Q96JP0 · FEM1C_HUMAN

  • Protein
    Protein fem-1 homolog C
  • Gene
    FEM1C
  • 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 (PubMed:29775578, 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:29775578, PubMed:29779948, PubMed:33398168, PubMed:33398170).
The CRL2(FEM1C) complex specifically recognizes proteins with an arginine at the C-terminus: recognizes and binds proteins ending with -Lys/Arg-Xaa-Arg and -Lys/Arg-Xaa-Xaa-Arg C-degrons, such as SIL1 or OR51B2, leading to their ubiquitination and degradation (PubMed:33398168, PubMed:33398170).
The CRL2(FEM1C) complex mediates ubiquitination and degradation of truncated MSRB1/SEPX1 selenoproteins produced by failed UGA/Sec decoding (PubMed:26138980).
Promotes ubiquitination and degradation of SLBP (PubMed:28118078).

Caution

Was initially thought to be the ortholog of mouse FEM1A.

Pathway

Protein modification; protein ubiquitination.

GO annotations

AspectTerm
Cellular ComponentCul2-RING ubiquitin ligase complex
Cellular Componentcytosol
Cellular Componentnucleoplasm
Cellular Componentubiquitin ligase complex
Molecular Functionubiquitin-like ligase-substrate adaptor activity
Biological Processproteasome-mediated ubiquitin-dependent protein catabolic process
Biological Processprotein ubiquitination
Biological Processubiquitin-dependent protein catabolic process
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 C
  • Short names
    FEM1c
  • Alternative names
    • FEM1-gamma

Gene names

    • Name
      FEM1C
    • Synonyms
      KIAA1785

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    Q96JP0
  • Secondary accessions
    • B2RE47
    • Q8N3V8
    • Q9H704
    • Q9NPL6
    • Q9NPL9

Proteomes

Organism-specific databases

Disease & Variants

Involvement in disease

  • A dominant de novo FEM1C variant was identified in a patient with neurodevelopmental disorder with absent speech, pyramidal signs, and limb ataxia

Features

Showing features for mutagenesis, natural variant.

TypeIDPosition(s)Description
Mutagenesis76Strongly reduced binding to C-degron with an arginine at the C-terminus.
Mutagenesis77Reduced binding to C-degron with an arginine at the C-terminus. Abolished binding to C-degron with an arginine at the C-terminus; when associated with A-126.
Mutagenesis117Abolished binding to C-degron with an arginine at the C-terminus.
Mutagenesis121Reduced binding to C-degron with an arginine at the C-terminus.
Mutagenesis125Strongly reduced binding to C-degron with an arginine at the C-terminus.
Natural variantVAR_087634126found in a patient with neurodevelopmental disorder with absent speech, pyramidal signs and limb ataxia; likely pathogenic
Mutagenesis126Reduced binding to C-degron with an arginine at the C-terminus. Abolished binding to C-degron with an arginine at the C-terminus; when associated with A-77.
Mutagenesis148Strongly reduced binding to C-degron with an arginine at the C-terminus.
Mutagenesis150Modifies specificity for C-degron at the C-terminus and promotes increased affinity for C-degrons usually recognized by FEM1B; when associated with A-183--F-188.
Mutagenesis158Strongly reduced binding to C-degron with an arginine at the C-terminus.
Mutagenesis183-188Modifies specificity for C-degron at the C-terminus and promotes increased affinity for C-degrons usually recognized by FEM1B; when associated with N-150.
Mutagenesis183-191Abolished binding to C-degron with an arginine at the C-terminus.
Mutagenesis188Reduced binding to C-degron with an arginine at the C-terminus.
Mutagenesis188Nearly abolished binding to C-degron with an arginine at the C-terminus.
Mutagenesis191Reduced binding to C-degron with an arginine at the C-terminus.
Mutagenesis191Strongly reduced binding to C-degron with an arginine at the C-terminus.
Natural variantVAR_039810434in a breast cancer sample; somatic mutation
Natural variantVAR_039811462in a breast cancer sample; somatic mutation; dbSNP:rs753336652

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 493 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Keywords

Organism-specific databases

Miscellaneous

Genetic variation databases

PTM/Processing

Features

Showing features for modified residue, chain.

TypeIDPosition(s)Description
Modified residue1N-acetylmethionine
ChainPRO_00003245361-617Protein fem-1 homolog C

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Widely expressed. Highly expressed in kidney, cardiac tissue, skeletal muscle and testis. Expressed at lower levels in other tissues, including cartilage.

Gene expression databases

Organism-specific 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 FEM1C.

Binary interactions

View interactors in UniProtKB
View CPX-2219 in Complex Portal

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for repeat.

TypeIDPosition(s)Description
Repeat2-31ANK 1
Repeat40-70ANK 2
Repeat82-111ANK 3
Repeat115-144ANK 4
Repeat148-177ANK 5
Repeat181-210ANK 6
Repeat213-242ANK 7
Repeat245-279TPR 1
Repeat338-371TPR 2
Repeat481-523ANK 8
Repeat527-556ANK 9

Domain

The first seven ANK repeats at the N-terminus (1-242) are essential for recognition of Lys/Arg-Xaa-Arg and -Lys/Arg-Xaa-Xaa-Arg C-degrons.

Sequence similarities

Belongs to the fem-1 family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    617
  • Mass (Da)
    68,673
  • Last updated
    2001-12-01 v1
  • Checksum
    6218B3963C486369
MDLKTAVFNAARDGKLRLLTKLLASKSKEEVSSLISEKTNGATPLLMAARYGHLDMVEFLLEQCSASIEVGGSVNFDGETIEGAPPLWAASAAGHLKVVQSLLNHGASVNNTTLTNSTPLRAACFDGHLEIVKYLVEHKADLEVSNRHGHTCLMISCYKGHKEIAQYLLEKGADVNRKSVKGNTALHDCAESGSLDIMKMLLMYCAKMEKDGYGMTPLLSASVTGHTNIVDFLTHHAQTSKTERINALELLGATFVDKKRDLLGALKYWKKAMNMRYSDRTNIISKPVPQTLIMAYDYAKEVNSAEELEGLIADPDEMRMQALLIRERILGPSHPDTSYYIRYRGAVYADSGNFKRCINLWKYALDMQQSNLDPLSPMTASSLLSFAELFSFMLQDRAKGLLGTTVTFDDLMGILCKSVLEIERAIKQTQCPADPLQLNKALSIILHLICLLEKVPCTLEQDHFKKQTIYRFLKLHPRGKNNFSPLHLAVDKNTTCVGRYPVCKFPSLQVTAILIECGADVNVRDSDDNSPLHIAALNNHPDIMNLLIKSGAHFDATNLHKQTASDLLDEKEIAKNLIQPINHTTLQCLAARVIVNHRIYYKGHIPEKLETFVSLHR

Sequence caution

The sequence BAB15096.1 differs from that shown. Reason: Erroneous initiation

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF391093
EMBL· GenBank· DDBJ
AAL37627.1
EMBL· GenBank· DDBJ
mRNA
AY249188
EMBL· GenBank· DDBJ
AAO64429.1
EMBL· GenBank· DDBJ
mRNA
AB058688
EMBL· GenBank· DDBJ
BAB47414.1
EMBL· GenBank· DDBJ
mRNA
AK025265
EMBL· GenBank· DDBJ
BAB15096.1
EMBL· GenBank· DDBJ
mRNA Different initiation
AK315803
EMBL· GenBank· DDBJ
BAG38144.1
EMBL· GenBank· DDBJ
mRNA
CH471086
EMBL· GenBank· DDBJ
EAW48963.1
EMBL· GenBank· DDBJ
Genomic DNA
BC028369
EMBL· GenBank· DDBJ
AAH28369.1
EMBL· GenBank· DDBJ
mRNA
AL365409
EMBL· GenBank· DDBJ
CAB96953.1
EMBL· GenBank· DDBJ
mRNA
AL365415
EMBL· GenBank· DDBJ
CAB96957.1
EMBL· GenBank· DDBJ
mRNA
AL831817
EMBL· GenBank· DDBJ
CAD38531.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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