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Q13191 (CBLB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 155. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
E3 ubiquitin-protein ligase CBL-B

EC=6.3.2.-
Alternative name(s):
Casitas B-lineage lymphoma proto-oncogene b
RING finger protein 56
SH3-binding protein CBL-B
Signal transduction protein CBL-B
Gene names
Name:CBLB
Synonyms:RNF56
ORF Names:Nbla00127
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length982 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Slightly promotes SRC ubiquitination. May be involved in EGFR ubiquitination and internalization. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3. Ref.10 Ref.11 Ref.12 Ref.14 Ref.16 Ref.21

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Interacts with SH3 domain-containing proteins LCK, CRK and SORBS1. Interacts with LCP2 and ZAP70. May interact with CBL. 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. Interacts with EGFR (phosphorylated). Ref.2 Ref.10 Ref.11 Ref.12 Ref.15 Ref.17 Ref.22 Ref.23 Ref.26

Subcellular location

Cytoplasm. Note: Upon EGF stimulation, associates with endocytic vesicles. Ref.15

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). Ref.2 Ref.10

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.

The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme.

The UBA domain interacts with poly-ubiquitinated proteins.

Post-translational modification

Phosphorylated on tyrosine and serine residues upon TCR or BCR activation, and upon various types of cell stimulation. Ref.10 Ref.11 Ref.20 Ref.21 Ref.24

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.

Sequence similarities

Contains 1 Cbl-PTB (Cbl-type phosphotyrosine-binding) domain.

Contains 1 RING-type zinc finger.

Contains 1 UBA domain.

Sequence caution

The sequence BAE45748.1 differs from that shown. Reason: Erroneous termination at position 904. Translated as Arg.

The sequence CAH56175.1 differs from that shown. Reason: Probable cloning artifact.

Ontologies

Keywords
   Biological processUbl conjugation pathway
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
Zinc-finger
   LigandCalcium
Metal-binding
Zinc
   Molecular functionLigase
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNLS-bearing protein import into nucleus

Traceable author statement Ref.1. Source: ProtInc

T cell activation

Inferred from electronic annotation. Source: Ensembl

cell surface receptor signaling pathway

Inferred from electronic annotation. Source: InterPro

immune response

Inferred from electronic annotation. Source: Ensembl

intracellular signal transduction

Inferred from electronic annotation. Source: Ensembl

negative regulation of T cell receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of alpha-beta T cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of T cell anergy

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein catabolic process

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentcytoplasm

Inferred from direct assay. Source: HPA

cytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay. Source: HPA

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functioncalcium ion binding

Inferred from electronic annotation. Source: InterPro

signal transducer activity

Inferred from electronic annotation. Source: InterPro

ubiquitin-protein ligase activity

Inferred from electronic annotation. Source: InterPro

zinc ion binding

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform Long (identifier: Q13191-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform Truncated 1 (identifier: Q13191-2)

The sequence of this isoform differs from the canonical sequence as follows:
     812-982: Missing.
Isoform Truncated 2 (identifier: Q13191-3)

The sequence of this isoform differs from the canonical sequence as follows:
     767-770: DVFD → TYRI
     771-982: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 982982E3 ubiquitin-protein ligase CBL-B
PRO_0000055860

Regions

Domain35 – 343309Cbl-PTB
Domain931 – 97040UBA
Calcium binding219 – 23214 By similarity
Zinc finger373 – 41240RING-type
Region35 – 1671334H
Region168 – 24073EF-hand-like
Region241 – 343103SH2-like
Region344 – 37229Linker
Region543 – 56826Interaction with VAV1
Region891 – 92737Interaction with SH3KBP1
Compositional bias477 – 925449Pro-rich

Sites

Binding site2861Phosphotyrosine By similarity

Amino acid modifications

Modified residue2821Phosphoserine; by PKC/PRKCQ Ref.20
Modified residue3631Phosphotyrosine Probable
Modified residue5211Phosphoserine Ref.19
Modified residue5251Phosphoserine Ref.19
Modified residue5291Phosphoserine Ref.19
Modified residue6341Phosphoserine By similarity
Modified residue6651Phosphotyrosine Ref.10
Modified residue7091Phosphotyrosine Ref.10
Modified residue8891Phosphotyrosine

Natural variations

Alternative sequence767 – 7704DVFD → TYRI in isoform Truncated 2.
VSP_005730
Alternative sequence771 – 982212Missing in isoform Truncated 2.
VSP_005731
Alternative sequence812 – 982171Missing in isoform Truncated 1.
VSP_005729
Natural variant5841R → K. Ref.7
Corresponds to variant rs17853100 [ dbSNP | Ensembl ].
VAR_025303
Natural variant8831N → D.
Corresponds to variant rs35835913 [ dbSNP | Ensembl ].
VAR_039241

Experimental info

Mutagenesis2981G → E: Inhibits interaction with SYK. No effect on E3 activity. Ref.10 Ref.12
Mutagenesis3631Y → E: Decreases affinity for E2 ubiquitin-conjugating enzymes. Ref.21
Mutagenesis3731C → A: Abolishes E3 activity but does not affect binding to substrates. Ref.12 Ref.13
Mutagenesis6651Y → F: Slightly inhibits interaction with CRKL. Abolishes interaction with CRKL; when associated with F-709. Ref.10
Mutagenesis7091Y → F: Inhibits interaction with CRKL. Abolishes interaction with CRKL; when associated with F-665. Ref.10
Mutagenesis9041R → A: No effect on interaction with CD2AP. Reduced interaction with SH3KBP1. Strongly reduced interaction with SH3KBP1; when associated with A-911. Ref.22 Ref.23
Mutagenesis9071K → A: No effect on interaction with SH3KBP1. Reduced interaction with CD2AP. Strongly reduced interaction with CD2AP; when associated with A-911. Ref.23
Mutagenesis9111R → A: Reduced interaction with CD2AP and with SH3KBP1. Strongly reduced interaction with CD2AP; when associated with A-907. Strongly reduced interaction with SH3KBP1; when associated with A-904. Ref.22 Ref.23
Mutagenesis9371A → E: Loss of ubiquitin binding. Reduced levels of tyrosine phosphorylation. Ref.24
Mutagenesis9401M → A: Loss of ubiquitin binding. Reduced levels of tyrosine phosphorylation. Ref.24
Mutagenesis943 – 9442GY → AQ: Abolishes interaction with ubiquitinated proteins.
Mutagenesis9461F → A: Loss of ubiquitin binding. Reduced levels of tyrosine phosphorylation. Ref.24
Mutagenesis9661I → E: Interferes with dimerization. Reduced E3 ubiquitin-protein ligase activity. Reduced levels of tyrosine phosphorylation. Ref.24
Mutagenesis9671L → A: No effect on interaction with ubiquitinated proteins. Ref.17
Sequence conflict2101G → S in AAB09291. Ref.1
Sequence conflict2101G → S in AAB09292. Ref.1
Sequence conflict2101G → S in AAB09293. Ref.1
Sequence conflict9111R → C in CAH56175. Ref.9

Secondary structure

................................................................................. 982
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Long [UniParc].

Last modified February 7, 2006. Version 2.
Checksum: B4E307D31B9F0779

FASTA982109,450
        10         20         30         40         50         60 
MANSMNGRNP GGRGGNPRKG RILGIIDAIQ DAVGPPKQAA ADRRTVEKTW KLMDKVVRLC 

        70         80         90        100        110        120 
QNPKLQLKNS PPYILDILPD TYQHLRLILS KYDDNQKLAQ LSENEYFKIY IDSLMKKSKR 

       130        140        150        160        170        180 
AIRLFKEGKE RMYEEQSQDR RNLTKLSLIF SHMLAEIKAI FPNGQFQGDN FRITKADAAE 

       190        200        210        220        230        240 
FWRKFFGDKT IVPWKVFRQC LHEVHQISSG LEAMALKSTI DLTCNDYISV FEFDIFTRLF 

       250        260        270        280        290        300 
QPWGSILRNW NFLAVTHPGY MAFLTYDEVK ARLQKYSTKP GSYIFRLSCT RLGQWAIGYV 

       310        320        330        340        350        360 
TGDGNILQTI PHNKPLFQAL IDGSREGFYL YPDGRSYNPD LTGLCEPTPH DHIKVTQEQY 

       370        380        390        400        410        420 
ELYCEMGSTF QLCKICAEND KDVKIEPCGH LMCTSCLTAW QESDGQGCPF CRCEIKGTEP 

       430        440        450        460        470        480 
IIVDPFDPRD EGSRCCSIID PFGMPMLDLD DDDDREESLM MNRLANVRKC TDRQNSPVTS 

       490        500        510        520        530        540 
PGSSPLAQRR KPQPDPLQIP HLSLPPVPPR LDLIQKGIVR SPCGSPTGSP KSSPCMVRKQ 

       550        560        570        580        590        600 
DKPLPAPPPP LRDPPPPPPE RPPPIPPDNR LSRHIHHVES VPSRDPPMPL EAWCPRDVFG 

       610        620        630        640        650        660 
TNQLVGCRLL GEGSPKPGIT ASSNVNGRHS RVGSDPVLMR KHRRHDLPLE GAKVFSNGHL 

       670        680        690        700        710        720 
GSEEYDVPPR LSPPPPVTTL LPSIKCTGPL ANSLSEKTRD PVEEDDDEYK IPSSHPVSLN 

       730        740        750        760        770        780 
SQPSHCHNVK PPVRSCDNGH CMLNGTHGPS SEKKSNIPDL SIYLKGDVFD SASDPVPLPP 

       790        800        810        820        830        840 
ARPPTRDNPK HGSSLNRTPS DYDLLIPPLG EDAFDALPPS LPPPPPPARH SLIEHSKPPG 

       850        860        870        880        890        900 
SSSRPSSGQD LFLLPSDPFV DLASGQVPLP PARRLPGENV KTNRTSQDYD QLPSCSDGSQ 

       910        920        930        940        950        960 
APARPPKPRP RRTAPEIHHR KPHGPEAALE NVDAKIAKLM GEGYAFEEVK RALEIAQNNV 

       970        980 
EVARSILREF AFPPPVSPRL NL 

« Hide

Isoform Truncated 1 [UniParc].

Checksum: A63D22F7C9C677DB
Show »

FASTA81190,883
Isoform Truncated 2 [UniParc].

Checksum: DEE458DFFEE1AF2F
Show »

FASTA77086,582

References

« Hide 'large scale' references
[1]"Cloning and characterization of cbl-b: a SH3 binding protein with homology to the c-cbl proto-oncogene."
Keane M.M., Rivero-Lezcano O.M., Mitchell J.A., Robbins K.C., Lipkowitz S.
Oncogene 10:2367-2377(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG; TRUNCATED 1 AND TRUNCATED 2).
[2]"Cbl-b, a member of the Sli-1/c-Cbl protein family, inhibits Vav-mediated c-Jun N-terminal kinase activation."
Bustelo X.R., Crespo P., Lopez-Barahona M., Gutkind J.S., Barbacid M.
Oncogene 15:2511-2520(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), TISSUE SPECIFICITY, INTERACTION WITH VAV1.
[3]"Cbl-b in Taiwan population."
Shen C.-R., Chen Y.-J., Pai L.-M., Liu C.-L.
Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
Tissue: Trachea.
[5]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG), VARIANT LYS-584.
Tissue: Testis.
[8]"Neuroblastoma oligo-capping cDNA project: toward the understanding of the genesis and biology of neuroblastoma."
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.
Cancer Lett. 197:63-68(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 543-982 (ISOFORM LONG).
Tissue: Neuroblastoma.
[9]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 857-982 (ISOFORM LONG).
Tissue: Small intestine.
[10]"Tyrosine phosphorylation and complex formation of Cbl-b upon T cell receptor stimulation."
Elly C., Witte S., Zhang Z., Rosnet O., Lipkowitz S., Altman A., Liu Y.-C.
Oncogene 18:1147-1156(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, MUTAGENESIS OF GLY-298; TYR-665 AND TYR-709, INTERACTION WITH GRB2 AND CRKL, PHOSPHORYLATION AT TYR-665 AND TYR-709, FUNCTION.
[11]"cbl-b inhibits epidermal growth factor receptor signaling."
Ettenberg S.A., Keane M.M., Nau M.M., Frankel M., Wang L.-M., Pierce J.H., Lipkowitz S.
Oncogene 18:1855-1866(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION, INTERACTION WITH GRB2 AND PIK3R1.
[12]"Cbl-b, a RING-type E3 ubiquitin ligase, targets phosphatidylinositol 3-kinase for ubiquitination in T cells."
Fang D., Wang H.-Y., Fang N., Altman Y., Elly C., Liu Y.-C.
J. Biol. Chem. 276:4872-4878(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PIK3R1, MUTAGENESIS OF GLY-298 AND CYS-373.
[13]"Cbl-b-dependent coordinated degradation of the epidermal growth factor receptor signaling complex."
Ettenberg S.A., Magnifico A., Cuello M., Nau M.M., Rubinstein Y.R., Yarden Y., Weissman A.M., Lipkowitz S.
J. Biol. Chem. 276:27677-27684(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, MUTAGENESIS OF CYS-373.
[14]"Proteolysis-independent regulation of PI3K by Cbl-b-mediated ubiquitination in T cells."
Fang D., Liu Y.-C.
Nat. Immunol. 2:870-875(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[15]"CIN85 participates in Cbl-b-mediated down-regulation of receptor tyrosine kinases."
Szymkiewicz I., Kowanetz K., Soubeyran P., Dinarina A., Lipkowitz S., Dikic I.
J. Biol. Chem. 277:39666-39672(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SH3KBP1, SUBCELLULAR LOCATION.
[16]"Cbl-c suppresses v-Src-induced transformation through ubiquitin-dependent protein degradation."
Kim M., Tezuka T., Tanaka K., Yamamoto T.
Oncogene 23:1645-1655(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[17]"Cbl-b interacts with ubiquitinated proteins; differential functions of the UBA domains of c-Cbl and Cbl-b."
Davies G.C., Ettenberg S.A., Coats A.O., Mussante M., Ravichandran S., Collins J., Nau M.M., Lipkowitz S.
Oncogene 23:7104-7115(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UBIQUITINATED PROTEINS, MUTAGENESIS OF 943-GLY-TYR-944 AND LEU-967.
[18]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[19]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-521; SER-525 AND SER-529, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[20]"PKC-theta modulates the strength of T cell responses by targeting Cbl-b for ubiquitination and degradation."
Gruber T., Hermann-Kleiter N., Hinterleitner R., Fresser F., Schneider R., Gastl G., Penninger J.M., Baier G.
Sci. Signal. 2:RA30-RA30(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-282.
[21]"The N terminus of Cbl-c regulates ubiquitin ligase activity by modulating affinity for the ubiquitin-conjugating enzyme."
Ryan P.E., Sivadasan-Nair N., Nau M.M., Nicholas S., Lipkowitz S.
J. Biol. Chem. 285:23687-23698(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS E3 UBIQUITIN-PROTEIN LIGASE, PHOSPHORYLATION AT TYR-363, MUTAGENESIS OF TYR-363.
[22]"Cbl promotes clustering of endocytic adaptor proteins."
Jozic D., Cardenes N., Deribe Y.L., Moncalian G., Hoeller D., Groemping Y., Dikic I., Rittinger K., Bravo J.
Nat. Struct. Mol. Biol. 12:972-979(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 899-914 IN COMPLEXES WITH SH3KBP1 AND ARHGEF7, MUTAGENESIS OF ARG-904 AND ARG-911, SUBUNIT.
[23]"Atypical polyproline recognition by the CMS N-terminal Src homology 3 domain."
Moncalian G., Cardenes N., Deribe Y.L., Spinola-Amilibia M., Dikic I., Bravo J.
J. Biol. Chem. 281:38845-38853(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 902-912 IN COMPLEX WITH CD2AP, MUTAGENESIS OF ARG-904; LYS-907 AND ARG-911, SUBUNIT.
[24]"Structural basis for ubiquitin-mediated dimerization and activation of the ubiquitin protein ligase Cbl-b."
Peschard P., Kozlov G., Lin T., Mirza I.A., Berghuis A.M., Lipkowitz S., Park M., Gehring K.
Mol. Cell 27:474-485(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.56 ANGSTROMS) OF 924-973 IN COMPLEX WITH UBIQUITIN, STRUCTURE BY NMR OF 924-973, TYROSINE PHOSPHORYLATION, MUTAGENESIS OF ALA-937; MET-940; PHE-946 AND ILE-966.
[25]"Solution structure of RSGI RUH-065, a UBA domain from human cDNA."
RIKEN structural genomics initiative (RSGI)
Submitted (MAY-2007) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 931-970.
[26]"Crystal structure of Cbl-b TKB domain in complex with EGFR pY1069 peptide."
Structural genomics consortium (SGC)
Submitted (OCT-2010) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.27 ANGSTROMS) OF 38-344 IN COMPLEX WITH PHOSPHO-EGFR PEPTIDE, INTERACTION WITH EGFR, HETERODIMER.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U26710 mRNA. Translation: AAB09291.1.
U26711 mRNA. Translation: AAB09292.1.
U26712 mRNA. Translation: AAB09293.1.
DQ349203 mRNA. Translation: ABC86700.1.
AK292792 mRNA. Translation: BAF85481.1.
AC016138 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW79752.1.
CH471052 Genomic DNA. Translation: EAW79753.1.
CH471052 Genomic DNA. Translation: EAW79754.1.
BC032851 mRNA. Translation: AAH32851.1.
AB075490 mRNA. Translation: BAE45748.1. Sequence problems.
BX537484 mRNA. Translation: CAH56175.1. Sequence problems.
RefSeqNP_733762.2. NM_170662.3.
XP_005247910.1. XM_005247853.1.
UniGeneHs.430589.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2AK5X-ray1.85D904-911[»]
2BZ8X-ray2.00C902-912[»]
2DO6NMR-A/B931-970[»]
2J6FX-ray1.70C902-912[»]
2JNHNMR-A926-971[»]
2LDRNMR-A351-426[»]
2OOAX-ray1.56A/B924-973[»]
2OOBX-ray1.90A924-973[»]
3PFVX-ray2.27A/B38-344[»]
3VGOX-ray3.10A/B/C39-426[»]
3ZNIX-ray2.21A/E/I/M36-427[»]
ProteinModelPortalQ13191.
SMRQ13191. Positions 38-427, 929-972.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107316. 46 interactions.
DIPDIP-33091N.
IntActQ13191. 18 interactions.
MINTMINT-256380.
STRING9606.ENSP00000264122.

PTM databases

PhosphoSiteQ13191.

Polymorphism databases

DMDM88911265.

Proteomic databases

PaxDbQ13191.
PRIDEQ13191.

Protocols and materials databases

DNASU868.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264122; ENSP00000264122; ENSG00000114423. [Q13191-1]
ENST00000403724; ENSP00000384816; ENSG00000114423. [Q13191-3]
GeneID868.
KEGGhsa:868.
UCSCuc003dwc.3. human. [Q13191-1]
uc003dwe.2. human. [Q13191-3]

Organism-specific databases

CTD868.
GeneCardsGC03M105374.
H-InvDBHIX0003518.
HGNCHGNC:1542. CBLB.
HPAHPA018327.
HPA019880.
MIM604491. gene.
neXtProtNX_Q13191.
PharmGKBPA26116.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG242251.
HOVERGENHBG005255.
InParanoidQ13191.
KOK04707.
OMASSPCMVR.
OrthoDBEOG7M0NQX.
PhylomeDBQ13191.
TreeFamTF314210.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
SignaLinkQ13191.
UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ13191.
BgeeQ13191.
CleanExHS_CBLB.
GenevestigatorQ13191.

Family and domain databases

Gene3D1.10.238.10. 1 hit.
1.20.930.20. 1 hit.
3.30.40.10. 1 hit.
3.30.505.10. 1 hit.
InterProIPR024162. Adaptor_Cbl.
IPR014741. Adaptor_Cbl_EF_hand-like.
IPR003153. Adaptor_Cbl_N_hlx.
IPR014742. Adaptor_Cbl_SH2-like.
IPR024159. Cbl_PTB.
IPR011992. EF-hand-dom_pair.
IPR000980. SH2.
IPR015940. UBA/transl_elong_EF1B_N_euk.
IPR000449. UBA/Ts_N.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PANTHERPTHR23007. PTHR23007. 1 hit.
PfamPF02262. Cbl_N. 1 hit.
PF02761. Cbl_N2. 1 hit.
PF02762. Cbl_N3. 1 hit.
PF00627. UBA. 1 hit.
[Graphical view]
SMARTSM00184. RING. 1 hit.
SM00252. SH2. 1 hit.
SM00165. UBA. 1 hit.
[Graphical view]
SUPFAMSSF47668. SSF47668. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEPS51506. CBL_PTB. 1 hit.
PS50030. UBA. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCBLB. human.
EvolutionaryTraceQ13191.
GeneWikiCBLB_(gene).
GenomeRNAi868.
NextBio3622.
PROQ13191.
SOURCESearch...

Entry information

Entry nameCBLB_HUMAN
AccessionPrimary (citable) accession number: Q13191
Secondary accession number(s): A8K9S7 expand/collapse secondary AC list , B7WNM4, Q13192, Q13193, Q3LIC0, Q63Z43, Q8IVC5
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: February 7, 2006
Last modified: April 16, 2014
This is version 155 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM