| Description | 982 amino acids; 120 kDa; the overall structure of CBLb is very close to the sructure of CBL: the evolutionarily conserved aminoterminal region of CBL is composed of three interacting domains: a four-helix bundle (4H), an EF-hand calcium binding domain, and a divergent SH2 domain; the three domains together form an integrated phosphoprotein -recognition module; this aminoterminal region is followed by a central Ring finger with a Cys3HisCys4 motif and an aminoterminal region with multiple proline-rich sequences, a putative leucine zipper and several potential tyrosine phosphorylation sites; two alternatively spliced mRNA code form CBLb proteins lacking the leucine zipper |
| Expression | expression of CBLb was seen in several human adult tissues including lung, spleen and testis but not in human brain, liver, pancreas, salivary gland or skeletal muscle; expression was also detected in fetal brain and liver, in hematopoietic cell lines and in normal and malignant mammary epithelial cell lines |
| Localisation | cytoplasmic |
| Function | regulation of signal transduction; CBLb has been shown to inhibit c-Jun terminal kinase (JNK) activation mediated by the (VAV oncoprotein and EGF receptor (EGFR) signaling; in contrast, a direct interaction between CBLb and the kinase ZAP-70 induces a positive signal in T cells |
| Nomenclature | | HGNC | CBLB 1542 |
| Entrez_Gene | CBLB 868 Cas-Br-M (murine) ecotropic retroviral transforming sequence b |
| Cards |
|---|
| Atlas | CBLbID193 |
| GeneCards | CBLB |
| Ensembl | ENSG00000114423 [Gene_View] CBLB [Vega] |
| Genatlas | CBLB |
| Genomic and cartography |
|---|
| GoldenPath | CBLB - 3q chr3:106859799-107070577 - 3q [Description] (hg18-Mar_2006) |
| Ensembl | CBLB - 3q [CytoView] |
| NCBI | Mapview |
| OMIM | 604491 Disease map [OMIM] |
| HomoloGene | CBLB |
| Gene and transcription | | Genbank | AA251219 [ ENTREZ ] |
| Genbank | AB075490 [ ENTREZ ] |
| Genbank | AK094184 [ ENTREZ ] |
| Genbank | AK123147 [ ENTREZ ] |
| Genbank | AK130668 [ ENTREZ ] |
| RefSeq | NM_170662 [ SRS ] NM_170662 [ ENTREZ ] |
| RefSeq | AC_000046 [ SRS ] AC_000046 [ ENTREZ ] |
| RefSeq | AC_000135 [ SRS ] AC_000135 [ ENTREZ ] |
| RefSeq | NC_000003 [ SRS ] NC_000003 [ ENTREZ ] |
| RefSeq | NT_005612 [ SRS ] NT_005612 [ ENTREZ ] |
| RefSeq | NW_001838881 [ SRS ] NW_001838881 [ ENTREZ ] |
| RefSeq | NW_921807 [ SRS ] NW_921807 [ ENTREZ ] |
| CCDS | CBLB CCDS - NCBI |
| AceView | CBLB AceView - NCBI |
| Unigene | Hs.430589 [ SRS ] Hs.430589 [ NCBI ] |
| Fast-db | 10535 (alternative variants) |
| Protein : pattern, domain, 3D structure |
|---|
| SwissProt | Q13191 [ SRS] Q13191 [ EXPASY ] Q13191 [ INTERPRO ] Q13191 [ UNIPROT ] Q13191 [ VarSplice FASTA ] |
| Prosite | PS50001 SH2 [ SRS ] PS50001 SH2 [ Expasy ] |
| Prosite | PS50030 UBA [ SRS ] PS50030 UBA [ Expasy ] |
| Prosite | PS00518 ZF_RING_1 [ SRS ] PS00518 ZF_RING_1 [ Expasy ] |
| Prosite | PS50089 ZF_RING_2 [ SRS ] PS50089 ZF_RING_2 [ Expasy ] |
| Interpro | IPR014741 Adaptor_Cbl_EF_Hand-like [ SRS ] IPR014741 Adaptor_Cbl_EF_Hand-like [ EBI ] |
| Interpro | IPR003153 Adaptor_Cbl_N [ SRS ] IPR003153 Adaptor_Cbl_N [ EBI ] |
| Interpro | IPR014742 Adaptor_Cbl_SH2-like [ SRS ] IPR014742 Adaptor_Cbl_SH2-like [ EBI ] |
| Interpro | IPR011992 EF-Hand_type [ SRS ] IPR011992 EF-Hand_type [ EBI ] |
| Interpro | IPR000980 SH2 [ SRS ] IPR000980 SH2 [ EBI ] |
| Interpro | IPR000449 UBA/transl_elong_EF1B_N [ SRS ] IPR000449 UBA/transl_elong_EF1B_N [ EBI ] |
| Interpro | IPR015940 UBA/transl_elong_EF1B_N_euk [ SRS ] IPR015940 UBA/transl_elong_EF1B_N_euk [ EBI ] |
| Interpro | IPR001841 Znf_RING [ SRS ] IPR001841 Znf_RING [ EBI ] |
| Interpro | IPR013083 Znf_RING/FYVE/PHD [ SRS ] IPR013083 Znf_RING/FYVE/PHD [ EBI ] |
| CluSTr | Q13191 |
| Pfam | PF02262 Cbl_N [ SRS ] PF02262 Cbl_N [ Sanger ] pfam02262 [ NCBI-CDD ] |
| Pfam | PF02761 Cbl_N2 [ SRS ] PF02761 Cbl_N2 [ Sanger ] pfam02761 [ NCBI-CDD ] |
| Pfam | PF02762 Cbl_N3 [ SRS ] PF02762 Cbl_N3 [ Sanger ] pfam02762 [ NCBI-CDD ] |
| Pfam | PF00627 UBA [ SRS ] PF00627 UBA [ Sanger ] pfam00627 [ NCBI-CDD ] |
| Pfam | PF00097 zf-C3HC4 [ SRS ] PF00097 zf-C3HC4 [ Sanger ] pfam00097 [ NCBI-CDD ] |
| Smart | SM00184 RING [EMBL] |
| Smart | SM00252 SH2 [EMBL] |
| Smart | SM00165 UBA [EMBL] |
| Blocks | Q13191 |
| PDB | 2AK5 [ SRS ] 2AK5 [ PdbSum ], 2AK5 [ IMB ] 2AK5 [ RSDB ] |
| PDB | 2BZ8 [ SRS ] 2BZ8 [ PdbSum ], 2BZ8 [ IMB ] 2BZ8 [ RSDB ] |
| PDB | 2DO6 [ SRS ] 2DO6 [ PdbSum ], 2DO6 [ IMB ] 2DO6 [ RSDB ] |
| PDB | 2J6F [ SRS ] 2J6F [ PdbSum ], 2J6F [ IMB ] 2J6F [ RSDB ] |
| PDB | 2JNH [ SRS ] 2JNH [ PdbSum ], 2JNH [ IMB ] 2JNH [ RSDB ] |
| PDB | 2OOA [ SRS ] 2OOA [ PdbSum ], 2OOA [ IMB ] 2OOA [ RSDB ] |
| PDB | 2OOB [ SRS ] 2OOB [ PdbSum ], 2OOB [ IMB ] 2OOB [ RSDB ] |
| HPRD | 05136 |
| Protein Interaction databases |
|---|
| DIP | Q13191 |
| IntAct | Q13191 |
| Polymorphism : SNP, mutations, diseases |
|---|
| OMIM | 604491 [ map ] |
| GENETests | 604491 |
| SNP | CBLB [dbSNP-NCBI] |
| SNP | NM_170662 [SNP-NCI] |
| SNP | CBLB [GeneSNPs - Utah] CBLB] [HGBASE - SRS] |
| HAPMAP | CBLB [HAPMAP] |
| COSMIC | CBLB [Somatic mutation (COSMIC-CGP-Sanger)] |
| HGMD | CBLB |
| Genetic Association | CBLB |
| CDC HuGE | CBLB |
| General knowledge |
|---|
| Family Browser | CBLB [UCSC Family Browser] |
| SOURCE | NM_170662 |
| SMD | Hs.430589 |
| SAGE | Hs.430589 |
| Enzyme | 6.3.2.- [ Enzyme-Expasy ] 6.3.2.- [ Enzyme-SRS ] 6.3.2.- [ IntEnz-EBI ] 6.3.2.- [ BRENDA ] 6.3.2.- [ KEGG ] |
| GO | signal transducer activity [Amigo] signal transducer activity |
| GO | calcium ion binding [Amigo] calcium ion binding |
| GO | protein binding [Amigo] protein binding |
| GO | nucleus [Amigo] nucleus |
| GO | cytoplasm [Amigo] cytoplasm |
| GO | NLS-bearing substrate import into nucleus [Amigo] NLS-bearing substrate import into nucleus |
| GO | immune response [Amigo] immune response |
| GO | cell surface receptor linked signal transduction [Amigo] cell surface receptor linked signal transduction |
| GO | zinc ion binding [Amigo] zinc ion binding |
| GO | ligase activity [Amigo] ligase activity |
| KEGG | Jak-STAT signaling pathway |
| KEGG | T cell receptor signaling pathway |
| KEGG | Insulin signaling pathway |
| PubGene | CBLB |
| TreeFam | CBLB |
| CTD | 868 [Comparative ToxicoGenomics Database] |
| Other databases |
|---|
| Probes |
|---|
| Probe | CBLB Related clones (RZPD - Berlin) |
| PubMed |
|---|
| PubMed | 43 Pubmed reference(s) in Entrez |
| Cloning and characterization of cbl-b: a SH3 binding protein with homology to the c-cbl proto-oncogene. |
| Keane MM, Rivero-Lezcano OM, Mitchell JA, Robbins KC, Lipkowitz S |
| Oncogene. 1995 ; 10 (12) : 2367-2377. |
| PMID 7784085 |
| |
| Cbl-b, a member of the Sli-1/c-Cbl protein family, inhibits Vav-mediated c-Jun N-terminal kinase activation. |
| Bustelo XR, Crespo P, Lˆ„pez-Barahona M, Gutkind JS, Barbacid M |
| Oncogene. 1997 ; 15 (21) : 2511-2520. |
| PMID 9399639 |
| |
| The CBL-related protein CBLB participates in FLT3 and interleukin-7 receptor signal transduction in pro-B cells. |
| Lavagna-Sˆ©venier C, Marchetto S, Birnbaum D, Rosnet O |
| The Journal of biological chemistry. 1998 ; 273 (24) : 14962-14967. |
| PMID 9614102 |
| |
| cbl-b inhibits epidermal growth factor receptor signaling. |
| Ettenberg SA, Keane MM, Nau MM, Frankel M, Wang LM, Pierce JH, Lipkowitz S |
| Oncogene. 1999 ; 18 (10) : 1855-1866. |
| PMID 10086340 |
| |
| A direct interaction between the adaptor protein Cbl-b and the kinase zap-70 induces a positive signal in T cells. |
| Zhang Z, Elly C, Qiu L, Altman A, Liu YC |
| Current biology : CB. 1999 ; 9 (4) : 203-206. |
| PMID 10074432 |
| |