FEM1B
entrez
10116
canonical
uniprot
Q9UK73
canonical
ensembl
ENSG00000169018
resolver
ensp
ENSP00000307298
resolver
enst
ENST00000306917
resolver
genesymbol
FEM1B
resolver
genesymbol_syn
F1AA
resolver
genesymbol_syn
KIAA0396
resolver
hgnc
HGNC:3649
resolver
uniprot
O43146
resolver
uniprot_entry
FEM1B_HUMAN
resolver
uniprot_sec
O43146
resolver
activity_regulation
ACTIVITY REGULATION: Activity of the CRL2(FEM1B) complex toward FNIP1 is inhibited by BEX family proteins (BEX1, BEX2, BEX3, BEX4 and/or BEX5) in absence of reductive stress. Mechanistically, BEX proteins act as pseudosubstrate inhibitors that associate with FEM1B via zinc in absence of reductive stress, thereby preventing association between FEM1B and FNIP1. {ECO:0000250|UniProtKB:Q9Z2G0}.
uniprot
proteins
amino_acid_sequence
MEGLAGYVYKAASEGKVLTLAALLLNRSESDIRYLLGYVSQQGGQRSTPLIIAARNGHAKVVRLLLEHYRVQTQQTGTVRFDGYVIDGATALWCAAGAGHFEVVKLLVSHGANVNHTTVTNSTPLRAACFDGRLDIVKYLVENNANISIANKYDNTCLMIAAYKGHTDVVRYLLEQRADPNAKAHCGATALHFAAEAGHIDIVKELIKWRAAIVVNGHGMTPLKVAAESCKADVVELLLSHADCDRRSRIEALELLGASFANDRENYDIIKTYHYLYLAMLERFQDGDNILEKEVLPPIHAYGNRTECRNPQELESIRQDRDALHMEGLIVRERILGADNIDVSHPIIYRGAVYADNMEFEQCIKLWLHALHLRQKGNRNTHKDLLRFAQVFSQMIHLNETVKAPDIECVLRCSVLEIEQSMNRVKNISDADVHNAMDNYECNLYTFLYLVCISTKTQCSEEDQCKINKQIYNLIHLDPRTREGFTLLHLAVNSNTPVDDFHTNDVCSFPNALVTKLLLDCGAEVNAVDNEGNSALHIIVQYNRPISDFLTLHSIIISLVEAGAHTDMTNKQNKTPLDKSTTGVSEILLKTQMKMSLKCLAARAVRANDINYQDQIPRTLEEFVGFH
uniprot
proteins
disease_involvement
DISEASE: Neurodevelopmental disorder with behavioral, ear, and skeletal abnormalities (NEDBES) [MIM:621263]: An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, impaired intellectual development, and behavioral abnormalities. Additional variable features include brain anomalies, clubfeet, skeletal abnormalities, facial dysmorphism, dysplastic ears, and hearing loss. {ECO:0000269|PubMed:38465576}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation (PubMed:29779948, PubMed:33398168, PubMed:33398170). The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms (PubMed:29779948, PubMed:33398168, PubMed:33398170). The CRL2(FEM1B) complex specifically recognizes proteins ending with -Gly-Leu-Asp-Arg, such as CDK5R1, leading to their ubiquitination and degradation (PubMed:33398168, PubMed:33398170). Also acts as a regulator of the reductive stress response by mediating ubiquitination of reduced FNIP1: in response to reductive stress, the CRL2(FEM1B) complex specifically recognizes a conserved Cys degron in FNIP1 when this degron is reduced, leading to FNIP1 degradation and subsequent activation of mitochondria to recalibrate reactive oxygen species (ROS) (By similarity). Mechanistically, recognizes and binds reduced FNIP1 through two interface zinc ions, which act as a molecular glue that recruit reduced FNIP1 to FEM1B (By similarity). Promotes ubiquitination of GLI1, suppressing GLI1 transcriptional activator activity (PubMed:24076122). Promotes ubiquitination and degradation of ANKRD37 (By similarity). Promotes ubiquitination and degradation of SLBP (PubMed:28118078). Involved in apoptosis by acting as a death receptor-associated protein that mediates apoptosis (PubMed:10542291). Also involved in glucose homeostasis in pancreatic islet (By similarity). May also act as an adapter/mediator in replication stress-induced signaling that leads to the activation of CHEK1 (PubMed:19330022). {ECO:0000250|UniProtKB:Q9Z2G0, ECO:0000269|PubMed:10542291, ECO:0000269|PubMed:19330022, ECO:0000269|PubMed:24076122, ECO:0000269|PubMed:28118078, ECO:0000269|PubMed:29779948, ECO:0000269|PubMed:33398168, ECO:0000269|PubMed:33398170}.
uniprot
proteins
mass_dalton
70264
uniprot
proteins
mutagenesis
MUTAGEN 82; /note="D->A: Abolished binding to -Gly-Leu-Asp-Arg C-degron at the C-terminus; when associated with A-131."; /evidence="ECO:0000269|PubMed:33398168"; MUTAGEN 130; /note="F->A: Abolished binding to -Gly-Leu-Asp-Arg C-degron at the C-terminus."; /evidence="ECO:0000269|PubMed:33398168"; MUTAGEN 131; /note="D->A: Abolished binding to -Gly-Leu-Asp-Arg C-degron at the C-terminus; when associated with A-82."; /evidence="ECO:0000269|PubMed:33398168"; MUTAGEN 163; /note="Y->A: Strongly reduced binding to -Gly-Leu-Asp-Arg C-degron at the C-terminus; when associated with A-193."; /evidence="ECO:0000269|PubMed:33398168"; MUTAGEN 193; /note="F->A: Strongly reduced binding to -Gly-Leu-Asp-Arg C-degron at the C-terminus; when associated with A-163."; /evidence="ECO:0000269|PubMed:33398168"; MUTAGEN 342; /note="D->A: Prevents cleavage by a caspase-3-like protease."; /evidence="ECO:0000269|PubMed:10542291"; MUTAGEN 356; /note="D->A: Does not affect cleavage by a caspase-3-like protease."; /evidence="ECO:0000269|PubMed:10542291"; MUTAGEN 597; /note="L->A: Abolished ability to promote ubiquitination of target proteins such as GLI1."; /evidence="ECO:0000269|PubMed:24076122
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:24076122, ECO:0000269|PubMed:28118078, ECO:0000269|PubMed:29779948, ECO:0000269|PubMed:33398168, ECO:0000269|PubMed:33398170}.
uniprot
proteins
protein_family
Fem-1 family
uniprot
proteins
pubmed
10542291
uniprot
proteins
pubmed
10623617
uniprot
proteins
pubmed
11559703
uniprot
proteins
pubmed
12168954
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15601820
uniprot
proteins
pubmed
16572171
uniprot
proteins
pubmed
19330022
uniprot
proteins
pubmed
24076122
uniprot
proteins
pubmed
28118078
uniprot
proteins
pubmed
29779948
uniprot
proteins
pubmed
33398168
uniprot
proteins
pubmed
33398170
uniprot
proteins
pubmed
38465576
uniprot
proteins
pubmed
9455477
uniprot
proteins
sequence_length
627
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19330022, ECO:0000269|PubMed:24076122}. Nucleus {ECO:0000269|PubMed:19330022}. Note=In the nucleus, the protein level increased slightly after camptothecin (CPT) treatment (PubMed:19330022). Associated with chromatin (PubMed:19330022). {ECO:0000269|PubMed:19330022}.
uniprot
proteins