Q8K4S7

SS
Gene name
Cblb
Protein name
E3 ubiquitin-protein ligase CBL-B
Names
EC 2.3.2.27 , Casitas B-lineage lymphoma proto-oncogene b , RING-type E3 ubiquitin transferase CBL-B , SH3-binding protein CBL-B , Signal transduction protein CBL-B
Species
Rattus norvegicus (Rat)
KEGG Pathway
rno:171136
EC number
2.3.2.27: Aminoacyltransferases
Protein Class

Descriptions

Cbls are adaptor proteins with RING ubiquitin ligase activity, which function as a negative regulator of many signaling pathways. In human CBL, the phosphorylation of Y371 is essential in regulation of the E3 activity of CBL. When Y371 is unmodified, the RING domain is spatially restricted to regions distal from the TKBD substrate-binding site. Phosphorylation facilitates LHR (linker-loop1 (LL1), linker-helix (LH) and linker-loop2 (LL2)) conformational changes that enable the RING domain to approach the N-terminal tyrosine kinase-binding domain (TKBD) substrate-binding site, leading to an increased activity. Specifically, the absence of LH-TKBD contact enables dramatic movement of the RING domain, bringing E2 closer to the TKBD substrate-binding site. Restricting and freeing the RING domain may be a general mechanism for regulating other RING E3s.

Autoinhibitory domains (AIDs)

356-367 (LH region) SS

Target domain

37-345 (TKBD)

Relief mechanism

PTM

Assay

375-426 (RING domain) SS

Target domain

39-343 (TKB domain)

Relief mechanism

PTM

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for Q8K4S7

Entry ID Method Resolution Chain Position Source
AF-Q8K4S7-F1 Predicted AlphaFoldDB

No variants for Q8K4S7

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q8K4S7

1 associated diseases with Q8K4S7

Without disease ID

9 regional properties for Q8K4S7

Type Name Position InterPro Accession
domain Zinc finger, RING-type 373 - 412 IPR001841
domain Adaptor protein Cbl, N-terminal helical 42 - 167 IPR003153
domain Adaptor protein Cbl, EF hand-like 171 - 254 IPR014741
domain Adaptor protein Cbl, SH2-like domain 248 - 344 IPR014742
domain Ubiquitin-associated domain 887 - 926 IPR015940
conserved_site Zinc finger, RING-type, conserved site 388 - 397 IPR017907
domain Zinc finger, C3HC4 RING-type 373 - 411 IPR018957
domain Adaptor protein Cbl, PTB domain 35 - 343 IPR024159
domain E3 ubiquitin-protein ligase CBL-B, RING finger, HC subclass 351 - 426 IPR039520

Functions

Description
EC Number 2.3.2.27 Aminoacyltransferases
Subcellular Localization
  • Cytoplasm
  • In mast cells, translocates to lipid raft upon FCER1 engagement
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

3 GO annotations of cellular component

Name Definition
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
membrane raft Any of the small (10-200 nm), heterogeneous, highly dynamic, sterol- and sphingolipid-enriched membrane domains that compartmentalize cellular processes. Small rafts can sometimes be stabilized to form larger platforms through protein-protein and protein-lipid interactions.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.

6 GO annotations of molecular function

Name Definition
calcium ion binding Binding to a calcium ion (Ca2+).
phosphotyrosine residue binding Binding to a phosphorylated tyrosine residue within a protein.
protein kinase binding Binding to a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate.
receptor tyrosine kinase binding Binding to a receptor that possesses protein tyrosine kinase activity.
SH3 domain binding Binding to a SH3 domain (Src homology 3) of a protein, small protein modules containing approximately 50 amino acid residues found in a great variety of intracellular or membrane-associated proteins.
ubiquitin protein ligase activity Catalysis of the transfer of ubiquitin to a substrate protein via the reaction X-ubiquitin + S -> X + S-ubiquitin, where X is either an E2 or E3 enzyme, the X-ubiquitin linkage is a thioester bond, and the S-ubiquitin linkage is an amide bond

20 GO annotations of biological process

Name Definition
CD4-positive, alpha-beta T cell proliferation The expansion of a CD4-positive, alpha-beta T cell population by cell division.
cellular response to hydrogen peroxide Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a hydrogen peroxide (H2O2) stimulus.
immune response Any immune system process that functions in the calibrated response of an organism to a potential internal or invasive threat.
intracellular signal transduction The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell.
negative regulation of apoptotic process Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process.
negative regulation of CD4-positive, alpha-beta T cell proliferation Any process that stops, prevents or reduces the frequency, rate or extent of CD4-positive, alpha-beta T cell proliferation.
negative regulation of T cell receptor signaling pathway Any process that stops, prevents, or reduces the frequency, rate or extent of signaling pathways initiated by the cross-linking of an antigen receptor on a T cell.
positive regulation of protein catabolic process Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the breakdown of a protein by the destruction of the native, active configuration, with or without the hydrolysis of peptide bonds.
positive regulation of protein ubiquitination Any process that activates or increases the frequency, rate or extent of the addition of ubiquitin groups to a protein.
positive regulation of T cell anergy Any process that activates or increases the frequency, rate, or extent of T cell anergy.
protein catabolic process The chemical reactions and pathways resulting in the breakdown of a protein by the destruction of the native, active configuration, with or without the hydrolysis of peptide bonds.
protein ubiquitination The process in which one or more ubiquitin groups are added to a protein.
regulation of cell adhesion Any process that modulates the frequency, rate or extent of attachment of a cell to another cell or to the extracellular matrix.
regulation of platelet-derived growth factor receptor-alpha signaling pathway Any process that modulates the frequency, rate or extent of platelet-derived growth factor receptor-alpha signaling pathway.
response to gravity Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a gravitational stimulus.
response to hormone Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a hormone stimulus.
signal transduction The cellular process in which a signal is conveyed to trigger a change in the activity or state of a cell. Signal transduction begins with reception of a signal (e.g. a ligand binding to a receptor or receptor activation by a stimulus such as light), or for signal transduction in the absence of ligand, signal-withdrawal or the activity of a constitutively active receptor. Signal transduction ends with regulation of a downstream cellular process, e.g. regulation of transcription or regulation of a metabolic process. Signal transduction covers signaling from receptors located on the surface of the cell and signaling via molecules located within the cell. For signaling between cells, signal transduction is restricted to events at and within the receiving cell.
T cell activation The change in morphology and behavior of a mature or immature T cell resulting from exposure to a mitogen, cytokine, chemokine, cellular ligand, or an antigen for which it is specific.
T cell anergy Any process contributing to anergy in T cells, a state of functional inactivation which is part of T cell tolerance induction.
T cell receptor signaling pathway The series of molecular signals initiated by the cross-linking of an antigen receptor on a T cell.

8 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
P22681 CBL E3 ubiquitin-protein ligase CBL Homo sapiens (Human) EV
Q9ULV8 CBLC E3 ubiquitin-protein ligase CBL-C Homo sapiens (Human) SS
Q13191 CBLB E3 ubiquitin-protein ligase CBL-B Homo sapiens (Human) EV
Q80XL1 Cblc E3 ubiquitin-protein ligase CBL-C Mus musculus (Mouse) SS
P22682 Cbl E3 ubiquitin-protein ligase CBL Mus musculus (Mouse) SS
Q3TTA7 Cblb E3 ubiquitin-protein ligase CBL-B Mus musculus (Mouse) SS
G3V8H4 Cblc E3 ubiquitin-protein ligase CBL-C Rattus norvegicus (Rat) SS
Q6DFR2 cblb E3 ubiquitin-protein ligase CBL-B Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) SS
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 PFSIPMLDLD DDDDREESLM MNRLASVRKC TDRQNSPVTS
490 500 510 520 530 540
PGSSPLAQRR KPQPDPLQIP HLSLPPVPPR LDLIQKGIVR SPCGSPTGSP KSSPCMVRKQ
550 560 570 580 590 600
DKPLPAPPPP LRDPPPPPER PPPIPPDSRL SRHFHHGESV PSRDQPMPLE AWCPRDAFGT
610 620 630 640 650 660
NQVMGCRILG DGSPKPGVTA NSNLNGRHSR MGSDQVLMRK HRRHDLPSEG AKVFSNGHLA
670 680 690 700 710 720
PEEYDVPPRL SPPPPVTALL PSIKCTGPIA NCLSEKTRDT VEEDDDEYKI PSSHPVSLNS
730 740 750 760 770 780
QPSHCHNVKP PVRSCDNGHC ILNGTHGTPS EMKKSNIPDL GIYLKGEDAF DALPPSLPPP
790 800 810 820 830 840
PPPARHSLIE HSKPPGSSSR PSSGQDLFLL PSDPFFDPAS GQVPLPPARR APGDGVKSNR
850 860 870 880 890 900
ASQDYDQLPS SSDGSQAPAR PPKPRPRRTA PEIHHRKPHG PEAALENVDA KIAKLMGEGY
910 920 930
AFEEVKRALE IAQNNLEVAR SILREFAFPP PVSPRLNL