UBE4A

Protein identityUniProt · HPA

UniProt accession

Q14139

Gene

UBE4A

Ensembl

ENSG00000110344

Chromosome

11

Canonical length

1066 aa

Protein class

Disease related genes, Enzymes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nuclear speckles

OverviewNCBI Gene

This gene encodes a member of the U-box ubiquitin ligase family. The encoded protein is involved in multiubiquitin chain assembly and plays a critical role in chromosome condensation and separation through the polyubiquitination of securin. Autoantibodies against the encoded protein may be markers for scleroderma and Crohn's disease. A pseudogene of this gene is located on the long arm of chromosome 3. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2011]

Canonical amino-acid sequenceUniProt

1066 residues, UniProt reviewed canonical sequence.

>Q14139|UBE4A
     1  MTDQENNNNI SSNPFAALFG SLADAKQFAA IQKEQLKQQS DELPASPDDS DNSVSESLDE
    61  FDYSVAEISR SFRSQQEICE QLNINHMIQR IFLITLDNSD PSLKSGNGIP SRCVYLEEMA
   121  VELEDQDWLD MSNVEQALFA RLLLQDPGNH LINMTSSTTL NLSADRDAGE RHIFCYLYSC
   181  FQRAKEEITK VPENLLPFAV QCRNLTVSNT RTVLLTPEIY VDQNIHEQLV DLMLEAIQGA
   241  HFEDVTEFLE EVIEALILDE EVRTFPEVMI PVFDILLGRI KDLELCQILL YAYLDILLYF
   301  TRQKDMAKVF VEYIQPKDPT NGQMYQKTLL GVILSISCLL KTPGVVENHG YFLNPSRSSP
   361  QEIKVQEANI HQFMAQFHEK IYQMLKNLLQ LSPETKHCIL SWLGNCLHAN AGRTKIWANQ
   421  MPEIFFQMYA SDAFFLNLGA ALLKLCQPFC KPRSSRLLTF NPTYCALKEL NDEERKIKNV
   481  HMRGLDKETC LIPAVQEPKF PQNYNLVTEN LALTEYTLYL GFHRLHDQMV KINQNLHRLQ
   541  VAWRDAQQSS SPAADNLREQ FERLMTIYLS TKTAMTEPQM LQNCLNLQVS MAVLLVQLAI
   601  GNEGSQPIEL TFPLPDGYSS LAYVPEFFAD NLGDFLIFLR RFADDILETS ADSLEHVLHF
   661  ITIFTGSIER MKNPHLRAKL AEVLEAVMPH LDQTPNPLVS SVFHRKRVFC NFQYAPQLAE
   721  ALIKVFVDIE FTGDPHQFEQ KFNYRRPMYP ILRYMWGTDT YRESIKDLAD YASKNLEAMN
   781  PPLFLRFLNL LMNDAIFLLD EAIQYLSKIK IQQIEKDRGE WDSLTPEARR EKEAGLQMFG
   841  QLARFHNIMS NETIGTLAFL TSEIKSLFVH PFLAERIISM LNYFLQHLVG PKMGALKVKD
   901  FSEFDFKPQQ LVSDICTIYL NLGDEENFCA TVPKDGRSYS PTLFAQTVRV LKKINKPGNM
   961  IMAFSNLAER IKSLADLQQQ EEETYADACD EFLDPIMSTL MCDPVVLPSS RVTVDRSTIA
  1021  RHLLSDQTDP FNRSPLTMDQ IRPNTELKEK IQRWLAERKQ QKEQLE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against UBE4A can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.26

Highest tissue expression

26 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about UBE4A.

Disease | AllUniProt

Conditions UBE4A is implicated in, by any mechanism.

• Neurodevelopmental disorder with hypotonia and gross motor and speech delay (NEDHMS) MIM:619639

Disease | GeneticClinVar

9 pathogenic / likely-pathogenic of 179 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Neurodevelopmental disorder with hypotonia and gross motor and speech delay
• UBE4A-related disorder
• Neurodevelopmental disorder
• Retinitis pigmentosa 11
• UBE4A-related neurodevelopmental disorder

ReferencesPubMed · IEDB

Publications for UBE4A from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.39

gnomAD pLI

0.11

gnomAD missense Z

2.21

DepMap mean gene effect

0.05

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• ERAD pathway
• protein polyubiquitination
• ubiquitin-dependent protein catabolic process

Molecular functions

• ubiquitin-ubiquitin ligase activity

Cellular components

• cytoplasm
• nucleus
• ubiquitin ligase complex

Protein domainsUniProt · Pfam · InterPro

• U-box domain
• Zinc finger, RING/FYVE/PHD-type
• Ubiquitin conjugation factor E4, core
• Ubiquitin conjugation factor E4
• U-box domain
• Ubiquitin elongating factor core

KeywordsUniProt

• Acetylation
• Cytoplasm
• Intellectual disability
• Transferase
• Ubl conjugation pathway

InteractionsUniProt · HPA

Protein binding partners of UBE4A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• IP6K1
• MAVS
• SEC61B
• UBXN4
• VCP