UNC51_CAEEL
ID UNC51_CAEEL Reviewed; 856 AA.
AC Q23023;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Serine/threonine-protein kinase unc-51;
DE EC=2.7.11.1 {ECO:0000269|PubMed:15539493};
DE AltName: Full=Uncoordinated protein 51;
GN Name=unc-51 {ECO:0000312|WormBase:Y60A3A.1};
GN ORFNames=Y60A3A.1 {ECO:0000312|WormBase:Y60A3A.1};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, MUTAGENESIS OF
RP LYS-39 AND ARG-841, AND DISRUPTION PHENOTYPE.
RC STRAIN=Bristol N2;
RX PubMed=7958904; DOI=10.1101/gad.8.20.2389;
RA Ogura K., Wicky C., Magnenat L., Tobler H., Mori I., Mueller F.,
RA Ohshima Y.;
RT "Caenorhabditis elegans unc-51 gene required for axonal elongation encodes
RT a novel serine/threonine kinase.";
RL Genes Dev. 8:2389-2400(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12958363; DOI=10.1126/science.1087782;
RA Melendez A., Talloczy Z., Seaman M., Eskelinen E.L., Hall D.H., Levine B.;
RT "Autophagy genes are essential for dauer development and life-span
RT extension in C. elegans.";
RL Science 301:1387-1391(2003).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, INTERACTION WITH UNC-14 AND VAB-8,
RP AND MUTAGENESIS OF LYS-39 AND 37-ALA--ILE-41.
RX PubMed=15539493; DOI=10.1242/dev.01457;
RA Lai T., Garriga G.;
RT "The conserved kinase UNC-51 acts with VAB-8 and UNC-14 to regulate axon
RT outgrowth in C. elegans.";
RL Development 131:5991-6000(2004).
RN [5]
RP FUNCTION.
RX PubMed=17890369; DOI=10.1534/genetics.107.075762;
RA Aladzsity I., Toth M.L., Sigmond T., Szabo E., Bicsak B., Barna J.,
RA Regos A., Orosz L., Kovacs A.L., Vellai T.;
RT "Autophagy genes unc-51 and bec-1 are required for normal cell size in
RT Caenorhabditis elegans.";
RL Genetics 177:655-660(2007).
RN [6]
RP FUNCTION, AND INTERACTION WITH ATG-13.
RX PubMed=19377305; DOI=10.4161/auto.5.5.8624;
RA Tian E., Wang F., Han J., Zhang H.;
RT "epg-1 functions in autophagy-regulated processes and may encode a highly
RT divergent Atg13 homolog in C. elegans.";
RL Autophagy 5:608-615(2009).
RN [7]
RP FUNCTION, INTERACTION WITH LGG-1, DOMAIN LIR MOTIF, AND MUTAGENESIS OF
RP PHE-358 AND PHE-360.
RX PubMed=26687600; DOI=10.1016/j.molcel.2015.11.019;
RA Wu F., Watanabe Y., Guo X.Y., Qi X., Wang P., Zhao H.Y., Wang Z.,
RA Fujioka Y., Zhang H., Ren J.Q., Fang T.C., Shen Y.X., Feng W., Hu J.J.,
RA Noda N.N., Zhang H.;
RT "Structural Basis of the Differential Function of the Two C. elegans Atg8
RT Homologs, LGG-1 and LGG-2, in Autophagy.";
RL Mol. Cell 60:914-929(2015).
RN [8]
RP FUNCTION.
RX PubMed=30133321; DOI=10.1152/ajpcell.00109.2018;
RA Hibshman J.D., Leuthner T.C., Shoben C., Mello D.F., Sherwood D.R.,
RA Meyer J.N., Baugh L.R.;
RT "Non-selective autophagy reduces mitochondrial content during starvation in
RT Caenorhabditis elegans.";
RL Am. J. Physiol. 2018:C0-C0(2018).
CC -!- FUNCTION: Protein kinase important for axonal elongation and axonal
CC guidance (PubMed:7958904, PubMed:15539493). Functions in the CAN axons
CC to direct both anterior and posterior migrations (PubMed:15539493).
CC Phosphorylates both unc-14 and vab-8 (PubMed:15539493). Component of
CC the unc-51/atg-13 complex that is probably recruited by lgg-1 to
CC preautophagosomes and is required for autophagosome formation
CC (PubMed:12958363, PubMed:17890369, PubMed:19377305, PubMed:26687600).
CC Interaction with autophagy related proteins such as atg-13 links it to
CC the autophagy machinery to in turn promote P-granule degradation in
CC somatic cells (PubMed:19377305). Plays a role in mitophagy during
CC limited food availability (PubMed:30133321). Regulates cell size
CC (PubMed:17890369). Plays a role in male tail ray pattern formation
CC (PubMed:17890369). May be required for normal dauer morphogenesis
CC (PubMed:12958363). {ECO:0000269|PubMed:12958363,
CC ECO:0000269|PubMed:15539493, ECO:0000269|PubMed:17890369,
CC ECO:0000269|PubMed:19377305, ECO:0000269|PubMed:26687600,
CC ECO:0000269|PubMed:30133321, ECO:0000269|PubMed:7958904}.
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:0000269|PubMed:15539493};
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:0000269|PubMed:15539493};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:15539493};
CC -!- SUBUNIT: Interacts with unc-14 and vab-8 (PubMed:15539493). Interacts
CC (via C-terminus) with atg-13 (PubMed:19377305). Interacts (via the LIR
CC motif) with lgg-1; the interaction is direct (PubMed:26687600).
CC {ECO:0000269|PubMed:15539493, ECO:0000269|PubMed:19377305,
CC ECO:0000269|PubMed:26687600}.
CC -!- INTERACTION:
CC Q23023; G5ECQ1: unc-14; NbExp=4; IntAct=EBI-329049, EBI-2419199;
CC Q23023; Q21441: vab-8; NbExp=4; IntAct=EBI-329049, EBI-2412191;
CC -!- DEVELOPMENTAL STAGE: During embryonic development unc-51 is expressed
CC extensively, particularly in the head region of late embryos. In the
CC larval stages, expression appears to be restricted to neurons.
CC {ECO:0000269|PubMed:7958904}.
CC -!- DOMAIN: The LIR motif (LC3-interacting region) is required for its
CC interaction with lgg-1. {ECO:0000269|PubMed:26687600}.
CC -!- DISRUPTION PHENOTYPE: Worms exhibit various abnormalities in axonal
CC elongation and axonal structures (PubMed:7958904). RNAi-mediated
CC knockdown causes abnormalities in constitutive dauer formation in daf-2
CC e1370 mutant including a lack of autophagosome formation
CC (PubMed:12958363). {ECO:0000269|PubMed:12958363,
CC ECO:0000269|PubMed:7958904}.
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; Z38016; CAA86114.1; -; mRNA.
DR EMBL; BX284605; CAB60406.1; -; Genomic_DNA.
DR PIR; T43631; T43631.
DR RefSeq; NP_507869.1; NM_075468.4.
DR PDB; 5AZG; X-ray; 1.81 A; C/D=353-361.
DR PDBsum; 5AZG; -.
DR AlphaFoldDB; Q23023; -.
DR SMR; Q23023; -.
DR BioGRID; 45271; 9.
DR ComplexPortal; CPX-4821; unc-51-atg-13 complex.
DR DIP; DIP-26124N; -.
DR IntAct; Q23023; 2.
DR STRING; 6239.Y60A3A.1; -.
DR iPTMnet; Q23023; -.
DR EPD; Q23023; -.
DR PaxDb; Q23023; -.
DR PeptideAtlas; Q23023; -.
DR EnsemblMetazoa; Y60A3A.1.1; Y60A3A.1.1; WBGene00006786.
DR GeneID; 180311; -.
DR KEGG; cel:CELE_Y60A3A.1; -.
DR UCSC; Y60A3A.1.1; c. elegans.
DR CTD; 180311; -.
DR WormBase; Y60A3A.1; CE24516; WBGene00006786; unc-51.
DR eggNOG; KOG0595; Eukaryota.
DR GeneTree; ENSGT00940000171394; -.
DR HOGENOM; CLU_011264_1_0_1; -.
DR InParanoid; Q23023; -.
DR OMA; MPNRTRT; -.
DR OrthoDB; 1084750at2759; -.
DR PhylomeDB; Q23023; -.
DR BRENDA; 2.7.11.1; 1045.
DR Reactome; R-CEL-1632852; Macroautophagy.
DR Reactome; R-CEL-8854214; TBC/RABGAPs.
DR Reactome; R-CEL-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR Reactome; R-CEL-8934903; Receptor Mediated Mitophagy.
DR PRO; PR:Q23023; -.
DR Proteomes; UP000001940; Chromosome V.
DR Bgee; WBGene00006786; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0005776; C:autophagosome; IC:ComplexPortal.
DR GO; GO:0030424; C:axon; IDA:WormBase.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; IDA:WormBase.
DR GO; GO:0043025; C:neuronal cell body; IDA:WormBase.
DR GO; GO:0034045; C:phagophore assembly site membrane; IBA:GO_Central.
DR GO; GO:1902554; C:serine/threonine protein kinase complex; IC:ComplexPortal.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IDA:WormBase.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0043277; P:apoptotic cell clearance; IMP:WormBase.
DR GO; GO:0000045; P:autophagosome assembly; IBA:GO_Central.
DR GO; GO:0006914; P:autophagy; IGI:WormBase.
DR GO; GO:0000422; P:autophagy of mitochondrion; IBA:GO_Central.
DR GO; GO:0048675; P:axon extension; IBA:GO_Central.
DR GO; GO:0007411; P:axon guidance; IMP:WormBase.
DR GO; GO:0007409; P:axonogenesis; IMP:WormBase.
DR GO; GO:0016477; P:cell migration; IMP:WormBase.
DR GO; GO:0040024; P:dauer larval development; IGI:WormBase.
DR GO; GO:0008340; P:determination of adult lifespan; IGI:WormBase.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IGI:WormBase.
DR GO; GO:0044805; P:late nucleophagy; IBA:GO_Central.
DR GO; GO:0016236; P:macroautophagy; IC:ComplexPortal.
DR GO; GO:0045138; P:nematode male tail tip morphogenesis; IMP:WormBase.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0034727; P:piecemeal microautophagy of the nucleus; IBA:GO_Central.
DR GO; GO:0010508; P:positive regulation of autophagy; IBA:GO_Central.
DR GO; GO:0012501; P:programmed cell death; IGI:WormBase.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:WormBase.
DR GO; GO:0006468; P:protein phosphorylation; IDA:WormBase.
DR GO; GO:0030516; P:regulation of axon extension; IMP:WormBase.
DR GO; GO:0008361; P:regulation of cell size; IMP:WormBase.
DR GO; GO:0040014; P:regulation of multicellular organism growth; IGI:WormBase.
DR GO; GO:0032880; P:regulation of protein localization; IMP:WormBase.
DR GO; GO:0042594; P:response to starvation; IBA:GO_Central.
DR GO; GO:0061709; P:reticulophagy; IBA:GO_Central.
DR InterPro; IPR045269; Atg1-like.
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; IPR022708; Ser/Thr_kinase_C.
DR InterPro; IPR017184; Ser/Thr_kinase_Unc51.
DR PANTHER; PTHR24348; PTHR24348; 2.
DR Pfam; PF12063; DUF3543; 1.
DR Pfam; PF00069; Pkinase; 1.
DR PIRSF; PIRSF037369; Ser/Thr_PK_unc51; 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.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Developmental protein; Differentiation; Kinase;
KW Magnesium; Metal-binding; Neurogenesis; Nucleotide-binding;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..856
FT /note="Serine/threonine-protein kinase unc-51"
FT /id="PRO_0000086785"
FT DOMAIN 9..275
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 304..327
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 362..391
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 405..471
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 520..582
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 750..856
FT /note="Required for interaction with unc-14 and vab-8"
FT /evidence="ECO:0000269|PubMed:15539493"
FT MOTIF 358..361
FT /note="LIR"
FT /evidence="ECO:0000269|PubMed:26687600"
FT COMPBIAS 411..442
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 520..537
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 548..582
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 134
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 15..23
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 39
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|PubMed:15539493,
FT ECO:0000305|PubMed:7958904"
FT SITE 357
FT /note="Required for interaction with lgg-1"
FT /evidence="ECO:0000269|PubMed:26687600"
FT MUTAGEN 37..41
FT /note="Missing: Abrogates kinase activity."
FT /evidence="ECO:0000269|PubMed:15539493"
FT MUTAGEN 39
FT /note="K->M: In KSEX9; variable effects."
FT /evidence="ECO:0000269|PubMed:15539493,
FT ECO:0000269|PubMed:7958904"
FT MUTAGEN 39
FT /note="K->R: Impairs kinase activity."
FT /evidence="ECO:0000269|PubMed:15539493,
FT ECO:0000269|PubMed:7958904"
FT MUTAGEN 358
FT /note="F->A: Impairs the interaction with lgg-1."
FT /evidence="ECO:0000269|PubMed:26687600"
FT MUTAGEN 360
FT /note="F->A: Impairs the interaction with lgg-1."
FT /evidence="ECO:0000269|PubMed:26687600"
FT MUTAGEN 841
FT /note="R->H: In E1120; paralyzed, egg laying defective and
FT dumpy."
FT /evidence="ECO:0000269|PubMed:7958904"
SQ SEQUENCE 856 AA; 94893 MW; 721F6F6FB0399F6E CRC64;
MEQFDGFEYS KRDLLGHGAF AIVYRGRYVD RTDVPVAIKA IAKKNISKSK NLLTKEIKIL
KELSSLKHEN LVGLLKCTET PTHVYLVMEF CNGGDLADYL QQKTTLNEDT IQHFVVQIAH
ALEAINKKGI VHRDLKPQNI LLCNNSRTQN PHFTDIVIKL ADFGFARFLN DGVMAATLCG
SPMYMAPEVI MSMQYDAKAD LWSIGTILFQ CLTGKAPFVA QTPPQLKAYY EKTRELRPNI
PEWCSPNLRD LLLRLLKRNA KDRISFEDFF NHPFLTSPLL PSPSKRILES ARSPLLANRR
IITPQSSLPV PKRAGSTKLD SPTPVRRIGE SPRVQRRVIT PGMPSPVPGA PMQESTDFTF
LPPRQESSPV KQVQVHTNVS PSLTTCKPVP VPSQRLTYQK MEERLAAARK TAVPSSSSPT
GSAVSAQHQH QHQQQQEPAS SPVVQRIERP DQLPRRTTLQ DPNAHDIERM TMPNPTFVVC
GSSTKPSPNN ANRVRRSTIT SPADTQDMVA ADQMLSNLDP TTTTTTIPKS ATTANIQGIP
RGARDRSVTS PPQPTIHENE PLDNAKYQQT DVNNSPTAPT EPFIIKNQTT CSTSSTSSSV
VEEEEAMSLP FASGSHLAAG FKKTPAEVPM DHGALPPALD QEIVLGEEHK QILAKLRFVA
ELVDTLIHVA EQKDNPLASA MASRRQLLTT GTSTTNTSSP YRRAEQLVVY VRALHMLSSA
LLLAQTNVAN RVLHPSVAVQ QVLNQLNDKY HQCLVRSQEL ASLGLPGQDP AMAVISAERI
MYRHAIELCQ AAALDELFGN PQLCSQRYQT AYMMLHTLAE QVNCDQDKTV LTRYKVAVEK
RLRILERQGF VAAVNT
