Q9Z2G0 · FEM1B_MOUSE
- ProteinProtein fem-1 homolog B
- GeneFem1b
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids627 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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 (By similarity).
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 (By similarity).
The CRL2(FEM1B) complex specifically recognizes proteins ending with -Gly-Leu-Asp-Arg, such as CDK5R1, leading to their ubiquitination and degradation (By similarity).
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) (PubMed:32941802, PubMed:34562363).
Mechanistically, recognizes and binds reduced FNIP1 through two interface zinc ions, which act as a molecular glue that recruit reduced FNIP1 to FEM1B (PubMed:34562363).
Promotes ubiquitination of GLI1, suppressing GLI1 transcriptional activator activity (By similarity).
Promotes ubiquitination and degradation of ANKRD37 (PubMed:21723927).
Promotes ubiquitination and degradation of SLBP (By similarity).
Involved in apoptosis by acting as a death receptor-associated protein that mediates apoptosis (By similarity).
Also involved in glucose homeostasis in pancreatic islet (PubMed:16024793).
May also act as an adapter/mediator in replication stress-induced signaling that leads to the activation of CHEK1 (By similarity).
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 (By similarity).
The CRL2(FEM1B) complex specifically recognizes proteins ending with -Gly-Leu-Asp-Arg, such as CDK5R1, leading to their ubiquitination and degradation (By similarity).
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) (PubMed:32941802, PubMed:34562363).
Mechanistically, recognizes and binds reduced FNIP1 through two interface zinc ions, which act as a molecular glue that recruit reduced FNIP1 to FEM1B (PubMed:34562363).
Promotes ubiquitination of GLI1, suppressing GLI1 transcriptional activator activity (By similarity).
Promotes ubiquitination and degradation of ANKRD37 (PubMed:21723927).
Promotes ubiquitination and degradation of SLBP (By similarity).
Involved in apoptosis by acting as a death receptor-associated protein that mediates apoptosis (By similarity).
Also involved in glucose homeostasis in pancreatic islet (PubMed:16024793).
May also act as an adapter/mediator in replication stress-induced signaling that leads to the activation of CHEK1 (By similarity).
Activity regulation
Activity of the CRL2(FEM1B) complex toward FNIP1 is inhibited by BEX family proteins (BEX1, BEX2, BEX3 and/or BEX4) in absence of reductive stress (PubMed:34562363).
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 (PubMed:34562363).
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 (PubMed:34562363).
Pathway
Protein modification; protein ubiquitination.
Features
Showing features for binding site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 185 | Zn2+ 1 (UniProtKB | ChEBI); ligand shared with FNIP1 | ||||
Sequence: H | ||||||
Binding site | 186 | Zn2+ 2 (UniProtKB | ChEBI); ligand shared with FNIP1 | ||||
Sequence: C | ||||||
Binding site | 186 | Zn2+ (UniProtKB | ChEBI); ligand shared with BEX proteins | ||||
Sequence: C | ||||||
Binding site | 218 | Zn2+ 2 (UniProtKB | ChEBI); ligand shared with FNIP1 | ||||
Sequence: H | ||||||
Site | 342-343 | Cleavage; by a caspase-3-like protease | ||||
Sequence: DV |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | Cul2-RING ubiquitin ligase complex | |
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Molecular Function | death receptor binding | |
Molecular Function | ubiquitin-like ligase-substrate adaptor activity | |
Biological Process | apoptotic process | |
Biological Process | branching involved in prostate gland morphogenesis | |
Biological Process | epithelial cell maturation | |
Biological Process | epithelial cell maturation involved in prostate gland development | |
Biological Process | proteasome-mediated ubiquitin-dependent protein catabolic process | |
Biological Process | protein ubiquitination | |
Biological Process | regulation of DNA damage checkpoint | |
Biological Process | regulation of extrinsic apoptotic signaling pathway via death domain receptors | |
Biological Process | ubiquitin-dependent protein catabolic process via the C-end degron rule pathway |
Keywords
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameProtein fem-1 homolog B
- Short namesFEM1b
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ9Z2G0
- Secondary accessions
Proteomes
Organism-specific databases
Phenotypes & Variants
Disruption phenotype
Abnormal glucose tolerance predominantly due to defective glucose-stimulated insulin secretion (PubMed:16024793).
Mice also show defects in prostate ductal morphogenesis and secretory protein expression (PubMed:18816836).
Mice also show defects in prostate ductal morphogenesis and secretory protein expression (PubMed:18816836).
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 126 | Abolished association with BEX family proteins (BEX1, BEX2, BEX3 and/or BEX4), leading to constitutive ubiquitination of FNIP1. | ||||
Sequence: R → A or Q | ||||||
Mutagenesis | 186 | Abolished ability to promote ubiquitination of reduced FNIP1. | ||||
Sequence: C → S | ||||||
Mutagenesis | 597 | Abolished ability to promote ubiquitination of reduced FNIP1. | ||||
Sequence: L → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 32 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000324531 | 1-627 | Protein fem-1 homolog B | |||
Sequence: MEGLAGYVYKAASEGKVLTLAALLLNRSESDIRYLLGYVSQQGGQRSTPLIIAARNGHAKVVRLLLEHYRVQTQQTGTVRFDGYVIDGATALWCAAGAGHFEVVKLLVSHGANVNHTTVTNSTPLRAACFDGRLDIVKYLVENNANISIANKYDNTCLMIAAYKGHTDVVRYLLEQRADPNAKAHCGATALHFAAEAGHIDIVKELIKWRAAIVVNGHGMTPLKVAAESCKADVVELLLSHADCDRRSRIEALELLGASFANDRENYDIMKTYHYLYLAMLERFQDGDNILEKEVLPPIHAYGNRTECRNPQELEAIRQDRDALHMEGLIVRERILGADNIDVSHPIIYRGAVYADNMEFEQCIKLWLHALHLRQKGNRNTHKDLLRFAQVFSQMIHLNEAVKAPDIECVLRCSVLEIEQSMNRVKNISDADVHSAMDNYECNLYTFLYLVCISTKTQCSEEDQCRINKQIYNLIHLDPRTREGFSLLHLAVNSNTPVDDFHTNDVCSFPNALVTKLLLDCGAEVNAVDNEGNSALHIIVQYNRPISDFLTLHSIIISLVEAGAHTDMTNKQNKTPLDKSTTGVSEILLKTQMKMSLKCLAARAVRANDINYQDQIPRTLEEFVGFH |
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in pancreatic islets, within both beta cells and non-beta cells (at protein level) (PubMed:16024793).
Highly expressed in adult testis; expressed in all types of spermatogonia (PubMed:18816836, PubMed:9828124).
Also expressed in the prostate of neonatal mice (PubMed:18816836).
Highly expressed in adult testis; expressed in all types of spermatogonia (PubMed:18816836, PubMed:9828124).
Also expressed in the prostate of neonatal mice (PubMed:18816836).
Gene expression databases
Interaction
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:32941802).
Homooligomer (By similarity).
Interacts with PPM1F and PHTF1 (PubMed:15601915).
Interacts with the death domain of FAS/TNFRSF6 and TNFRSF1A. Interacts with CHEK1 (By similarity).
Interacts with NKX3-1 (PubMed:18816836).
Homooligomer (By similarity).
Interacts with PPM1F and PHTF1 (PubMed:15601915).
Interacts with the death domain of FAS/TNFRSF6 and TNFRSF1A. Interacts with CHEK1 (By similarity).
Interacts with NKX3-1 (PubMed:18816836).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for repeat.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Repeat | 45-74 | ANK 1 | ||||
Sequence: QRSTPLIIAARNGHAKVVRLLLEHYRVQTQ | ||||||
Repeat | 87-116 | ANK 2 | ||||
Sequence: DGATALWCAAGAGHFEVVKLLVSHGANVNH | ||||||
Repeat | 120-149 | ANK 3 | ||||
Sequence: TNSTPLRAACFDGRLDIVKYLVENNANISI | ||||||
Repeat | 153-182 | ANK 4 | ||||
Sequence: YDNTCLMIAAYKGHTDVVRYLLEQRADPNA | ||||||
Repeat | 186-215 | ANK 5 | ||||
Sequence: CGATALHFAAEAGHIDIVKELIKWRAAIVV | ||||||
Repeat | 218-248 | ANK 6 | ||||
Sequence: HGMTPLKVAAESCKADVVELLLSHADCDRRS | ||||||
Repeat | 344-377 | TPR | ||||
Sequence: SHPIIYRGAVYADNMEFEQCIKLWLHALHLRQKG | ||||||
Repeat | 483-527 | ANK 7 | ||||
Sequence: EGFSLLHLAVNSNTPVDDFHTNDVCSFPNALVTKLLLDCGAEVNA | ||||||
Repeat | 531-568 | ANK 8 | ||||
Sequence: EGNSALHIIVQYNRPISDFLTLHSIIISLVEAGAHTDM |
Sequence similarities
Belongs to the fem-1 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length627
- Mass (Da)70,223
- Last updated1999-05-01 v1
- Checksum72D4ABA2D4576F1B
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 184 | in Ref. 4; BAE21305 | ||||
Sequence: A → V | ||||||
Sequence conflict | 201 | in Ref. 2; AAF05315 | ||||
Sequence: D → G | ||||||
Sequence conflict | 513 | in Ref. 3; BAB33298 | ||||
Sequence: L → R | ||||||
Sequence conflict | 540 | in Ref. 2; AAF05315 | ||||
Sequence: V → A |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF064448 EMBL· GenBank· DDBJ | AAC82373.1 EMBL· GenBank· DDBJ | mRNA | ||
AF178633 EMBL· GenBank· DDBJ | AAF05315.1 EMBL· GenBank· DDBJ | mRNA | ||
AB022863 EMBL· GenBank· DDBJ | BAB33298.1 EMBL· GenBank· DDBJ | mRNA | ||
AK032338 EMBL· GenBank· DDBJ | BAC27822.1 EMBL· GenBank· DDBJ | mRNA | ||
AK132692 EMBL· GenBank· DDBJ | BAE21305.1 EMBL· GenBank· DDBJ | mRNA | ||
AK145371 EMBL· GenBank· DDBJ | BAE26395.1 EMBL· GenBank· DDBJ | mRNA | ||
AK149329 EMBL· GenBank· DDBJ | BAE28816.1 EMBL· GenBank· DDBJ | mRNA | ||
AK154060 EMBL· GenBank· DDBJ | BAE32347.1 EMBL· GenBank· DDBJ | mRNA | ||
AK160393 EMBL· GenBank· DDBJ | BAE35763.1 EMBL· GenBank· DDBJ | mRNA | ||
BC068236 EMBL· GenBank· DDBJ | AAH68236.1 EMBL· GenBank· DDBJ | mRNA | ||
AK122272 EMBL· GenBank· DDBJ | BAC65554.1 EMBL· GenBank· DDBJ | mRNA |