Hmdb loader
Survey

Showing Protein E3 ubiquitin-protein ligase CBL-B (HMDBP07559)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 1 metabolite
Identification
HMDB Protein ID HMDBP07559
Secondary Accession Numbers
  • 13267
Name E3 ubiquitin-protein ligase CBL-B
Synonyms
  1. Casitas B-lineage lymphoma proto-oncogene b
  2. RING finger protein 56
  3. SH3-binding protein CBL-B
  4. Signal transduction protein CBL-B
Gene Name CBLB
Protein Type Unknown
Biological Properties
General Function Involved in signal transducer activity
Specific 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
Pathways Not Available
Reactions Not Available
GO Classification
Component
organelle
membrane-bounded organelle
intracellular membrane-bounded organelle
nucleus
Function
ion binding
cation binding
metal ion binding
binding
transition metal ion binding
zinc ion binding
protein binding
molecular transducer activity
signal transducer activity
calcium ion binding
Process
signaling
signaling pathway
cell surface receptor linked signaling pathway
Cellular Location
  1. Cytoplasm
Gene Properties
Chromosome Location Chromosome:3
Locus 3q13.11
SNPs CBLB
Gene Sequence 
>2949 bp
ATGGCAAACTCAATGAATGGCAGAAACCCTGGTGGTCGAGGAGGAAATCCCCGAAAAGGT
CGAATTTTGGGTATTATTGATGCTATTCAGGATGCAGTTGGACCCCCTAAGCAAGCTGCC
GCAGATCGCAGGACCGTGGAGAAGACTTGGAAGCTCATGGACAAAGTGGTAAGACTGTGC
CAAAATCCCAAACTTCAGTTGAAAAATAGCCCACCATATATACTTGATATTTTGCCTGAT
ACATATCAGCATTTACGACTTATATTGAGTAAATATGATGACAACCAGAAACTTGCCCAA
CTCAGTGAGAATGAGTACTTTAAAATCTACATTGATAGCCTTATGAAAAAGTCAAAACGG
GCAATAAGACTCTTTAAAGAAGGCAAGGAGAGAATGTATGAAGAACAGTCACAGGACAGA
CGAAATCTCACAAAACTGTCCCTTATCTTCAGTCACATGCTGGCAGAAATCAAAGCAATC
TTTCCCAATGGTCAATTCCAGGGAGATAACTTTCGTATCACAAAAGCAGATGCTGCTGAA
TTCTGGAGAAAGTTTTTTGGAGACAAAACTATCGTACCATGGAAAGTATTCAGACAGTGC
CTTCATGAGGTCCACCAGATTAGCTCTGGCCTGGAAGCAATGGCTCTAAAATCAACAATT
GATTTAACTTGCAATGATTACATTTCAGTTTTTGAATTTGATATTTTTACCAGGCTGTTT
CAGCCTTGGGGCTCTATTTTGCGGAATTGGAATTTCTTAGCTGTGACACATCCAGGTTAC
ATGGCATTTCTCACATATGATGAAGTTAAAGCACGACTACAGAAATATAGCACCAAACCC
GGAAGCTATATTTTCCGGTTAAGTTGCACTCGATTGGGACAGTGGGCCATTGGCTATGTG
ACTGGGGATGGGAATATCTTACAGACCATACCTCATAACAAGCCCTTATTTCAAGCCCTG
ATTGATGGCAGCAGGGAAGGATTTTATCTTTATCCTGATGGGAGGAGTTATAATCCTGAT
TTAACTGGATTATGTGAACCTACACCTCATGACCATATAAAAGTTACACAGGAACAATAT
GAATTATATTGTGAAATGGGCTCCACTTTTCAGCTCTGTAAGATTTGTGCAGAGAATGAC
AAAGATGTCAAGATTGAGCCTTGTGGGCATTTGATGTGCACCTCTTGCCTTACGGCATGG
CAGGAGTCGGATGGTCAGGGCTGCCCTTTCTGTCGTTGTGAAATAAAAGGAACTGAGCCC
ATAATCGTGGACCCCTTTGATCCAAGAGATGAAGGCTCCAGGTGTTGCAGCATCATTGAC
CCCTTTGGCATGCCGATGCTAGACTTGGACGACGATGATGATCGTGAGGAGTCCTTGATG
ATGAATCGGTTGGCAAACGTCCGAAAGTGCACTGACAGGCAGAACTCACCAGTCACATCA
CCAGGATCCTCTCCCCTTGCCCAGAGAAGAAAGCCACAGCCTGACCCACTCCAGATCCCA
CATCTAAGCCTGCCACCCGTGCCTCCTCGCCTGGATCTAATTCAGAAAGGCATAGTTAGA
TCTCCCTGTGGCAGCCCAACGGGTTCACCAAAGTCTTCTCCTTGCATGGTGAGAAAACAA
GATAAACCACTCCCAGCACCACCTCCTCCCTTAAGAGATCCTCCTCCACCGCCACCTGAA
AGACCTCCACCAATCCCACCAGACAATAGACTGAGTAGACACATCCATCATGTGGAAAGC
GTGCCTTCCAGAGACCCGCCAATGCCTCTTGAAGCATGGTGCCCTCGGGATGTGTTTGGG
ACTAATCAGCTTGTGGGATGTCGACTCCTAGGGGAGGGCTCTCCAAAACCTGGAATCACA
GCGAGTTCAAATGTCAATGGAAGGCACAGTAGAGTGGGCTCTGACCCAGTGCTTATGCGG
AAACACAGACGCCATGATTTGCCTTTAGAAGGAGCTAAGGTCTTTTCCAATGGTCACCTT
GGAAGTGAAGAATATGATGTTCCTCCCCGGCTTTCTCCTCCTCCTCCAGTTACCACCCTC
CTCCCTAGCATAAAGTGTACTGGTCCGTTAGCAAATTCTCTTTCAGAGAAAACAAGAGAC
CCAGTAGAGGAAGATGATGATGAATACAAGATTCCTTCATCCCACCCTGTTTCCCTGAAT
TCACAACCATCTCATTGTCATAATGTAAAACCTCCTGTTCGGTCTTGTGATAATGGTCAC
TGTATGCTGAATGGAACACATGGTCCATCTTCAGAGAAGAAATCAAACATCCCTGACTTA
AGCATATATTTAAAGGGAGATGTTTTTGATTCAGCCTCTGATCCCGTGCCATTACCACCT
GCCAGGCCTCCAACTCGGGACAATCCAAAGCATGGTTCTTCACTCAACAGGACGCCCTCT
GATTATGATCTTCTCATCCCTCCATTAGGTGAAGATGCTTTTGATGCCCTCCCTCCATCT
CTCCCACCTCCCCCACCTCCTGCAAGGCATAGTCTCATTGAACATTCAAAACCTCCTGGC
TCCAGTAGCCGGCCATCCTCAGGACAGGATCTTTTTCTTCTTCCTTCAGATCCCTTTGTT
GATCTAGCAAGTGGCCAAGTTCCTTTGCCTCCTGCTAGAAGGTTACCAGGTGAAAATGTC
AAAACTAACAGAACATCACAGGACTATGATCAGCTTCCTTCATGTTCAGATGGTTCACAG
GCACCAGCCAGACCCCCTAAACCACGACCGCGCAGGACTGCACCAGAAATTCACCACAGA
AAACCCCATGGGCCTGAGGCGGCATTGGAAAATGTCGATGCAAAAATTGCAAAACTCATG
GGAGAGGGTTATGCCTTTGAAGAGGTGAAGAGAGCCTTAGAGATAGCCCAGAATAATGTC
GAAGTTGCCCGGAGCATCCTCCGAGAATTTGCCTTCCCTCCTCCAGTATCCCCACGTCTA
AATCTATAG
Protein Properties
Number of Residues 982
Molecular Weight 109448.6
Theoretical pI 7.94
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence 
>E3 ubiquitin-protein ligase CBL-B
MANSMNGRNPGGRGGNPRKGRILGIIDAIQDAVGPPKQAAADRRTVEKTWKLMDKVVRLC
QNPKLQLKNSPPYILDILPDTYQHLRLILSKYDDNQKLAQLSENEYFKIYIDSLMKKSKR
AIRLFKEGKERMYEEQSQDRRNLTKLSLIFSHMLAEIKAIFPNGQFQGDNFRITKADAAE
FWRKFFGDKTIVPWKVFRQCLHEVHQISSGLEAMALKSTIDLTCNDYISVFEFDIFTRLF
QPWGSILRNWNFLAVTHPGYMAFLTYDEVKARLQKYSTKPGSYIFRLSCTRLGQWAIGYV
TGDGNILQTIPHNKPLFQALIDGSREGFYLYPDGRSYNPDLTGLCEPTPHDHIKVTQEQY
ELYCEMGSTFQLCKICAENDKDVKIEPCGHLMCTSCLTAWQESDGQGCPFCRCEIKGTEP
IIVDPFDPRDEGSRCCSIIDPFGMPMLDLDDDDDREESLMMNRLANVRKCTDRQNSPVTS
PGSSPLAQRRKPQPDPLQIPHLSLPPVPPRLDLIQKGIVRSPCGSPTGSPKSSPCMVRKQ
DKPLPAPPPPLRDPPPPPPERPPPIPPDNRLSRHIHHVESVPSRDPPMPLEAWCPRDVFG
TNQLVGCRLLGEGSPKPGITASSNVNGRHSRVGSDPVLMRKHRRHDLPLEGAKVFSNGHL
GSEEYDVPPRLSPPPPVTTLLPSIKCTGPLANSLSEKTRDPVEEDDDEYKIPSSHPVSLN
SQPSHCHNVKPPVRSCDNGHCMLNGTHGPSSEKKSNIPDLSIYLKGDVFDSASDPVPLPP
ARPPTRDNPKHGSSLNRTPSDYDLLIPPLGEDAFDALPPSLPPPPPPARHSLIEHSKPPG
SSSRPSSGQDLFLLPSDPFVDLASGQVPLPPARRLPGENVKTNRTSQDYDQLPSCSDGSQ
APARPPKPRPRRTAPEIHHRKPHGPEAALENVDAKIAKLMGEGYAFEEVKRALEIAQNNV
EVARSILREFAFPPPVSPRLNL
GenBank ID Protein 54112420
UniProtKB/Swiss-Prot ID Q13191
UniProtKB/Swiss-Prot Entry Name CBLB_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_170662.3
GeneCard ID CBLB
GenAtlas ID CBLB
HGNC ID HGNC:1542
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  3. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [PubMed:18691976 ]
  4. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [PubMed:17081983 ]
  5. Rikova K, Guo A, Zeng Q, Possemato A, Yu J, Haack H, Nardone J, Lee K, Reeves C, Li Y, Hu Y, Tan Z, Stokes M, Sullivan L, Mitchell J, Wetzel R, Macneill J, Ren JM, Yuan J, Bakalarski CE, Villen J, Kornhauser JM, Smith B, Li D, Zhou X, Gygi SP, Gu TL, Polakiewicz RD, Rush J, Comb MJ: Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell. 2007 Dec 14;131(6):1190-203. [PubMed:18083107 ]
  6. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [PubMed:17974005 ]
  7. Heibeck TH, Ding SJ, Opresko LK, Zhao R, Schepmoes AA, Yang F, Tolmachev AV, Monroe ME, Camp DG 2nd, Smith RD, Wiley HS, Qian WJ: An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells. J Proteome Res. 2009 Aug;8(8):3852-61. doi: 10.1021/pr900044c. [PubMed:19534553 ]
  8. Muzny DM, Scherer SE, Kaul R, Wang J, Yu J, Sudbrak R, Buhay CJ, Chen R, Cree A, Ding Y, Dugan-Rocha S, Gill R, Gunaratne P, Harris RA, Hawes AC, Hernandez J, Hodgson AV, Hume J, Jackson A, Khan ZM, Kovar-Smith C, Lewis LR, Lozado RJ, Metzker ML, Milosavljevic A, Miner GR, Morgan MB, Nazareth LV, Scott G, Sodergren E, Song XZ, Steffen D, Wei S, Wheeler DA, Wright MW, Worley KC, Yuan Y, Zhang Z, Adams CQ, Ansari-Lari MA, Ayele M, Brown MJ, Chen G, Chen Z, Clendenning J, Clerc-Blankenburg KP, Chen R, Chen Z, Davis C, Delgado O, Dinh HH, Dong W, Draper H, Ernst S, Fu G, Gonzalez-Garay ML, Garcia DK, Gillett W, Gu J, Hao B, Haugen E, Havlak P, He X, Hennig S, Hu S, Huang W, Jackson LR, Jacob LS, Kelly SH, Kube M, Levy R, Li Z, Liu B, Liu J, Liu W, Lu J, Maheshwari M, Nguyen BV, Okwuonu GO, Palmeiri A, Pasternak S, Perez LM, Phelps KA, Plopper FJ, Qiang B, Raymond C, Rodriguez R, Saenphimmachak C, Santibanez J, Shen H, Shen Y, Subramanian S, Tabor PE, Verduzco D, Waldron L, Wang J, Wang J, Wang Q, Williams GA, Wong GK, Yao Z, Zhang J, Zhang X, Zhao G, Zhou J, Zhou Y, Nelson D, Lehrach H, Reinhardt R, Naylor SL, Yang H, Olson M, Weinstock G, Gibbs RA: The DNA sequence, annotation and analysis of human chromosome 3. Nature. 2006 Apr 27;440(7088):1194-8. [PubMed:16641997 ]
  9. Ohira M, Morohashi A, Nakamura Y, Isogai E, Furuya K, Hamano S, Machida T, Aoyama M, Fukumura M, Miyazaki K, Suzuki Y, Sugano S, Hirato J, Nakagawara A: Neuroblastoma oligo-capping cDNA project: toward the understanding of the genesis and biology of neuroblastoma. Cancer Lett. 2003 Jul 18;197(1-2):63-8. [PubMed:12880961 ]
  10. Ettenberg SA, Keane MM, Nau MM, Frankel M, Wang LM, Pierce JH, Lipkowitz S: cbl-b inhibits epidermal growth factor receptor signaling. Oncogene. 1999 Mar 11;18(10):1855-66. [PubMed:10086340 ]
  11. Fang D, Wang HY, Fang N, Altman Y, Elly C, Liu YC: Cbl-b, a RING-type E3 ubiquitin ligase, targets phosphatidylinositol 3-kinase for ubiquitination in T cells. J Biol Chem. 2001 Feb 16;276(7):4872-8. Epub 2000 Nov 21. [PubMed:11087752 ]
  12. Fang D, Liu YC: Proteolysis-independent regulation of PI3K by Cbl-b-mediated ubiquitination in T cells. Nat Immunol. 2001 Sep;2(9):870-5. [PubMed:11526404 ]
  13. Keane MM, Rivero-Lezcano OM, Mitchell JA, Robbins KC, Lipkowitz S: Cloning and characterization of cbl-b: a SH3 binding protein with homology to the c-cbl proto-oncogene. Oncogene. 1995 Jun 15;10(12):2367-77. [PubMed:7784085 ]
  14. Bustelo XR, Crespo P, Lopez-Barahona M, Gutkind JS, Barbacid M: Cbl-b, a member of the Sli-1/c-Cbl protein family, inhibits Vav-mediated c-Jun N-terminal kinase activation. Oncogene. 1997 Nov 20;15(21):2511-20. [PubMed:9399639 ]
  15. Elly C, Witte S, Zhang Z, Rosnet O, Lipkowitz S, Altman A, Liu YC: Tyrosine phosphorylation and complex formation of Cbl-b upon T cell receptor stimulation. Oncogene. 1999 Feb 4;18(5):1147-56. [PubMed:10022120 ]
  16. Ettenberg SA, Magnifico A, Cuello M, Nau MM, Rubinstein YR, Yarden Y, Weissman AM, Lipkowitz S: Cbl-b-dependent coordinated degradation of the epidermal growth factor receptor signaling complex. J Biol Chem. 2001 Jul 20;276(29):27677-84. Epub 2001 May 24. [PubMed:11375397 ]
  17. Szymkiewicz I, Kowanetz K, Soubeyran P, Dinarina A, Lipkowitz S, Dikic I: CIN85 participates in Cbl-b-mediated down-regulation of receptor tyrosine kinases. J Biol Chem. 2002 Oct 18;277(42):39666-72. Epub 2002 Aug 12. [PubMed:12177062 ]
  18. Davies GC, Ettenberg SA, Coats AO, Mussante M, Ravichandran S, Collins J, Nau MM, Lipkowitz S: Cbl-b interacts with ubiquitinated proteins; differential functions of the UBA domains of c-Cbl and Cbl-b. Oncogene. 2004 Sep 16;23(42):7104-15. [PubMed:15273720 ]
  19. Jozic D, Cardenes N, Deribe YL, Moncalian G, Hoeller D, Groemping Y, Dikic I, Rittinger K, Bravo J: Cbl promotes clustering of endocytic adaptor proteins. Nat Struct Mol Biol. 2005 Nov;12(11):972-9. [PubMed:16228008 ]
  20. Moncalian G, Cardenes N, Deribe YL, Spinola-Amilibia M, Dikic I, Bravo J: Atypical polyproline recognition by the CMS N-terminal Src homology 3 domain. J Biol Chem. 2006 Dec 15;281(50):38845-53. Epub 2006 Oct 3. [PubMed:17020880 ]
  21. Peschard P, Kozlov G, Lin T, Mirza IA, Berghuis AM, Lipkowitz S, Park M, Gehring K: Structural basis for ubiquitin-mediated dimerization and activation of the ubiquitin protein ligase Cbl-b. Mol Cell. 2007 Aug 3;27(3):474-85. [PubMed:17679095 ]