FEM1A_BOVIN
ID FEM1A_BOVIN Reviewed; 653 AA.
AC Q29RM5;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 04-APR-2006, sequence version 1.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Protein fem-1 homolog A {ECO:0000305};
DE Short=FEM1a {ECO:0000305};
DE AltName: Full=FEM1-alpha {ECO:0000305};
GN Name=FEM1A {ECO:0000250|UniProtKB:Q9BSK4};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Heart ventricle;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Substrate-recognition component of a Cul2-RING (CRL2) E3
CC ubiquitin-protein ligase complex of the DesCEND (destruction via C-end
CC degrons) pathway, which recognizes a C-degron located at the extreme C
CC terminus of target proteins, leading to their ubiquitination and
CC degradation. The C-degron recognized by the DesCEND pathway is usually
CC a motif of less than ten residues and can be present in full-length
CC proteins, truncated proteins or proteolytically cleaved forms. The
CC CRL2(FEM1A) complex specifically recognizes proteins with an arginine
CC at the C-terminus: recognizes and binds proteins ending with -Lys/Arg-
CC Xaa-Arg and -Lys/Arg-Xaa-Xaa-Arg C-degrons, such as SIL1 or OR51B2,
CC leading to their ubiquitination and degradation (By similarity).
CC Involved in PGE2-EP4-mediated inhibition of inflammation of macrophages
CC via interaction with NFKB1 and PTGER4. Promotes inflammation in brain
CC microglia through MAP2K4/MKK4-mediated signaling (By similarity).
CC {ECO:0000250|UniProtKB:Q9BSK4, ECO:0000250|UniProtKB:Q9Z2G1}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q9BSK4}.
CC -!- SUBUNIT: Component of a CRL2 E3 ubiquitin-protein ligase complex, also
CC named ECS (Elongin BC-CUL2/5-SOCS-box protein) complex, composed of
CC CUL2, Elongin BC (ELOB and ELOC), RBX1 and substrate-specific adapter
CC FEM1A. Interacts with PTGER4 (By similarity). Interacts with NFKB1; the
CC interaction is direct (By similarity). {ECO:0000250|UniProtKB:Q9BSK4,
CC ECO:0000250|UniProtKB:Q9Z2G1}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q9BSK4}.
CC Cytoplasm {ECO:0000250|UniProtKB:Q9BSK4}.
CC -!- PTM: Phosphorylated; highly phosphorylated in myoblasts and myotubes.
CC Phosphorylation at Ser-108 promotes PGE2-EP4-mediated inhibition of
CC inflammation. Dephosphorylated by protein phosphatase 2A (PP2A).
CC {ECO:0000250|UniProtKB:Q9Z2G1}.
CC -!- SIMILARITY: Belongs to the fem-1 family. {ECO:0000305}.
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DR EMBL; BC114111; AAI14112.1; -; mRNA.
DR RefSeq; NP_001039691.1; NM_001046226.1.
DR AlphaFoldDB; Q29RM5; -.
DR SMR; Q29RM5; -.
DR STRING; 9913.ENSBTAP00000004519; -.
DR PaxDb; Q29RM5; -.
DR PRIDE; Q29RM5; -.
DR Ensembl; ENSBTAT00000004519; ENSBTAP00000004519; ENSBTAG00000003476.
DR GeneID; 516550; -.
DR KEGG; bta:516550; -.
DR CTD; 55527; -.
DR VEuPathDB; HostDB:ENSBTAG00000003476; -.
DR VGNC; VGNC:28944; FEM1A.
DR eggNOG; KOG0508; Eukaryota.
DR GeneTree; ENSGT00940000161210; -.
DR HOGENOM; CLU_020042_2_0_1; -.
DR InParanoid; Q29RM5; -.
DR OMA; DHCGARV; -.
DR OrthoDB; 252380at2759; -.
DR TreeFam; TF351376; -.
DR Reactome; R-BTA-8951664; Neddylation.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000009136; Chromosome 7.
DR Bgee; ENSBTAG00000003476; Expressed in choroid plexus and 105 other tissues.
DR GO; GO:0031462; C:Cul2-RING ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0000151; C:ubiquitin ligase complex; IBA:GO_Central.
DR GO; GO:0031867; F:EP4 subtype prostaglandin E2 receptor binding; IEA:Ensembl.
DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; ISS:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IBA:GO_Central.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0051438; P:regulation of ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0140627; P:ubiquitin-dependent protein catabolic process via the C-end degron rule pathway; ISS:UniProtKB.
DR Gene3D; 1.25.40.10; -; 1.
DR Gene3D; 1.25.40.20; -; 3.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR Pfam; PF12796; Ank_2; 4.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 9.
DR SUPFAM; SSF48403; SSF48403; 2.
DR SUPFAM; SSF48452; SSF48452; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 2.
DR PROSITE; PS50088; ANK_REPEAT; 7.
PE 2: Evidence at transcript level;
KW ANK repeat; Cytoplasm; Mitochondrion; Phosphoprotein; Reference proteome;
KW Repeat; TPR repeat; Ubl conjugation pathway.
FT CHAIN 1..653
FT /note="Protein fem-1 homolog A"
FT /id="PRO_0000324524"
FT REPEAT 2..31
FT /note="ANK 1"
FT REPEAT 40..70
FT /note="ANK 2"
FT REPEAT 82..111
FT /note="ANK 3"
FT REPEAT 115..145
FT /note="ANK 4"
FT REPEAT 149..178
FT /note="ANK 5"
FT REPEAT 182..211
FT /note="ANK 6"
FT REPEAT 214..243
FT /note="ANK 7"
FT REPEAT 282..316
FT /note="TPR 1"
FT REPEAT 374..407
FT /note="TPR 2"
FT REPEAT 518..560
FT /note="ANK 8"
FT REPEAT 564..593
FT /note="ANK 9"
FT REGION 242..274
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 259..273
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 108
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2G1"
SQ SEQUENCE 653 AA; 72100 MW; A3A4B8DB835CD94E CRC64;
MDLHTAVYNA ARDGKLQLLQ KLLSGRSREE LEELTGEVAS GGTPLLIAAR YGHLDVVEYL
VDRCGASVEA GGSVHFDGEI IEGAPPLWAA SAAGHLDVVR SLLRRGASVN RTTRTNSTPL
RAACFDGHLE VVRYLVGEHQ ADLEVANRHG HTCLMISCYK GHREIARYLL EQGAQVNRRS
AKGNTALHDC AESGSLEILQ LLLGCNARME RDGYGMTPLL AASVTGHTNI VEYLIQEQPA
GDEQAQPGLA RVQPQGARSS PEEPPSGESY ESCCPTSREA AVEALELLGA TYVDKKRDLL
GALKHWRRAM ELRHQGGEYL PKPEPPQLVL AYDYSREVNT TEELEALITD PDEMRMQALL
IRERILGPSH PDTSYYIRYR GAVYADSGNF ERCIRLWKYA LDMQQNNLEP LSPMTASSFL
SFAELFSYVL QDRSAKGSLG TPIGFADLMG VLCKGVREVE RALQLPKEPG DSAQFTKALA
IILHLLYLLE KVECTPDQEH LKHQTVYRLL KCAPRGKNGF TPLHMAVDAE TTNVGRYPVG
RFPSLQVVKV LLDCGADPDS RDFDNNTPLH IAAQNNCPGI MNALIEAGAH MDATNAFKKT
AYELLDEKLL AKSTIQPFNY VTLQCLAARA LDKNKIPYKG FIPEELEAFI ELH
