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

106 regional properties for G3V8H4

Type Name Position InterPro Accession
domain Protein kinase domain 15934 - 16189 IPR000719
domain Immunoglobulin subtype 2 102 - 167 IPR003598-1
domain Immunoglobulin subtype 2 833 - 904 IPR003598-2
domain Immunoglobulin subtype 2 957 - 1025 IPR003598-3
domain Immunoglobulin subtype 2 1147 - 1214 IPR003598-4
domain Immunoglobulin subtype 2 1691 - 1758 IPR003598-5
domain Immunoglobulin subtype 2 3192 - 3261 IPR003598-6
domain Immunoglobulin subtype 2 3910 - 3976 IPR003598-7
domain Immunoglobulin subtype 2 4245 - 4311 IPR003598-8
domain Immunoglobulin subtype 2 12296 - 12367 IPR003598-9
domain Immunoglobulin subtype 2 12452 - 12523 IPR003598-10
domain Immunoglobulin subtype 2 13977 - 14044 IPR003598-11
domain Immunoglobulin subtype 2 14463 - 14531 IPR003598-12
domain Immunoglobulin subtype 2 14559 - 14625 IPR003598-13
domain Immunoglobulin subtype 2 14651 - 14718 IPR003598-14
domain Immunoglobulin subtype 2 15208 - 15266 IPR003598-15
domain Immunoglobulin subtype 2 15295 - 15362 IPR003598-16
domain Immunoglobulin subtype 2 15611 - 15678 IPR003598-17
domain Immunoglobulin subtype 2 15707 - 15775 IPR003598-18
domain Immunoglobulin subtype 2 16280 - 16349 IPR003598-19
domain Immunoglobulin subtype 2 16410 - 16478 IPR003598-20
domain Immunoglobulin subtype 2 16509 - 16578 IPR003598-21
domain Immunoglobulin subtype 2 16618 - 16684 IPR003598-22
domain Immunoglobulin subtype 2 16717 - 16785 IPR003598-23
domain Immunoglobulin subtype 2 16842 - 16909 IPR003598-24
domain Immunoglobulin subtype 2 16945 - 17014 IPR003598-25
domain Immunoglobulin subtype 2 17050 - 17117 IPR003598-26
domain Immunoglobulin subtype 2 17262 - 17327 IPR003598-27
domain Immunoglobulin subtype 2 17370 - 17438 IPR003598-28
domain Immunoglobulin subtype 2 17469 - 17537 IPR003598-29
domain Immunoglobulin subtype 2 17583 - 17652 IPR003598-30
domain Immunoglobulin subtype 2 17688 - 17761 IPR003598-31
domain Immunoglobulin subtype 2 17794 - 17862 IPR003598-32
domain Immunoglobulin subtype 2 18021 - 18088 IPR003598-33
domain Immunoglobulin subtype 2 18134 - 18202 IPR003598-34
domain Immunoglobulin subtype 2 18239 - 18307 IPR003598-35
domain Immunoglobulin subtype 2 18341 - 18408 IPR003598-36
domain Immunoglobulin subtype 2 18441 - 18509 IPR003598-37
domain Immunoglobulin subtype 96 - 178 IPR003599-1
domain Immunoglobulin subtype 211 - 294 IPR003599-2
domain Immunoglobulin subtype 413 - 495 IPR003599-3
domain Immunoglobulin subtype 713 - 802 IPR003599-4
domain Immunoglobulin subtype 827 - 915 IPR003599-5
domain Immunoglobulin subtype 955 - 1038 IPR003599-6
domain Immunoglobulin subtype 1141 - 1225 IPR003599-7
domain Immunoglobulin subtype 1685 - 1769 IPR003599-8
domain Immunoglobulin subtype 2911 - 2995 IPR003599-9
domain Immunoglobulin subtype 3009 - 3089 IPR003599-10
domain Immunoglobulin subtype 3111 - 3269 IPR003599-11
domain Immunoglobulin subtype 3795 - 3880 IPR003599-12
domain Immunoglobulin subtype 3904 - 3987 IPR003599-13
domain Immunoglobulin subtype 4239 - 4318 IPR003599-14
domain Immunoglobulin subtype 8772 - 8945 IPR003599-15
domain Immunoglobulin subtype 10279 - 10364 IPR003599-16
domain Immunoglobulin subtype 10373 - 10468 IPR003599-17
domain Immunoglobulin subtype 12180 - 12268 IPR003599-18
domain Immunoglobulin subtype 12290 - 12378 IPR003599-19
domain Immunoglobulin subtype 12446 - 12534 IPR003599-20
domain Immunoglobulin subtype 13880 - 13960 IPR003599-21
domain Immunoglobulin subtype 13971 - 14052 IPR003599-22
domain Immunoglobulin subtype 14064 - 14148 IPR003599-23
domain Immunoglobulin subtype 14457 - 14542 IPR003599-24
domain Immunoglobulin subtype 14553 - 14634 IPR003599-25
domain Immunoglobulin subtype 14644 - 14727 IPR003599-26
domain Immunoglobulin subtype 14739 - 14821 IPR003599-27
domain Immunoglobulin subtype 15196 - 15278 IPR003599-28
domain Immunoglobulin subtype 15289 - 15373 IPR003599-29
domain Immunoglobulin subtype 15605 - 15689 IPR003599-30
domain Immunoglobulin subtype 15701 - 15788 IPR003599-31
domain Immunoglobulin subtype 16274 - 16360 IPR003599-32
domain Immunoglobulin subtype 16404 - 16489 IPR003599-33
domain Immunoglobulin subtype 16503 - 16589 IPR003599-34
domain Immunoglobulin subtype 16612 - 16695 IPR003599-35
domain Immunoglobulin subtype 16711 - 16796 IPR003599-36
domain Immunoglobulin subtype 16836 - 16920 IPR003599-37
domain Immunoglobulin subtype 16939 - 17025 IPR003599-38
domain Immunoglobulin subtype 17044 - 17128 IPR003599-39
domain Immunoglobulin subtype 17256 - 17338 IPR003599-40
domain Immunoglobulin subtype 17364 - 17449 IPR003599-41
domain Immunoglobulin subtype 17463 - 17548 IPR003599-42
domain Immunoglobulin subtype 17577 - 17663 IPR003599-43
domain Immunoglobulin subtype 17682 - 17772 IPR003599-44
domain Immunoglobulin subtype 17788 - 17873 IPR003599-45
domain Immunoglobulin subtype 18015 - 18099 IPR003599-46
domain Immunoglobulin subtype 18128 - 18213 IPR003599-47
domain Immunoglobulin subtype 18233 - 18318 IPR003599-48
domain Immunoglobulin subtype 18335 - 18419 IPR003599-49
domain Immunoglobulin subtype 18435 - 18520 IPR003599-50
domain Fibronectin type III 8948 - 9041 IPR003961-1
domain Fibronectin type III 10459 - 10553 IPR003961-2
domain Fibronectin type III 14151 - 14247 IPR003961-3
domain Fibronectin type III 14251 - 14348 IPR003961-4
domain Fibronectin type III 14350 - 14448 IPR003961-5
domain Fibronectin type III 14824 - 14920 IPR003961-6
domain Fibronectin type III 14937 - 15027 IPR003961-7
domain Fibronectin type III 15380 - 15475 IPR003961-8
domain Fibronectin type III 15501 - 15596 IPR003961-9
domain Fibronectin type III 15602 - 15680 IPR003961-10
domain Fibronectin type III 15789 - 15883 IPR003961-11
domain Fibronectin type III 17152 - 17245 IPR003961-12
active_site Serine/threonine-protein kinase, active site 16051 - 16063 IPR008271
domain Immunoglobulin V-set domain 14563 - 14620 IPR013106-1
domain Immunoglobulin V-set domain 16721 - 16780 IPR013106-2
domain Immunoglobulin V-set domain 17374 - 17433 IPR013106-3
domain Immunoglobulin V-set domain 17473 - 17532 IPR013106-4
binding_site Protein kinase, ATP binding site 15940 - 15963 IPR017441

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