ID:CBLB_HUMAN DESCRIPTION: RecName: Full=E3 ubiquitin-protein ligase CBL-B; EC=6.3.2.-; AltName: Full=Casitas B-lineage lymphoma proto-oncogene b; AltName: Full=RING finger protein 56; AltName: Full=SH3-binding protein CBL-B; AltName: Full=Signal transduction protein CBL-B; FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome. Negatively regulates TCR (T-cell receptor), BCR (B- cell receptor) and FCER1 (high affinity immunoglobulin epsilon receptor) signal transduction pathways. In naive T-cells, inhibits VAV1 activation upon TCR engagement and imposes a requirement for CD28 costimulation for proliferation and IL-2 production. Also acts by promoting PIK3R1/p85 ubiquitination, which impairs its recruitment to the TCR and subsequent activation. In activated T- cells, inhibits PLCG1 activation and calcium mobilization upon restimulation and promotes anergy. In B-cells, acts by ubiquitinating SYK and promoting its proteasomal degradation. May also be involved in EGFR ubiquitination and internalization. PATHWAY: Protein modification; protein ubiquitination. SUBUNIT: Interacts with SH3 domain-containing proteins LCK, CRK and SORBS1. Interacts with LCP2 and ZAP70. May interact with CBL (By similarity). Interacts with SH3 domain-containing proteins VAV1, FYN, FGR, PLCG1, GRB2, CRKL, PIK3R1 and SH3KBP1/CIN85. Identified in heterotrimeric complexes with SH3KBP1/CIN85, CD2AP and ARHGEF7, where one CBLB peptide binds two copies of the other protein. Interacts with poly-ubiquitinated proteins. Dimerization is required for the binding of poly-ubiquitin, but not for the binding of mono-ubiquitin. INTERACTION: P62993:GRB2; NbExp=4; IntAct=EBI-744027, EBI-401755; SUBCELLULAR LOCATION: Cytoplasm. Note=Upon EGF stimulation, associates with endocytic vesicles. TISSUE SPECIFICITY: Expressed in placenta, heart, lung, kidney, spleen, ovary and testis, as well as fetal brain and liver and hematopoietic cell lines, but not in adult brain, liver, pancreas, salivary gland, or skeletal muscle. Present in lymphocytes (at protein level). DOMAIN: The N-terminus is composed of the phosphotyrosine binding (PTB) domain, a short linker region and the RING-type zinc finger. The PTB domain, which is also called TKB (tyrosine kinase binding) domain, is composed of three different subdomains: a four-helix bundle (4H), a calcium-binding EF hand and a divergent SH2 domain. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme. DOMAIN: The UBA domain interacts with poly-ubiquitinated proteins. PTM: Phosphorylated on tyrosine and serine residues upon TCR or BCR activation, and upon various types of cell stimulation. PTM: Auto-ubiquitinated upon EGF-mediated cell activation or upon T-cell costimulation by CD28; which promotes proteasomal degradation. MISCELLANEOUS: This protein has one functional calcium-binding site (By similarity). SIMILARITY: Contains 1 Cbl-PTB (Cbl-type phosphotyrosine-binding) domain. SIMILARITY: Contains 1 RING-type zinc finger. SIMILARITY: Contains 1 UBA domain. SEQUENCE CAUTION: Sequence=BAE45748.1; Type=Erroneous termination; Positions=904; Note=Translated as Arg; Sequence=CAH56175.1; Type=Erroneous initiation; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/CBLbID193.html";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q13191
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
LF210628 - JP 2014500723-A/18131: Polycomb-Associated Non-Coding RNAs. CR749655 - Homo sapiens mRNA; cDNA DKFZp779A0729 (from clone DKFZp779A0729). LF213805 - JP 2014500723-A/21308: Polycomb-Associated Non-Coding RNAs. BC065915 - Homo sapiens cDNA clone IMAGE:4747358, partial cds. BX537484 - Homo sapiens mRNA; cDNA DKFZp686J10223 (from clone DKFZp686J10223). BX649066 - Homo sapiens mRNA; cDNA DKFZp779F1443 (from clone DKFZp779F1443). U26710 - Human cbl-b mRNA, complete cds. AK130668 - Homo sapiens cDNA FLJ27158 fis, clone SYN00808, highly similar to CBLB_HUMAN Signal transduction protein CBL-B. AK292792 - Homo sapiens cDNA FLJ77240 complete cds, highly similar to Homo sapiens Cas-Br-M (murine) ecotropic retroviral transforming sequence b (CBLB), mRNA. BC032851 - Homo sapiens Cas-Br-M (murine) ecotropic retroviral transforming sequence b, mRNA (cDNA clone MGC:33110 IMAGE:5269036), complete cds. AB075490 - Homo sapiens neuroblastoma cDNA, clone:Nbla00127, full insert sequence. AK094184 - Homo sapiens cDNA FLJ36865 fis, clone ASTRO2016148, highly similar to E3 ubiquitin-protein ligase CBL-B (EC 6.3.2.-). AK123147 - Homo sapiens cDNA FLJ41152 fis, clone BRACE2038329, highly similar to E3 ubiquitin-protein ligase CBL-B (EC 6.3.2.-). AK316276 - Homo sapiens cDNA, FLJ79175 complete cds, highly similar to E3 ubiquitin-protein ligase CBL-B (EC 6.3.2.-). AK302533 - Homo sapiens cDNA FLJ56894 complete cds, highly similar to E3 ubiquitin-protein ligase CBL-B (EC 6.3.2.-). EU176266 - Synthetic construct Homo sapiens clone IMAGE:100006378; FLH170562.01X; RZPDo839F10250D Cas-Br-M (murine) ecotropic retroviral transforming sequence b (CBLB) gene, encodes complete protein. DQ349203 - Homo sapiens CBL-B mRNA, complete cds. DQ349204 - Homo sapiens CBL-B variant mRNA, complete cds. KJ896545 - Synthetic construct Homo sapiens clone ccsbBroadEn_05939 CBLB gene, encodes complete protein. KR709530 - Synthetic construct Homo sapiens clone CCSBHm_00002954 CBLB (CBLB) mRNA, encodes complete protein. KR709531 - Synthetic construct Homo sapiens clone CCSBHm_00002955 CBLB (CBLB) mRNA, encodes complete protein. KR709532 - Synthetic construct Homo sapiens clone CCSBHm_00002956 CBLB (CBLB) mRNA, encodes complete protein. KR709533 - Synthetic construct Homo sapiens clone CCSBHm_00002958 CBLB (CBLB) mRNA, encodes complete protein. DQ894452 - Synthetic construct Homo sapiens clone IMAGE:100008912; FLH170555.01L; RZPDo839G0997D Cas-Br-M (murine) ecotropic retroviral transforming sequence b (CBLB) gene, encodes complete protein. AB590326 - Synthetic construct DNA, clone: pFN21AE1387, Homo sapiens CBLB gene for Cas-Br-M (murine) ecotropic retroviral transforming sequence b, without stop codon, in Flexi system. U26711 - Human cbl-b truncated form 1 lacking leucine zipper mRNA, complete cds. U26712 - Human cbl-b truncated form 2 lacking leucine zipper mRNA, complete cds. AK302892 - Homo sapiens cDNA FLJ52897 complete cds, moderately similar to E3 ubiquitin-protein ligase CBL-B (EC 6.3.2.-). CU689562 - Synthetic construct Homo sapiens gateway clone IMAGE:100017873 5' read CBLB mRNA. MA446205 - JP 2018138019-A/18131: Polycomb-Associated Non-Coding RNAs. MA449382 - JP 2018138019-A/21308: Polycomb-Associated Non-Coding RNAs. JD559199 - Sequence 540223 from Patent EP1572962. JD280628 - Sequence 261652 from Patent EP1572962. JD440377 - Sequence 421401 from Patent EP1572962. JD203031 - Sequence 184055 from Patent EP1572962. LF339538 - JP 2014500723-A/147041: Polycomb-Associated Non-Coding RNAs. MA575115 - JP 2018138019-A/147041: Polycomb-Associated Non-Coding RNAs. LF339534 - JP 2014500723-A/147037: Polycomb-Associated Non-Coding RNAs. JD269931 - Sequence 250955 from Patent EP1572962. LF339529 - JP 2014500723-A/147032: Polycomb-Associated Non-Coding RNAs. LF339519 - JP 2014500723-A/147022: Polycomb-Associated Non-Coding RNAs. MA575111 - JP 2018138019-A/147037: Polycomb-Associated Non-Coding RNAs. MA575106 - JP 2018138019-A/147032: Polycomb-Associated Non-Coding RNAs. MA575096 - JP 2018138019-A/147022: Polycomb-Associated Non-Coding RNAs. LF339490 - JP 2014500723-A/146993: Polycomb-Associated Non-Coding RNAs. LF339483 - JP 2014500723-A/146986: Polycomb-Associated Non-Coding RNAs. JD259604 - Sequence 240628 from Patent EP1572962. JD386597 - Sequence 367621 from Patent EP1572962. MA575067 - JP 2018138019-A/146993: Polycomb-Associated Non-Coding RNAs. MA575060 - JP 2018138019-A/146986: Polycomb-Associated Non-Coding RNAs.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q13191 (Reactome details) participates in the following event(s):
R-HSA-983703 p-6Y-SYK phosphorylates BLNK (SLP65) R-HSA-983157 Interaction of E3 with substrate and E2-Ub complex R-HSA-983147 Release of E3 from polyubiquitinated substrate R-HSA-983140 Transfer of Ub from E2 to substrate and release of E2 R-HSA-1112666 BLNK (SLP-65) Signalosome hydrolyzes phosphatidyinositol bisphosphate forming diacylglycerol and inositol-1,4,5-trisphosphate R-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messengers R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation R-HSA-983705 Signaling by the B Cell Receptor (BCR) R-HSA-983169 Class I MHC mediated antigen processing & presentation R-HSA-1280218 Adaptive Immune System R-HSA-168256 Immune System
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
