##gff-version 3 P22681 UniProtKB Chain 1 906 . . . ID=PRO_0000055858;Note=E3 ubiquitin-protein ligase CBL P22681 UniProtKB Domain 47 351 . . . Note=Cbl-PTB;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00839 P22681 UniProtKB Domain 856 895 . . . Note=UBA;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00212 P22681 UniProtKB Zinc finger 381 420 . . . Note=RING-type;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00175 P22681 UniProtKB Region 1 357 . . . Note=Sufficient for interaction with EPHB1;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:18034775;Dbxref=PMID:18034775 P22681 UniProtKB Region 1 21 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P22681 UniProtKB Region 47 175 . . . Note=4H P22681 UniProtKB Region 176 248 . . . Note=EF-hand-like P22681 UniProtKB Region 249 351 . . . Note=SH2-like P22681 UniProtKB Region 352 380 . . . Note=Linker P22681 UniProtKB Region 358 906 . . . Note=Required for ubiquitination of SPRED2;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:17094949;Dbxref=PMID:17094949 P22681 UniProtKB Region 432 462 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P22681 UniProtKB Region 477 498 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P22681 UniProtKB Region 519 667 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P22681 UniProtKB Region 648 906 . . . Note=Interaction with CD2AP;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11067845;Dbxref=PMID:11067845 P22681 UniProtKB Region 680 719 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P22681 UniProtKB Region 743 781 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P22681 UniProtKB Region 799 854 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P22681 UniProtKB Compositional bias 536 553 . . . Note=Pro residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P22681 UniProtKB Compositional bias 603 623 . . . Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P22681 UniProtKB Compositional bias 639 653 . . . Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P22681 UniProtKB Compositional bias 799 818 . . . Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P22681 UniProtKB Compositional bias 835 854 . . . Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P22681 UniProtKB Binding site 229 229 . . . Ontology_term=ECO:0007744,ECO:0007744;evidence=ECO:0007744|PDB:1B47,ECO:0007744|PDB:2CBL P22681 UniProtKB Binding site 231 231 . . . Ontology_term=ECO:0007744,ECO:0007744;evidence=ECO:0007744|PDB:1B47,ECO:0007744|PDB:2CBL P22681 UniProtKB Binding site 233 233 . . . Ontology_term=ECO:0007744,ECO:0007744;evidence=ECO:0007744|PDB:1B47,ECO:0007744|PDB:2CBL P22681 UniProtKB Binding site 235 235 . . . Ontology_term=ECO:0007744,ECO:0007744;evidence=ECO:0007744|PDB:1B47,ECO:0007744|PDB:2CBL P22681 UniProtKB Binding site 240 240 . . . Ontology_term=ECO:0007744,ECO:0007744;evidence=ECO:0007744|PDB:1B47,ECO:0007744|PDB:2CBL P22681 UniProtKB Binding site 294 294 . . . Ontology_term=ECO:0000250;evidence=ECO:0000250 P22681 UniProtKB Modified residue 371 371 . . . Note=Phosphotyrosine%3B by INSR;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11997497;Dbxref=PMID:11997497 P22681 UniProtKB Modified residue 439 439 . . . Note=Phosphoserine;Ontology_term=ECO:0007744;evidence=ECO:0007744|PubMed:23186163;Dbxref=PMID:23186163 P22681 UniProtKB Modified residue 452 452 . . . Note=Phosphoserine;Ontology_term=ECO:0007744;evidence=ECO:0007744|PubMed:19690332;Dbxref=PMID:19690332 P22681 UniProtKB Modified residue 483 483 . . . Note=Phosphoserine;Ontology_term=ECO:0007744;evidence=ECO:0007744|PubMed:23186163;Dbxref=PMID:23186163 P22681 UniProtKB Modified residue 619 619 . . . Note=Phosphoserine;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P22682 P22681 UniProtKB Modified residue 642 642 . . . Note=Phosphoserine;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P22682 P22681 UniProtKB Modified residue 668 668 . . . Note=Phosphoserine;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P22682 P22681 UniProtKB Modified residue 669 669 . . . Note=Phosphoserine;Ontology_term=ECO:0007744;evidence=ECO:0007744|PubMed:23186163;Dbxref=PMID:23186163 P22681 UniProtKB Modified residue 674 674 . . . Note=Phosphotyrosine;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20622007;Dbxref=PMID:20622007 P22681 UniProtKB Modified residue 700 700 . . . Note=Phosphotyrosine%3B by ABL1;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:11997497,ECO:0000269|PubMed:15556646,ECO:0000269|PubMed:20622007;Dbxref=PMID:11997497,PMID:15556646,PMID:20622007 P22681 UniProtKB Modified residue 731 731 . . . Note=Phosphotyrosine%3B by SRC;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:14739300;Dbxref=PMID:14739300 P22681 UniProtKB Modified residue 774 774 . . . Note=Phosphotyrosine;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:11997497,ECO:0000269|PubMed:20622007;Dbxref=PMID:11997497,PMID:20622007 P22681 UniProtKB Modified residue 900 900 . . . Note=Phosphoserine;Ontology_term=ECO:0007744;evidence=ECO:0007744|PubMed:16964243;Dbxref=PMID:16964243 P22681 UniProtKB Natural variant 287 287 . . . ID=VAR_071040;Note=Found in patients with acute myeloid leukemia%3B uncertain significance. K->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20622007;Dbxref=PMID:20622007 P22681 UniProtKB Natural variant 365 365 . . . ID=VAR_071041;Note=Found in patients with acute myeloid leukemia%3B uncertain significance%3B loss of the ability to negatively regulate signaling pathways%3B promotes cell cycle progression%3B decreases apoptosis. Q->QSK P22681 UniProtKB Natural variant 367 367 . . . ID=VAR_064332;Note=In NSLL. Q->P;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20619386;Dbxref=dbSNP:rs267606704,PMID:20619386 P22681 UniProtKB Natural variant 371 371 . . . ID=VAR_071042;Note=Found in patients with acute myeloid leukemia%3B uncertain significance%3B loss of the ability to negatively regulate signaling pathways%3B promotes cell cycle progression%3B decreases apoptosis. Y->H;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20622007;Dbxref=dbSNP:rs267606706,PMID:20622007 P22681 UniProtKB Natural variant 382 382 . . . ID=VAR_064333;Note=In NSLL%3B dominant-negative%3B impairs CBL-mediated ubiquitination%2C internalization and degradation of the EGF receptor/EGFR%3B decreases the ability to negatively regulate EGFR signaling. K->E;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:25178484;Dbxref=dbSNP:rs267606705,PMID:25178484 P22681 UniProtKB Natural variant 390 390 . . . ID=VAR_064334;Note=In NSLL%3B dominant-negative%3B impairs CBL-mediated ubiquitination%2C internalization and degradation of the EGF receptor/EGFR%3B decreases the ability to negatively regulate EGFR signaling. D->Y;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:20619386,ECO:0000269|PubMed:25178484;Dbxref=dbSNP:rs267606707,PMID:20619386,PMID:25178484 P22681 UniProtKB Natural variant 420 420 . . . ID=VAR_064335;Note=In NSLL%3B dominant-negative%3B impairs CBL-mediated ubiquitination%2C internalization and degradation of the EGF receptor/EGFR%3B decreases the ability to negatively regulate EGFR signaling. R->Q;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:20619386,ECO:0000269|PubMed:25178484;Dbxref=dbSNP:rs267606708,PMID:20619386,PMID:25178484 P22681 UniProtKB Natural variant 499 499 . . . ID=VAR_071043;Note=Found in patients with acute myeloid leukemia%3B uncertain significance. R->L;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20622007;Dbxref=PMID:20622007 P22681 UniProtKB Natural variant 620 620 . . . ID=VAR_057211;Note=L->F;Dbxref=dbSNP:rs2227988 P22681 UniProtKB Natural variant 782 782 . . . ID=VAR_057212;Note=P->L;Dbxref=dbSNP:rs2229073 P22681 UniProtKB Natural variant 904 904 . . . ID=VAR_057213;Note=V->I;Dbxref=dbSNP:rs17122769 P22681 UniProtKB Mutagenesis 80 80 . . . Note=Abolishes interaction with ZAP70. S->D;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:10078535;Dbxref=PMID:10078535 P22681 UniProtKB Mutagenesis 82 82 . . . Note=Abolishes interaction with ZAP70. P->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:10078535;Dbxref=PMID:10078535 P22681 UniProtKB Mutagenesis 229 229 . . . Note=Abolishes interaction with ZAP70. D->Q;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:10078535;Dbxref=PMID:10078535 P22681 UniProtKB Mutagenesis 240 240 . . . Note=Abolishes interaction with ZAP70. E->S;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:10078535;Dbxref=PMID:10078535 P22681 UniProtKB Mutagenesis 294 294 . . . Note=Abolishes interaction with ZAP70. R->K;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:10078535;Dbxref=PMID:10078535 P22681 UniProtKB Mutagenesis 306 306 . . . Note=Abolishes interaction with ZAP70 and EPHB1%2C but does not affect interaction with SLA. Reduces ubiquitination and therefore proteasomal degradation of SPRED2. G->E;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:10078535,ECO:0000269|PubMed:10449770,ECO:0000269|PubMed:17094949;Dbxref=PMID:10078535,PMID:10449770,PMID:17094949 P22681 UniProtKB Mutagenesis 371 371 . . . Note=Strongly reduces tyrosine phosphorylation by INSR%3B when associated with F-700 and F-774. Y->F;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11997497;Dbxref=PMID:11997497 P22681 UniProtKB Mutagenesis 381 381 . . . Note=Loss of ubiquitin ligase activity. C->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11896602;Dbxref=PMID:11896602 P22681 UniProtKB Mutagenesis 674 674 . . . Note=Does not affect interaction with TNS4 following EGF stimulation. Y->F;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:23774213;Dbxref=PMID:23774213 P22681 UniProtKB Mutagenesis 700 700 . . . Note=Does not affect interaction with TNS4 following EGF stimulation. Strongly reduces tyrosine phosphorylation by INSR%3B when associated with F-371 and F-774. Y->F;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:11997497,ECO:0000269|PubMed:23774213;Dbxref=PMID:11997497,PMID:23774213 P22681 UniProtKB Mutagenesis 731 731 . . . Note=No effect on tyrosine phosphorylation by INSR. Loss of phosphorylation by SRC. Inhibition of bone resorption. Abolishes interaction with PIK3R1. Does not affect interaction with TNS4 following EGF stimulation. Y->F;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:11997497,ECO:0000269|PubMed:14739300,ECO:0000269|PubMed:23774213;Dbxref=PMID:11997497,PMID:14739300,PMID:23774213 P22681 UniProtKB Mutagenesis 774 774 . . . Note=Loss of interaction with TNS4 following EGF stimulation. Strongly reduces tyrosine phosphorylation by INSR%3B when associated with F-371 and F-700. Y->F;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:11997497,ECO:0000269|PubMed:23774213;Dbxref=PMID:11997497,PMID:23774213 P22681 UniProtKB Sequence conflict 15 15 . . . Note=S->T;Ontology_term=ECO:0000305;evidence=ECO:0000305 P22681 UniProtKB Helix 53 70 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3BUX P22681 UniProtKB Helix 73 75 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3BUX P22681 UniProtKB Beta strand 79 82 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7SIY P22681 UniProtKB Helix 84 101 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3BUX P22681 UniProtKB Turn 102 104 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7SIY P22681 UniProtKB Helix 106 111 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3BUX P22681 UniProtKB Helix 113 136 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3BUX P22681 UniProtKB Helix 137 141 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3BUX P22681 UniProtKB Beta strand 142 144 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:6XAR P22681 UniProtKB Helix 146 168 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3BUX P22681 UniProtKB Helix 170 172 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3BUX P22681 UniProtKB Helix 176 178 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3BUX P22681 UniProtKB Helix 184 194 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3BUX P22681 UniProtKB Beta strand 198 201 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3BUX P22681 UniProtKB Helix 202 212 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3BUX P22681 UniProtKB Helix 218 228 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3BUX P22681 UniProtKB Beta strand 233 237 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3BUX P22681 UniProtKB Helix 238 247 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3BUX P22681 UniProtKB Helix 251 253 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3BUX P22681 UniProtKB Helix 254 261 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3BUX P22681 UniProtKB Turn 262 264 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2Y1M P22681 UniProtKB Beta strand 268 271 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:5HKX P22681 UniProtKB Helix 274 281 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3BUX P22681 UniProtKB Helix 282 284 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3BUX P22681 UniProtKB Beta strand 290 295 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3BUX P22681 UniProtKB Beta strand 297 299 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3BUX P22681 UniProtKB Beta strand 302 308 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3BUX P22681 UniProtKB Turn 310 312 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3BUO P22681 UniProtKB Beta strand 314 317 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3BUX P22681 UniProtKB Beta strand 320 322 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3BUW P22681 UniProtKB Helix 324 333 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3BUX P22681 UniProtKB Helix 350 352 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:5HKX P22681 UniProtKB Beta strand 354 356 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1FBV P22681 UniProtKB Beta strand 360 362 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:4A49 P22681 UniProtKB Helix 365 378 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:5HKX P22681 UniProtKB Turn 382 384 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:5HKX P22681 UniProtKB Beta strand 385 388 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:5HKX P22681 UniProtKB Beta strand 391 394 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:5HKX P22681 UniProtKB Beta strand 398 400 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2K4D P22681 UniProtKB Helix 402 410 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:5HKX P22681 UniProtKB Turn 417 419 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:5HKX P22681 UniProtKB Beta strand 425 428 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:5HKX P22681 UniProtKB Beta strand 430 432 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:4A49 P22681 UniProtKB Helix 856 866 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2OO9 P22681 UniProtKB Helix 871 880 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2OO9 P22681 UniProtKB Turn 881 883 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2OO9 P22681 UniProtKB Helix 885 895 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2OO9