Q96JP0 · FEM1C_HUMAN
- ProteinProtein fem-1 homolog C
- GeneFEM1C
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids617 (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 (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).
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).
Pathway
Protein modification; protein ubiquitination.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | Cul2-RING ubiquitin ligase complex | |
Cellular Component | cytosol | |
Cellular Component | nucleoplasm | |
Cellular Component | ubiquitin ligase complex | |
Molecular Function | ubiquitin-like ligase-substrate adaptor activity | |
Biological Process | proteasome-mediated ubiquitin-dependent protein catabolic process | |
Biological Process | protein ubiquitination | |
Biological Process | ubiquitin-dependent protein catabolic process | |
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 C
- Short namesFEM1c
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ96JP0
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Disease & Variants
Involvement in disease
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 76 | Strongly reduced binding to C-degron with an arginine at the C-terminus. | ||||
Sequence: F → A | ||||||
Mutagenesis | 77 | Reduced 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. | ||||
Sequence: D → A | ||||||
Mutagenesis | 117 | Abolished binding to C-degron with an arginine at the C-terminus. | ||||
Sequence: S → A | ||||||
Mutagenesis | 121 | Reduced binding to C-degron with an arginine at the C-terminus. | ||||
Sequence: R → A | ||||||
Mutagenesis | 125 | Strongly reduced binding to C-degron with an arginine at the C-terminus. | ||||
Sequence: F → A | ||||||
Natural variant | VAR_087634 | 126 | found in a patient with neurodevelopmental disorder with absent speech, pyramidal signs and limb ataxia; likely pathogenic | |||
Sequence: D → H | ||||||
Mutagenesis | 126 | Reduced 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. | ||||
Sequence: D → A | ||||||
Mutagenesis | 148 | Strongly reduced binding to C-degron with an arginine at the C-terminus. | ||||
Sequence: H → A | ||||||
Mutagenesis | 150 | Modifies 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. | ||||
Sequence: H → N | ||||||
Mutagenesis | 158 | Strongly reduced binding to C-degron with an arginine at the C-terminus. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 183-188 | Modifies specificity for C-degron at the C-terminus and promotes increased affinity for C-degrons usually recognized by FEM1B; when associated with N-150. | ||||
Sequence: NTALHD → ATALHF | ||||||
Mutagenesis | 183-191 | Abolished binding to C-degron with an arginine at the C-terminus. | ||||
Sequence: NTALHDCAE → ATALHACAA | ||||||
Mutagenesis | 188 | Reduced binding to C-degron with an arginine at the C-terminus. | ||||
Sequence: D → A | ||||||
Mutagenesis | 188 | Nearly abolished binding to C-degron with an arginine at the C-terminus. | ||||
Sequence: D → K | ||||||
Mutagenesis | 191 | Reduced binding to C-degron with an arginine at the C-terminus. | ||||
Sequence: E → A | ||||||
Mutagenesis | 191 | Strongly reduced binding to C-degron with an arginine at the C-terminus. | ||||
Sequence: E → K | ||||||
Natural variant | VAR_039810 | 434 | in a breast cancer sample; somatic mutation | |||
Sequence: D → N | ||||||
Natural variant | VAR_039811 | 462 | in a breast cancer sample; somatic mutation; dbSNP:rs753336652 | |||
Sequence: D → N |
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.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Modified residue | 1 | N-acetylmethionine | ||||
Sequence: M | ||||||
Chain | PRO_0000324536 | 1-617 | Protein fem-1 homolog C | |||
Sequence: MDLKTAVFNAARDGKLRLLTKLLASKSKEEVSSLISEKTNGATPLLMAARYGHLDMVEFLLEQCSASIEVGGSVNFDGETIEGAPPLWAASAAGHLKVVQSLLNHGASVNNTTLTNSTPLRAACFDGHLEIVKYLVEHKADLEVSNRHGHTCLMISCYKGHKEIAQYLLEKGADVNRKSVKGNTALHDCAESGSLDIMKMLLMYCAKMEKDGYGMTPLLSASVTGHTNIVDFLTHHAQTSKTERINALELLGATFVDKKRDLLGALKYWKKAMNMRYSDRTNIISKPVPQTLIMAYDYAKEVNSAEELEGLIADPDEMRMQALLIRERILGPSHPDTSYYIRYRGAVYADSGNFKRCINLWKYALDMQQSNLDPLSPMTASSLLSFAELFSFMLQDRAKGLLGTTVTFDDLMGILCKSVLEIERAIKQTQCPADPLQLNKALSIILHLICLLEKVPCTLEQDHFKKQTIYRFLKLHPRGKNNFSPLHLAVDKNTTCVGRYPVCKFPSLQVTAILIECGADVNVRDSDDNSPLHIAALNNHPDIMNLLIKSGAHFDATNLHKQTASDLLDEKEIAKNLIQPINHTTLQCLAARVIVNHRIYYKGHIPEKLETFVSLHR |
Keywords
- PTM
Proteomic databases
PTM 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
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q96JP0 | CEP63 Q96MT8-3 | 3 | EBI-2515330, EBI-11522539 | |
BINARY | Q96JP0 | LZTS2 Q9BRK4 | 3 | EBI-2515330, EBI-741037 | |
BINARY | Q96JP0 | MALT1 Q9UDY8-2 | 3 | EBI-2515330, EBI-12056869 | |
BINARY | Q96JP0 | MCM8 Q9UJA3-4 | 3 | EBI-2515330, EBI-13052514 | |
BINARY | Q96JP0 | PNMA1 Q8ND90 | 3 | EBI-2515330, EBI-302345 | |
BINARY | Q96JP0 | RPGRIP1 Q96KN7 | 3 | EBI-2515330, EBI-1050213 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for repeat.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Repeat | 2-31 | ANK 1 | ||||
Sequence: DLKTAVFNAARDGKLRLLTKLLASKSKEEV | ||||||
Repeat | 40-70 | ANK 2 | ||||
Sequence: NGATPLLMAARYGHLDMVEFLLEQCSASIEV | ||||||
Repeat | 82-111 | ANK 3 | ||||
Sequence: EGAPPLWAASAAGHLKVVQSLLNHGASVNN | ||||||
Repeat | 115-144 | ANK 4 | ||||
Sequence: TNSTPLRAACFDGHLEIVKYLVEHKADLEV | ||||||
Repeat | 148-177 | ANK 5 | ||||
Sequence: HGHTCLMISCYKGHKEIAQYLLEKGADVNR | ||||||
Repeat | 181-210 | ANK 6 | ||||
Sequence: KGNTALHDCAESGSLDIMKMLLMYCAKMEK | ||||||
Repeat | 213-242 | ANK 7 | ||||
Sequence: YGMTPLLSASVTGHTNIVDFLTHHAQTSKT | ||||||
Repeat | 245-279 | TPR 1 | ||||
Sequence: INALELLGATFVDKKRDLLGALKYWKKAMNMRYSD | ||||||
Repeat | 338-371 | TPR 2 | ||||
Sequence: SYYIRYRGAVYADSGNFKRCINLWKYALDMQQSN | ||||||
Repeat | 481-523 | ANK 8 | ||||
Sequence: NNFSPLHLAVDKNTTCVGRYPVCKFPSLQVTAILIECGADVNV | ||||||
Repeat | 527-556 | ANK 9 | ||||
Sequence: DDNSPLHIAALNNHPDIMNLLIKSGAHFDA |
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
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length617
- Mass (Da)68,673
- Last updated2001-12-01 v1
- Checksum6218B3963C486369
Sequence caution
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |