ULK3_MOUSE
ID ULK3_MOUSE Reviewed; 472 AA.
AC Q3U3Q1; B2RXB9; Q8K1X6; Q9DBR8;
DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 137.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Lung;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=FVB/N; TISSUE=Brain, and Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q3U3Q1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3U3Q1-2; Sequence=VSP_020604;
CC Name=3;
CC IsoId=Q3U3Q1-3; Sequence=VSP_020602, VSP_020603;
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH37093.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK004783; BAB23561.1; -; mRNA.
DR EMBL; AK154642; BAE32734.1; -; mRNA.
DR EMBL; CH466522; EDL25913.1; -; Genomic_DNA.
DR EMBL; BC037093; AAH37093.1; ALT_INIT; mRNA.
DR EMBL; BC151153; AAI51154.1; -; mRNA.
DR CCDS; CCDS52809.1; -. [Q3U3Q1-1]
DR RefSeq; NP_082171.1; NM_027895.1. [Q3U3Q1-1]
DR AlphaFoldDB; Q3U3Q1; -.
DR SMR; Q3U3Q1; -.
DR STRING; 10090.ENSMUSP00000059947; -.
DR BindingDB; Q3U3Q1; -.
DR ChEMBL; CHEMBL3832; -.
DR DrugCentral; Q3U3Q1; -.
DR iPTMnet; Q3U3Q1; -.
DR PhosphoSitePlus; Q3U3Q1; -.
DR EPD; Q3U3Q1; -.
DR MaxQB; Q3U3Q1; -.
DR PaxDb; Q3U3Q1; -.
DR PRIDE; Q3U3Q1; -.
DR ProteomicsDB; 298480; -. [Q3U3Q1-1]
DR ProteomicsDB; 298481; -. [Q3U3Q1-2]
DR ProteomicsDB; 298482; -. [Q3U3Q1-3]
DR Antibodypedia; 27077; 409 antibodies from 34 providers.
DR Ensembl; ENSMUST00000053230; ENSMUSP00000059947; ENSMUSG00000032308. [Q3U3Q1-1]
DR GeneID; 71742; -.
DR KEGG; mmu:71742; -.
DR UCSC; uc009pvf.2; mouse. [Q3U3Q1-1]
DR CTD; 25989; -.
DR MGI; MGI:1918992; Ulk3.
DR VEuPathDB; HostDB:ENSMUSG00000032308; -.
DR eggNOG; KOG0595; Eukaryota.
DR GeneTree; ENSGT00940000157689; -.
DR HOGENOM; CLU_000288_63_58_1; -.
DR InParanoid; Q3U3Q1; -.
DR OMA; TQAVEHD; -.
DR OrthoDB; 1084750at2759; -.
DR PhylomeDB; Q3U3Q1; -.
DR TreeFam; TF324551; -.
DR Reactome; R-MMU-5632684; Hedgehog 'on' state.
DR BioGRID-ORCS; 71742; 4 hits in 76 CRISPR screens.
DR ChiTaRS; Ulk3; mouse.
DR PRO; PR:Q3U3Q1; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q3U3Q1; protein.
DR Bgee; ENSMUSG00000032308; Expressed in retinal neural layer and 68 other tissues.
DR ExpressionAtlas; Q3U3Q1; baseline and differential.
DR Genevisible; Q3U3Q1; MM.
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:MGI.
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:MGI.
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 2: Evidence at transcript level;
KW Alternative splicing; ATP-binding; Autophagy; Cytoplasm; Kinase;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..472
FT /note="Serine/threonine-protein kinase ULK3"
FT /id="PRO_0000250151"
FT DOMAIN 14..270
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 280..348
FT /note="MIT 1"
FT DOMAIN 375..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; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q6PHR2"
FT VAR_SEQ 205..295
FT /note="EALFGQPPFASRSFSELEEKIRSNRVIELPLRPQLSLDCRDLLQRLLERDPA
FT RRISFKDFFAHPWVDLEHMPSGESLAQARALVVEAVKKD -> GETSLPLLSTLRVTLY
FT LGQAFLGLSWVQMRIKGSTLRDFWSPFCGRARPDLTLFPSGPSSAFFHRSPLWAAPLCL
FT QIVLRARRKDSQQSGD (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_020602"
FT VAR_SEQ 296..472
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_020603"
FT VAR_SEQ 431..472
FT /note="QNLMARAEYLKEQIKIRESHWEAESLDKEGLSESVRSSCTLQ -> GVGVEK
FT CSFPSSYSGLWDINRSHMDFPCLRIVRSVTQDFCA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_020604"
FT CONFLICT 151
FT /note="P -> S (in Ref. 3; AAH37093)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 472 AA; 53572 MW; 9FBAA9761CC80292 CRC64;
MAGPSWGLPR LDGFILTERL GSGTYATVYK AYAKKDTREV VAIKCVAKKS LNKASVENLL
TEIEILKGIR HPHIVQLKDF QWDNDNIYLI MEFCAGGDLS RFIHTRRILP EKVARVFMQQ
LASALQFLHE RNISHLDLKP QNILLSSLEK PHLKLADFGF AQHMSPWDEK HVLRGSPLYM
APEMVCRRQY DARVDLWSVG VILYEALFGQ PPFASRSFSE LEEKIRSNRV IELPLRPQLS
LDCRDLLQRL LERDPARRIS FKDFFAHPWV DLEHMPSGES LAQARALVVE AVKKDQEGDA
AAALSLYCKA LDFFVPALHY EVDAQRKEAI KAKVGQYVSR AEELKAIVSS SNQALLRQGT
TVQELLREMA RDKPRLLAAL EVASAALAKE EEAGKEQDAL DLYQHSLGEL LVLLAAEAPG
RRRELLHTEV QNLMARAEYL KEQIKIRESH WEAESLDKEG LSESVRSSCT LQ
