SIK2_PONAB
ID SIK2_PONAB Reviewed; 925 AA.
AC Q5REX1; Q5RD38;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 96.
DE RecName: Full=Serine/threonine-protein kinase SIK2;
DE EC=2.7.11.1;
DE AltName: Full=Salt-inducible kinase 2;
DE Short=SIK-2;
DE AltName: Full=Serine/threonine-protein kinase SNF1-like kinase 2;
GN Name=SIK2; Synonyms=SNF1LK2;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1] {ECO:0000305, ECO:0000312|EMBL:CAH89686.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex {ECO:0000312|EMBL:CAH89686.1};
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Serine/threonine-protein kinase that plays a role in many
CC biological processes such as fatty acid oxidation, autophagy, immune
CC response or glucose metabolism. Phosphorylates 'Ser-794' of IRS1 in
CC insulin-stimulated adipocytes, potentially modulating the efficiency of
CC insulin signal transduction. Inhibits CREB activity by phosphorylating
CC and repressing TORCs, the CREB-specific coactivators. Phosphorylates
CC EP300 and thus inhibits its histone acetyltransferase activity. In
CC turn, regulates the DNA-binding ability of several transcription
CC factors such as PPARA or MLXIPL (By similarity). Also plays a role in
CC thymic T-cell development (By similarity).
CC {ECO:0000250|UniProtKB:Q8CFH6, ECO:0000250|UniProtKB:Q9H0K1}.
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 Evidence={ECO:0000250|UniProtKB:Q9H0K1};
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; Evidence={ECO:0000250|UniProtKB:Q9H0K1};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9H0K1};
CC -!- ACTIVITY REGULATION: Activated by phosphorylation on Thr-175.
CC {ECO:0000250}.
CC -!- SUBUNIT: Interacts with and phosphorylates TORC2/CRTC2. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9H0K1}.
CC Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q9H0K1}.
CC -!- PTM: Phosphorylated at Thr-175 by STK11/LKB1 in complex with STE20-
CC related adapter-alpha (STRADA) pseudo kinase and CAB39. Phosphorylated
CC at Thr-484 in response to insulin in adipocytes.
CC {ECO:0000250|UniProtKB:Q9H0K1}.
CC -!- PTM: Acetylation at Lys-53 inhibits kinase activity. Deacetylated by
CC HDAC6. {ECO:0000250|UniProtKB:Q9H0K1}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. SNF1 subfamily. {ECO:0000305}.
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DR EMBL; CR857393; CAH89686.1; -; mRNA.
DR EMBL; CR858080; CAH90319.1; -; mRNA.
DR RefSeq; NP_001124763.1; NM_001131291.1.
DR AlphaFoldDB; Q5REX1; -.
DR SMR; Q5REX1; -.
DR STRING; 9601.ENSPPYP00000004424; -.
DR GeneID; 100171614; -.
DR KEGG; pon:100171614; -.
DR CTD; 23235; -.
DR eggNOG; KOG0586; Eukaryota.
DR InParanoid; Q5REX1; -.
DR OrthoDB; 1127668at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0046626; P:regulation of insulin receptor signaling pathway; ISS:UniProtKB.
DR CDD; cd14071; STKc_SIK; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR017090; Ser/Thr_kinase_SIK1/2.
DR InterPro; IPR034672; SIK.
DR InterPro; IPR015940; UBA.
DR Pfam; PF00069; Pkinase; 1.
DR PIRSF; PIRSF037014; Ser/Thr_PK_SNF1-like; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS50030; UBA; 1.
PE 2: Evidence at transcript level;
KW Acetylation; ATP-binding; Cytoplasm; Endoplasmic reticulum; Kinase;
KW Magnesium; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..925
FT /note="Serine/threonine-protein kinase SIK2"
FT /id="PRO_0000086664"
FT DOMAIN 20..271
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 295..335
FT /note="UBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT REGION 564..586
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 630..674
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 742..776
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 800..895
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 641..674
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 752..767
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 800..816
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 817..837
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 142
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q13131,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 26..34
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q13131,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 49
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8CFH6,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 25
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9H0K1"
FT MOD_RES 53
FT /note="N6-acetyllysine; by EP300"
FT /evidence="ECO:0000250|UniProtKB:Q9H0K1"
FT MOD_RES 175
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9H0K1"
FT MOD_RES 534
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CFH6"
FT MOD_RES 587
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H0K1"
FT CONFLICT 548
FT /note="K -> M (in Ref. 1; CAH90319)"
FT /evidence="ECO:0000305"
FT CONFLICT 642
FT /note="H -> L (in Ref. 1; CAH90319)"
FT /evidence="ECO:0000305"
FT CONFLICT 797
FT /note="M -> I (in Ref. 1; CAH90319)"
FT /evidence="ECO:0000305"
FT CONFLICT 855
FT /note="P -> S (in Ref. 1; CAH90319)"
FT /evidence="ECO:0000305"
FT CONFLICT 924
FT /note="A -> V (in Ref. 1; CAH90319)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 925 AA; 103934 MW; FF70EC944C7F30E6 CRC64;
MVMADGPRHL QRGPVRVGFY DIEGTLGKGN FAVVKLGRHR ITKTEVAIKI IDKSQLDAVN
LEKIYREVQI MKMLDHPHII KLYQVMETKS MLYLVTEYAK NGEIFDYLAN HGRLNESEAR
RKFWQILSAV DYCHGRKIVH RDLKAENLLL DNNMNIKIAD FSFGNFFKSG ELLATWRGSP
PYAAPEVFEG QQYEGPQLDI WSMGVVLYVL VCGALPFDGP TLPILRQRVL EGRFRIPYFM
SEDCEHLIRR MLVLDPSKRL TIAQIKEHKW MLIEVPVQRP VLYPQEQENE PSIGEFNEQV
LRLMHSLGID QQKTIESLQN KSYNHFAAIY FLLVERLKSH RSSFPVEQRL DGRQRRPSAI
AEQTVAKAQT VGLPVTMHSP NMRLLRSALL PQASNVEAFS FPASGCQAET AFMEEECVDT
PKVNGCLLDP VPPVLVRKGC QSLPSNMMET SIDEGLETEG EAEEDPAHAF EAFQSTRSGQ
RRHTLSEVTN QLVVMPGAGK IFSMNDSPSL DSVDSEYDMG SVQRDLNFLE DNPSLKDIML
ANQPSPRKTS PFISLRPTNP AMQALSSQKR EVHNRSPVSF REGRRASDTS LTQGIVAFRQ
HLQNLARTKG ILELNKVQLL YEQIGPEADP NLAPAAPQLQ DHASSCPQEE VSQQQESVST
LPASVHPQLS PRQSLETQYL QHRLQKPSLL SKAQNTCQLY CKEPPRSLEQ QLQEHRLQQK
RLFLQKQSQL QAYFNQMQIA ESSYPQPSQQ LPLPRQETPP PSQQAPPFSL TQPLSPVLEP
SSEQMQYSPF LSQYQEMQLQ PLPSTSSPRA APLPTQLQQQ QPPPPPPPPP PRQPGAAPAP
LQFSYQTCEL PSAAPPAPDY PTPCQYPVDG AQQSDLTGPD CPRSPGLQEA PSSYDPLALS
ELPGLFDCEM LDAVDPQHNG YVLAN
