Q9Z2G0 · FEM1B_MOUSE

  • Protein
    Protein fem-1 homolog B
  • Gene
    Fem1b
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

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).

Pathway

Protein modification; protein ubiquitination.

Features

Showing features for binding site, site.

TypeIDPosition(s)Description
Binding site185Zn2+ 1 (UniProtKB | ChEBI); ligand shared with FNIP1
Binding site186Zn2+ 2 (UniProtKB | ChEBI); ligand shared with FNIP1
Binding site186Zn2+ (UniProtKB | ChEBI); ligand shared with BEX proteins
Binding site218Zn2+ 2 (UniProtKB | ChEBI); ligand shared with FNIP1
Site342-343Cleavage; by a caspase-3-like protease

GO annotations

AspectTerm
Cellular ComponentCul2-RING ubiquitin ligase complex
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular Componentnucleoplasm
Cellular Componentnucleus
Molecular Functiondeath receptor binding
Molecular Functionubiquitin-like ligase-substrate adaptor activity
Biological Processapoptotic process
Biological Processbranching involved in prostate gland morphogenesis
Biological Processepithelial cell maturation
Biological Processepithelial cell maturation involved in prostate gland development
Biological Processproteasome-mediated ubiquitin-dependent protein catabolic process
Biological Processprotein ubiquitination
Biological Processregulation of DNA damage checkpoint
Biological Processregulation of extrinsic apoptotic signaling pathway via death domain receptors
Biological Processubiquitin-dependent protein catabolic process via the C-end degron rule pathway

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Protein fem-1 homolog B
  • Short names
    FEM1b
  • Alternative names
    • FEM1-beta
    • Fem-1-like death receptor-binding protein alpha
    • Fem-1-like in apoptotic pathway protein alpha
      (F1A-alpha
      )
    • mt-Fem

Gene names

    • Name
      Fem1b
    • Synonyms
      F1aa
      , Kiaa0396

Organism names

  • Taxonomic identifier
  • Strains
    • CD-1
    • C57BL/6J
    • NOD
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q9Z2G0
  • Secondary accessions
    • Q3TV57
    • Q3ULQ3
    • Q3V148
    • Q80U13
    • Q99NC9
    • Q9QZL3

Proteomes

Organism-specific databases

Subcellular Location

Cytoplasm
Nucleus
Note: In the nucleus, the protein level increased slightly after camptothecin (CPT) treatment. Associated with chromatin.

Keywords

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).

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis126Abolished association with BEX family proteins (BEX1, BEX2, BEX3 and/or BEX4), leading to constitutive ubiquitination of FNIP1.
Mutagenesis186Abolished ability to promote ubiquitination of reduced FNIP1.
Mutagenesis597Abolished ability to promote ubiquitination of reduced FNIP1.

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.

Go to variant viewer

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00003245311-627Protein fem-1 homolog B

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).

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).

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for repeat.

TypeIDPosition(s)Description
Repeat45-74ANK 1
Repeat87-116ANK 2
Repeat120-149ANK 3
Repeat153-182ANK 4
Repeat186-215ANK 5
Repeat218-248ANK 6
Repeat344-377TPR
Repeat483-527ANK 7
Repeat531-568ANK 8

Sequence similarities

Belongs to the fem-1 family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    627
  • Mass (Da)
    70,223
  • Last updated
    1999-05-01 v1
  • Checksum
    72D4ABA2D4576F1B
MEGLAGYVYKAASEGKVLTLAALLLNRSESDIRYLLGYVSQQGGQRSTPLIIAARNGHAKVVRLLLEHYRVQTQQTGTVRFDGYVIDGATALWCAAGAGHFEVVKLLVSHGANVNHTTVTNSTPLRAACFDGRLDIVKYLVENNANISIANKYDNTCLMIAAYKGHTDVVRYLLEQRADPNAKAHCGATALHFAAEAGHIDIVKELIKWRAAIVVNGHGMTPLKVAAESCKADVVELLLSHADCDRRSRIEALELLGASFANDRENYDIMKTYHYLYLAMLERFQDGDNILEKEVLPPIHAYGNRTECRNPQELEAIRQDRDALHMEGLIVRERILGADNIDVSHPIIYRGAVYADNMEFEQCIKLWLHALHLRQKGNRNTHKDLLRFAQVFSQMIHLNEAVKAPDIECVLRCSVLEIEQSMNRVKNISDADVHSAMDNYECNLYTFLYLVCISTKTQCSEEDQCRINKQIYNLIHLDPRTREGFSLLHLAVNSNTPVDDFHTNDVCSFPNALVTKLLLDCGAEVNAVDNEGNSALHIIVQYNRPISDFLTLHSIIISLVEAGAHTDMTNKQNKTPLDKSTTGVSEILLKTQMKMSLKCLAARAVRANDINYQDQIPRTLEEFVGFH

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict184in Ref. 4; BAE21305
Sequence conflict201in Ref. 2; AAF05315
Sequence conflict513in Ref. 3; BAB33298
Sequence conflict540in Ref. 2; AAF05315

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

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