Descriptions

The E3 ubiquitin-protein ligase CBL-B (CBL-B) is an E3 ubiquitin-protein ligase that functions as a negative regulator of T-cell activation. The expression of CBL-B in T cells causes ligand-induced down-modulation of T-cell receptors, thereby controlling the activation degree of T-cells during antigen presentation. Autoinhibition of Cbl-b involves the masking of the E2 binding site due to an interaction between the RING domain and the tyrosine kinase binding domain (TKB). The phosphorylation of Y363 results in a structural rearrangement that unblocks the E2 binding site, thereby activating the E3 ligase activity.

Autoinhibitory domains (AIDs)

Target domain

50-354 (TKB domain)

Relief mechanism

PTM

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for Q6DFR2

Entry ID Method Resolution Chain Position Source
AF-Q6DFR2-F1 Predicted AlphaFoldDB

No variants for Q6DFR2

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q6DFR2

No associated diseases with Q6DFR2

8 regional properties for Q6DFR2

Type Name Position InterPro Accession
domain Zinc finger, RING-type 384 - 423 IPR001841
domain Adaptor protein Cbl, N-terminal helical 53 - 178 IPR003153
domain Adaptor protein Cbl, EF hand-like 182 - 265 IPR014741
domain Adaptor protein Cbl, SH2-like domain 259 - 353 IPR014742
domain Ubiquitin-associated domain 927 - 970 IPR015940
conserved_site Zinc finger, RING-type, conserved site 399 - 408 IPR017907
domain Zinc finger, C3HC4 RING-type 384 - 422 IPR018957
domain Adaptor protein Cbl, PTB domain 46 - 354 IPR024159

Functions

Description
EC Number 2.3.2.- Aminoacyltransferases
Subcellular Localization
  • Cytoplasm
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.

5 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.
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

3 GO annotations of biological process

Name Definition
cell surface receptor signaling pathway The series of molecular signals initiated by activation of a receptor on the surface of a cell. The pathway begins with binding of an extracellular ligand to a cell surface receptor, or for receptors that signal in the absence of a ligand, by ligand-withdrawal or the activity of a constitutively active receptor. The pathway ends with regulation of a downstream cellular process, e.g. transcription.
protein ubiquitination The process in which one or more ubiquitin groups are added to a protein.
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.

3 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q13191 CBLB E3 ubiquitin-protein ligase CBL-B Homo sapiens (Human) EV
Q3TTA7 Cblb E3 ubiquitin-protein ligase CBL-B Mus musculus (Mouse) SS
Q8K4S7 Cblb E3 ubiquitin-protein ligase CBL-B Rattus norvegicus (Rat) SS
10 20 30 40 50 60
MASSSSSSSS TNSSAVTGRL PGARSANPRK ARILGLFDAI QDAVGPPKQA AADRRTVEKT
70 80 90 100 110 120
WKLMDKVVRL CQNPKLQLKN SPPYILDILP DTYQHLRLIL SKYDDNQKLA QLSENEYFKI
130 140 150 160 170 180
YIDSLMKKSK RAIRLFKEGK ERMYEEQSQE RRNLTKLSLI FSHMLAEIKA IFPSGQFQGD
190 200 210 220 230 240
NFRITKADAA EFWRKFFGER TIVPWKIFRQ CLHEVHQISS GLEAMALKST IDLTCNDYIS
250 260 270 280 290 300
VFEFDIFTRL FQPWTSILRN WNFLAVTHPG YMAFLTYDEV KARLQKYSTK PGSYIFRLSC
310 320 330 340 350 360
TRLGQWAIGY VTADGNILQT IPHNKPLFQA LIDGSREGFY LYPDGRSYNP DLTDLCEPTP
370 380 390 400 410 420
HDHIKVTQEQ YELYCEMGST FQLCKICAEN DKDVKIEPCG HLMCTSCLTS WQESDGQGCP
430 440 450 460 470 480
FCRCEIKGTE PIVVDPFDPR DENRCCSFND SLCTPMLDFD DDDLREECLI MNRLASLRKM
490 500 510 520 530 540
NERQNSPVTS PGSSPLSQRR KTPPDPLQIP HLNLPPVPPR LDLIQKGLAR SPCASPTGSP
550 560 570 580 590 600
KSSPCMVRKQ DKPLPAPPPP LREPPPPPER PPPIPPDSRT CRHLHHTENV PCRDQSTQHD
610 620 630 640 650 660
AWCTRDISGA SQPSICRVAH DGSPKLGVPS SSVLNGRHSR MSTEAGFIRH KHHKRRESPL
670 680 690 700 710 720
ETIRVYNGLS GNEEYDVPPR LSPPPPPPTI TIHPAIKCPL LVNSVSDKVR NSAEEDDSEY
730 740 750 760 770 780
KIPSSHPVSS RLPLHCHSIK HFPRLCENGQ CLSNGTHNGI SEIKKLKQPD QGDVIATSTV
790 800 810 820 830 840
PVPLPSARTS ARENHPHGSS LTRTPSDYDL LVPHPGEESF DSSPPSQPPP PPPARTCVPE
850 860 870 880 890 900
HAMPTASGCR PNSDVDLFLP HSDPCPEAPL PPARRGPGEA KSNRLSQEYD QLPSCPDCPQ
910 920 930 940 950 960
APARPPKPVP RRTAPEIHHR RHYNCDSLAE NVDAKIAKLM GEGFPFEEVK RALEIAQNNV
970 980
DVARSILREF AFPPPVCPRL HL