ULK3_RAT
ID ULK3_RAT Reviewed; 472 AA.
AC D3ZHP7;
DT 02-NOV-2010, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 79.
DE RecName: Full=Serine/threonine-protein kinase ULK3;
DE EC=2.7.11.1;
DE AltName: Full=Unc-51-like kinase 3;
GN Name=Ulk3;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-464, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Serine/threonine protein kinase that acts as a regulator of
CC Sonic hedgehog (SHH) signaling and autophagy. Acts as a negative
CC regulator of SHH signaling in the absence of SHH ligand: interacts with
CC SUFU, thereby inactivating the protein kinase activity and preventing
CC phosphorylation of GLI proteins (GLI1, GLI2 and/or GLI3). Positively
CC regulates SHH signaling in the presence of SHH: dissociates from SUFU,
CC autophosphorylates and mediates phosphorylation of GLI2, activating it
CC and promoting its nuclear translocation. Phosphorylates in vitro GLI2,
CC as well as GLI1 and GLI3, although less efficiently. Also acts as a
CC regulator of autophagy: following cellular senescence, able to induce
CC autophagy (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 -!- SUBUNIT: Interacts (via protein kinase domain) with SUFU.
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Note=Localizes to pre-
CC autophagosomal structure during cellular senescence. {ECO:0000250}.
CC -!- PTM: Autophosphorylated. Autophosphorylation is blocked by interaction
CC with SUFU (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. APG1/unc-51/ULK1 subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; CH473975; EDL95639.1; -; Genomic_DNA.
DR RefSeq; NP_001258064.1; NM_001271135.1.
DR AlphaFoldDB; D3ZHP7; -.
DR SMR; D3ZHP7; -.
DR STRING; 10116.ENSRNOP00000025885; -.
DR iPTMnet; D3ZHP7; -.
DR PhosphoSitePlus; D3ZHP7; -.
DR jPOST; D3ZHP7; -.
DR PaxDb; D3ZHP7; -.
DR Ensembl; ENSRNOT00000025885; ENSRNOP00000025885; ENSRNOG00000038459.
DR GeneID; 691171; -.
DR KEGG; rno:691171; -.
DR UCSC; RGD:1587417; rat.
DR CTD; 25989; -.
DR RGD; 1587417; Ulk3.
DR eggNOG; KOG0595; Eukaryota.
DR GeneTree; ENSGT00940000157689; -.
DR HOGENOM; CLU_000288_63_58_1; -.
DR InParanoid; D3ZHP7; -.
DR OMA; TQAVEHD; -.
DR OrthoDB; 1084750at2759; -.
DR PhylomeDB; D3ZHP7; -.
DR TreeFam; TF324551; -.
DR Reactome; R-RNO-5632684; Hedgehog 'on' state.
DR PRO; PR:D3ZHP7; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Proteomes; UP000234681; Chromosome 8.
DR Bgee; ENSRNOG00000038459; Expressed in thymus and 19 other tissues.
DR GO; GO:0005776; C:autophagosome; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0000407; C:phagophore assembly site; IEA:UniProt.
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; ISS:UniProtKB.
DR GO; GO:1905037; P:autophagosome organization; IBA:GO_Central.
DR GO; GO:0072537; P:fibroblast activation; ISO:RGD.
DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; ISS:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0007224; P:smoothened signaling pathway; ISO:RGD.
DR InterPro; IPR045269; Atg1-like.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR007330; MIT_dom.
DR InterPro; IPR036181; MIT_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR24348; PTHR24348; 1.
DR Pfam; PF04212; MIT; 2.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00745; MIT; 2.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF116846; SSF116846; 2.
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.
PE 1: Evidence at protein level;
KW ATP-binding; Autophagy; Cytoplasm; Kinase; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..472
FT /note="Serine/threonine-protein kinase ULK3"
FT /id="PRO_0000399831"
FT DOMAIN 14..270
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 281..347
FT /note="MIT 1"
FT DOMAIN 376..444
FT /note="MIT 2"
FT ACT_SITE 137
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 20..28
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 44
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 176
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PHR2"
FT MOD_RES 350
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q6PHR2"
FT MOD_RES 384
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q6PHR2"
FT MOD_RES 464
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 472 AA; 53419 MW; EF5FF1A5E4D3CEB1 CRC64;
MAGSGWGLPR LDGFILTERL GSGTYATVYK AYAKKATREV VAIKCVAKKS LNKASVENLL
TEIEILKGIR HPHIVQLKDF QWDNDNIYLI MEFCAGGDLS RFIHTRRILP EKVARVFMQQ
LASALQFLHE RNISHLDLKP QNILLSSLEK PHLKLADFGF AQHMSPWDEK HVLRGSPLYM
APEMVCRRQY DARVDLWSVG VILYEALFGQ PPFASRSFSE LEEKIRSNRV IELPLRPQLS
LDCRDLLQRL LERDPSHRIS FQDFFAHPWV DLEHMPSGES LAQATALVVE AVKKDQEGDA
AAALSLYCKA LDFFVPALHY EVDAQRKEAI KAKVGQYVSR AEELKAIVSS SNQALLRQGT
TGQELLREMA RDKPRLLAAL EVASAAMAKE EEAGKEQDAL DLYQHSLGEL LLLLAAEAPG
RRRELLHTEV QNLMARAEYL KEQIKIRESH WEAESLDKEG LSESVRSSCT LQ
