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Protein

E3 ubiquitin-protein transferase MAEA

Gene

Maea

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Core component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1. MAEA and RMND5A are both required for catalytic activity of the CTLH E3 ubiquitin-protein ligase complex. MAEA is required for normal cell proliferation. The CTLH E3 ubiquitin-protein ligase complex is not required for the degradation of enzymes involved in gluconeogenesis, such as FBP1 (By similarity). Plays a role in erythroblast enucleation during erythrocyte maturation and in the development of mature macrophages (PubMed:16707498). Mediates the attachment of erythroid cell to mature macrophages; this MAEA-mediated contact inhibits erythroid cell apoptosis (By similarity). Participates in erythroblastic island formation, which is the functional unit of definitive erythropoiesis (PubMed:16707498, PubMed:17071116). Associates with F-actin to regulate actin distribution in erythroblasts and macrophages (PubMed:16707498). May contribute to nuclear architecture and cells division events (By similarity).By similarity2 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei314Essential for ubiquitin ligase activityBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri314 – 381RING-Gid-typePROSITE-ProRule annotationAdd BLAST68

GO - Molecular functioni

  • actin binding Source: MGI
  • metal ion binding Source: UniProtKB-KW
  • transferase activity Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Molecular functionActin-binding, Transferase
Biological processCell cycle, Cell division, Erythrocyte maturation, Ubl conjugation pathway
LigandMetal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein transferase MAEA (EC:2.3.2.27By similarity)
Alternative name(s):
Erythroblast macrophage protein1 Publication
Macrophage erythroblast attacher
Gene namesi
Name:Maea
Synonyms:Emp1 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1891748 Maea

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice die perinatally and exhibit profound alterations in the hematopoietic system. Blood of E14.5-16.5 embryos contained mostly nucleated erythrocytes suggesting a defect in terminal maturation and enucleation of precursor cells. In the fetal liver, large immature erythroblasts predominate, macrophage exhibit an immature morphology and their number is reduced; No erythroblasts are attached to the macrophages suggesting impairment of erythroblastic island formation.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002849381 – 396E3 ubiquitin-protein transferase MAEAAdd BLAST396

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei28PhosphothreonineBy similarity1

Post-translational modificationi

Autoubiquitinated as component of the CTLH E3 ubiquitin-protein ligase complex (in vitro).By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ4VC33
PaxDbiQ4VC33
PeptideAtlasiQ4VC33
PRIDEiQ4VC33

PTM databases

iPTMnetiQ4VC33
PhosphoSitePlusiQ4VC33

Expressioni

Tissue specificityi

Detected in embryonic fibroblasts (PubMed:16707498). Detected in macrophages (PubMed:17071116). Detected in heart. liver, spleen and kidney (at protein level) (PubMed:16510120).3 Publications

Gene expression databases

BgeeiENSMUSG00000079562 Expressed in 290 organ(s), highest expression level in placenta
CleanExiMM_MAEA
ExpressionAtlasiQ4VC33 baseline and differential
GenevisibleiQ4VC33 MM

Interactioni

Subunit structurei

Identified in the CTLH complex that contains GID4, RANBP9 and/or RANBP10, MKLN1, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, ARMC8, WDR26 and YPEL5. Within this complex, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, WDR26, and RANBP9 and/or RANBP10 form the catalytic core, while GID4, MKLN1, ARMC8 and YPEL5 have ancillary roles (By similarity). Interacts with F-actin (PubMed:16707498).By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ4VC33, 1 interactor
STRINGi10090.ENSMUSP00000110093

Structurei

3D structure databases

ProteinModelPortaliQ4VC33
SMRiQ4VC33
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini121 – 153LisHPROSITE-ProRule annotationAdd BLAST33
Domaini159 – 216CTLHPROSITE-ProRule annotationAdd BLAST58

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 124Extracellular and involved in cell to cell contactBy similarityAdd BLAST124

Domaini

The expected RING-type zinc finger domain is highly divergent and most of the expected Cys residues are not conserved. Still, the protein is required for CTLH complex E3 ubiquitin-protein transferase activity. In addition, the conserved Cys-314 in this highly divergent region is required for ubiquitination by the yeast GID complex, suggesting a direct role in catalyzing ubiquitination.By similarity

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri314 – 381RING-Gid-typePROSITE-ProRule annotationAdd BLAST68

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG0396 Eukaryota
ENOG410XPGU LUCA
GeneTreeiENSGT00720000108841
HOVERGENiHBG053270
InParanoidiQ4VC33
KOiK18624
OMAiFAHCSQS
OrthoDBiEOG091G0E8J
PhylomeDBiQ4VC33
TreeFamiTF314273

Family and domain databases

InterProiView protein in InterPro
IPR013144 CRA_dom
IPR024964 CTLH/CRA
IPR006595 CTLH_C
IPR027714 Fyv10/EMP
IPR006594 LisH
PANTHERiPTHR12170:SF2 PTHR12170:SF2, 1 hit
PfamiView protein in Pfam
PF10607 CLTH, 1 hit
SMARTiView protein in SMART
SM00757 CRA, 1 hit
SM00668 CTLH, 1 hit
SM00667 LisH, 1 hit
PROSITEiView protein in PROSITE
PS50897 CTLH, 1 hit
PS50896 LISH, 1 hit
PS51867 ZF_RING_GID, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q4VC33-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MAVQESAAQL SMTLKVQEYP TLKVPYETLN KRFRAAQKNI DRETSHVTMV
60 70 80 90 100
VAELEKTLSS CPAVDSVVSL LDGVVEKLSV LKRKAVESIQ AEDESAKLCK
110 120 130 140 150
RRIEHLKEHS SDQPAAASMW KRKRMDRMMV EHLLRCGYYN TAVKLARQSG
160 170 180 190 200
IEDLVNIEMF LTAKEVEESL ERRETATCLA WCHDNKSRLR KMKSCLEFSL
210 220 230 240 250
RIQEFIELVR QNKRLDAVRH ARKHFSQAEG SQLDEVRQVM GMLAFPPDTH
260 270 280 290 300
ISPYKDLLDP ARWRMLIQQF RYDNYRLHQL GNSSVFTLTL QAGLSAIKTP
310 320 330 340 350
QCYKEDGSSK SPDCPVCSRS LNKLAQPLPM AHCANSRLVC KISGDVMNEN
360 370 380 390
NPPMMLPNGY VYGYNSLLSI RQDDKVVCPR TKEVFHFSQA EKVYIM
Length:396
Mass (Da):45,336
Last modified:July 5, 2005 - v1
Checksum:i686F1E086742B99B
GO
Isoform 2 (identifier: Q4VC33-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     396-396: M → MYAPSCYGHALGQSGGGWEPCPPALTPDPRPQPASTFVSCDQRSVSNDKYS

Show »
Length:446
Mass (Da):50,602
Checksum:i3D84FB9200D658ED
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0J9YVB4A0A0J9YVB4_MOUSE
E3 ubiquitin-protein transferase MA...
Maea
147Annotation score:
A0A0J9YUL5A0A0J9YUL5_MOUSE
E3 ubiquitin-protein transferase MA...
Maea
53Annotation score:
A0A0J9YVB7A0A0J9YVB7_MOUSE
E3 ubiquitin-protein transferase MA...
Maea
40Annotation score:

Sequence cautioni

The sequence BAC35873 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti148Q → R in BAE31283 (PubMed:16141072).Curated1
Sequence conflicti203Q → R in BAC28857 (PubMed:16141072).Curated1
Sequence conflicti206I → V in BAE40928 (PubMed:16141072).Curated1
Sequence conflicti326Q → R in BAE31283 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_024797396M → MYAPSCYGHALGQSGGGWEP CPPALTPDPRPQPASTFVSC DQRSVSNDKYS in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK034859 mRNA Translation: BAC28857.1
AK075637 mRNA Translation: BAC35873.1 Different initiation.
AK145800 mRNA Translation: BAE26657.1
AK152523 mRNA Translation: BAE31283.1
AK169149 mRNA Translation: BAE40928.1
BC039054 mRNA Translation: AAH39054.1
BC058687 mRNA Translation: AAH58687.1
AF263247 mRNA Translation: AAF72195.1
CCDSiCCDS39063.1 [Q4VC33-1]
RefSeqiNP_067475.2, NM_021500.2 [Q4VC33-1]
UniGeneiMm.138617
Mm.281642

Genome annotation databases

EnsembliENSMUST00000114449; ENSMUSP00000110093; ENSMUSG00000079562 [Q4VC33-1]
GeneIDi59003
KEGGimmu:59003
UCSCiuc008xap.1 mouse [Q4VC33-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK034859 mRNA Translation: BAC28857.1
AK075637 mRNA Translation: BAC35873.1 Different initiation.
AK145800 mRNA Translation: BAE26657.1
AK152523 mRNA Translation: BAE31283.1
AK169149 mRNA Translation: BAE40928.1
BC039054 mRNA Translation: AAH39054.1
BC058687 mRNA Translation: AAH58687.1
AF263247 mRNA Translation: AAF72195.1
CCDSiCCDS39063.1 [Q4VC33-1]
RefSeqiNP_067475.2, NM_021500.2 [Q4VC33-1]
UniGeneiMm.138617
Mm.281642

3D structure databases

ProteinModelPortaliQ4VC33
SMRiQ4VC33
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ4VC33, 1 interactor
STRINGi10090.ENSMUSP00000110093

PTM databases

iPTMnetiQ4VC33
PhosphoSitePlusiQ4VC33

Proteomic databases

EPDiQ4VC33
PaxDbiQ4VC33
PeptideAtlasiQ4VC33
PRIDEiQ4VC33

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000114449; ENSMUSP00000110093; ENSMUSG00000079562 [Q4VC33-1]
GeneIDi59003
KEGGimmu:59003
UCSCiuc008xap.1 mouse [Q4VC33-1]

Organism-specific databases

CTDi10296
MGIiMGI:1891748 Maea

Phylogenomic databases

eggNOGiKOG0396 Eukaryota
ENOG410XPGU LUCA
GeneTreeiENSGT00720000108841
HOVERGENiHBG053270
InParanoidiQ4VC33
KOiK18624
OMAiFAHCSQS
OrthoDBiEOG091G0E8J
PhylomeDBiQ4VC33
TreeFamiTF314273

Miscellaneous databases

ChiTaRSiMaea mouse
PROiPR:Q4VC33
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000079562 Expressed in 290 organ(s), highest expression level in placenta
CleanExiMM_MAEA
ExpressionAtlasiQ4VC33 baseline and differential
GenevisibleiQ4VC33 MM

Family and domain databases

InterProiView protein in InterPro
IPR013144 CRA_dom
IPR024964 CTLH/CRA
IPR006595 CTLH_C
IPR027714 Fyv10/EMP
IPR006594 LisH
PANTHERiPTHR12170:SF2 PTHR12170:SF2, 1 hit
PfamiView protein in Pfam
PF10607 CLTH, 1 hit
SMARTiView protein in SMART
SM00757 CRA, 1 hit
SM00668 CTLH, 1 hit
SM00667 LisH, 1 hit
PROSITEiView protein in PROSITE
PS50897 CTLH, 1 hit
PS50896 LISH, 1 hit
PS51867 ZF_RING_GID, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMAEA_MOUSE
AccessioniPrimary (citable) accession number: Q4VC33
Secondary accession number(s): Q3TFH0
, Q3U7T6, Q5XKE6, Q8BPI3, Q8BSA1, Q9JK49
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 2007
Last sequence update: July 5, 2005
Last modified: November 7, 2018
This is version 112 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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