G3V8H4

SS
Gene name
Cblc (Cbl-3)
Protein name
E3 ubiquitin-protein ligase CBL-C
Names
EC 2.3.2.27 , RING-type E3 ubiquitin transferase CBL-C
Species
Rattus norvegicus (Rat)
KEGG Pathway
rno:292699
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)

334-345 (LH region) SS

Target domain

9-323 (TKBD)

Relief mechanism

PTM

Assay

353-397 (RING domain) SS

Target domain

11-321 (TKB domain)

Relief mechanism

PTM

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for G3V8H4

Entry ID Method Resolution Chain Position Source
AF-G3V8H4-F1 Predicted AlphaFoldDB

2 variants for G3V8H4

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3318948483 326 V>E No EVA
rs3318941450 453 N>D No EVA

No associated diseases with G3V8H4

6 regional properties for G3V8H4

Type Name Position InterPro Accession
domain Zinc finger, RING-type 351 - 390 IPR001841
domain Adaptor protein Cbl, N-terminal helical 14 - 145 IPR003153
domain Adaptor protein Cbl, EF hand-like 149 - 232 IPR014741
domain Adaptor protein Cbl, SH2-like domain 226 - 322 IPR014742
conserved_site Zinc finger, RING-type, conserved site 366 - 375 IPR017907
domain Adaptor protein Cbl, PTB domain 7 - 321 IPR024159

Functions

Description
EC Number 2.3.2.27 Aminoacyltransferases
Subcellular Localization
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

2 GO annotations of cellular component

Name Definition
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+).
epidermal growth factor receptor binding Binding to an epidermal growth factor receptor.
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

9 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.
negative regulation of epidermal growth factor receptor signaling pathway Any process that stops, prevents, or reduces the frequency, rate or extent of epidermal growth factor receptor signaling pathway activity.
negative regulation of neuron apoptotic process Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process in neurons.
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 stabilization Any process involved in maintaining the structure and integrity of a protein and preventing it from degradation or aggregation.
protein ubiquitination The process in which one or more ubiquitin groups are added to a protein.
response to glial cell derived neurotrophic factor 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 glial cell derived neurotrophic factor 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.
ubiquitin-dependent protein catabolic process The chemical reactions and pathways resulting in the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of a ubiquitin group, or multiple ubiquitin groups, to the protein.

7 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
P22681 CBL E3 ubiquitin-protein ligase CBL Homo sapiens (Human) EV
Q13191 CBLB E3 ubiquitin-protein ligase CBL-B Homo sapiens (Human) EV
Q9ULV8 CBLC E3 ubiquitin-protein ligase CBL-C Homo sapiens (Human) SS
P22682 Cbl E3 ubiquitin-protein ligase CBL Mus musculus (Mouse) SS
Q3TTA7 Cblb E3 ubiquitin-protein ligase CBL-B Mus musculus (Mouse) SS
Q80XL1 Cblc E3 ubiquitin-protein ligase CBL-C Mus musculus (Mouse) SS
Q8K4S7 Cblb E3 ubiquitin-protein ligase CBL-B Rattus norvegicus (Rat) SS
10 20 30 40 50 60
MAAATAPQGW QWGEPRALGR AVKLLQRLEE QCRDLRLFVG PPSLRDLLPR TAQLLREVAK
70 80 90 100 110 120
ARSDKTRGDP EGPGGAGDFL VIYLTNLEAK GRQVAELLPH RGKKDANQDV FPEGSRFRRQ
130 140 150 160 170 180
LAKLALIFSH MHAELSALFP EGKYCGHLYQ ITKGSANTFW RENCGVRCVL PWAEFQSLLC
190 200 210 220 230 240
SCHPVEPGPI MQALRSTLDL TCSGHVSVFE FDIFTRLFQP WPTLLKNWQL LAVNHPGYMA
250 260 270 280 290 300
FLTYDEVQTR LQAYRDKPGS YIFRPSCTRL GQWAIGYVSS NGSILQTIPL NKPLLQVLLK
310 320 330 340 350 360
GQKDGIFLYP DGKNHNPDLT ELCRAVLNQC IQVSQEQLQL YQAMNSTFEL CKICTERDKD
370 380 390 400 410 420
VRIEPCGHLL CSCCLAAWQH SDSQTCPFCR CEIKGREAVS ICQAQERSME VRTTAGDSGD
430 440 450 460 470 480
NCHQEAAEWK LESVTPSAPP LPPEVPCPQR PQNKGWLTLA PFTLPRLRPP LPLPKMASVL
490
WEVTSRPQVR EGATESS