FEM1A_RAT
ID FEM1A_RAT Reviewed; 654 AA.
AC Q4V890;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 110.
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:0000312|RGD:1561112};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
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 and Ser-608 promote PGE2-EP4-mediated
CC inhibition of inflammation. Dephosphorylated by protein phosphatase 2A
CC (PP2A). {ECO:0000250|UniProtKB:Q9Z2G1}.
CC -!- SIMILARITY: Belongs to the fem-1 family. {ECO:0000305}.
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DR EMBL; BC097490; AAH97490.1; -; mRNA.
DR RefSeq; NP_001020877.1; NM_001025706.1.
DR AlphaFoldDB; Q4V890; -.
DR SMR; Q4V890; -.
DR STRING; 10116.ENSRNOP00000067295; -.
DR iPTMnet; Q4V890; -.
DR PhosphoSitePlus; Q4V890; -.
DR jPOST; Q4V890; -.
DR PaxDb; Q4V890; -.
DR PRIDE; Q4V890; -.
DR Ensembl; ENSRNOT00000099590; ENSRNOP00000091315; ENSRNOG00000066151.
DR GeneID; 316131; -.
DR KEGG; rno:316131; -.
DR CTD; 55527; -.
DR RGD; 1561112; Fem1a.
DR eggNOG; KOG0508; Eukaryota.
DR GeneTree; ENSGT00940000161210; -.
DR HOGENOM; CLU_020042_2_0_1; -.
DR InParanoid; Q4V890; -.
DR OMA; DHCGARV; -.
DR OrthoDB; 252380at2759; -.
DR PhylomeDB; Q4V890; -.
DR Reactome; R-RNO-8951664; Neddylation.
DR UniPathway; UPA00143; -.
DR PRO; PR:Q4V890; -.
DR Proteomes; UP000002494; Chromosome 9.
DR Bgee; ENSRNOG00000050646; Expressed in skeletal muscle tissue and 19 other tissues.
DR Genevisible; Q4V890; RN.
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; ISO:RGD.
DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; ISS:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISO:RGD.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; ISO:RGD.
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; 3.
DR Pfam; PF13606; Ank_3; 1.
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..654
FT /note="Protein fem-1 homolog A"
FT /id="PRO_0000324528"
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 283..317
FT /note="TPR 1"
FT REPEAT 375..408
FT /note="TPR 2"
FT REPEAT 519..561
FT /note="ANK 8"
FT REPEAT 565..594
FT /note="ANK 9"
FT REGION 241..265
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 241..262
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 108
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2G1"
FT MOD_RES 608
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2G1"
SQ SEQUENCE 654 AA; 72118 MW; DE3BFC58447C37C2 CRC64;
MDLHTAVYNA AHDGKLLLLQ KLLAGRGREE IEELLGEVAG GGTPLLIAAR RGHLDVVEYL
VDNCGASVEA SGSVHFDGET IEGAPPLWAA SAAGHLAVVR SLLRRGASVN RTTRTNSTPL
RAACFDGHLD VVRYLVGEHK ADLEVANRHG HTCLMISCYK GHREIARYLL ERGAQVNRRS
AKGNTALHDC AESGSLEILQ LLLGCHARME RDGYGMTPLL AASVTGHTNI VEYLIQEQPG
HGQLSGTELP GEGSSQMAGN HCSTPEEAEP YESCCPTSRE AAVEALELLG ATYVDKKRDL
LGALKHWRRA MELRHQGGDY LPKPEPQQLV LAYDYSREVS TPQELEALIT DPDEMRMQAL
LIRERILGPS HPDTSYYIRY RGAVYADSGN FERCIRLWKY ALDMQQNNLE PLSPMTASSF
LSFAELFSYV LQDRSAKGNL GMQLGFADLM GVLSKGVREV ERALQLPKEP GDSAQFTKAI
AIILHLLYLL EKVECTPSQE HLKHQTVYRL LKCAPRGKNG FTPLHMAVDK ETTNVGRYRV
GIFPSLQVVK VLLDCGADPD SRDFDNNTPL HVAAQNNCPA IMDALIEAGA HMDATNAFKK
TAYELLDSKL LAKSTMQPFN YVTLQCLAAR ALDRNKVPYK GFIPEELEAF IQLH
