessary for localization to the mitochondria"
FT                   /evidence="ECO:0000250"
FT   REGION          66..92
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           131..141
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        222
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   BINDING         104..112
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         127
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         74
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O00141"
FT   MOD_RES         78
FT                   /note="Phosphoserine; by MAPK7"
FT                   /evidence="ECO:0000250|UniProtKB:O00141"
FT   MOD_RES         256
FT                   /note="Phosphothreonine; by PDPK1"
FT                   /evidence="ECO:0000250|UniProtKB:O00141"
FT   MOD_RES         369
FT                   /note="Phosphothreonine; by PKA"
FT                   /evidence="ECO:0000250|UniProtKB:O00141"
FT   MOD_RES         397
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O00141"
FT   MOD_RES         401
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O00141"
FT   MOD_RES         422
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O00141"
FT   DISULFID        193
FT                   /note="Interchain (with C-258)"
FT                   /evidence="ECO:0000250"
FT   DISULFID        258
FT                   /note="Interchain (with C-193)"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   431 AA;  49017 MW;  E52B06B4102F4115 CRC64;
     MTVKTEAAKG TLTYSRMRGM VAILIAFMKQ RRMGLNDFIQ KIANNSYACK HPEVQSILKI
     SQPQEPELMN ANPSPPPSPS QQINLGPSSN PHAKPSDFHF LKVIGKGSFG KVLLARHKAE
     EVFYAVKVLQ KKAILKKKEE KHIMSERNVL LKNVKHPFLV GLHFSFQTAD KLYFVLDYIN
     GGELFYHLQR ERCFLEPRAR FYAAEIASAL GYLHSLNIVY RDLKPENILL DSQGHIVLTD
     FGLCKENIEH NSTTSTFCGT PEYLAPEVLH KQPYDRTVDW WCLGAVLYEM LYGLPPFYSR
     NTAEMYDNIL NKPLQLKPNI TNSARHLLEG LLQKDRMKRL GAKDDFMEIK SHVFFSLINW
     DDLINKKITP PFNPNVSGPN DLRHFDPEFT EEPVPNSIGK SPDSILVTAS VKEAAETFLG
     FSYAPPTDSF L
 
 
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