NUMB1_CAEEL
ID NUMB1_CAEEL Reviewed; 593 AA.
AC Q9XTY6; Q9BKB5; Q9XTY4;
DT 13-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Numb-related protein 1;
DE AltName: Full=CKA1;
DE AltName: Full=Protein kinase C adapter 1;
GN Name=num-1 {ECO:0000312|WormBase:T03D8.1c}; Synonyms=cka-1;
GN ORFNames=T03D8.1;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAK28740.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND C), FUNCTION, INTERACTION WITH
RP PKC-3, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP MUTAGENESIS OF PHE-175 AND PHE-221.
RC STRAIN=Bristol N2 {ECO:0000269|PubMed:11134024};
RX PubMed=11134024; DOI=10.1074/jbc.m008990200;
RA Zhang L., Wu S.-L., Rubin C.S.;
RT "A novel adapter protein employs a phosphotyrosine binding domain and
RT exceptionally basic N-terminal domains to capture and localize an atypical
RT protein kinase C: characterization of Caenorhabditis elegans C kinase
RT adapter 1, a protein that avidly binds protein kinase C3.";
RL J. Biol. Chem. 276:10463-10475(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING.
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] {ECO:0000305}
RP SUBCELLULAR LOCATION, INTERACTION WITH PKC-3, PHOSPHORYLATION AT SER-17 AND
RP SER-65, AND MUTAGENESIS OF SER-17 AND SER-65.
RX PubMed=11134025; DOI=10.1074/jbc.m008991200;
RA Zhang L., Wu S.-L., Rubin C.S.;
RT "Structural properties and mechanisms that govern association of C kinase
RT adapter 1 with protein kinase C3 and the cell periphery.";
RL J. Biol. Chem. 276:10476-10484(2001).
CC -!- FUNCTION: Involved in the tethering and targeting of pkc-3 to modulate
CC the intracellular distribution of the kinase. The complex formed with
CC pkc-3 complexes are likely to be involved in assembly, maintenance,
CC and/or regulation of protein complexes that execute asymmetric and/or
CC polarized cell functions. {ECO:0000269|PubMed:11134024}.
CC -!- SUBUNIT: Interacts with pkc-3. {ECO:0000269|PubMed:11134024,
CC ECO:0000269|PubMed:11134025}.
CC -!- INTERACTION:
CC Q9XTY6; Q9U2T9: itsn-1; NbExp=3; IntAct=EBI-495781, EBI-2414252;
CC Q9XTY6; Q19266: pkc-3; NbExp=5; IntAct=EBI-495781, EBI-319158;
CC Q9XTY6-1; Q19266: pkc-3; NbExp=5; IntAct=EBI-495798, EBI-319158;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cell cortex. Cytoplasm, cytoskeleton.
CC Membrane; Peripheral membrane protein. Note=Expressed at the inner
CC surface of the plasma membrane at the cell periphery (which includes a
CC region corresponding to plasma membrane and/or actin cortical
CC cytoskeleton) in early embryos. Tightly associated with organelles
CC and/or cytoskeletal structures with some diffuse expression in the
CC cytoplasm. Differentially routed to lateral junctions between polarized
CC cells.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=3;
CC Name=a {ECO:0000269|PubMed:11134024}; Synonyms=cka1
CC {ECO:0000303|PubMed:11134024};
CC IsoId=Q9XTY6-1; Sequence=Displayed;
CC Name=b;
CC IsoId=Q9XTY6-3; Sequence=VSP_051598, VSP_051599;
CC Name=c;
CC IsoId=Q9XTY6-4; Sequence=VSP_018786;
CC -!- TISSUE SPECIFICITY: Expressed in cells comprising the intestine,
CC pharyngeal cells, the anal sphincter and depressor muscles.
CC {ECO:0000269|PubMed:11134024}.
CC -!- DEVELOPMENTAL STAGE: Expressed at each stage of development with
CC predominance of isoform c in early larvae and isoform a in adults.
CC {ECO:0000269|PubMed:11134024}.
CC -!- DOMAIN: The PID domain (phosphotyrosine interaction domain) of isoform
CC a and isoform c is capable of binding residues 212-224 of pkc-3.
CC -!- MISCELLANEOUS: [Isoform b]: Produced by alternative splicing.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform c]: Produced by alternative initiation at Met-
CC 45 of isoform a. {ECO:0000305}.
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DR EMBL; AF286205; AAK28740.1; -; mRNA.
DR EMBL; AF286206; AAK28741.1; -; mRNA.
DR EMBL; Z92838; CAB07407.1; -; Genomic_DNA.
DR EMBL; Z92838; CAB07405.1; -; Genomic_DNA.
DR EMBL; Z92838; CAD30449.1; -; Genomic_DNA.
DR PIR; T24379; T24379.
DR PIR; T24381; T24381.
DR RefSeq; NP_001024097.1; NM_001028926.2. [Q9XTY6-3]
DR RefSeq; NP_001024098.1; NM_001028927.1. [Q9XTY6-4]
DR RefSeq; NP_508021.1; NM_075620.5. [Q9XTY6-1]
DR AlphaFoldDB; Q9XTY6; -.
DR SMR; Q9XTY6; -.
DR BioGRID; 45323; 3.
DR IntAct; Q9XTY6; 3.
DR MINT; Q9XTY6; -.
DR STRING; 6239.T03D8.1d; -.
DR iPTMnet; Q9XTY6; -.
DR EPD; Q9XTY6; -.
DR PaxDb; Q9XTY6; -.
DR PeptideAtlas; Q9XTY6; -.
DR PRIDE; Q9XTY6; -.
DR EnsemblMetazoa; T03D8.1a.1; T03D8.1a.1; WBGene00003830. [Q9XTY6-1]
DR EnsemblMetazoa; T03D8.1b.1; T03D8.1b.1; WBGene00003830. [Q9XTY6-3]
DR EnsemblMetazoa; T03D8.1c.1; T03D8.1c.1; WBGene00003830. [Q9XTY6-4]
DR GeneID; 180367; -.
DR UCSC; C28D4.2; c. elegans. [Q9XTY6-1]
DR CTD; 180367; -.
DR WormBase; T03D8.1a; CE18918; WBGene00003830; num-1. [Q9XTY6-1]
DR WormBase; T03D8.1b; CE18919; WBGene00003830; num-1. [Q9XTY6-3]
DR WormBase; T03D8.1c; CE30563; WBGene00003830; num-1. [Q9XTY6-4]
DR eggNOG; KOG3537; Eukaryota.
DR GeneTree; ENSGT00940000172612; -.
DR InParanoid; Q9XTY6; -.
DR PhylomeDB; Q9XTY6; -.
DR Reactome; R-CEL-437239; Recycling pathway of L1.
DR Reactome; R-CEL-5610780; Degradation of GLI1 by the proteasome.
DR Reactome; R-CEL-5632684; Hedgehog 'on' state.
DR PRO; PR:Q9XTY6; -.
DR Proteomes; UP000001940; Chromosome V.
DR Bgee; WBGene00003830; Expressed in embryo and 4 other tissues.
DR ExpressionAtlas; Q9XTY6; baseline and differential.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:WormBase.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0051117; F:ATPase binding; IPI:WormBase.
DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB.
DR GO; GO:0005080; F:protein kinase C binding; IPI:UniProtKB.
DR GO; GO:0005068; F:transmembrane receptor protein tyrosine kinase adaptor activity; IPI:UniProtKB.
DR GO; GO:0032456; P:endocytic recycling; IMP:WormBase.
DR GO; GO:0015914; P:phospholipid transport; IMP:WormBase.
DR GO; GO:0006612; P:protein targeting to membrane; IDA:UniProtKB.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR016698; Numb/numb-like.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR006020; PTB/PI_dom.
DR Pfam; PF00640; PID; 1.
DR PIRSF; PIRSF017607; Numb/numb-like; 1.
DR SMART; SM00462; PTB; 1.
DR PROSITE; PS01179; PID; 1.
PE 1: Evidence at protein level;
KW Alternative initiation; Alternative splicing; Cytoplasm; Cytoskeleton;
KW Developmental protein; Membrane; Phosphoprotein; Reference proteome.
FT CHAIN 1..593
FT /note="Numb-related protein 1"
FT /id="PRO_0000021867"
FT DOMAIN 102..255
FT /note="PID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT REGION 1..97
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 235..278
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 331..375
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 493..581
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 237..254
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 261..278
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 339..373
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 493..514
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 532..568
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 17
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000269|PubMed:11134025"
FT MOD_RES 65
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000269|PubMed:11134025"
FT VAR_SEQ 1..192
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_051598"
FT VAR_SEQ 1..44
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000303|PubMed:11134024"
FT /id="VSP_018786"
FT VAR_SEQ 193..370
FT /note="GASRRWMCHGFLATKETGERLSHAVGCAFSICLEKKKRRDEETAQVNVQSAQ
FT ESTSSTPPKDIFHPNWEDNTSEGTSTQNPSNSRSNLAYQSFRKHVSIEDRYLDPQSVII
FT NEVPASNHMDEIRRISKPRPTGNPALFLRQGSLRAPPDMPSSSDQFKRNMSLRTVSNNP
FT TERSPEKK -> MVLIDTEYVRAVVHNVGHRARCGVASKVRALKLAHSQARLRSYSQAC
FT ERASYIDGRCEYYPSLDVASSSRNSEMLNSGFFDGYSWNTPNIQSQSSSDVTAKTELRR
FT LMTETSEDPIHKEDSETLRRLIMWQEFRDAGVDVNTTQPGYGYGIEAKVEPFPQKLQNY
FT ESIHLETRRSSCP (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_051599"
FT MUTAGEN 17
FT /note="S->A: Has no effect on efficiently routing num-1 to
FT the cell periphery; when associated with A-65."
FT /evidence="ECO:0000269|PubMed:11134025"
FT MUTAGEN 17
FT /note="S->Q: Promotes accumulation of num-1 in the
FT cytoplasm; when associated with Q-65."
FT /evidence="ECO:0000269|PubMed:11134025"
FT MUTAGEN 65
FT /note="S->A: Has no effect on efficiently routing num-1 to
FT the cell periphery; when associated with A-17."
FT /evidence="ECO:0000269|PubMed:11134025"
FT MUTAGEN 65
FT /note="S->Q: Promotes accumulation of num-1 in the
FT cytoplasm; when associated with Q-17."
FT /evidence="ECO:0000269|PubMed:11134025"
FT MUTAGEN 175
FT /note="F->L: Prevents binding to pkc-3."
FT /evidence="ECO:0000269|PubMed:11134024"
FT MUTAGEN 221
FT /note="F->L: Prevents binding to pkc-3."
FT /evidence="ECO:0000269|PubMed:11134024"
SQ SEQUENCE 593 AA; 65510 MW; A3B0FE9C821D27D4 CRC64;
MSASQGNVFT RGLSRISRRK KKTKSIQNSL VSEQQPSFDA AIVPMPIPND KSSIFSKGMD
RLRRSLRLPK KRRDRSHDRH LSPDVTGGSK TEQWQPDEGA VRTGTCCFNV KYLGSVEVYE
SRGMQVCEGA LKSLKASRRK PVKAVLYVSG DGLRVVDQGN SRGLLVDQTI EKVSFCAPDR
QTDKGFAYIC RDGASRRWMC HGFLATKETG ERLSHAVGCA FSICLEKKKR RDEETAQVNV
QSAQESTSST PPKDIFHPNW EDNTSEGTST QNPSNSRSNL AYQSFRKHVS IEDRYLDPQS
VIINEVPASN HMDEIRRISK PRPTGNPALF LRQGSLRAPP DMPSSSDQFK RNMSLRTVSN
NPTERSPEKK SFGTQLYNEP IYEGDEDPLG LGITPPVVTK TSGSLSNNGL DGINLNWKSI
PAPVHQMQQH NANGDFVAAW PQNTIEKPTV GPLDKLQKQF EDIKLISISS GENTPTTRSK
ADEWLDDVLR VSMSMSPTSP SSDPPSTSSY SVLPKSGPPP AHAPPPLPVR QAVSNGSPSI
YQQQLQQANS TRNSPAGINW NSSPNPMKIS QPPAKPVDPF DVQWSRLAVN NTH
