MADD3_CAEEL
ID MADD3_CAEEL Reviewed; 887 AA.
AC G5EDB2; G5EGK0;
DT 22-NOV-2017, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 71.
DE RecName: Full=Probable dual specificity protein kinase madd-3 {ECO:0000305};
DE EC=2.7.11.- {ECO:0000255|PROSITE-ProRule:PRU00159};
DE AltName: Full=Muscle arm development defective protein 3 {ECO:0000312|WormBase:E02H4.3a};
GN Name=madd-3 {ECO:0000312|WormBase:E02H4.3a};
GN Synonyms=tag-172 {ECO:0000312|WormBase:E02H4.3a};
GN ORFNames=E02H4.3 {ECO:0000312|WormBase:E02H4.3a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
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 [2] {ECO:0000305}
RP FUNCTION (ISOFORM A), SUBCELLULAR LOCATION (ISOFORM A), TISSUE SPECIFICITY
RP (ISOFORM A), DEVELOPMENTAL STAGE (ISOFORM A), DISRUPTION PHENOTYPE, AND
RP MUTAGENESIS OF LYS-580.
RX PubMed=27123983; DOI=10.1371/journal.pgen.1006010;
RA D'Souza S.A., Rajendran L., Bagg R., Barbier L., van Pel D.M., Moshiri H.,
RA Roy P.J.;
RT "The MADD-3 LAMMER kinase interacts with a p38 MAP kinase pathway to
RT regulate the display of the EVA-1 guidance receptor in Caenorhabditis
RT elegans.";
RL PLoS Genet. 12:E1006010-E1006010(2016).
CC -!- FUNCTION: [Isoform a]: Probable dual specificity kinase acting on both
CC serine/threonine and tyrosine-containing substrates. Negatively
CC regulates p38 MAPK signaling to allow for the plasma membrane of body
CC wall muscle cells to form projections, also called muscle arms, that
CC extend and connect the body wall muscles to target motor neurons.
CC Negative regulation of p38 MAPK signaling may in turn modulate the
CC trafficking of the muscle specific receptor eva-1 to the lysosome, to
CC ensure proper display of the eva-1 receptor on the plasma membrane of
CC muscle cells and allow for muscle arm extension towards guidance cues.
CC {ECO:0000269|PubMed:27123983}.
CC -!- SUBCELLULAR LOCATION: [Isoform a]: Cytoplasm
CC {ECO:0000269|PubMed:27123983}. Nucleus {ECO:0000269|PubMed:27123983}.
CC Note=Enriched in the cytoplasm. {ECO:0000269|PubMed:27123983}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:E02H4.3a};
CC IsoId=G5EDB2-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:E02H4.3b};
CC IsoId=G5EDB2-2; Sequence=VSP_059228;
CC -!- TISSUE SPECIFICITY: [Isoform a]: Expressed in body wall, vulval and
CC anal depressor muscles. {ECO:0000269|PubMed:27123983}.
CC -!- DEVELOPMENTAL STAGE: [Isoform a]: Expressed from embryogenesis to
CC adulthood. {ECO:0000269|PubMed:27123983}.
CC -!- DISRUPTION PHENOTYPE: Viable, but sterile. Defective extension of body
CC wall muscle connections or arms towards the ventral nerve cord. Reduced
CC expression of the late endosome marker rab-7, and the eva-1 and unc-40
CC receptors, which are expressed in muscles, and impaired recruitment of
CC madd-4 to the muscle membrane. Double knockout with cup-5 results in
CC increased expression of the eva-1 receptor and rab-7 positive
CC endosomes. Double knockout with eva-1, gex-2, madd-2, madd-4, mkk-4,
CC unc-15, unc-60, unc-93 or unc-98 results in severe muscle arm extension
CC defects as compared to the single knockouts. Double knockout with
CC proteins involved in the p38 MAPK signaling pathway including cebp-1,
CC mak-2, pmk-3 or sek-3 suppress the muscle arm extension defects and
CC eva-1 expression defects in the madd-3 single knockout. Double knockout
CC with dlk-1 also suppresses the eva-1 expression defect, but does not
CC suppress the muscle arm extension defects in the madd-3 single
CC knockout. Double knockout with cebp-1, mak-2 or pmk-3 restores the
CC defect in the recruitment of madd-4 to the muscle membrane in the madd-
CC 3 single knockout. Furthermore, double knockout with pmk-3 restores the
CC reduced rab-7 expression level defect in the madd-3 single knockout.
CC Double knockout with unc-54 results in lethality. Triple knockout with
CC unc-54, and either cebp-1, dlk-1, mak-2, pmk-3 or sek-3 results in
CC paralysis (as in the unc-54 single knockout), and suppresses the
CC lethality phenotype in the double madd-3 and unc-54 mutant.
CC {ECO:0000269|PubMed:27123983}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. Lammer subfamily. {ECO:0000305}.
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DR EMBL; BX284606; CAA91979.2; -; Genomic_DNA.
DR EMBL; BX284606; CAD44105.1; -; Genomic_DNA.
DR PIR; T19209; T19209.
DR RefSeq; NP_741927.1; NM_171798.1.
DR RefSeq; NP_741928.1; NM_171799.4. [G5EDB2-1]
DR AlphaFoldDB; G5EDB2; -.
DR SMR; G5EDB2; -.
DR STRING; 6239.E02H4.3a; -.
DR EPD; G5EDB2; -.
DR PaxDb; G5EDB2; -.
DR PeptideAtlas; G5EDB2; -.
DR EnsemblMetazoa; E02H4.3a.1; E02H4.3a.1; WBGene00006517. [G5EDB2-1]
DR EnsemblMetazoa; E02H4.3b.1; E02H4.3b.1; WBGene00006517.
DR GeneID; 3565068; -.
DR CTD; 3565068; -.
DR WormBase; E02H4.3a; CE31462; WBGene00006517; madd-3. [G5EDB2-1]
DR WormBase; E02H4.3b; CE52798; WBGene00006517; madd-3. [G5EDB2-2]
DR eggNOG; KOG0671; Eukaryota.
DR GeneTree; ENSGT00940000154947; -.
DR HOGENOM; CLU_004425_0_0_1; -.
DR InParanoid; G5EDB2; -.
DR OMA; LNDHANE; -.
DR OrthoDB; 290680at2759; -.
DR PRO; PR:G5EDB2; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00006517; Expressed in embryo and 4 other tissues.
DR ExpressionAtlas; G5EDB2; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0043484; P:regulation of RNA splicing; IBA:GO_Central.
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; Cytoplasm; Kinase; Nucleotide-binding;
KW Nucleus; Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Tyrosine-protein kinase.
FT CHAIN 1..887
FT /note="Probable dual specificity protein kinase madd-3"
FT /evidence="ECO:0000305"
FT /id="PRO_0000442342"
FT DOMAIN 551..863
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 77..147
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 163..299
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 313..333
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 347..475
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 504..533
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 87..113
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 174..199
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 256..270
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 347..367
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 368..383
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 401..421
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 435..466
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 508..527
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 677
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 557..565
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 580
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT VAR_SEQ 1..512
FT /note="MPILHQKIASTGGQPSTNSLALRRLPLVVIPRKRKYKNYVSRRRNTQLLASL
FT RRCVSDPNVYKSYNHWKALLRPMTPIKSGAPTPKTVTPMPVPQIPPHQKMTPNPTPTQN
FT PVQLPLPHAVSEKPGDKKSTGPTPSPVPSKAPISAAKLPGTVTKVAPLLSAAQPPPKTL
FT APAPGASETNSGSGPVSKQVSGKLTELKSKNGTVTEKTEKAVLRIPSSASTRAKAASAV
FT APEANPAPVPTATKPSPFAPAIAPLRDGAPAQPPAPIQASAPLRPPVAKQNSLQKPPEP
FT KRSVGAPPKALPSELVNKIDGIEFLPQSSNQNTDDGQQPTTSTGGAKALRRAYGSKSGT
FT TICAIGSPNVPSTSQPQQGDNEKRLIEKKLSLRKKKLSGEGVPPAGSMLTGSKSGVEIG
FT LSSNLTTTNNNNNKEQTDEQRAKKTVNAVAAAFSTQAGSGNATTVDDPASTTTSKENPA
FT AQPPKPKSAAVQNLISQLQLPASVSAKVDKIIACGDKARKPSRSGLQ -> MIANSKTI
FT KIVNKKQAAISRPRVPIVPHQRTPIP (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_059228"
FT MUTAGEN 580
FT /note="K->R: Kinase dead. Defective extension of muscle
FT arms towards motor neuron targets."
FT /evidence="ECO:0000269|PubMed:27123983"
SQ SEQUENCE 887 AA; 96910 MW; 58DB91BC2CAE6C76 CRC64;
MPILHQKIAS TGGQPSTNSL ALRRLPLVVI PRKRKYKNYV SRRRNTQLLA SLRRCVSDPN
VYKSYNHWKA LLRPMTPIKS GAPTPKTVTP MPVPQIPPHQ KMTPNPTPTQ NPVQLPLPHA
VSEKPGDKKS TGPTPSPVPS KAPISAAKLP GTVTKVAPLL SAAQPPPKTL APAPGASETN
SGSGPVSKQV SGKLTELKSK NGTVTEKTEK AVLRIPSSAS TRAKAASAVA PEANPAPVPT
ATKPSPFAPA IAPLRDGAPA QPPAPIQASA PLRPPVAKQN SLQKPPEPKR SVGAPPKALP
SELVNKIDGI EFLPQSSNQN TDDGQQPTTS TGGAKALRRA YGSKSGTTIC AIGSPNVPST
SQPQQGDNEK RLIEKKLSLR KKKLSGEGVP PAGSMLTGSK SGVEIGLSSN LTTTNNNNNK
EQTDEQRAKK TVNAVAAAFS TQAGSGNATT VDDPASTTTS KENPAAQPPK PKSAAVQNLI
SQLQLPASVS AKVDKIIACG DKARKPSRSG LQASQARPKV PEIVSSQRTQ HQDDKDGHLI
YSKGDFILNR FTIYDTLGEG TFGKVVRVND SLSDTFMALK IIKNVSKYRE AAKLEVKVLQ
KLAEKDPEKK NWVIHMGSYF DYNGHICLLF DLMGSSIFDF LKANHYKPYP MEQTLHITWQ
LCNAVKFLHD NKLTHTDLKP ENILFVDSRY TTKLVDKKPL RVLHSTHVRL IDFGSATFDH
EHHSIIVSTR HYRAPEVILE LGWSQPCDVW SIGCILYELY TGVTLFQTHE NREHLAMMER
VLGDIPLRMA KRTKTKFFIN GRLDWVNTSA DAAYVRDNCK PLRRSMSCTD PEHVELFELI
ENMLMFEPLA RMKLPEALQH RYFNRLPENL KIPCKMDAST NPRINGD
