MAEA_MOUSE
ID MAEA_MOUSE Reviewed; 396 AA.
AC Q4VC33; Q3TFH0; Q3U7T6; Q5XKE6; Q8BPI3; Q8BSA1; Q9JK49;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=E3 ubiquitin-protein transferase MAEA;
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q7L5Y9};
DE AltName: Full=Erythroblast macrophage protein {ECO:0000303|PubMed:16707498};
DE AltName: Full=Macrophage erythroblast attacher;
GN Name=Maea; Synonyms=Emp {ECO:0000303|PubMed:16510120};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, Embryo, and Heart;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Brain, and Mammary tumor;
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).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 12-396 (ISOFORM 2).
RA Dua M., Peters L.L., Hanspal M.;
RT "cDNA sequence and genomic structure of the mouse erythroblast macrophage
RT protein (EMP) gene.";
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=16510120; DOI=10.1016/j.bbrc.2006.02.060;
RA Bala S., Kumar A., Soni S., Sinha S., Hanspal M.;
RT "Emp is a component of the nuclear matrix of mammalian cells and undergoes
RT dynamic rearrangements during cell division.";
RL Biochem. Biophys. Res. Commun. 342:1040-1048(2006).
RN [5]
RP DISRUPTION PHENOTYPE, SUBUNIT, FUNCTION, TISSUE SPECIFICITY, AND
RP SUBCELLULAR LOCATION.
RX PubMed=16707498; DOI=10.1074/jbc.m603226200;
RA Soni S., Bala S., Gwynn B., Sahr K.E., Peters L.L., Hanspal M.;
RT "Absence of erythroblast macrophage protein (Emp) leads to failure of
RT erythroblast nuclear extrusion.";
RL J. Biol. Chem. 281:20181-20189(2006).
RN [6]
RP SUBCELLULAR LOCATION, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17071116; DOI=10.1016/j.bcmd.2006.09.005;
RA Soni S., Bala S., Kumar A., Hanspal M.;
RT "Changing pattern of the subcellular distribution of erythroblast
RT macrophage protein (Emp) during macrophage differentiation.";
RL Blood Cells Mol. Dis. 38:25-31(2007).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 (PubMed:16707498). 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 (PubMed:16707498, PubMed:17071116).
CC Associates with F-actin to regulate actin distribution in erythroblasts
CC and macrophages (PubMed:16707498). May contribute to nuclear
CC architecture and cells division events (By similarity).
CC {ECO:0000250|UniProtKB:Q7L5Y9, ECO:0000269|PubMed:16707498,
CC ECO:0000269|PubMed:17071116}.
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 (By similarity). Interacts with F-actin
CC (PubMed:16707498). {ECO:0000250|UniProtKB:Q7L5Y9,
CC ECO:0000269|PubMed:16707498}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17071116}. Nucleus,
CC nucleoplasm {ECO:0000250|UniProtKB:Q7L5Y9}. Nucleus matrix
CC {ECO:0000269|PubMed:17071116}. Cell membrane
CC {ECO:0000269|PubMed:17071116}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:16707498, ECO:0000269|PubMed:17071116}.
CC Note=Detected in a nuclear, speckled-like pattern (PubMed:17071116).
CC Localized with condensed chromatin at prophase; Detected in nuclear
CC spindle poles at metaphase and in the contractile ring during telophase
CC and cytokinesis (By similarity). Present in cytoplasm, nuclear matrix
CC and at the cell surface in macrophages; predominantly nuclear in
CC immature macrophages and predominantly detected at the cell surface in
CC mature macrophages (PubMed:17071116). Colocalizes with F-actin in
CC macrophages (PubMed:16707498). {ECO:0000250|UniProtKB:Q7L5Y9,
CC ECO:0000269|PubMed:16707498, ECO:0000269|PubMed:17071116}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q4VC33-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q4VC33-2; Sequence=VSP_024797;
CC -!- TISSUE SPECIFICITY: Detected in embryonic fibroblasts
CC (PubMed:16707498). Detected in macrophages (PubMed:17071116). Detected
CC in heart. liver, spleen and kidney (at protein level)
CC (PubMed:16510120). {ECO:0000269|PubMed:16510120,
CC ECO:0000269|PubMed:16707498, ECO:0000269|PubMed:17071116}.
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}.
CC -!- DISRUPTION PHENOTYPE: Mice die perinatally and exhibit profound
CC alterations in the hematopoietic system. Blood of 14.5-16.5 dpc embryos
CC contained mostly nucleated erythrocytes suggesting a defect in terminal
CC maturation and enucleation of precursor cells. In the fetal liver,
CC large immature erythroblasts predominate, macrophage exhibit an
CC immature morphology and their number is reduced; No erythroblasts are
CC attached to the macrophages suggesting impairment of erythroblastic
CC island formation. {ECO:0000269|PubMed:16707498}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC35873.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK034859; BAC28857.1; -; mRNA.
DR EMBL; AK075637; BAC35873.1; ALT_INIT; mRNA.
DR EMBL; AK145800; BAE26657.1; -; mRNA.
DR EMBL; AK152523; BAE31283.1; -; mRNA.
DR EMBL; AK169149; BAE40928.1; -; mRNA.
DR EMBL; BC039054; AAH39054.1; -; mRNA.
DR EMBL; BC058687; AAH58687.1; -; mRNA.
DR EMBL; AF263247; AAF72195.1; -; mRNA.
DR CCDS; CCDS39063.1; -. [Q4VC33-1]
DR RefSeq; NP_067475.2; NM_021500.2. [Q4VC33-1]
DR AlphaFoldDB; Q4VC33; -.
DR SMR; Q4VC33; -.
DR BioGRID; 208474; 3.
DR IntAct; Q4VC33; 1.
DR STRING; 10090.ENSMUSP00000110093; -.
DR iPTMnet; Q4VC33; -.
DR PhosphoSitePlus; Q4VC33; -.
DR EPD; Q4VC33; -.
DR MaxQB; Q4VC33; -.
DR PaxDb; Q4VC33; -.
DR PeptideAtlas; Q4VC33; -.
DR PRIDE; Q4VC33; -.
DR ProteomicsDB; 252710; -. [Q4VC33-1]
DR ProteomicsDB; 252711; -. [Q4VC33-2]
DR Antibodypedia; 8374; 280 antibodies from 32 providers.
DR DNASU; 59003; -.
DR Ensembl; ENSMUST00000114449; ENSMUSP00000110093; ENSMUSG00000079562. [Q4VC33-1]
DR GeneID; 59003; -.
DR KEGG; mmu:59003; -.
DR UCSC; uc008xap.1; mouse. [Q4VC33-1]
DR CTD; 10296; -.
DR MGI; MGI:1891748; Maea.
DR VEuPathDB; HostDB:ENSMUSG00000079562; -.
DR eggNOG; KOG0396; Eukaryota.
DR GeneTree; ENSGT00940000153203; -.
DR HOGENOM; CLU_027445_0_1_1; -.
DR InParanoid; Q4VC33; -.
DR OMA; DVKYDEW; -.
DR OrthoDB; 1087488at2759; -.
DR PhylomeDB; Q4VC33; -.
DR TreeFam; TF314273; -.
DR BioGRID-ORCS; 59003; 7 hits in 75 CRISPR screens.
DR ChiTaRS; Maea; mouse.
DR PRO; PR:Q4VC33; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q4VC33; protein.
DR Bgee; ENSMUSG00000079562; Expressed in granulocyte and 263 other tissues.
DR ExpressionAtlas; Q4VC33; baseline and differential.
DR Genevisible; Q4VC33; MM.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:MGI.
DR GO; GO:0005826; C:actomyosin contractile ring; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; ISO:MGI.
DR GO; GO:0034657; C:GID complex; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
DR GO; GO:0016363; C:nuclear matrix; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005819; C:spindle; ISO:MGI.
DR GO; GO:0000151; C:ubiquitin ligase complex; ISO:MGI.
DR GO; GO:0003779; F:actin binding; IDA:MGI.
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:0007155; P:cell adhesion; ISO:MGI.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007010; P:cytoskeleton organization; IMP:MGI.
DR GO; GO:0048822; P:enucleate erythrocyte development; IMP:MGI.
DR GO; GO:0048821; P:erythrocyte development; IMP:MGI.
DR GO; GO:0043249; P:erythrocyte maturation; IEA:UniProtKB-KW.
DR GO; GO:0033033; P:negative regulation of myeloid cell apoptotic process; ISO:MGI.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
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 1: Evidence at protein 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_0000284938"
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 396
FT /note="M -> MYAPSCYGHALGQSGGGWEPCPPALTPDPRPQPASTFVSCDQRSVSN
FT DKYS (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_024797"
FT CONFLICT 148
FT /note="Q -> R (in Ref. 1; BAE31283)"
FT /evidence="ECO:0000305"
FT CONFLICT 203
FT /note="Q -> R (in Ref. 1; BAC28857)"
FT /evidence="ECO:0000305"
FT CONFLICT 206
FT /note="I -> V (in Ref. 1; BAE40928)"
FT /evidence="ECO:0000305"
FT CONFLICT 326
FT /note="Q -> R (in Ref. 1; BAE31283)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 396 AA; 45336 MW; 686F1E086742B99B CRC64;
MAVQESAAQL SMTLKVQEYP TLKVPYETLN KRFRAAQKNI DRETSHVTMV VAELEKTLSS
CPAVDSVVSL LDGVVEKLSV LKRKAVESIQ AEDESAKLCK RRIEHLKEHS SDQPAAASMW
KRKRMDRMMV EHLLRCGYYN TAVKLARQSG IEDLVNIEMF LTAKEVEESL ERRETATCLA
WCHDNKSRLR KMKSCLEFSL RIQEFIELVR QNKRLDAVRH ARKHFSQAEG SQLDEVRQVM
GMLAFPPDTH ISPYKDLLDP ARWRMLIQQF RYDNYRLHQL GNSSVFTLTL QAGLSAIKTP
QCYKEDGSSK SPDCPVCSRS LNKLAQPLPM AHCANSRLVC KISGDVMNEN NPPMMLPNGY
VYGYNSLLSI RQDDKVVCPR TKEVFHFSQA EKVYIM
