SAD1_CAEEL
ID SAD1_CAEEL Reviewed; 914 AA.
AC Q19469; A3FPL0; Q9BMN6;
DT 10-AUG-2010, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2001, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Serine/threonine kinase SAD-1 {ECO:0000312|EMBL:AAG50270.1};
DE EC=2.7.11.1;
DE AltName: Full=Synapses of Amphids Defective {ECO:0000303|PubMed:17151015};
GN Name=sad-1 {ECO:0000312|WormBase:F15A2.6a}; ORFNames=F15A2.6;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAG50270.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, TISSUE SPECIFICITY, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=11182085; DOI=10.1016/s0896-6273(01)00184-2;
RA Crump J.G., Zhen M., Jin Y., Bargmann C.I.;
RT "The SAD-1 kinase regulates presynaptic vesicle clustering and axon
RT termination.";
RL Neuron 29:115-129(2001).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B), FUNCTION, INTERACTION WITH
RP NAB-1, AND DISRUPTION PHENOTYPE.
RX PubMed=17151015; DOI=10.1242/dev.02725;
RA Hung W., Hwang C., Po M.D., Zhen M.;
RT "Neuronal polarity is regulated by a direct interaction between a
RT scaffolding protein, Neurabin, and a presynaptic SAD-1 kinase in
RT Caenorhabditis elegans.";
RL Development 134:237-249(2007).
RN [3] {ECO:0000312|EMBL:CAA94127.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:CAA94127.2};
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 [4] {ECO:0000305}
RP FUNCTION, INTERACTION WITH STRD-1, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=20023164; DOI=10.1242/dev.041459;
RA Kim J.S., Hung W., Narbonne P., Roy R., Zhen M.;
RT "C. elegans STRADalpha and SAD cooperatively regulate neuronal polarity and
RT synaptic organization.";
RL Development 137:93-102(2010).
CC -!- FUNCTION: Regulates both neuronal polarity and synaptic organization
CC when bound to strd-1. Kinase activity is required for the
CC establishment, but not the maintenance, of both processes. Binding to
CC nab-1 is essential for role in restricting axonal fate during neuronal
CC polarization but is not required for regulating synapse morphology.
CC {ECO:0000269|PubMed:11182085, ECO:0000269|PubMed:17151015,
CC ECO:0000269|PubMed:20023164}.
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:20023164};
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:20023164};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:20023164};
CC -!- SUBUNIT: Interacts with strd-1 and nab-1. {ECO:0000269|PubMed:17151015,
CC ECO:0000269|PubMed:20023164}.
CC -!- SUBCELLULAR LOCATION: Synapse {ECO:0000269|PubMed:20023164}.
CC Note=Synapse localization is regulated by strd-1. Co-localizes with
CC strd-1 in synapses. {ECO:0000269|PubMed:20023164}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000269|PubMed:11182085, ECO:0000269|PubMed:17151015,
CC ECO:0000269|PubMed:9851916};
CC IsoId=Q19469-1; Sequence=Displayed;
CC Name=b {ECO:0000269|PubMed:17151015, ECO:0000269|PubMed:9851916};
CC IsoId=Q19469-2; Sequence=VSP_039684, VSP_039685;
CC -!- TISSUE SPECIFICITY: Expressed in neurons. Colocalizes with strd-1 along
CC the dorsal nerve cord. {ECO:0000269|PubMed:11182085,
CC ECO:0000269|PubMed:20023164}.
CC -!- DISRUPTION PHENOTYPE: Pre-synaptic vesicle and active zone proteins
CC fail to be restricted to the axons of motor and sensory neurons.
CC Synaptic vesicles fail to form tight clusters implying aberrant
CC synaptic organization in addition to defects in neuronal polarity.
CC Overexpression causes mislocalization of vesicle proteins to dendrites.
CC {ECO:0000269|PubMed:11182085, ECO:0000269|PubMed:17151015}.
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; AF316542; AAG50270.1; -; mRNA.
DR EMBL; Z70207; CAA94127.2; -; Genomic_DNA.
DR EMBL; Z70207; CAM33501.1; -; Genomic_DNA.
DR PIR; T20941; T20941.
DR RefSeq; NP_001076760.1; NM_001083291.2. [Q19469-1]
DR RefSeq; NP_001076761.1; NM_001083292.1. [Q19469-2]
DR AlphaFoldDB; Q19469; -.
DR SMR; Q19469; -.
DR BioGRID; 46373; 4.
DR STRING; 6239.F15A2.6a; -.
DR EPD; Q19469; -.
DR PaxDb; Q19469; -.
DR PeptideAtlas; Q19469; -.
DR EnsemblMetazoa; F15A2.6a.1; F15A2.6a.1; WBGene00004719. [Q19469-1]
DR EnsemblMetazoa; F15A2.6b.1; F15A2.6b.1; WBGene00004719. [Q19469-2]
DR GeneID; 181471; -.
DR KEGG; cel:CELE_F15A2.6; -.
DR UCSC; F15A2.6a; c. elegans.
DR CTD; 181471; -.
DR WormBase; F15A2.6a; CE28218; WBGene00004719; sad-1. [Q19469-1]
DR WormBase; F15A2.6b; CE40646; WBGene00004719; sad-1. [Q19469-2]
DR eggNOG; KOG0588; Eukaryota.
DR GeneTree; ENSGT00940000166887; -.
DR HOGENOM; CLU_000288_156_1_1; -.
DR InParanoid; Q19469; -.
DR OMA; LFALLVX; -.
DR OrthoDB; 1127668at2759; -.
DR PhylomeDB; Q19469; -.
DR PRO; PR:Q19469; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00004719; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IDA:WormBase.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0030425; C:dendrite; IDA:WormBase.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion 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; IBA:GO_Central.
DR GO; GO:0050321; F:tau-protein kinase activity; IDA:WormBase.
DR GO; GO:0008088; P:axo-dendritic transport; IGI:WormBase.
DR GO; GO:0007411; P:axon guidance; IMP:WormBase.
DR GO; GO:0007409; P:axonogenesis; IBA:GO_Central.
DR GO; GO:0042149; P:cellular response to glucose starvation; IBA:GO_Central.
DR GO; GO:0030010; P:establishment of cell polarity; IBA:GO_Central.
DR GO; GO:0007163; P:establishment or maintenance of cell polarity; IMP:WormBase.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:WormBase.
DR GO; GO:0099172; P:presynapse organization; IMP:WormBase.
DR GO; GO:0008104; P:protein localization; IGI:WormBase.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0030516; P:regulation of axon extension; IMP:WormBase.
DR GO; GO:0007416; P:synapse assembly; IMP:WormBase.
DR GO; GO:0050808; P:synapse organization; IMP:WormBase.
DR GO; GO:0048489; P:synaptic vesicle transport; IMP:WormBase.
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 Pfam; PF00069; Pkinase; 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 Alternative splicing; ATP-binding; Kinase; Magnesium; Metal-binding;
KW Neurogenesis; Nucleotide-binding; Reference proteome;
KW Serine/threonine-protein kinase; Synapse; Transferase.
FT CHAIN 1..914
FT /note="Serine/threonine kinase SAD-1"
FT /id="PRO_0000397233"
FT DOMAIN 47..298
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 375..551
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 563..590
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 757..914
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 420..461
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 494..529
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 530..551
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 781..906
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 169
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 53..61
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 76
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT VAR_SEQ 832..835
FT /note="ANSY -> GITS (in isoform b)"
FT /evidence="ECO:0000303|PubMed:17151015,
FT ECO:0000303|PubMed:9851916"
FT /id="VSP_039684"
FT VAR_SEQ 836..914
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000303|PubMed:17151015,
FT ECO:0000303|PubMed:9851916"
FT /id="VSP_039685"
SQ SEQUENCE 914 AA; 100840 MW; FDE311D31B249D3E CRC64;
MFEALKEVLG EINSKLAAVN NELSSKIMSE NIVSTRPVAQ AQYCGPYKLE KTLGKGQTGL
VKTGTHCITG RKVAIKIVNK EKLSESVLQK VEREIAIMKL IEHPHVLHLY DVYENKKYLY
LLLEHVSGGE LFDYLVRKGR LMSKEARKFF RQIISALDFC HAHNICHRDL KPENLLLDER
NNIKVADFGM ASLQVEGSML ETSCGSPHYA CPEVIRGEKY DGRKADVWSC GVILYALLVG
ALPFDDDNLR NLLEKVKRGV FHIPHFVPAD VQSLLRAMIE VDPGKRYSLA DVFKHPWVSG
TTKADPELEL PMSQVVQTHV IPGEDSIDPD VLRHMNCLGC FKDKQKLINE LLSPKHNTEK
MVYFLLLDRK RRRPAQEDDT EIVLRGAAQN NDPPKKRTDS SRTSRYPMGS IADGSPINPR
KTYGRNQKSG RHSSLGGSPT ESPRSSTRDL FGSSSSGSYS ARAGEDRDRG RSASRSTNSY
HYYTQPVDPQ TLAEAARHVR DAQERRESRD SGRGSSRKES KDRSDKSASS SSCKNDASST
SSVPHKYSPP SVMSESVVVS SSTMNSTNSS TNSLIAGNSQ TSIGSTSGPW RSKLNNIKNS
FLGTPRFHRR KMSNGTAESD SEDSQMIDTT DLVKKSWFGS LASSMSVERD DTHCVPVQGK
TLNSIKAELI RAFLQIHELS HSVVGQNCFR VEYKRGPTVG GSVFSRGIKM NVDIIPSPQQ
VVIAGETPTY VVQFVLLAGP VRRFKRLVEH LSAILQNSTQ QRADRQQQAA LMVRPRRLSD
SSVGSACSDS ESNASSINMI ARHSDKTETT SATSSDPYGP SPSMRSVGSG TANSYKSPTP
HRRNTTAVTA SSSSASNRYG PSSSSSGSYS NNADYSYHPE YSQRSNGSSA PKNQYSPGSQ
RSFAFSMFNK ADKV
