CBLA_DICDI
ID CBLA_DICDI Reviewed; 665 AA.
AC Q557E7; Q86HZ3;
DT 22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 02-MAY-2006, sequence version 1.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=E3 ubiquitin-protein ligase cblA;
DE EC=2.3.2.27 {ECO:0000305};
DE AltName: Full=Cbl-like protein A;
DE AltName: Full=RING finger protein cblA;
DE AltName: Full=RING-type E3 ubiquitin transferase cblA {ECO:0000305};
GN Name=cblA-1; ORFNames=DDB_G0273141;
GN and
GN Name=cblA-2; ORFNames=DDB_G0273609;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=12097910; DOI=10.1038/nature00847;
RA Gloeckner G., Eichinger L., Szafranski K., Pachebat J.A., Bankier A.T.,
RA Dear P.H., Lehmann R., Baumgart C., Parra G., Abril J.F., Guigo R.,
RA Kumpf K., Tunggal B., Cox E.C., Quail M.A., Platzer M., Rosenthal A.,
RA Noegel A.A.;
RT "Sequence and analysis of chromosome 2 of Dictyostelium discoideum.";
RL Nature 418:79-85(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [3]
RP DISRUPTION PHENOTYPE, FUNCTION, DEVELOPMENTAL STAGE, AND SUBCELLULAR
RP LOCATION.
RX PubMed=18840649; DOI=10.1242/jcs.036798;
RA Langenick J., Araki T., Yamada Y., Williams J.G.;
RT "A Dictyostelium homologue of the metazoan Cbl proteins regulates STAT
RT signalling.";
RL J. Cell Sci. 121:3524-3530(2008).
CC -!- FUNCTION: Acts as an E3 ubiquitin-protein ligase, which accepts
CC ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then
CC transfers it to substrates promoting their degradation by the
CC proteasome. Up-regulates STATc tyrosine phosphorylation via an
CC inhibitory effect on ptpC accumulation. Recognizes activated receptor
CC tyrosine kinases, RTKs and terminates signaling.
CC {ECO:0000269|PubMed:18840649}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000305};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18840649}. Nucleus
CC {ECO:0000269|PubMed:18840649}. Note=A very small proportion appears to
CC be nuclear but this may reflect cytoplasmic contamination of the
CC nuclei.
CC -!- DEVELOPMENTAL STAGE: Expressed in the slug stages (at protein level).
CC Expressed at a relatively low level in growing cells. Accumulates
CC during the first few hours of development, to reach a plateau during
CC aggregation. {ECO:0000269|PubMed:18840649}.
CC -!- DOMAIN: The RING-type zinc finger domain mediates binding to an E2
CC ubiquitin-conjugating enzyme. {ECO:0000250}.
CC -!- DOMAIN: The N-terminus is composed of the phosphotyrosine binding (PTB)
CC domain, a short linker region and the RING-type zinc finger. The PTB
CC domain, which is also called TKB (tyrosine kinase binding) domain, is
CC composed of three different subdomains: a four-helix bundle (4H), a
CC calcium-binding EF hand and a divergent SH2 domain.
CC {ECO:0000255|PROSITE-ProRule:PRU00839}.
CC -!- PTM: Ubiquitinated. {ECO:0000305}.
CC -!- DISRUPTION PHENOTYPE: Migrating slugs frequently fragment and the basal
CC disk of the culminants that are formed are absent or much reduced.
CC {ECO:0000269|PubMed:18840649}.
CC -!- CAUTION: The gene for this protein is duplicated in strains AX3 and
CC AX4. These strains contain a duplication of a segment of 750 kb of
CC chromosome 2 compared to the corresponding sequence in strain AX2.
CC {ECO:0000305}.
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DR EMBL; AAFI02000011; EAL70495.1; -; Genomic_DNA.
DR EMBL; AAFI02000009; EAL70788.1; -; Genomic_DNA.
DR RefSeq; XP_644421.1; XM_639329.1.
DR RefSeq; XP_644829.1; XM_639737.1.
DR AlphaFoldDB; Q557E7; -.
DR SMR; Q557E7; -.
DR STRING; 44689.DDB0238372; -.
DR PaxDb; Q557E7; -.
DR EnsemblProtists; EAL70495; EAL70495; DDB_G0273609.
DR EnsemblProtists; EAL70788; EAL70788; DDB_G0273141.
DR GeneID; 8618931; -.
DR GeneID; 8619046; -.
DR KEGG; ddi:DDB_G0273141; -.
DR KEGG; ddi:DDB_G0273609; -.
DR dictyBase; DDB_G0273141; cblA-1.
DR dictyBase; DDB_G0273609; cblA-2.
DR eggNOG; KOG1571; Eukaryota.
DR HOGENOM; CLU_413020_0_0_1; -.
DR InParanoid; Q557E7; -.
DR OMA; CMDNEIN; -.
DR Reactome; R-DDI-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR PRO; PR:Q557E7; -.
DR Proteomes; UP000002195; Chromosome 2.
DR GO; GO:0005829; C:cytosol; IDA:dictyBase.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IEA:InterPro.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0035556; P:intracellular signal transduction; IMP:dictyBase.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0030587; P:sorocarp development; IMP:dictyBase.
DR Gene3D; 3.30.40.10; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR014741; Adaptor_Cbl_EF_hand-like.
DR InterPro; IPR024159; Cbl_PTB.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF02761; Cbl_N2; 1.
DR Pfam; PF00017; SH2; 1.
DR SMART; SM00184; RING; 1.
DR SMART; SM00252; SH2; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS51506; CBL_PTB; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Calcium; Coiled coil; Cytoplasm; Metal-binding; Nucleus;
KW Reference proteome; Transferase; Ubl conjugation; Ubl conjugation pathway;
KW Zinc; Zinc-finger.
FT CHAIN 1..665
FT /note="E3 ubiquitin-protein ligase cblA"
FT /id="PRO_0000384443"
FT DOMAIN 109..400
FT /note="Cbl-PTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00839"
FT ZN_FING 618..653
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 30..50
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 109..231
FT /note="4H"
FT REGION 232..306
FT /note="EF-hand-like"
FT REGION 307..400
FT /note="SH2-like"
FT REGION 437..456
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 467..609
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 479..544
FT /evidence="ECO:0000255"
FT COMPBIAS 480..514
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 516..609
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 287
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P22681"
FT BINDING 289
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P22681"
FT BINDING 291
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P22681"
FT BINDING 293
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P22681"
SQ SEQUENCE 665 AA; 74962 MW; BD4072D145F87BAD CRC64;
MNRATITSNK SNAPSFLSIP LLAHNNNINN NNNNINNNNN NNNINSNNNG TTTTTTTTTI
TTISYKNNIS ELITIIDKII KDLNNFKSKT VLNDQEFSEL NNTIQFTKTS LVNYIHYENE
NKINFNLSDS KIICSEIKII EYGIESFIFS ICKLYQDLIQ FQQLLLKLSS PPTTITFNTT
INSTNSFTSN LIINNLLKVD SILKQSIDQL LALFPPSSSS LNNENNNNNN NNYNPYELLS
NEAKVLWNQF GGNKITFVPW SIFFKGFQKF FNKEILAYES SLRYTLDFTR DGYVTPFKLS
VFIKWFGALP VSLGIFQDVI NSKIFSGFIS GIEATQLLSR QQVGYYLLRC SKTIVGAFAI
TFVDSTNHIR HCLLYPVTSS INGGLTLQKP PDIFKSILSF ILSFSSKLKY PIGPLDNDLL
PPLSIINNNP ILILPDENNN NQNNNQNNNN NNINTFSTSP SSFFTIDSSN SSDTNKSPTK
SRKSSFKNDK DKKEKEKEKG KDKEKEKERV SDENFDNLPT FLNSEDENDN NNNNNNNNNN
NNNNNNNNNN NNNNNSSNNN NCNIKETHQT TSNGSSGNNN NNNNNNNNNN NNNNNNNSSS
TTKRNNNNNG SDESKDLCTV CMDNEINTVF LECGHLSCCS LCSVKLKKCP ICRSRITRVI
NIFKS
