CBLC_HUMAN
ID CBLC_HUMAN Reviewed; 474 AA.
AC Q9ULV8; Q8N1E5; Q9Y5Z2; Q9Y5Z3;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 3.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=E3 ubiquitin-protein ligase CBL-C;
DE EC=2.3.2.27 {ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:20525694, ECO:0000269|PubMed:23145173};
DE AltName: Full=RING finger protein 57;
DE AltName: Full=RING-type E3 ubiquitin transferase CBL-C {ECO:0000305};
DE AltName: Full=SH3-binding protein CBL-3;
DE AltName: Full=SH3-binding protein CBL-C;
DE AltName: Full=Signal transduction protein CBL-C;
GN Name=CBLC; Synonyms=CBL3, RNF57;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT TYR-405.
RX PubMed=10571044; DOI=10.1016/s0378-1119(99)00356-x;
RA Kim M., Tezuka T., Suzuki Y., Sugano S., Hirai M., Yamamoto T.;
RT "Molecular cloning and characterization of a novel cbl-family gene, cbl-
RT c.";
RL Gene 239:145-154(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANT TYR-405, FUNCTION AS
RP EGF SIGNALING NEGATIVE REGULATOR, PHOSPHORYLATION BY EGFR (ISOFORM 1),
RP TISSUE SPECIFICITY, AND INTERACTION WITH CRK AND LYN.
RC TISSUE=Pancreatic adenocarcinoma;
RX PubMed=10362357; DOI=10.1038/sj.onc.1202753;
RA Keane M.M., Ettenberg S.A., Nau M.M., Banerjee P., Cuello M., Penninger J.,
RA Lipkowitz S.;
RT "cbl-3: a new mammalian cbl family protein.";
RL Oncogene 18:3365-3375(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION AS E3 UBIQUITIN-PROTEIN LIGASE, CATALYTIC ACTIVITY, INTERACTION
RP WITH SRC, AUTOUBIQUITINATION, AND MUTAGENESIS OF GLY-276; TYR-341 AND
RP CYS-351.
RX PubMed=14661060; DOI=10.1038/sj.onc.1207298;
RA Kim M., Tezuka T., Tanaka K., Yamamoto T.;
RT "Cbl-c suppresses v-Src-induced transformation through ubiquitin-dependent
RT protein degradation.";
RL Oncogene 23:1645-1655(2004).
RN [5]
RP FUNCTION IN RET STABILITY, INTERACTION WITH RET, AND MUTAGENESIS OF GLY-276
RP AND CYS-351.
RX PubMed=18753381; DOI=10.1523/jneurosci.2738-08.2008;
RA Tsui C.C., Pierchala B.A.;
RT "CD2AP and Cbl-3/Cbl-c constitute a critical checkpoint in the regulation
RT of ret signal transduction.";
RL J. Neurosci. 28:8789-8800(2008).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, DOMAIN, INTERACTION WITH
RP UBE2D2 AND UBE2D3, PHOSPHORYLATION AT TYR-341, AND MUTAGENESIS OF TYR-341.
RX PubMed=20525694; DOI=10.1074/jbc.m109.091157;
RA Ryan P.E., Sivadasan-Nair N., Nau M.M., Nicholas S., Lipkowitz S.;
RT "The N terminus of Cbl-c regulates ubiquitin ligase activity by modulating
RT affinity for the ubiquitin-conjugating enzyme.";
RL J. Biol. Chem. 285:23687-23698(2010).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AUTOUBIQUITINATION, PHOSPHORYLATION AT
RP TYR-341, INTERACTION WITH TGFB1I1, AND MUTAGENESIS OF TYR-341; CYS-351 AND
RP CYS-366.
RX PubMed=23145173; DOI=10.1371/journal.pone.0049428;
RA Ryan P.E., Kales S.C., Yadavalli R., Nau M.M., Zhang H., Lipkowitz S.;
RT "Cbl-c ubiquitin ligase activity is increased via the interaction of its
RT RING finger domain with a LIM domain of the paxillin homolog, Hic 5.";
RL PLoS ONE 7:E49428-E49428(2012).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.52 ANGSTROMS) OF 9-323 IN COMPLEX WITH EGFR
RP PEPTIDE.
RG Structural genomics consortium (SGC);
RT "Crystal structure of Cbl-c (Cbl-3) TKB domain in complex with EGFR py1069
RT peptide.";
RL Submitted (OCT-2010) to the PDB data bank.
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.52 ANGSTROMS) OF 1-323 IN COMPLEX WITH CALCIUM;
RP SRC AND EGFR PEPTIDES, CALCIUM-BINDING, INTERACTION WITH EGFR AND SRC, AND
RP MUTAGENESIS OF TYR-244; ARG-264; PRO-265; SER-266; THR-268 AND GLY-276.
RX PubMed=22888118; DOI=10.1093/jb/mvs085;
RA Takeshita K., Tezuka T., Isozaki Y., Yamashita E., Suzuki M., Kim M.,
RA Yamanashi Y., Yamamoto T., Nakagawa A.;
RT "Structural flexibility regulates phosphopeptide-binding activity of the
RT tyrosine kinase binding domain of Cbl-c.";
RL J. Biochem. 152:487-495(2012).
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. Functionally coupled with the E2 ubiquitin-protein ligases
CC UB2D1, UB2D2 and UB2D3. Regulator of EGFR mediated signal transduction;
CC upon EGF activation, ubiquitinates EGFR. Isoform 1, but not isoform 2,
CC inhibits EGF stimulated MAPK1 activation. Promotes ubiquitination of
CC SRC phosphorylated at 'Tyr-419'. In collaboration with CD2AP may act as
CC regulatory checkpoint for Ret signaling by modulating the rate of RET
CC degradation after ligand activation; CD2AP converts it from an
CC inhibitor to a promoter of RET degradation; the function limits the
CC potency of GDNF on neuronal survival. {ECO:0000269|PubMed:10362357,
CC ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:18753381,
CC ECO:0000269|PubMed:20525694, ECO:0000269|PubMed:23145173}.
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:0000269|PubMed:14661060,
CC ECO:0000269|PubMed:20525694, ECO:0000269|PubMed:23145173};
CC -!- ACTIVITY REGULATION: Phosphorylation at Tyr-341 is necessary and
CC sufficient for the activation of E3 activity.
CC {ECO:0000269|PubMed:20525694}.
CC -!- SUBUNIT: Interacts with ubiquitin-conjugating enzyme E2 UBE2D2 and
CC UBE2D3. Isoform 1 interacts with EGFR (tyrosine phosphorylated).
CC Interacts with the SH3 domain proteins LYN and CRK. Interacts (via
CC RING-type zinc finger) with TGFB1I1 (via LIM zinc-binding domain 2);
CC the interaction is direct and enhances the E3 activity. Interacts
CC directly with RET (inactive) and CD2AP; dissociates from RET upon RET
CC activation by GDNF which also increases the interaction with CD2AP
CC suggesting dissociation as CBLC:CD2AP complex. Interacts with SRC; the
CC interaction is enhanced when SRC is phosphorylated at 'Tyr-419'.
CC {ECO:0000269|PubMed:10362357, ECO:0000269|PubMed:14661060,
CC ECO:0000269|PubMed:18753381, ECO:0000269|PubMed:20525694,
CC ECO:0000269|PubMed:22888118, ECO:0000269|PubMed:23145173,
CC ECO:0000269|Ref.8}.
CC -!- INTERACTION:
CC Q9ULV8; P54253: ATXN1; NbExp=6; IntAct=EBI-2341018, EBI-930964;
CC Q9ULV8; Q13148: TARDBP; NbExp=3; IntAct=EBI-2341018, EBI-372899;
CC Q9ULV8; P61086: UBE2K; NbExp=3; IntAct=EBI-2341018, EBI-473850;
CC Q9ULV8; P07947: YES1; NbExp=3; IntAct=EBI-2341018, EBI-515331;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Long;
CC IsoId=Q9ULV8-1; Sequence=Displayed;
CC Name=2; Synonyms=Short;
CC IsoId=Q9ULV8-2; Sequence=VSP_005732;
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:10362357}.
CC -!- DOMAIN: EF-hand-like and Sh2-like domains are required for N-terminal
CC inhibition of E3 activity. {ECO:0000269|PubMed:20525694}.
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, ECO:0000269|PubMed:20525694}.
CC -!- DOMAIN: The RING-type zinc finger domain mediates binding to an E2
CC ubiquitin-conjugating enzyme. {ECO:0000250}.
CC -!- PTM: Phosphorylated on multiple tyrosine residues by SRC. Isoform 1,
CC but not isoform 2, is phosphorylated on tyrosines by EGFR.
CC -!- PTM: Autoubiquitinated when phosphorylated at Tyr-341, enhanced by SRC;
CC suggesting proteasomal degradation. {ECO:0000269|PubMed:14661060,
CC ECO:0000269|PubMed:20525694, ECO:0000269|PubMed:23145173}.
CC -!- MISCELLANEOUS: This protein has one functional calcium-binding site.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CBLcID194.html";
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DR EMBL; AB028645; BAA86298.1; -; mRNA.
DR EMBL; AF117646; AAD34341.1; -; mRNA.
DR EMBL; AF117647; AAD34342.1; -; mRNA.
DR EMBL; BC028915; AAH28915.1; -; mRNA.
DR CCDS; CCDS12643.1; -. [Q9ULV8-1]
DR CCDS; CCDS46109.1; -. [Q9ULV8-2]
DR RefSeq; NP_001124324.1; NM_001130852.1. [Q9ULV8-2]
DR RefSeq; NP_036248.3; NM_012116.3. [Q9ULV8-1]
DR PDB; 3OP0; X-ray; 2.52 A; A/B=9-323.
DR PDB; 3VRN; X-ray; 1.64 A; A=1-323.
DR PDB; 3VRO; X-ray; 1.80 A; A=1-323.
DR PDB; 3VRP; X-ray; 1.52 A; A=1-323.
DR PDB; 3VRQ; X-ray; 2.39 A; A/B=1-323.
DR PDB; 3VRR; X-ray; 2.00 A; A=1-323.
DR PDBsum; 3OP0; -.
DR PDBsum; 3VRN; -.
DR PDBsum; 3VRO; -.
DR PDBsum; 3VRP; -.
DR PDBsum; 3VRQ; -.
DR PDBsum; 3VRR; -.
DR AlphaFoldDB; Q9ULV8; -.
DR SMR; Q9ULV8; -.
DR BioGRID; 117156; 69.
DR IntAct; Q9ULV8; 35.
DR MINT; Q9ULV8; -.
DR STRING; 9606.ENSP00000270279; -.
DR iPTMnet; Q9ULV8; -.
DR PhosphoSitePlus; Q9ULV8; -.
DR BioMuta; CBLC; -.
DR DMDM; 125987803; -.
DR EPD; Q9ULV8; -.
DR jPOST; Q9ULV8; -.
DR MassIVE; Q9ULV8; -.
DR MaxQB; Q9ULV8; -.
DR PaxDb; Q9ULV8; -.
DR PeptideAtlas; Q9ULV8; -.
DR PRIDE; Q9ULV8; -.
DR ProteomicsDB; 85137; -. [Q9ULV8-1]
DR ProteomicsDB; 85138; -. [Q9ULV8-2]
DR Antibodypedia; 3762; 391 antibodies from 31 providers.
DR DNASU; 23624; -.
DR Ensembl; ENST00000341505.4; ENSP00000340250.4; ENSG00000142273.13. [Q9ULV8-2]
DR Ensembl; ENST00000647358.2; ENSP00000494162.1; ENSG00000142273.13. [Q9ULV8-1]
DR GeneID; 23624; -.
DR KEGG; hsa:23624; -.
DR MANE-Select; ENST00000647358.2; ENSP00000494162.1; NM_012116.4; NP_036248.3.
DR UCSC; uc002ozs.4; human. [Q9ULV8-1]
DR CTD; 23624; -.
DR DisGeNET; 23624; -.
DR GeneCards; CBLC; -.
DR HGNC; HGNC:15961; CBLC.
DR HPA; ENSG00000142273; Tissue enhanced (esophagus, intestine, skin).
DR MIM; 608453; gene.
DR neXtProt; NX_Q9ULV8; -.
DR OpenTargets; ENSG00000142273; -.
DR PharmGKB; PA26117; -.
DR VEuPathDB; HostDB:ENSG00000142273; -.
DR eggNOG; KOG1785; Eukaryota.
DR GeneTree; ENSGT00940000162336; -.
DR HOGENOM; CLU_013535_2_0_1; -.
DR InParanoid; Q9ULV8; -.
DR OMA; GGTCPFC; -.
DR OrthoDB; 540689at2759; -.
DR PhylomeDB; Q9ULV8; -.
DR TreeFam; TF314210; -.
DR PathwayCommons; Q9ULV8; -.
DR SignaLink; Q9ULV8; -.
DR SIGNOR; Q9ULV8; -.
DR BioGRID-ORCS; 23624; 17 hits in 1110 CRISPR screens.
DR GeneWiki; CBLC; -.
DR GenomeRNAi; 23624; -.
DR Pharos; Q9ULV8; Tbio.
DR PRO; PR:Q9ULV8; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9ULV8; protein.
DR Bgee; ENSG00000142273; Expressed in mucosa of transverse colon and 94 other tissues.
DR ExpressionAtlas; Q9ULV8; baseline and differential.
DR Genevisible; Q9ULV8; HS.
DR GO; GO:0045121; C:membrane raft; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; IDA:BHF-UCL.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IDA:BHF-UCL.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IBA:GO_Central.
DR GO; GO:0017124; F:SH3 domain binding; IDA:BHF-UCL.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:BHF-UCL.
DR GO; GO:0008270; F:zinc ion binding; TAS:ProtInc.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IEA:InterPro.
DR GO; GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0007175; P:negative regulation of epidermal growth factor-activated receptor activity; IDA:BHF-UCL.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; IDA:BHF-UCL.
DR GO; GO:0016567; P:protein ubiquitination; IDA:BHF-UCL.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:BHF-UCL.
DR CDD; cd09920; SH2_Cbl-b_TKB; 1.
DR Gene3D; 1.20.930.20; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR IDEAL; IID00287; -.
DR InterPro; IPR024162; Adaptor_Cbl.
DR InterPro; IPR014741; Adaptor_Cbl_EF_hand-like.
DR InterPro; IPR036537; Adaptor_Cbl_N_dom_sf.
DR InterPro; IPR003153; Adaptor_Cbl_N_hlx.
DR InterPro; IPR014742; Adaptor_Cbl_SH2-like.
DR InterPro; IPR024159; Cbl_PTB.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR23007; PTHR23007; 1.
DR Pfam; PF02262; Cbl_N; 1.
DR Pfam; PF02761; Cbl_N2; 1.
DR Pfam; PF02762; Cbl_N3; 1.
DR SMART; SM00184; RING; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF47668; SSF47668; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS51506; CBL_PTB; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Metal-binding; Phosphoprotein;
KW Reference proteome; Repeat; SH3-binding; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..474
FT /note="E3 ubiquitin-protein ligase CBL-C"
FT /id="PRO_0000055866"
FT DOMAIN 7..321
FT /note="Cbl-PTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00839"
FT ZN_FING 351..390
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 7..145
FT /note="4H"
FT REGION 146..218
FT /note="EF-hand-like"
FT REGION 219..321
FT /note="SH2-like"
FT REGION 322..350
FT /note="Linker"
FT REGION 351..474
FT /note="Interaction with RET"
FT /evidence="ECO:0000269|PubMed:18753381"
FT REGION 409..474
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 431..447
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 199
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P22681"
FT BINDING 201
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P22681"
FT BINDING 210
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P22681"
FT BINDING 264
FT /ligand="4-O-phospho-L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:62338"
FT MOD_RES 341
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000269|PubMed:20525694,
FT ECO:0000269|PubMed:23145173"
FT VAR_SEQ 261..306
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10362357"
FT /id="VSP_005732"
FT VARIANT 405
FT /note="H -> Y (in dbSNP:rs3208856)"
FT /evidence="ECO:0000269|PubMed:10362357,
FT ECO:0000269|PubMed:10571044"
FT /id="VAR_018298"
FT MUTAGEN 244
FT /note="Y->A: Abolishes interaction with EGFR. Decreases
FT interaction with SRC and abolishes SRC ubiquitination."
FT /evidence="ECO:0000269|PubMed:22888118"
FT MUTAGEN 244
FT /note="Y->F: No effect on interaction with EGFR and SRC as
FT well as on SRC ubiquitination."
FT /evidence="ECO:0000269|PubMed:22888118"
FT MUTAGEN 264
FT /note="R->A: Abolishes interaction with EGFR. Decreases
FT interaction with SRC and abolishes SRC ubiquitination."
FT /evidence="ECO:0000269|PubMed:22888118"
FT MUTAGEN 265
FT /note="P->L: Enhances interaction with EGFR and SRC as well
FT as SRC ubiquitination."
FT /evidence="ECO:0000269|PubMed:22888118"
FT MUTAGEN 266
FT /note="S->A: Decreases interactions with EGFR and SRC as
FT well as SRC ubiquitination."
FT /evidence="ECO:0000269|PubMed:22888118"
FT MUTAGEN 268
FT /note="T->A: Abolishes interaction with EGFR. Decreases
FT interaction with and ubiquitination of SRC."
FT /evidence="ECO:0000269|PubMed:22888118"
FT MUTAGEN 276
FT /note="G->E: No effect on interaction with RET. Binds
FT slightly to SRC, this interaction is independent of SRC
FT phosphorylation. Strongly decreases SRC ubiquitination.
FT Abolishes interaction with EGFR."
FT /evidence="ECO:0000269|PubMed:14661060,
FT ECO:0000269|PubMed:18753381, ECO:0000269|PubMed:22888118"
FT MUTAGEN 341
FT /note="Y->E: Induces E3 activity and autoubiquitination.
FT Releases ubiquitin-conjugating enzyme E2 UBE2D2 faster."
FT /evidence="ECO:0000269|PubMed:14661060,
FT ECO:0000269|PubMed:20525694, ECO:0000269|PubMed:23145173"
FT MUTAGEN 341
FT /note="Y->F: Abolishes activation by EGF stimulation and
FT enhancement by TGFB1I1 of E3 activity."
FT /evidence="ECO:0000269|PubMed:14661060,
FT ECO:0000269|PubMed:20525694, ECO:0000269|PubMed:23145173"
FT MUTAGEN 341
FT /note="Missing: Abolishes E3 activity."
FT /evidence="ECO:0000269|PubMed:14661060,
FT ECO:0000269|PubMed:20525694, ECO:0000269|PubMed:23145173"
FT MUTAGEN 351
FT /note="C->A: No effect on TGFB1I1 and SRC interactions.
FT Abolishes SRC ubiquitination. Abolishes interaction with
FT TGFB1I1; when associated with A-366. Abolishes interaction
FT with RET and inhibition of RET degradation."
FT /evidence="ECO:0000269|PubMed:14661060,
FT ECO:0000269|PubMed:18753381, ECO:0000269|PubMed:23145173"
FT MUTAGEN 366
FT /note="C->A: Abolishes interaction with TGFB1I1. Abolishes
FT interaction with TGFB1I1; when associated with A-351."
FT /evidence="ECO:0000269|PubMed:23145173"
FT CONFLICT 234
FT /note="N -> T (in Ref. 1; BAA86298)"
FT /evidence="ECO:0000305"
FT CONFLICT 413
FT /note="S -> P (in Ref. 3; AAH28915)"
FT /evidence="ECO:0000305"
FT HELIX 13..31
FT /evidence="ECO:0007829|PDB:3VRP"
FT STRAND 40..42
FT /evidence="ECO:0007829|PDB:3OP0"
FT HELIX 44..62
FT /evidence="ECO:0007829|PDB:3VRP"
FT STRAND 64..66
FT /evidence="ECO:0007829|PDB:3VRP"
FT HELIX 76..97
FT /evidence="ECO:0007829|PDB:3VRP"
FT STRAND 100..102
FT /evidence="ECO:0007829|PDB:3OP0"
FT HELIX 108..111
FT /evidence="ECO:0007829|PDB:3OP0"
FT HELIX 116..138
FT /evidence="ECO:0007829|PDB:3VRP"
FT HELIX 140..142
FT /evidence="ECO:0007829|PDB:3VRP"
FT TURN 146..148
FT /evidence="ECO:0007829|PDB:3VRP"
FT HELIX 154..164
FT /evidence="ECO:0007829|PDB:3VRP"
FT STRAND 168..171
FT /evidence="ECO:0007829|PDB:3VRP"
FT HELIX 172..179
FT /evidence="ECO:0007829|PDB:3VRP"
FT TURN 180..182
FT /evidence="ECO:0007829|PDB:3VRP"
FT HELIX 189..198
FT /evidence="ECO:0007829|PDB:3VRP"
FT STRAND 203..207
FT /evidence="ECO:0007829|PDB:3VRP"
FT HELIX 208..217
FT /evidence="ECO:0007829|PDB:3VRP"
FT HELIX 221..223
FT /evidence="ECO:0007829|PDB:3VRP"
FT HELIX 224..232
FT /evidence="ECO:0007829|PDB:3VRP"
FT STRAND 238..241
FT /evidence="ECO:0007829|PDB:3VRQ"
FT HELIX 244..251
FT /evidence="ECO:0007829|PDB:3VRP"
FT HELIX 252..254
FT /evidence="ECO:0007829|PDB:3VRP"
FT STRAND 260..265
FT /evidence="ECO:0007829|PDB:3VRP"
FT STRAND 267..269
FT /evidence="ECO:0007829|PDB:3VRP"
FT STRAND 273..278
FT /evidence="ECO:0007829|PDB:3VRP"
FT STRAND 284..287
FT /evidence="ECO:0007829|PDB:3VRP"
FT HELIX 294..303
FT /evidence="ECO:0007829|PDB:3VRP"
FT HELIX 320..323
FT /evidence="ECO:0007829|PDB:3OP0"
SQ SEQUENCE 474 AA; 52456 MW; 202634AEDE434544 CRC64;
MALAVAPWGR QWEEARALGR AVRMLQRLEE QCVDPRLSVS PPSLRDLLPR TAQLLREVAH
SRRAAGGGGP GGPGGSGDFL LIYLANLEAK SRQVAALLPP RGRRSANDEL FRAGSRLRRQ
LAKLAIIFSH MHAELHALFP GGKYCGHMYQ LTKAPAHTFW RESCGARCVL PWAEFESLLG
TCHPVEPGCT ALALRTTIDL TCSGHVSIFE FDVFTRLFQP WPTLLKNWQL LAVNHPGYMA
FLTYDEVQER LQACRDKPGS YIFRPSCTRL GQWAIGYVSS DGSILQTIPA NKPLSQVLLE
GQKDGFYLYP DGKTHNPDLT ELGQAEPQQR IHVSEEQLQL YWAMDSTFEL CKICAESNKD
VKIEPCGHLL CSCCLAAWQH SDSQTCPFCR CEIKGWEAVS IYQFHGQATA EDSGNSSDQE
GRELELGQVP LSAPPLPPRP DLPPRKPRNA QPKVRLLKGN SPPAALGPQD PAPA
