MAEA_MACFA
ID MAEA_MACFA Reviewed; 396 AA.
AC Q4R9A8; Q4R8Z9; Q9GMU8;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 25-MAY-2022, entry version 60.
DE RecName: Full=E3 ubiquitin-protein transferase MAEA;
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q7L5Y9};
DE AltName: Full=Macrophage erythroblast attacher;
GN Name=MAEA; ORFNames=QnpA-13115, QtsA-10391, QtsA-11053;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RA Osada N., Hida M., Kusuda J., Tanuma R., Iseki K., Hirai M., Terao K.,
RA Suzuki Y., Sugano S., Hashimoto K.;
RT "Isolation of full-length cDNA clones from macaque brain cDNA libraries.";
RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Testis;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Core component of the CTLH E3 ubiquitin-protein ligase
CC complex that selectively accepts ubiquitin from UBE2H and mediates
CC ubiquitination and subsequent proteasomal degradation of the
CC transcription factor HBP1. MAEA and RMND5A are both required for
CC catalytic activity of the CTLH E3 ubiquitin-protein ligase complex.
CC MAEA is required for normal cell proliferation. The CTLH E3 ubiquitin-
CC protein ligase complex is not required for the degradation of enzymes
CC involved in gluconeogenesis, such as FBP1 (By similarity). Plays a role
CC in erythroblast enucleation during erythrocyte maturation and in the
CC development of mature macrophages (By similarity). Mediates the
CC attachment of erythroid cell to mature macrophages; this MAEA-mediated
CC contact inhibits erythroid cell apoptosis (By similarity). Participates
CC in erythroblastic island formation, which is the functional unit of
CC definitive erythropoiesis. Associates with F-actin to regulate actin
CC distribution in erythroblasts and macrophages (By similarity). May
CC contribute to nuclear architecture and cells division events (By
CC similarity). {ECO:0000250|UniProtKB:Q4VC33,
CC ECO:0000250|UniProtKB:Q7L5Y9}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000250|UniProtKB:Q7L5Y9};
CC -!- SUBUNIT: Identified in the CTLH complex that contains GID4, RANBP9
CC and/or RANBP10, MKLN1, MAEA, RMND5A (or alternatively its paralog
CC RMND5B), GID8, ARMC8, WDR26 and YPEL5. Within this complex, MAEA,
CC RMND5A (or alternatively its paralog RMND5B), GID8, WDR26, and RANBP9
CC and/or RANBP10 form the catalytic core, while GID4, MKLN1, ARMC8 and
CC YPEL5 have ancillary roles. Interacts with F-actin.
CC {ECO:0000250|UniProtKB:Q7L5Y9}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q4VC33}.
CC Nucleus, nucleoplasm {ECO:0000250|UniProtKB:Q7L5Y9}. Nucleus matrix
CC {ECO:0000250|UniProtKB:Q4VC33}. Cell membrane
CC {ECO:0000250|UniProtKB:Q4VC33}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:Q4VC33}. Note=Detected in a nuclear, speckled-
CC like pattern (By similarity). Localized with condensed chromatin at
CC prophase; Detected in nuclear spindle poles at metaphase and in the
CC contractile ring during telophase and cytokinesis (By similarity).
CC Present in cytoplasm, nuclear matrix and at the cell surface in
CC macrophages; predominantly nuclear in immature macrophages and
CC predominantly detected at the cell surface in mature macrophages.
CC Colocalizes with F-actin in macrophages (By similarity).
CC {ECO:0000250|UniProtKB:Q4VC33, ECO:0000250|UniProtKB:Q7L5Y9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q4R9A8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q4R9A8-2; Sequence=VSP_024795;
CC Name=3;
CC IsoId=Q4R9A8-3; Sequence=VSP_024794, VSP_024796;
CC -!- DOMAIN: The expected RING-type zinc finger domain is highly divergent
CC and most of the expected Cys residues are not conserved. Still, the
CC protein is required for CTLH complex E3 ubiquitin-protein transferase
CC activity. In addition, the conserved Cys-314 in this highly divergent
CC region is required for ubiquitination by the yeast GID complex,
CC suggesting a direct role in catalyzing ubiquitination.
CC {ECO:0000250|UniProtKB:Q7L5Y9}.
CC -!- PTM: Autoubiquitinated as component of the CTLH E3 ubiquitin-protein
CC ligase complex (in vitro). {ECO:0000250|UniProtKB:Q7L5Y9}.
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DR EMBL; AB047627; BAB12151.1; -; mRNA.
DR EMBL; AB168188; BAE00313.1; -; mRNA.
DR EMBL; AB168298; BAE00422.1; -; mRNA.
DR AlphaFoldDB; Q4R9A8; -.
DR SMR; Q4R9A8; -.
DR STRING; 9541.XP_005554323.1; -.
DR eggNOG; KOG0396; Eukaryota.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0016363; C:nuclear matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:InterPro.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0043249; P:erythrocyte maturation; IEA:UniProtKB-KW.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR InterPro; IPR013144; CRA_dom.
DR InterPro; IPR024964; CTLH/CRA.
DR InterPro; IPR006595; CTLH_C.
DR InterPro; IPR027714; Fyv10/MAEA.
DR InterPro; IPR045098; Fyv10_fam.
DR InterPro; IPR006594; LisH.
DR InterPro; IPR044063; ZF_RING_GID.
DR PANTHER; PTHR12170; PTHR12170; 1.
DR PANTHER; PTHR12170:SF2; PTHR12170:SF2; 1.
DR Pfam; PF10607; CLTH; 1.
DR SMART; SM00757; CRA; 1.
DR SMART; SM00668; CTLH; 1.
DR SMART; SM00667; LisH; 1.
DR PROSITE; PS50897; CTLH; 1.
DR PROSITE; PS50896; LISH; 1.
DR PROSITE; PS51867; ZF_RING_GID; 1.
PE 2: Evidence at transcript level;
KW Actin-binding; Alternative splicing; Cell cycle; Cell division;
KW Cell membrane; Cytoplasm; Cytoskeleton; Erythrocyte maturation; Membrane;
KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Transferase;
KW Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..396
FT /note="E3 ubiquitin-protein transferase MAEA"
FT /id="PRO_0000284937"
FT DOMAIN 121..153
FT /note="LisH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00126"
FT DOMAIN 159..216
FT /note="CTLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00058"
FT ZN_FING 314..381
FT /note="RING-Gid-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01215"
FT REGION 1..124
FT /note="Extracellular and involved in cell to cell contact"
FT /evidence="ECO:0000250|UniProtKB:Q7L5Y9"
FT SITE 314
FT /note="Essential for ubiquitin ligase activity"
FT /evidence="ECO:0000250|UniProtKB:P40492"
FT MOD_RES 28
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q7L5Y9"
FT VAR_SEQ 1..214
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_024794"
FT VAR_SEQ 145..242
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_024795"
FT VAR_SEQ 215..218
FT /note="LDAV -> MLFF (in isoform 3)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_024796"
FT CONFLICT 8
FT /note="V -> A (in Ref. 2; BAE00422)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 396 AA; 45315 MW; 32E5D1EDD47936BA CRC64;
MAVQESAVQL SMTLKVQEYP TLKVPYETLN KRFRAAQKNI DRETSHVTMV VAELEKTLSG
CPAVDSVVSL LDGVVEKLSV LKRKAVESIQ AEDESAKLCK RRIEHLKEHS SDQPAAASVW
KRKRMDRMMV EHLLRCGYYN TAVKLARQSG IEDLVNIEMF LTAKEVEESL ERRETATCLA
WCHDNKSRLR KMKSCLEFSL RIQEFIELIR QNKRLDAVRH ARKHFSQAEG SQLDEVRQAM
GMLAFPPDTH ISPYKDLLDP ARWRMLIQQF RYDNYRLHQL GNNSVFTLTL QAGLSAIKTP
QCYKEDGSSK SPDCPVCSRS LNKLAQPLPM AHCANSRLVC KISGDVMNEN NPPMMLPNGY
VYGYNSLLSI RQDDKVVCPR TKEVFHFSQA EKVYIM
