CBLB_MOUSE
ID CBLB_MOUSE Reviewed; 982 AA.
AC Q3TTA7; E9QMY2;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=E3 ubiquitin-protein ligase CBL-B;
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q13191};
DE AltName: Full=Casitas B-lineage lymphoma proto-oncogene b;
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;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP FUNCTION.
RX PubMed=11070165; DOI=10.1016/s1074-7613(00)00046-7;
RA Krawczyk C., Bachmaier K., Sasaki T., Jones R.G., Snapper S.B.,
RA Bouchard D., Kozieradzki I., Ohashi P.S., Alt F.W., Penninger J.M.;
RT "Cbl-b is a negative regulator of receptor clustering and raft aggregation
RT in T cells.";
RL Immunity 13:463-473(2000).
RN [4]
RP FUNCTION, AND INTERACTION WITH PIK3R1; LCP2; ZAP70; LCK; PLCG1 AND VAV1.
RX PubMed=10646608; DOI=10.1038/35003228;
RA Bachmaier K., Krawczyk C., Kozieradzki I., Kong Y.-Y., Sasaki T.,
RA Oliveira-dos-Santos A., Mariathasan S., Bouchard D., Wakeham A., Itie A.,
RA Le J., Ohashi P.S., Sarosi I., Nishina H., Lipkowitz S., Penninger J.M.;
RT "Negative regulation of lymphocyte activation and autoimmunity by the
RT molecular adaptor Cbl-b.";
RL Nature 403:211-216(2000).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10646609; DOI=10.1038/35003235;
RA Chiang Y.J., Kole H.K., Brown K., Naramura M., Fukuhara S., Hu R.-J.,
RA Jang I.K., Gutkind J.S., Shevach E., Gu H.;
RT "Cbl-b regulates the CD28 dependence of T-cell activation.";
RL Nature 403:216-220(2000).
RN [6]
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 [7]
RP UBIQUITINATION.
RX PubMed=12193687; DOI=10.4049/jimmunol.169.5.2236;
RA Zhang J., Bardos T., Li D., Gal I., Vermes C., Xu J., Mikecz K.,
RA Finnegan A., Lipkowitz S., Glant T.T.;
RT "Regulation of T cell activation threshold by CD28 costimulation through
RT targeting Cbl-b for ubiquitination.";
RL J. Immunol. 169:2236-2240(2002).
RN [8]
RP PHOSPHORYLATION AT TYR-664 AND TYR-708, INTERACTION WITH CBL; CRK AND
RP SORBS1, AND SUBCELLULAR LOCATION.
RX PubMed=12842890; DOI=10.1074/jbc.m300664200;
RA Liu J., DeYoung S.M., Hwang J.B., O'Leary E.E., Saltiel A.R.;
RT "The roles of Cbl-b and c-Cbl in insulin-stimulated glucose transport.";
RL J. Biol. Chem. 278:36754-36762(2003).
RN [9]
RP PHOSPHORYLATION, AND FUNCTION.
RX PubMed=12771181; DOI=10.1084/jem.20021686;
RA Sohn H.W., Gu H., Pierce S.K.;
RT "Cbl-b negatively regulates B cell antigen receptor signaling in mature B
RT cells through ubiquitination of the tyrosine kinase Syk.";
RL J. Exp. Med. 197:1511-1524(2003).
RN [10]
RP FUNCTION.
RX PubMed=15308098; DOI=10.1016/j.immuni.2004.07.013;
RA Jeon M.-S., Atfield A., Venuprasad K., Krawczyk C., Sarao R., Elly C.,
RA Yang C., Arya S., Bachmaier K., Su L., Bouchard D., Jones R., Gronski M.,
RA Ohashi P., Wada T., Bloom D., Fathman C.G., Liu Y.-C., Penninger J.M.;
RT "Essential role of the E3 ubiquitin ligase Cbl-b in T cell anergy
RT induction.";
RL Immunity 21:167-177(2004).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-889, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-480; SER-484 AND SER-521, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [13]
RP FUNCTION, AND INDUCTION.
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).
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 (PubMed:29237719).
CC {ECO:0000269|PubMed:10646608, ECO:0000269|PubMed:10646609,
CC ECO:0000269|PubMed:11070165, ECO:0000269|PubMed:11526404,
CC ECO:0000269|PubMed:12771181, ECO:0000269|PubMed:15308098,
CC ECO:0000269|PubMed:29237719}.
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:0000250|UniProtKB:Q13191};
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. Interacts
CC with SH3 domain-containing proteins VAV1, FYN, FGR, PLCG1, GRB2, CRKL,
CC PIK3R1 and SH3KBP1/CIN85. Identified in heterotrimeric complexes with
CC SH3KBP1/CIN85, CD2AP and ARHGEF7, where one CBLB peptide binds two
CC copies of the other protein. Interacts with poly-ubiquitinated
CC proteins. Dimerization is required for the binding of poly-ubiquitin,
CC but not for the binding of mono-ubiquitin. Interacts with EGFR
CC (phosphorylated). Interacts with IFT20 (By similarity).
CC {ECO:0000250|UniProtKB:Q13191, ECO:0000269|PubMed:10646608,
CC ECO:0000269|PubMed:12842890}.
CC -!- INTERACTION:
CC Q3TTA7; P13379: Cd5; NbExp=4; IntAct=EBI-3649276, EBI-12600513;
CC Q3TTA7; P22366: Myd88; NbExp=2; IntAct=EBI-3649276, EBI-525108;
CC Q3TTA7; Q80UF7: Ticam1; NbExp=2; IntAct=EBI-3649276, EBI-3649271;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12842890}. Note=In
CC adipocytes, translocates to the plasma membrane upon insulin
CC stimulation.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q3TTA7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3TTA7-2; Sequence=VSP_017222;
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 {ECO:0000250|UniProtKB:Q13191}.
CC -!- PTM: Phosphorylated on tyrosine and serine residues upon TCR or BCR
CC activation. Phosphorylated on Tyr-664 and Tyr-708 in adipocytes
CC following insulin stimulation. {ECO:0000269|PubMed:12771181,
CC ECO:0000269|PubMed:12842890}.
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:12193687}.
CC -!- DISRUPTION PHENOTYPE: Mice are fertile and grossly normal. However,
CC they show a high sensitivity to autoimmune diseases and may develop a
CC spontaneous generalized autoimmune disorder characterized by auto-
CC antibody production, infiltration of activated T- and B-lymphocytes
CC into various organs and parenchymal damage.
CC {ECO:0000269|PubMed:10646609}.
CC -!- MISCELLANEOUS: This protein has one functional calcium-binding site.
CC {ECO:0000250}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK147367; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK161486; BAE36418.1; -; mRNA.
DR EMBL; AC117780; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC154251; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC154478; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001028410.1; NM_001033238.1.
DR RefSeq; XP_006522010.1; XM_006521947.1. [Q3TTA7-1]
DR RefSeq; XP_006522011.1; XM_006521948.1. [Q3TTA7-1]
DR RefSeq; XP_006522012.1; XM_006521949.1. [Q3TTA7-1]
DR RefSeq; XP_006522013.1; XM_006521950.2. [Q3TTA7-1]
DR RefSeq; XP_006522015.1; XM_006521952.3. [Q3TTA7-2]
DR PDB; 5AXI; X-ray; 2.50 A; A/B/C=38-343.
DR PDBsum; 5AXI; -.
DR AlphaFoldDB; Q3TTA7; -.
DR BMRB; Q3TTA7; -.
DR SMR; Q3TTA7; -.
DR BioGRID; 229001; 33.
DR CORUM; Q3TTA7; -.
DR IntAct; Q3TTA7; 48.
DR MINT; Q3TTA7; -.
DR STRING; 10090.ENSMUSP00000110115; -.
DR iPTMnet; Q3TTA7; -.
DR PhosphoSitePlus; Q3TTA7; -.
DR EPD; Q3TTA7; -.
DR jPOST; Q3TTA7; -.
DR MaxQB; Q3TTA7; -.
DR PaxDb; Q3TTA7; -.
DR PeptideAtlas; Q3TTA7; -.
DR PRIDE; Q3TTA7; -.
DR ProteomicsDB; 265341; -. [Q3TTA7-1]
DR ProteomicsDB; 265342; -. [Q3TTA7-2]
DR Antibodypedia; 16015; 264 antibodies from 33 providers.
DR Ensembl; ENSMUST00000226593; ENSMUSP00000154755; ENSMUSG00000022637. [Q3TTA7-1]
DR Ensembl; ENSMUST00000227756; ENSMUSP00000153753; ENSMUSG00000022637. [Q3TTA7-2]
DR Ensembl; ENSMUST00000227879; ENSMUSP00000153787; ENSMUSG00000022637. [Q3TTA7-1]
DR GeneID; 208650; -.
DR KEGG; mmu:208650; -.
DR UCSC; uc007zlf.1; mouse. [Q3TTA7-1]
DR CTD; 868; -.
DR MGI; MGI:2146430; Cblb.
DR VEuPathDB; HostDB:ENSMUSG00000022637; -.
DR eggNOG; KOG1785; Eukaryota.
DR GeneTree; ENSGT00940000156631; -.
DR InParanoid; Q3TTA7; -.
DR OMA; FACFPPP; -.
DR OrthoDB; 540689at2759; -.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 208650; 0 hits in 74 CRISPR screens.
DR ChiTaRS; Cblb; mouse.
DR PRO; PR:Q3TTA7; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q3TTA7; protein.
DR Bgee; ENSMUSG00000022637; Expressed in manus and 241 other tissues.
DR ExpressionAtlas; Q3TTA7; baseline and differential.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
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:0019901; F:protein kinase binding; ISO:MGI.
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:0035739; P:CD4-positive, alpha-beta T cell proliferation; IMP:MGI.
DR GO; GO:0006955; P:immune response; IMP:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IMP:MGI.
DR GO; GO:2000562; P:negative regulation of CD4-positive, alpha-beta T cell proliferation; IMP:MGI.
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; IMP:MGI.
DR GO; GO:0018193; P:peptidyl-amino acid modification; IDA:MGI.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IMP:MGI.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:MGI.
DR GO; GO:0002669; P:positive regulation of T cell anergy; IMP:MGI.
DR GO; GO:0030163; P:protein catabolic process; IMP:MGI.
DR GO; GO:0030155; P:regulation of cell adhesion; IMP:MGI.
DR GO; GO:0043087; P:regulation of GTPase activity; IMP:MGI.
DR GO; GO:2000583; P:regulation of platelet-derived growth factor receptor-alpha signaling pathway; IMP:UniProtKB.
DR GO; GO:0043393; P:regulation of protein binding; IMP:MGI.
DR GO; GO:0050856; P:regulation of T cell receptor signaling pathway; ISO:MGI.
DR GO; GO:0007165; P:signal transduction; ISO:MGI.
DR GO; GO:0042110; P:T cell activation; IMP:MGI.
DR GO; GO:0002870; P:T cell anergy; IMP:MGI.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IMP:MGI.
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 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_0000055861"
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 465..588
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 543..567
FT /note="Interaction with VAV1"
FT /evidence="ECO:0000250"
FT REGION 702..723
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 745..929
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 891..927
FT /note="Interaction with SH3KBP1"
FT /evidence="ECO:0000250"
FT COMPBIAS 468..487
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 541..568
FT /note="Pro 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 884..901
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:0000250|UniProtKB:Q13191"
FT MOD_RES 363
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q13191"
FT MOD_RES 476
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4S7"
FT MOD_RES 480
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 484
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 521
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 525
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13191"
FT MOD_RES 529
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13191"
FT MOD_RES 633
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4S7"
FT MOD_RES 664
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:12842890"
FT MOD_RES 708
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:12842890"
FT MOD_RES 889
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455"
FT VAR_SEQ 1..152
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_017222"
FT CONFLICT 176
FT /note="A -> T (in Ref. 1; BAE36418)"
FT /evidence="ECO:0000305"
FT HELIX 43..60
FT /evidence="ECO:0007829|PDB:5AXI"
FT HELIX 63..65
FT /evidence="ECO:0007829|PDB:5AXI"
FT STRAND 69..72
FT /evidence="ECO:0007829|PDB:5AXI"
FT HELIX 74..94
FT /evidence="ECO:0007829|PDB:5AXI"
FT HELIX 98..103
FT /evidence="ECO:0007829|PDB:5AXI"
FT HELIX 105..128
FT /evidence="ECO:0007829|PDB:5AXI"
FT HELIX 129..133
FT /evidence="ECO:0007829|PDB:5AXI"
FT HELIX 138..160
FT /evidence="ECO:0007829|PDB:5AXI"
FT HELIX 162..164
FT /evidence="ECO:0007829|PDB:5AXI"
FT HELIX 168..170
FT /evidence="ECO:0007829|PDB:5AXI"
FT HELIX 176..186
FT /evidence="ECO:0007829|PDB:5AXI"
FT STRAND 190..193
FT /evidence="ECO:0007829|PDB:5AXI"
FT HELIX 194..204
FT /evidence="ECO:0007829|PDB:5AXI"
FT HELIX 210..220
FT /evidence="ECO:0007829|PDB:5AXI"
FT STRAND 225..229
FT /evidence="ECO:0007829|PDB:5AXI"
FT HELIX 230..240
FT /evidence="ECO:0007829|PDB:5AXI"
FT HELIX 243..245
FT /evidence="ECO:0007829|PDB:5AXI"
FT HELIX 246..254
FT /evidence="ECO:0007829|PDB:5AXI"
FT STRAND 260..263
FT /evidence="ECO:0007829|PDB:5AXI"
FT HELIX 266..273
FT /evidence="ECO:0007829|PDB:5AXI"
FT HELIX 274..276
FT /evidence="ECO:0007829|PDB:5AXI"
FT STRAND 282..287
FT /evidence="ECO:0007829|PDB:5AXI"
FT STRAND 289..291
FT /evidence="ECO:0007829|PDB:5AXI"
FT STRAND 295..300
FT /evidence="ECO:0007829|PDB:5AXI"
FT STRAND 306..309
FT /evidence="ECO:0007829|PDB:5AXI"
FT STRAND 312..314
FT /evidence="ECO:0007829|PDB:5AXI"
FT HELIX 316..325
FT /evidence="ECO:0007829|PDB:5AXI"
SQ SEQUENCE 982 AA; 109092 MW; 14B55C4106F84A86 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 PFSIPMLDLD DDDDREESLM MNRLASVRKC TDRQNSPVTS
PGSSPLAQRR KPQPDPLQIP HLSLPPVPPR LDLIQKGIVR SPCGSPTGSP KSSPCMVRKQ
DKPLPAPPPP LRDPPPPPER PPPIPPDNRL SRHFHHGESV PSRDQPMPLE AWCPRDAFGT
NQVMGCRILG DGSPKPGVTA NSSLNGRHSR MGSEQVLMRK HRRHDLPSEG AKVFSNGHLA
TEEYDVPPRL SPPPPVTTLL PSIKCTGPLA NCLSEKTRDT VEDDDDEYKI PSSHPVSLNS
QPSHCHNVKA PVRSCDNGHC ILNGTHGAPS EMKKSNIPDL GIYLKGGGSD SASDPVPLPP
ARPPPRDSPK HGSSVNRTPS DYDLLIPPLG EDAFDALPPS LPPPPPPARH SLIEHSKPPG
SSSRPSSGQD LFLLPSDPFF DPTSGQVPLP PARRAAGDSG KANRASQDYD QLPSSSDGSQ
APARPPKPRP RRTAPEIHHR KPHGPEAALE NVDAKIAKLM GEGYAFEEVK RALEIAQNNV
EVARSILREF AFPPPVSPRL NL
