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Q13191

- CBLB_HUMAN

UniProt

Q13191 - CBLB_HUMAN

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Protein

E3 ubiquitin-protein ligase CBL-B

Gene

CBLB

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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 UB2D3.6 Publications

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei286 – 2861PhosphotyrosineBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Calcium bindingi219 – 23214PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri373 – 41240RING-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. calcium ion binding Source: InterPro
  2. ligase activity Source: UniProtKB-KW
  3. signal transducer activity Source: InterPro
  4. ubiquitin-protein transferase activity Source: InterPro
  5. zinc ion binding Source: ProtInc

GO - Biological processi

  1. cell surface receptor signaling pathway Source: InterPro
  2. immune response Source: Ensembl
  3. intracellular signal transduction Source: Ensembl
  4. negative regulation of alpha-beta T cell proliferation Source: Ensembl
  5. negative regulation of T cell receptor signaling pathway Source: Ensembl
  6. NLS-bearing protein import into nucleus Source: ProtInc
  7. positive regulation of protein catabolic process Source: Ensembl
  8. positive regulation of T cell anergy Source: Ensembl
  9. signal transduction Source: ProtInc
  10. T cell activation Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_118700. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
REACT_75842. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinkiQ13191.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:CBLB
Synonyms:RNF56
ORF Names:Nbla00127
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 3

Organism-specific databases

HGNCiHGNC:1542. CBLB.

Subcellular locationi

Cytoplasm 1 Publication
Note: Upon EGF stimulation, associates with endocytic vesicles.

GO - Cellular componenti

  1. cytoplasm Source: HPA
  2. cytosol Source: Reactome
  3. nucleus Source: HPA
  4. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi298 – 2981G → E: Inhibits interaction with SYK. No effect on E3 activity. 2 Publications
Mutagenesisi363 – 3631Y → E: Decreases affinity for E2 ubiquitin-conjugating enzymes. 1 Publication
Mutagenesisi373 – 3731C → A: Abolishes E3 activity but does not affect binding to substrates. 2 Publications
Mutagenesisi665 – 6651Y → F: Slightly inhibits interaction with CRKL. Abolishes interaction with CRKL; when associated with F-709. 1 Publication
Mutagenesisi709 – 7091Y → F: Inhibits interaction with CRKL. Abolishes interaction with CRKL; when associated with F-665. 1 Publication
Mutagenesisi904 – 9041R → A: No effect on interaction with CD2AP. Reduced interaction with SH3KBP1. Strongly reduced interaction with SH3KBP1; when associated with A-911. 2 Publications
Mutagenesisi907 – 9071K → A: No effect on interaction with SH3KBP1. Reduced interaction with CD2AP. Strongly reduced interaction with CD2AP; when associated with A-911. 1 Publication
Mutagenesisi911 – 9111R → 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. 2 Publications
Mutagenesisi937 – 9371A → E: Loss of ubiquitin binding. Reduced levels of tyrosine phosphorylation. 1 Publication
Mutagenesisi940 – 9401M → A: Loss of ubiquitin binding. Reduced levels of tyrosine phosphorylation. 1 Publication
Mutagenesisi943 – 9442GY → AQ: Abolishes interaction with ubiquitinated proteins. 1 Publication
Mutagenesisi946 – 9461F → A: Loss of ubiquitin binding. Reduced levels of tyrosine phosphorylation. 1 Publication
Mutagenesisi966 – 9661I → E: Interferes with dimerization. Reduced E3 ubiquitin-protein ligase activity. Reduced levels of tyrosine phosphorylation. 1 Publication
Mutagenesisi967 – 9671L → A: No effect on interaction with ubiquitinated proteins. 1 Publication

Organism-specific databases

PharmGKBiPA26116.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 982982E3 ubiquitin-protein ligase CBL-BPRO_0000055860Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei282 – 2821Phosphoserine; by PKC/PRKCQ1 Publication
Modified residuei363 – 3631Phosphotyrosine1 Publication
Modified residuei521 – 5211Phosphoserine1 Publication
Modified residuei525 – 5251Phosphoserine1 Publication
Modified residuei529 – 5291Phosphoserine1 Publication
Modified residuei634 – 6341PhosphoserineBy similarity
Modified residuei665 – 6651Phosphotyrosine1 Publication
Modified residuei709 – 7091Phosphotyrosine1 Publication
Modified residuei889 – 8891PhosphotyrosineBy similarity

Post-translational modificationi

Phosphorylated on tyrosine and serine residues upon TCR or BCR activation, and upon various types of cell stimulation.5 Publications
Auto-ubiquitinated upon EGF-mediated cell activation or upon T-cell costimulation by CD28; which promotes proteasomal degradation.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ13191.
PaxDbiQ13191.
PRIDEiQ13191.

PTM databases

PhosphoSiteiQ13191.

Expressioni

Tissue specificityi

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).2 Publications

Gene expression databases

BgeeiQ13191.
CleanExiHS_CBLB.
ExpressionAtlasiQ13191. baseline and differential.
GenevestigatoriQ13191.

Organism-specific databases

HPAiHPA018327.
HPA019880.

Interactioni

Subunit structurei

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).10 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ASAP1Q9ULH12EBI-744027,EBI-346622
CD2APQ9Y5K611EBI-744027,EBI-298152
GRB2P629935EBI-744027,EBI-401755
SH3KBP1Q96B9719EBI-744027,EBI-346595

Protein-protein interaction databases

BioGridi107316. 48 interactions.
DIPiDIP-33091N.
IntActiQ13191. 20 interactions.
MINTiMINT-256380.
STRINGi9606.ENSP00000264122.

Structurei

Secondary structure

1
982
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi43 – 6018
Helixi63 – 653
Beta strandi69 – 724
Helixi74 – 9118
Helixi95 – 1028
Helixi105 – 12824
Helixi129 – 1335
Helixi138 – 16023
Helixi162 – 1643
Helixi168 – 1703
Helixi176 – 18611
Beta strandi190 – 1934
Helixi194 – 20411
Helixi210 – 22011
Beta strandi225 – 2295
Helixi230 – 23910
Helixi243 – 2453
Helixi246 – 2538
Beta strandi260 – 2634
Helixi266 – 2738
Helixi274 – 2763
Beta strandi282 – 2876
Beta strandi289 – 2913
Beta strandi295 – 3006
Beta strandi306 – 3094
Beta strandi312 – 3143
Helixi316 – 32510
Helixi332 – 3343
Helixi342 – 3443
Beta strandi352 – 3543
Helixi357 – 3648
Turni365 – 3673
Beta strandi370 – 3723
Turni374 – 3763
Beta strandi377 – 3804
Beta strandi383 – 3864
Helixi394 – 4029
Turni409 – 4113
Beta strandi417 – 4204
Beta strandi422 – 4243
Helixi933 – 9419
Helixi946 – 95510
Turni956 – 9583
Helixi960 – 97011

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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[»]
ProteinModelPortaliQ13191.
SMRiQ13191. Positions 38-427, 929-972.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13191.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini35 – 343309Cbl-PTBPROSITE-ProRule annotationAdd
BLAST
Domaini931 – 97040UBAPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni35 – 1671334HAdd
BLAST
Regioni168 – 24073EF-hand-likeAdd
BLAST
Regioni241 – 343103SH2-likeAdd
BLAST
Regioni344 – 37229LinkerAdd
BLAST
Regioni543 – 56826Interaction with VAV1Add
BLAST
Regioni891 – 92737Interaction with SH3KBP1Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi477 – 925449Pro-richAdd
BLAST

Domaini

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.

Sequence similaritiesi

Contains 1 Cbl-PTB (Cbl-type phosphotyrosine-binding) domain.PROSITE-ProRule annotation
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation
Contains 1 UBA domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri373 – 41240RING-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiNOG242251.
GeneTreeiENSGT00390000011617.
HOVERGENiHBG005255.
InParanoidiQ13191.
KOiK04707.
OMAiSSPCMVR.
OrthoDBiEOG7M0NQX.
PhylomeDBiQ13191.
TreeFamiTF314210.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
1.20.930.20. 1 hit.
3.30.40.10. 1 hit.
3.30.505.10. 1 hit.
InterProiIPR024162. 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]
PANTHERiPTHR23007. PTHR23007. 1 hit.
PfamiPF02262. Cbl_N. 1 hit.
PF02761. Cbl_N2. 1 hit.
PF02762. Cbl_N3. 1 hit.
PF00627. UBA. 1 hit.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
SM00252. SH2. 1 hit.
SM00165. UBA. 1 hit.
[Graphical view]
SUPFAMiSSF47668. SSF47668. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS51506. CBL_PTB. 1 hit.
PS50030. UBA. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform Long (identifier: Q13191) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MANSMNGRNP GGRGGNPRKG RILGIIDAIQ DAVGPPKQAA ADRRTVEKTW
60 70 80 90 100
KLMDKVVRLC QNPKLQLKNS PPYILDILPD TYQHLRLILS KYDDNQKLAQ
110 120 130 140 150
LSENEYFKIY IDSLMKKSKR AIRLFKEGKE RMYEEQSQDR RNLTKLSLIF
160 170 180 190 200
SHMLAEIKAI FPNGQFQGDN FRITKADAAE FWRKFFGDKT IVPWKVFRQC
210 220 230 240 250
LHEVHQISSG LEAMALKSTI DLTCNDYISV FEFDIFTRLF QPWGSILRNW
260 270 280 290 300
NFLAVTHPGY MAFLTYDEVK ARLQKYSTKP GSYIFRLSCT RLGQWAIGYV
310 320 330 340 350
TGDGNILQTI PHNKPLFQAL IDGSREGFYL YPDGRSYNPD LTGLCEPTPH
360 370 380 390 400
DHIKVTQEQY ELYCEMGSTF QLCKICAEND KDVKIEPCGH LMCTSCLTAW
410 420 430 440 450
QESDGQGCPF CRCEIKGTEP IIVDPFDPRD EGSRCCSIID PFGMPMLDLD
460 470 480 490 500
DDDDREESLM MNRLANVRKC TDRQNSPVTS PGSSPLAQRR KPQPDPLQIP
510 520 530 540 550
HLSLPPVPPR LDLIQKGIVR SPCGSPTGSP KSSPCMVRKQ DKPLPAPPPP
560 570 580 590 600
LRDPPPPPPE RPPPIPPDNR LSRHIHHVES VPSRDPPMPL EAWCPRDVFG
610 620 630 640 650
TNQLVGCRLL GEGSPKPGIT ASSNVNGRHS RVGSDPVLMR KHRRHDLPLE
660 670 680 690 700
GAKVFSNGHL GSEEYDVPPR LSPPPPVTTL LPSIKCTGPL ANSLSEKTRD
710 720 730 740 750
PVEEDDDEYK IPSSHPVSLN SQPSHCHNVK PPVRSCDNGH CMLNGTHGPS
760 770 780 790 800
SEKKSNIPDL SIYLKGDVFD SASDPVPLPP ARPPTRDNPK HGSSLNRTPS
810 820 830 840 850
DYDLLIPPLG EDAFDALPPS LPPPPPPARH SLIEHSKPPG SSSRPSSGQD
860 870 880 890 900
LFLLPSDPFV DLASGQVPLP PARRLPGENV KTNRTSQDYD QLPSCSDGSQ
910 920 930 940 950
APARPPKPRP RRTAPEIHHR KPHGPEAALE NVDAKIAKLM GEGYAFEEVK
960 970 980
RALEIAQNNV EVARSILREF AFPPPVSPRL NL
Length:982
Mass (Da):109,450
Last modified:February 7, 2006 - v2
Checksum:iB4E307D31B9F0779
GO
Isoform Truncated 1 (identifier: Q13191-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     812-982: Missing.

Show »
Length:811
Mass (Da):90,883
Checksum:iA63D22F7C9C677DB
GO
Isoform Truncated 2 (identifier: Q13191-3) [UniParc]FASTAAdd to Basket

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

Show »
Length:770
Mass (Da):86,582
Checksum:iDEE458DFFEE1AF2F
GO

Sequence cautioni

The sequence CAH56175.1 differs from that shown. Reason: Probable cloning artifact.
The sequence BAE45748.1 differs from that shown. Reason: Erroneous termination at position 904. Translated as Arg.

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti210 – 2101G → S in AAB09291. (PubMed:7784085)Curated
Sequence conflicti210 – 2101G → S in AAB09292. (PubMed:7784085)Curated
Sequence conflicti210 – 2101G → S in AAB09293. (PubMed:7784085)Curated
Sequence conflicti911 – 9111R → C in CAH56175. (PubMed:17974005)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti584 – 5841R → K.1 Publication
Corresponds to variant rs17853100 [ dbSNP | Ensembl ].
VAR_025303
Natural varianti883 – 8831N → D.
Corresponds to variant rs35835913 [ dbSNP | Ensembl ].
VAR_039241

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei767 – 7704DVFD → TYRI in isoform Truncated 2. 1 PublicationVSP_005730
Alternative sequencei771 – 982212Missing in isoform Truncated 2. 1 PublicationVSP_005731Add
BLAST
Alternative sequencei812 – 982171Missing in isoform Truncated 1. 1 PublicationVSP_005729Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS2948.1. [Q13191-1]
RefSeqiNP_733762.2. NM_170662.3. [Q13191-1]
XP_005247910.1. XM_005247853.1. [Q13191-1]
UniGeneiHs.430589.

Genome annotation databases

EnsembliENST00000264122; ENSP00000264122; ENSG00000114423. [Q13191-1]
ENST00000403724; ENSP00000384816; ENSG00000114423. [Q13191-3]
GeneIDi868.
KEGGihsa:868.
UCSCiuc003dwc.3. human. [Q13191-1]
uc003dwe.2. human. [Q13191-3]

Polymorphism databases

DMDMi88911265.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSi CCDS2948.1. [Q13191-1 ]
RefSeqi NP_733762.2. NM_170662.3. [Q13191-1 ]
XP_005247910.1. XM_005247853.1. [Q13191-1 ]
UniGenei Hs.430589.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2AK5 X-ray 1.85 D 904-911 [» ]
2BZ8 X-ray 2.00 C 902-912 [» ]
2DO6 NMR - A/B 931-970 [» ]
2J6F X-ray 1.70 C 902-912 [» ]
2JNH NMR - A 926-971 [» ]
2LDR NMR - A 351-426 [» ]
2OOA X-ray 1.56 A/B 924-973 [» ]
2OOB X-ray 1.90 A 924-973 [» ]
3PFV X-ray 2.27 A/B 38-344 [» ]
3VGO X-ray 3.10 A/B/C 39-426 [» ]
3ZNI X-ray 2.21 A/E/I/M 36-427 [» ]
ProteinModelPortali Q13191.
SMRi Q13191. Positions 38-427, 929-972.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 107316. 48 interactions.
DIPi DIP-33091N.
IntActi Q13191. 20 interactions.
MINTi MINT-256380.
STRINGi 9606.ENSP00000264122.

PTM databases

PhosphoSitei Q13191.

Polymorphism databases

DMDMi 88911265.

Proteomic databases

MaxQBi Q13191.
PaxDbi Q13191.
PRIDEi Q13191.

Protocols and materials databases

DNASUi 868.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000264122 ; ENSP00000264122 ; ENSG00000114423 . [Q13191-1 ]
ENST00000403724 ; ENSP00000384816 ; ENSG00000114423 . [Q13191-3 ]
GeneIDi 868.
KEGGi hsa:868.
UCSCi uc003dwc.3. human. [Q13191-1 ]
uc003dwe.2. human. [Q13191-3 ]

Organism-specific databases

CTDi 868.
GeneCardsi GC03M105374.
H-InvDB HIX0003518.
HGNCi HGNC:1542. CBLB.
HPAi HPA018327.
HPA019880.
MIMi 604491. gene.
neXtProti NX_Q13191.
PharmGKBi PA26116.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG242251.
GeneTreei ENSGT00390000011617.
HOVERGENi HBG005255.
InParanoidi Q13191.
KOi K04707.
OMAi SSPCMVR.
OrthoDBi EOG7M0NQX.
PhylomeDBi Q13191.
TreeFami TF314210.

Enzyme and pathway databases

UniPathwayi UPA00143 .
Reactomei REACT_118700. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
REACT_75842. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinki Q13191.

Miscellaneous databases

ChiTaRSi CBLB. human.
EvolutionaryTracei Q13191.
GeneWikii CBLB_(gene).
GenomeRNAii 868.
NextBioi 3622.
PROi Q13191.
SOURCEi Search...

Gene expression databases

Bgeei Q13191.
CleanExi HS_CBLB.
ExpressionAtlasi Q13191. baseline and differential.
Genevestigatori Q13191.

Family and domain databases

Gene3Di 1.10.238.10. 1 hit.
1.20.930.20. 1 hit.
3.30.40.10. 1 hit.
3.30.505.10. 1 hit.
InterProi IPR024162. 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 ]
PANTHERi PTHR23007. PTHR23007. 1 hit.
Pfami PF02262. Cbl_N. 1 hit.
PF02761. Cbl_N2. 1 hit.
PF02762. Cbl_N3. 1 hit.
PF00627. UBA. 1 hit.
[Graphical view ]
SMARTi SM00184. RING. 1 hit.
SM00252. SH2. 1 hit.
SM00165. UBA. 1 hit.
[Graphical view ]
SUPFAMi SSF47668. SSF47668. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEi PS51506. CBL_PTB. 1 hit.
PS50030. UBA. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.
    , 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. 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. 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. 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. 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. 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.

Entry informationi

Entry nameiCBLB_HUMAN
AccessioniPrimary (citable) accession number: Q13191
Secondary accession number(s): A8K9S7
, B7WNM4, Q13192, Q13193, Q3LIC0, Q63Z43, Q8IVC5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: February 7, 2006
Last modified: October 29, 2014
This is version 161 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Miscellaneous

This protein has one functional calcium-binding site.By similarity

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3