UniProt:Q9UK73 FEM1B

chain
  • chain:1-627
checksum 85DA943663A988C1
comment
  • 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).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.PATHWAY Protein modification; protein ubiquitination.SUBUNIT Component of a CRL2 E3 ubiquitin-protein ligase complex, also named ECS (Elongin BC-CUL2/5-SOCS-box protein) complex, composed of CUL2, Elongin BC (ELOB and ELOC), RBX1 and substrate-specific adapter FEM1B (PubMed:15601820, PubMed:29779948). Homooligomer (PubMed:10542291). Interacts with PPM1F and PHTF1 (PubMed:11559703). Interacts with the death domain of FAS/TNFRSF6 and TNFRSF1A (PubMed:10542291). Interacts with CHEK1 (PubMed:19330022). Interacts with NKX3-1 (By similarity).INTERACTION In the nucleus, the protein level increased slightly after camptothecin (CPT) treatment (PubMed:19330022). Associated with chromatin (PubMed:19330022).TISSUE SPECIFICITY Widely expressed (PubMed:10542291). Highly expressed in testis (PubMed:10542291). Weakly expressed in other tissues (PubMed:10542291).DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the fem-1 family.
created [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53
crossReference
databaseName UniProt
dbId 229509
description
  • recommendedName: fullName evidence="15"Protein fem-1 homolog B shortName evidence="13"FEM1b alternativeName: FEM1-beta alternativeName: fullName evidence="12"Fem-1-like death receptor-binding protein alpha alternativeName: fullName evidence="12"Fem-1-like in apoptotic pathway protein alpha shortName evidence="12"F1A-alpha
displayName UniProt:Q9UK73 FEM1B
geneName
  • FEM1B
  • F1AA
  • KIAA0396
identifier Q9UK73
isSequenceChanged false
keyword
  • 3D-structure
  • ANK repeat
  • Apoptosis
  • Cytoplasm
  • Deafness
  • Disease variant
  • Intellectual disability
  • Metal-binding
  • Nucleus
  • Proteomics identification
  • Reference proteome
  • Repeat
  • TPR repeat
  • Ubl conjugation pathway
  • Zinc
modified [InstanceEdit:9983091] Weiser, Joel, 2026-02-20
moleculeType Protein
name
  • FEM1B
otherIdentifier
  • 10116
  • 11734988_s_at
  • 16802408
  • 212367_PM_at
  • 212367_at
  • 212373_PM_at
  • 212373_at
  • 212374_PM_at
  • 212374_at
  • 35346_at
  • 3599436
  • 3599437
  • 3599438
  • 3599439
  • 3599440
  • 3599441
  • 3599444
  • 3599445
  • 3599446
  • 3599447
  • 3599448
  • 3599449
  • 3599454
  • 3599456
  • 3599458
  • 3599459
  • 7984470
  • A_14_P134430
  • A_23_P151970
  • GE53157
  • GE81996
  • GO:0000151
  • GO:0002070
  • GO:0005123
  • GO:0005515
  • GO:0005634
  • GO:0005654
  • GO:0005737
  • GO:0005739
  • GO:0005829
  • GO:0006915
  • GO:0016567
  • GO:0030163
  • GO:0031462
  • GO:0043161
  • GO:0046872
  • GO:0051438
  • GO:0060090
  • GO:0060442
  • GO:0060743
  • GO:0140627
  • GO:1902041
  • GO:1990756
  • GO:2000001
  • HMNXSV003040323
  • Hs.6048.0.S1_3p_at
  • Hs.6048.0.S2_3p_at
  • Hs.6048.0.S3_3p_at
  • ILMN_1744239
  • ILMN_1836860
  • PH_hs_0035836
  • TC15000628.hg
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • FEM1B_HUMAN
  • O43146
sequenceLength 627
species [Species:48887] Homo sapiens
stId uniprot:Q9UK73
url http://purl.uniprot.org/uniprot/Q9UK73
Cite Us!