CBLB_HUMAN
ID CBLB_HUMAN Reviewed; 982 AA.
AC Q13191; A8K9S7; B7WNM4; Q13192; Q13193; Q3LIC0; Q63Z43; Q8IVC5;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 07-FEB-2006, sequence version 2.
DT 03-AUG-2022, entry version 225.
DE RecName: Full=E3 ubiquitin-protein ligase CBL-B;
DE EC=2.3.2.27 {ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:20525694};
DE AltName: Full=Casitas B-lineage lymphoma proto-oncogene b;
DE AltName: Full=RING finger protein 56;
DE AltName: Full=RING-type E3 ubiquitin transferase CBL-B {ECO:0000305};
DE AltName: Full=SH3-binding protein CBL-B;
DE AltName: Full=Signal transduction protein CBL-B;
GN Name=CBLB; Synonyms=RNF56; ORFNames=Nbla00127;
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] (ISOFORMS LONG; TRUNCATED 1 AND TRUNCATED 2).
RX PubMed=7784085;
RA Keane M.M., Rivero-Lezcano O.M., Mitchell J.A., Robbins K.C., Lipkowitz S.;
RT "Cloning and characterization of cbl-b: a SH3 binding protein with homology
RT to the c-cbl proto-oncogene.";
RL Oncogene 10:2367-2377(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), TISSUE SPECIFICITY, AND
RP INTERACTION WITH VAV1.
RX PubMed=9399639; DOI=10.1038/sj.onc.1201430;
RA Bustelo X.R., Crespo P., Lopez-Barahona M., Gutkind J.S., Barbacid M.;
RT "Cbl-b, a member of the Sli-1/c-Cbl protein family, inhibits Vav-mediated
RT c-Jun N-terminal kinase activation.";
RL Oncogene 15:2511-2520(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
RA Shen C.-R., Chen Y.-J., Pai L.-M., Liu C.-L.;
RT "Cbl-b in Taiwan population.";
RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
RC TISSUE=Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG), AND VARIANT LYS-584.
RC TISSUE=Testis;
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 543-982 (ISOFORM LONG).
RC TISSUE=Neuroblastoma;
RX PubMed=12880961; DOI=10.1016/s0304-3835(03)00085-5;
RA Ohira M., Morohashi A., Nakamura Y., Isogai E., Furuya K., Hamano S.,
RA Machida T., Aoyama M., Fukumura M., Miyazaki K., Suzuki Y., Sugano S.,
RA Hirato J., Nakagawara A.;
RT "Neuroblastoma oligo-capping cDNA project: toward the understanding of the
RT genesis and biology of neuroblastoma.";
RL Cancer Lett. 197:63-68(2003).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 857-982 (ISOFORM LONG).
RC TISSUE=Small intestine;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [10]
RP TISSUE SPECIFICITY, MUTAGENESIS OF GLY-298; TYR-665 AND TYR-709,
RP INTERACTION WITH GRB2 AND CRKL, PHOSPHORYLATION AT TYR-665 AND TYR-709, AND
RP FUNCTION.
RX PubMed=10022120; DOI=10.1038/sj.onc.1202411;
RA Elly C., Witte S., Zhang Z., Rosnet O., Lipkowitz S., Altman A., Liu Y.-C.;
RT "Tyrosine phosphorylation and complex formation of Cbl-b upon T cell
RT receptor stimulation.";
RL Oncogene 18:1147-1156(1999).
RN [11]
RP FUNCTION, PHOSPHORYLATION, AND INTERACTION WITH GRB2 AND PIK3R1.
RX PubMed=10086340; DOI=10.1038/sj.onc.1202499;
RA Ettenberg S.A., Keane M.M., Nau M.M., Frankel M., Wang L.-M., Pierce J.H.,
RA Lipkowitz S.;
RT "cbl-b inhibits epidermal growth factor receptor signaling.";
RL Oncogene 18:1855-1866(1999).
RN [12]
RP FUNCTION, INTERACTION WITH PIK3R1, AND MUTAGENESIS OF GLY-298 AND CYS-373.
RX PubMed=11087752; DOI=10.1074/jbc.m008901200;
RA Fang D., Wang H.-Y., Fang N., Altman Y., Elly C., Liu Y.-C.;
RT "Cbl-b, a RING-type E3 ubiquitin ligase, targets phosphatidylinositol 3-
RT kinase for ubiquitination in T cells.";
RL J. Biol. Chem. 276:4872-4878(2001).
RN [13]
RP UBIQUITINATION, AND MUTAGENESIS OF CYS-373.
RX PubMed=11375397; DOI=10.1074/jbc.m102641200;
RA Ettenberg S.A., Magnifico A., Cuello M., Nau M.M., Rubinstein Y.R.,
RA Yarden Y., Weissman A.M., Lipkowitz S.;
RT "Cbl-b-dependent coordinated degradation of the epidermal growth factor
RT receptor signaling complex.";
RL J. Biol. Chem. 276:27677-27684(2001).
RN [14]
RP FUNCTION.
RX PubMed=11526404; DOI=10.1038/ni0901-870;
RA Fang D., Liu Y.-C.;
RT "Proteolysis-independent regulation of PI3K by Cbl-b-mediated
RT ubiquitination in T cells.";
RL Nat. Immunol. 2:870-875(2001).
RN [15]
RP INTERACTION WITH SH3KBP1, AND SUBCELLULAR LOCATION.
RX PubMed=12177062; DOI=10.1074/jbc.m205535200;
RA Szymkiewicz I., Kowanetz K., Soubeyran P., Dinarina A., Lipkowitz S.,
RA Dikic I.;
RT "CIN85 participates in Cbl-b-mediated down-regulation of receptor tyrosine
RT kinases.";
RL J. Biol. Chem. 277:39666-39672(2002).
RN [16]
RP FUNCTION, AND CATALYTIC ACTIVITY.
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 [17]
RP INTERACTION WITH UBIQUITINATED PROTEINS, AND MUTAGENESIS OF 943-GLY-TYR-944
RP AND LEU-967.
RX PubMed=15273720; DOI=10.1038/sj.onc.1207952;
RA Davies G.C., Ettenberg S.A., Coats A.O., Mussante M., Ravichandran S.,
RA Collins J., Nau M.M., Lipkowitz S.;
RT "Cbl-b interacts with ubiquitinated proteins; differential functions of the
RT UBA domains of c-Cbl and Cbl-b.";
RL Oncogene 23:7104-7115(2004).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-521; SER-525 AND SER-529, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [20]
RP PHOSPHORYLATION AT SER-282.
RX PubMed=19549985; DOI=10.1126/scisignal.2000046;
RA Gruber T., Hermann-Kleiter N., Hinterleitner R., Fresser F., Schneider R.,
RA Gastl G., Penninger J.M., Baier G.;
RT "PKC-theta modulates the strength of T cell responses by targeting Cbl-b
RT for ubiquitination and degradation.";
RL Sci. Signal. 2:RA30-RA30(2009).
RN [21]
RP FUNCTION AS E3 UBIQUITIN-PROTEIN LIGASE, CATALYTIC ACTIVITY,
RP PHOSPHORYLATION AT TYR-363, AND MUTAGENESIS OF TYR-363.
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 [22]
RP INDUCTION, AND INTERACTION WITH IFT20 AND CBL.
RX PubMed=29237719; DOI=10.1083/jcb.201611050;
RA Schmid F.M., Schou K.B., Vilhelm M.J., Holm M.S., Breslin L., Farinelli P.,
RA Larsen L.A., Andersen J.S., Pedersen L.B., Christensen S.T.;
RT "IFT20 modulates ciliary PDGFRalpha signaling by regulating the stability
RT of Cbl E3 ubiquitin ligases.";
RL J. Cell Biol. 217:151-161(2018).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 899-914 IN COMPLEXES WITH SH3KBP1
RP AND ARHGEF7, MUTAGENESIS OF ARG-904 AND ARG-911, AND SUBUNIT.
RX PubMed=16228008; DOI=10.1038/nsmb1000;
RA Jozic D., Cardenes N., Deribe Y.L., Moncalian G., Hoeller D., Groemping Y.,
RA Dikic I., Rittinger K., Bravo J.;
RT "Cbl promotes clustering of endocytic adaptor proteins.";
RL Nat. Struct. Mol. Biol. 12:972-979(2005).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 902-912 IN COMPLEX WITH CD2AP,
RP MUTAGENESIS OF ARG-904; LYS-907 AND ARG-911, AND SUBUNIT.
RX PubMed=17020880; DOI=10.1074/jbc.m606411200;
RA Moncalian G., Cardenes N., Deribe Y.L., Spinola-Amilibia M., Dikic I.,
RA Bravo J.;
RT "Atypical polyproline recognition by the CMS N-terminal Src homology 3
RT domain.";
RL J. Biol. Chem. 281:38845-38853(2006).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (1.56 ANGSTROMS) OF 924-973 IN COMPLEX WITH
RP UBIQUITIN, STRUCTURE BY NMR OF 924-973, TYROSINE PHOSPHORYLATION, AND
RP MUTAGENESIS OF ALA-937; MET-940; PHE-946 AND ILE-966.
RX PubMed=17679095; DOI=10.1016/j.molcel.2007.06.023;
RA Peschard P., Kozlov G., Lin T., Mirza I.A., Berghuis A.M., Lipkowitz S.,
RA Park M., Gehring K.;
RT "Structural basis for ubiquitin-mediated dimerization and activation of the
RT ubiquitin protein ligase Cbl-b.";
RL Mol. Cell 27:474-485(2007).
RN [26]
RP STRUCTURE BY NMR OF 931-970.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of RSGI RUH-065, a UBA domain from human cDNA.";
RL Submitted (MAY-2007) to the PDB data bank.
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.27 ANGSTROMS) OF 38-344 IN COMPLEX WITH
RP PHOSPHO-EGFR PEPTIDE, INTERACTION WITH EGFR, AND HETERODIMER.
RG Structural genomics consortium (SGC);
RT "Crystal structure of Cbl-b TKB domain in complex with EGFR pY1069
RT peptide.";
RL Submitted (OCT-2010) to the PDB data bank.
CC -!- FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from
CC specific E2 ubiquitin-conjugating enzymes, and transfers it to
CC substrates, generally promoting their degradation by the proteasome.
CC Negatively regulates TCR (T-cell receptor), BCR (B-cell receptor) and
CC FCER1 (high affinity immunoglobulin epsilon receptor) signal
CC transduction pathways. In naive T-cells, inhibits VAV1 activation upon
CC TCR engagement and imposes a requirement for CD28 costimulation for
CC proliferation and IL-2 production. Also acts by promoting PIK3R1/p85
CC ubiquitination, which impairs its recruitment to the TCR and subsequent
CC activation. In activated T-cells, inhibits PLCG1 activation and calcium
CC mobilization upon restimulation and promotes anergy. In B-cells, acts
CC by ubiquitinating SYK and promoting its proteasomal degradation.
CC Slightly promotes SRC ubiquitination. May be involved in EGFR
CC ubiquitination and internalization. May be functionally coupled with
CC the E2 ubiquitin-protein ligase UB2D3. In association with CBL,
CC required for proper feedback inhibition of ciliary platelet-derived
CC growth factor receptor-alpha (PDGFRA) signaling pathway via
CC ubiquitination and internalization of PDGFRA (By similarity).
CC {ECO:0000250|UniProtKB:Q3TTA7, ECO:0000269|PubMed:10022120,
CC ECO:0000269|PubMed:10086340, ECO:0000269|PubMed:11087752,
CC ECO:0000269|PubMed:11526404, ECO:0000269|PubMed:14661060,
CC ECO:0000269|PubMed:20525694}.
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};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with SH3 domain-containing proteins LCK, CRK and
CC SORBS1. Interacts with LCP2 and ZAP70. Interacts with CBL
CC (PubMed:29237719). Interacts with SH3 domain-containing proteins VAV1,
CC FYN, FGR, PLCG1, GRB2, CRKL, PIK3R1 and SH3KBP1/CIN85. Identified in
CC heterotrimeric complexes with SH3KBP1/CIN85, CD2AP and ARHGEF7, where
CC one CBLB peptide binds two copies of the other protein. Interacts with
CC poly-ubiquitinated proteins. Dimerization is required for the binding
CC of poly-ubiquitin, but not for the binding of mono-ubiquitin. Interacts
CC with EGFR (phosphorylated). Interacts with IFT20 (PubMed:29237719).
CC {ECO:0000269|PubMed:10022120, ECO:0000269|PubMed:10086340,
CC ECO:0000269|PubMed:11087752, ECO:0000269|PubMed:12177062,
CC ECO:0000269|PubMed:15273720, ECO:0000269|PubMed:16228008,
CC ECO:0000269|PubMed:17020880, ECO:0000269|PubMed:17679095,
CC ECO:0000269|PubMed:29237719, ECO:0000269|PubMed:9399639,
CC ECO:0000269|Ref.27}.
CC -!- INTERACTION:
CC Q13191; Q8IZP0: ABI1; NbExp=2; IntAct=EBI-744027, EBI-375446;
CC Q13191; Q9ULH1: ASAP1; NbExp=2; IntAct=EBI-744027, EBI-346622;
CC Q13191; Q9Y5K6: CD2AP; NbExp=11; IntAct=EBI-744027, EBI-298152;
CC Q13191; P46108: CRK; NbExp=4; IntAct=EBI-744027, EBI-886;
CC Q13191; P46109: CRKL; NbExp=4; IntAct=EBI-744027, EBI-910;
CC Q13191; O75190: DNAJB6; NbExp=3; IntAct=EBI-744027, EBI-1053164;
CC Q13191; Q01658: DR1; NbExp=3; IntAct=EBI-744027, EBI-750300;
CC Q13191; P35637: FUS; NbExp=3; IntAct=EBI-744027, EBI-400434;
CC Q13191; P06241-3: FYN; NbExp=4; IntAct=EBI-744027, EBI-10691738;
CC Q13191; O76003: GLRX3; NbExp=3; IntAct=EBI-744027, EBI-374781;
CC Q13191; Q9H8Y8: GORASP2; NbExp=8; IntAct=EBI-744027, EBI-739467;
CC Q13191; P62993: GRB2; NbExp=26; IntAct=EBI-744027, EBI-401755;
CC Q13191; Q00403: GTF2B; NbExp=3; IntAct=EBI-744027, EBI-389564;
CC Q13191; Q9Y5Q9: GTF3C3; NbExp=3; IntAct=EBI-744027, EBI-1054873;
CC Q13191; Q5S007: LRRK2; NbExp=4; IntAct=EBI-744027, EBI-5323863;
CC Q13191; P16333: NCK1; NbExp=4; IntAct=EBI-744027, EBI-389883;
CC Q13191; O43639: NCK2; NbExp=8; IntAct=EBI-744027, EBI-713635;
CC Q13191; P35240-4: NF2; NbExp=3; IntAct=EBI-744027, EBI-1014514;
CC Q13191; P55345: PRMT2; NbExp=3; IntAct=EBI-744027, EBI-78458;
CC Q13191; Q13882: PTK6; NbExp=3; IntAct=EBI-744027, EBI-1383632;
CC Q13191; Q96B97: SH3KBP1; NbExp=22; IntAct=EBI-744027, EBI-346595;
CC Q13191; P00441: SOD1; NbExp=3; IntAct=EBI-744027, EBI-990792;
CC Q13191; O94875-10: SORBS2; NbExp=3; IntAct=EBI-744027, EBI-12037893;
CC Q13191; Q6NUL7: SPTLC1; NbExp=3; IntAct=EBI-744027, EBI-25912847;
CC Q13191; Q13148: TARDBP; NbExp=6; IntAct=EBI-744027, EBI-372899;
CC Q13191; P57075-2: UBASH3A; NbExp=3; IntAct=EBI-744027, EBI-7353612;
CC Q13191; Q8TF42: UBASH3B; NbExp=6; IntAct=EBI-744027, EBI-1380492;
CC Q13191; Q9UKW4: VAV3; NbExp=3; IntAct=EBI-744027, EBI-297568;
CC Q13191; O14972: VPS26C; NbExp=3; IntAct=EBI-744027, EBI-7207091;
CC Q13191; P07947: YES1; NbExp=3; IntAct=EBI-744027, EBI-515331;
CC Q13191-1; Q9BXL7: CARD11; NbExp=4; IntAct=EBI-15555129, EBI-7006141;
CC Q13191-1; Q96B97-1: SH3KBP1; NbExp=3; IntAct=EBI-15555129, EBI-7585212;
CC Q13191-1; P62837: UBE2D2; NbExp=2; IntAct=EBI-15555129, EBI-347677;
CC Q13191-1; O55043: Arhgef7; Xeno; NbExp=2; IntAct=EBI-15555129, EBI-3649585;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12177062}.
CC Note=Upon EGF stimulation, associates with endocytic vesicles.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=Long;
CC IsoId=Q13191-1; Sequence=Displayed;
CC Name=Truncated 1;
CC IsoId=Q13191-2; Sequence=VSP_005729;
CC Name=Truncated 2;
CC IsoId=Q13191-3; Sequence=VSP_005730, VSP_005731;
CC -!- TISSUE SPECIFICITY: Expressed in placenta, heart, lung, kidney, spleen,
CC ovary and testis, as well as fetal brain and liver and hematopoietic
CC cell lines, but not in adult brain, liver, pancreas, salivary gland, or
CC skeletal muscle. Present in lymphocytes (at protein level).
CC {ECO:0000269|PubMed:10022120, ECO:0000269|PubMed:9399639}.
CC -!- INDUCTION: By serum starvation. {ECO:0000269|PubMed:29237719}.
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 -!- DOMAIN: The RING-type zinc finger domain mediates binding to an E2
CC ubiquitin-conjugating enzyme.
CC -!- DOMAIN: The UBA domain interacts with poly-ubiquitinated proteins.
CC -!- PTM: Phosphorylated on tyrosine and serine residues upon TCR or BCR
CC activation, and upon various types of cell stimulation.
CC {ECO:0000269|PubMed:10022120, ECO:0000269|PubMed:10086340,
CC ECO:0000269|PubMed:19549985, ECO:0000269|PubMed:20525694}.
CC -!- PTM: Auto-ubiquitinated upon EGF-mediated cell activation or upon T-
CC cell costimulation by CD28; which promotes proteasomal degradation.
CC {ECO:0000269|PubMed:11375397}.
CC -!- MISCELLANEOUS: This protein has one functional calcium-binding site.
CC {ECO:0000250}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAE45748.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC Sequence=CAH56175.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CBLbID193.html";
CC ---------------------------------------------------------------------------
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DR EMBL; U26710; AAB09291.1; -; mRNA.
DR EMBL; U26711; AAB09292.1; -; mRNA.
DR EMBL; U26712; AAB09293.1; -; mRNA.
DR EMBL; DQ349203; ABC86700.1; -; mRNA.
DR EMBL; AK292792; BAF85481.1; -; mRNA.
DR EMBL; AC016138; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471052; EAW79752.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79753.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79754.1; -; Genomic_DNA.
DR EMBL; BC032851; AAH32851.1; -; mRNA.
DR EMBL; AB075490; BAE45748.1; ALT_SEQ; mRNA.
DR EMBL; BX537484; CAH56175.1; ALT_SEQ; mRNA.
DR CCDS; CCDS2948.1; -. [Q13191-1]
DR RefSeq; NP_001308717.1; NM_001321788.1. [Q13191-1]
DR RefSeq; NP_733762.2; NM_170662.4. [Q13191-1]
DR RefSeq; XP_011511559.1; XM_011513257.1. [Q13191-1]
DR PDB; 2AK5; X-ray; 1.85 A; D=904-911.
DR PDB; 2BZ8; X-ray; 2.00 A; C=902-912.
DR PDB; 2DO6; NMR; -; A/B=931-970.
DR PDB; 2J6F; X-ray; 1.70 A; C=902-912.
DR PDB; 2JNH; NMR; -; A=926-971.
DR PDB; 2LDR; NMR; -; A=351-426.
DR PDB; 2OOA; X-ray; 1.56 A; A/B=924-973.
DR PDB; 2OOB; X-ray; 1.90 A; A=924-973.
DR PDB; 3PFV; X-ray; 2.27 A; A/B=38-344.
DR PDB; 3VGO; X-ray; 3.10 A; A/B/C=39-426.
DR PDB; 3ZNI; X-ray; 2.21 A; A/E/I/M=36-427.
DR PDBsum; 2AK5; -.
DR PDBsum; 2BZ8; -.
DR PDBsum; 2DO6; -.
DR PDBsum; 2J6F; -.
DR PDBsum; 2JNH; -.
DR PDBsum; 2LDR; -.
DR PDBsum; 2OOA; -.
DR PDBsum; 2OOB; -.
DR PDBsum; 3PFV; -.
DR PDBsum; 3VGO; -.
DR PDBsum; 3ZNI; -.
DR AlphaFoldDB; Q13191; -.
DR BMRB; Q13191; -.
DR SMR; Q13191; -.
DR BioGRID; 107316; 91.
DR CORUM; Q13191; -.
DR DIP; DIP-33091N; -.
DR IntAct; Q13191; 69.
DR MINT; Q13191; -.
DR STRING; 9606.ENSP00000264122; -.
DR iPTMnet; Q13191; -.
DR PhosphoSitePlus; Q13191; -.
DR BioMuta; CBLB; -.
DR DMDM; 88911265; -.
DR EPD; Q13191; -.
DR jPOST; Q13191; -.
DR MassIVE; Q13191; -.
DR MaxQB; Q13191; -.
DR PaxDb; Q13191; -.
DR PeptideAtlas; Q13191; -.
DR PRIDE; Q13191; -.
DR ProteomicsDB; 59215; -. [Q13191-1]
DR ProteomicsDB; 59216; -. [Q13191-2]
DR ProteomicsDB; 59217; -. [Q13191-3]
DR Antibodypedia; 16015; 264 antibodies from 33 providers.
DR DNASU; 868; -.
DR Ensembl; ENST00000394030.8; ENSP00000377598.4; ENSG00000114423.23. [Q13191-1]
DR Ensembl; ENST00000403724.5; ENSP00000384816.1; ENSG00000114423.23. [Q13191-3]
DR Ensembl; ENST00000405772.5; ENSP00000384938.1; ENSG00000114423.23. [Q13191-2]
DR GeneID; 868; -.
DR KEGG; hsa:868; -.
DR MANE-Select; ENST00000394030.8; ENSP00000377598.4; NM_170662.5; NP_733762.2.
DR UCSC; uc003dwc.4; human. [Q13191-1]
DR CTD; 868; -.
DR DisGeNET; 868; -.
DR GeneCards; CBLB; -.
DR HGNC; HGNC:1542; CBLB.
DR HPA; ENSG00000114423; Low tissue specificity.
DR MIM; 604491; gene.
DR neXtProt; NX_Q13191; -.
DR OpenTargets; ENSG00000114423; -.
DR PharmGKB; PA26116; -.
DR VEuPathDB; HostDB:ENSG00000114423; -.
DR eggNOG; KOG1785; Eukaryota.
DR GeneTree; ENSGT00940000156631; -.
DR HOGENOM; CLU_013535_3_0_1; -.
DR InParanoid; Q13191; -.
DR OMA; FACFPPP; -.
DR OrthoDB; 540689at2759; -.
DR PhylomeDB; Q13191; -.
DR TreeFam; TF314210; -.
DR PathwayCommons; Q13191; -.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q13191; -.
DR SIGNOR; Q13191; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 868; 25 hits in 1126 CRISPR screens.
DR ChiTaRS; CBLB; human.
DR EvolutionaryTrace; Q13191; -.
DR GeneWiki; CBLB_(gene); -.
DR GenomeRNAi; 868; -.
DR Pharos; Q13191; Tbio.
DR PRO; PR:Q13191; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q13191; protein.
DR Bgee; ENSG00000114423; Expressed in pericardium and 189 other tissues.
DR ExpressionAtlas; Q13191; baseline and differential.
DR Genevisible; Q13191; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0045121; C:membrane raft; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IEA:InterPro.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IBA:GO_Central.
DR GO; GO:0017124; F:SH3 domain binding; IBA:GO_Central.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; TAS:ProtInc.
DR GO; GO:0035739; P:CD4-positive, alpha-beta T cell proliferation; IEA:Ensembl.
DR GO; GO:0006955; P:immune response; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:Ensembl.
DR GO; GO:2000562; P:negative regulation of CD4-positive, alpha-beta T cell proliferation; IEA:Ensembl.
DR GO; GO:0007175; P:negative regulation of epidermal growth factor-activated receptor activity; IBA:GO_Central.
DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0006607; P:NLS-bearing protein import into nucleus; TAS:ProtInc.
DR GO; GO:0018193; P:peptidyl-amino acid modification; IEA:Ensembl.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IEA:Ensembl.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IEA:Ensembl.
DR GO; GO:0002669; P:positive regulation of T cell anergy; IEA:Ensembl.
DR GO; GO:0030163; P:protein catabolic process; IEA:Ensembl.
DR GO; GO:0043087; P:regulation of GTPase activity; IEA:Ensembl.
DR GO; GO:2000583; P:regulation of platelet-derived growth factor receptor-alpha signaling pathway; ISS:UniProtKB.
DR GO; GO:0043393; P:regulation of protein binding; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0002870; P:T cell anergy; IEA:Ensembl.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IEA:Ensembl.
DR CDD; cd16709; RING-HC_Cbl-b; 1.
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; IID00319; -.
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; IPR039520; CBL-B_RING-HC.
DR InterPro; IPR024159; Cbl_PTB.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR015940; UBA.
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 SMART; SM00165; UBA; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF47668; SSF47668; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS51506; CBL_PTB; 1.
DR PROSITE; PS50030; UBA; 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; Cytoplasm; Metal-binding;
KW Phosphoprotein; Reference proteome; Repeat; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..982
FT /note="E3 ubiquitin-protein ligase CBL-B"
FT /id="PRO_0000055860"
FT DOMAIN 35..343
FT /note="Cbl-PTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00839"
FT DOMAIN 931..970
FT /note="UBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT ZN_FING 373..412
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 35..167
FT /note="4H"
FT REGION 168..240
FT /note="EF-hand-like"
FT REGION 241..343
FT /note="SH2-like"
FT REGION 344..372
FT /note="Linker"
FT REGION 466..571
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 543..568
FT /note="Interaction with VAV1"
FT /evidence="ECO:0000269|PubMed:9399639"
FT REGION 688..731
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 769..929
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 891..927
FT /note="Interaction with SH3KBP1"
FT /evidence="ECO:0000269|PubMed:12177062"
FT COMPBIAS 468..487
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 541..569
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 697..712
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 714..728
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 817..832
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 836..850
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 879..898
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 221
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P22681"
FT BINDING 223
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P22681"
FT BINDING 225
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P22681"
FT BINDING 227
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P22681"
FT BINDING 232
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P22681"
FT BINDING 286
FT /ligand="4-O-phospho-L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:62338"
FT /evidence="ECO:0000250"
FT MOD_RES 282
FT /note="Phosphoserine; by PKC/PRKCQ"
FT /evidence="ECO:0000269|PubMed:19549985"
FT MOD_RES 363
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305|PubMed:20525694"
FT MOD_RES 476
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4S7"
FT MOD_RES 480
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3TTA7"
FT MOD_RES 484
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3TTA7"
FT MOD_RES 521
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 525
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 529
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 634
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4S7"
FT MOD_RES 665
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:10022120"
FT MOD_RES 709
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:10022120"
FT MOD_RES 889
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q3TTA7"
FT VAR_SEQ 767..770
FT /note="DVFD -> TYRI (in isoform Truncated 2)"
FT /evidence="ECO:0000303|PubMed:7784085"
FT /id="VSP_005730"
FT VAR_SEQ 771..982
FT /note="Missing (in isoform Truncated 2)"
FT /evidence="ECO:0000303|PubMed:7784085"
FT /id="VSP_005731"
FT VAR_SEQ 811..982
FT /note="Missing (in isoform Truncated 1)"
FT /evidence="ECO:0000303|PubMed:7784085"
FT /id="VSP_005729"
FT VARIANT 584
FT /note="R -> K (in dbSNP:rs17853100)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_025303"
FT VARIANT 883
FT /note="N -> D (in dbSNP:rs35835913)"
FT /id="VAR_039241"
FT MUTAGEN 298
FT /note="G->E: Inhibits interaction with SYK. No effect on E3
FT activity."
FT /evidence="ECO:0000269|PubMed:10022120,
FT ECO:0000269|PubMed:11087752"
FT MUTAGEN 363
FT /note="Y->E: Decreases affinity for E2 ubiquitin-
FT conjugating enzymes."
FT /evidence="ECO:0000269|PubMed:20525694"
FT MUTAGEN 373
FT /note="C->A: Abolishes E3 activity but does not affect
FT binding to substrates."
FT /evidence="ECO:0000269|PubMed:11087752,
FT ECO:0000269|PubMed:11375397"
FT MUTAGEN 665
FT /note="Y->F: Slightly inhibits interaction with CRKL.
FT Abolishes interaction with CRKL; when associated with F-
FT 709."
FT /evidence="ECO:0000269|PubMed:10022120"
FT MUTAGEN 709
FT /note="Y->F: Inhibits interaction with CRKL. Abolishes
FT interaction with CRKL; when associated with F-665."
FT /evidence="ECO:0000269|PubMed:10022120"
FT MUTAGEN 904
FT /note="R->A: No effect on interaction with CD2AP. Reduced
FT interaction with SH3KBP1. Strongly reduced interaction with
FT SH3KBP1; when associated with A-911."
FT /evidence="ECO:0000269|PubMed:16228008,
FT ECO:0000269|PubMed:17020880"
FT MUTAGEN 907
FT /note="K->A: No effect on interaction with SH3KBP1. Reduced
FT interaction with CD2AP. Strongly reduced interaction with
FT CD2AP; when associated with A-911."
FT /evidence="ECO:0000269|PubMed:17020880"
FT MUTAGEN 911
FT /note="R->A: Reduced interaction with CD2AP and with
FT SH3KBP1. Strongly reduced interaction with CD2AP; when
FT associated with A-907. Strongly reduced interaction with
FT SH3KBP1; when associated with A-904."
FT /evidence="ECO:0000269|PubMed:16228008,
FT ECO:0000269|PubMed:17020880"
FT MUTAGEN 937
FT /note="A->E: Loss of ubiquitin binding. Reduced levels of
FT tyrosine phosphorylation."
FT /evidence="ECO:0000269|PubMed:17679095"
FT MUTAGEN 940
FT /note="M->A: Loss of ubiquitin binding. Reduced levels of
FT tyrosine phosphorylation."
FT /evidence="ECO:0000269|PubMed:17679095"
FT MUTAGEN 943..944
FT /note="GY->AQ: Abolishes interaction with ubiquitinated
FT proteins."
FT /evidence="ECO:0000269|PubMed:15273720"
FT MUTAGEN 946
FT /note="F->A: Loss of ubiquitin binding. Reduced levels of
FT tyrosine phosphorylation."
FT /evidence="ECO:0000269|PubMed:17679095"
FT MUTAGEN 966
FT /note="I->E: Interferes with dimerization. Reduced E3
FT ubiquitin-protein ligase activity. Reduced levels of
FT tyrosine phosphorylation."
FT /evidence="ECO:0000269|PubMed:17679095"
FT MUTAGEN 967
FT /note="L->A: No effect on interaction with ubiquitinated
FT proteins."
FT /evidence="ECO:0000269|PubMed:15273720"
FT CONFLICT 210
FT /note="G -> S (in Ref. 1; AAB09291/AAB09292/AAB09293)"
FT /evidence="ECO:0000305"
FT CONFLICT 911
FT /note="R -> C (in Ref. 9; CAH56175)"
FT /evidence="ECO:0000305"
FT HELIX 43..60
FT /evidence="ECO:0007829|PDB:3ZNI"
FT HELIX 63..65
FT /evidence="ECO:0007829|PDB:3ZNI"
FT STRAND 69..72
FT /evidence="ECO:0007829|PDB:3ZNI"
FT HELIX 74..91
FT /evidence="ECO:0007829|PDB:3ZNI"
FT HELIX 95..102
FT /evidence="ECO:0007829|PDB:3ZNI"
FT HELIX 105..128
FT /evidence="ECO:0007829|PDB:3ZNI"
FT HELIX 129..133
FT /evidence="ECO:0007829|PDB:3ZNI"
FT HELIX 138..160
FT /evidence="ECO:0007829|PDB:3ZNI"
FT HELIX 162..164
FT /evidence="ECO:0007829|PDB:3ZNI"
FT HELIX 168..170
FT /evidence="ECO:0007829|PDB:3ZNI"
FT HELIX 176..186
FT /evidence="ECO:0007829|PDB:3ZNI"
FT STRAND 190..193
FT /evidence="ECO:0007829|PDB:3ZNI"
FT HELIX 194..204
FT /evidence="ECO:0007829|PDB:3ZNI"
FT HELIX 210..220
FT /evidence="ECO:0007829|PDB:3ZNI"
FT STRAND 225..229
FT /evidence="ECO:0007829|PDB:3ZNI"
FT HELIX 230..239
FT /evidence="ECO:0007829|PDB:3ZNI"
FT HELIX 243..245
FT /evidence="ECO:0007829|PDB:3ZNI"
FT HELIX 246..253
FT /evidence="ECO:0007829|PDB:3ZNI"
FT STRAND 260..263
FT /evidence="ECO:0007829|PDB:3VGO"
FT HELIX 266..273
FT /evidence="ECO:0007829|PDB:3ZNI"
FT HELIX 274..276
FT /evidence="ECO:0007829|PDB:3ZNI"
FT STRAND 282..287
FT /evidence="ECO:0007829|PDB:3ZNI"
FT STRAND 289..291
FT /evidence="ECO:0007829|PDB:3ZNI"
FT STRAND 295..300
FT /evidence="ECO:0007829|PDB:3ZNI"
FT STRAND 306..309
FT /evidence="ECO:0007829|PDB:3ZNI"
FT STRAND 312..314
FT /evidence="ECO:0007829|PDB:3PFV"
FT HELIX 316..325
FT /evidence="ECO:0007829|PDB:3ZNI"
FT HELIX 332..334
FT /evidence="ECO:0007829|PDB:3VGO"
FT HELIX 342..344
FT /evidence="ECO:0007829|PDB:3PFV"
FT STRAND 352..354
FT /evidence="ECO:0007829|PDB:3ZNI"
FT HELIX 357..364
FT /evidence="ECO:0007829|PDB:3ZNI"
FT TURN 365..367
FT /evidence="ECO:0007829|PDB:3ZNI"
FT STRAND 370..372
FT /evidence="ECO:0007829|PDB:3ZNI"
FT TURN 374..376
FT /evidence="ECO:0007829|PDB:3ZNI"
FT STRAND 377..380
FT /evidence="ECO:0007829|PDB:3ZNI"
FT STRAND 383..386
FT /evidence="ECO:0007829|PDB:3ZNI"
FT HELIX 394..402
FT /evidence="ECO:0007829|PDB:3ZNI"
FT TURN 409..411
FT /evidence="ECO:0007829|PDB:3ZNI"
FT STRAND 417..420
FT /evidence="ECO:0007829|PDB:3ZNI"
FT STRAND 422..424
FT /evidence="ECO:0007829|PDB:3ZNI"
FT HELIX 933..941
FT /evidence="ECO:0007829|PDB:2OOA"
FT HELIX 946..955
FT /evidence="ECO:0007829|PDB:2OOA"
FT TURN 956..958
FT /evidence="ECO:0007829|PDB:2OOA"
FT HELIX 960..970
FT /evidence="ECO:0007829|PDB:2OOA"
SQ SEQUENCE 982 AA; 109450 MW; B4E307D31B9F0779 CRC64;
MANSMNGRNP GGRGGNPRKG RILGIIDAIQ DAVGPPKQAA ADRRTVEKTW KLMDKVVRLC
QNPKLQLKNS PPYILDILPD TYQHLRLILS KYDDNQKLAQ LSENEYFKIY IDSLMKKSKR
AIRLFKEGKE RMYEEQSQDR RNLTKLSLIF SHMLAEIKAI FPNGQFQGDN FRITKADAAE
FWRKFFGDKT IVPWKVFRQC LHEVHQISSG LEAMALKSTI DLTCNDYISV FEFDIFTRLF
QPWGSILRNW NFLAVTHPGY MAFLTYDEVK ARLQKYSTKP GSYIFRLSCT RLGQWAIGYV
TGDGNILQTI PHNKPLFQAL IDGSREGFYL YPDGRSYNPD LTGLCEPTPH DHIKVTQEQY
ELYCEMGSTF QLCKICAEND KDVKIEPCGH LMCTSCLTAW QESDGQGCPF CRCEIKGTEP
IIVDPFDPRD EGSRCCSIID PFGMPMLDLD DDDDREESLM MNRLANVRKC TDRQNSPVTS
PGSSPLAQRR KPQPDPLQIP HLSLPPVPPR LDLIQKGIVR SPCGSPTGSP KSSPCMVRKQ
DKPLPAPPPP LRDPPPPPPE RPPPIPPDNR LSRHIHHVES VPSRDPPMPL EAWCPRDVFG
TNQLVGCRLL GEGSPKPGIT ASSNVNGRHS RVGSDPVLMR KHRRHDLPLE GAKVFSNGHL
GSEEYDVPPR LSPPPPVTTL LPSIKCTGPL ANSLSEKTRD PVEEDDDEYK IPSSHPVSLN
SQPSHCHNVK PPVRSCDNGH CMLNGTHGPS SEKKSNIPDL SIYLKGDVFD SASDPVPLPP
ARPPTRDNPK HGSSLNRTPS DYDLLIPPLG EDAFDALPPS LPPPPPPARH SLIEHSKPPG
SSSRPSSGQD LFLLPSDPFV DLASGQVPLP PARRLPGENV KTNRTSQDYD QLPSCSDGSQ
APARPPKPRP RRTAPEIHHR KPHGPEAALE NVDAKIAKLM GEGYAFEEVK RALEIAQNNV
EVARSILREF AFPPPVSPRL NL
