Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Ubiquitin-like modifier-activating enzyme 5

Gene

UBA5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

E1-like enzyme which activates UFM1 and SUMO2.5 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei83ATP; via amide nitrogen1 Publication1
Binding sitei104ATP1 Publication1
Binding sitei127ATP1 Publication1
Binding sitei150ATP1 Publication1
Binding sitei184ATP1 Publication1
Metal bindingi226Zinc1 Publication1
Metal bindingi229Zinc1 Publication1
Active sitei250Glycyl thioester intermediate2 Publications1
Metal bindingi303Zinc1 Publication1
Metal bindingi308Zinc1 Publication1

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW
  • UFM1 activating enzyme activity Source: UniProtKB

GO - Biological processi

  • neuromuscular process Source: UniProtKB
  • protein K69-linked ufmylation Source: UniProtKB
  • protein ufmylation Source: UniProtKB
  • regulation of intracellular estrogen receptor signaling pathway Source: UniProtKB
  • response to endoplasmic reticulum stress Source: MGI

Keywordsi

Biological processUbl conjugation pathway
LigandATP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDAi6.2.1.B9 2681
ReactomeiR-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin-like modifier-activating enzyme 5
Short name:
Ubiquitin-activating enzyme 5
Alternative name(s):
ThiFP1
UFM1-activating enzyme
Ubiquitin-activating enzyme E1 domain-containing protein 1
Gene namesi
Name:UBA5
Synonyms:UBE1DC1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000081307.12
HGNCiHGNC:23230 UBA5
MIMi610552 gene
neXtProtiNX_Q9GZZ9

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

Cytoplasm, Golgi apparatus, Nucleus

Pathology & Biotechi

Involvement in diseasei

Epileptic encephalopathy, early infantile, 44 (EIEE44)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. EIEE44 transmission pattern is consistent with autosomal recessive inheritance.
See also OMIM:617132
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07715355R → H in EIEE44; reduces UFM1 activating enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs774318611EnsemblClinVar.1
Natural variantiVAR_07715457M → V in EIEE44; reduces UFM1 activating enzyme activity; reduces UFM1-DDRGK1 formation. 1 PublicationCorresponds to variant dbSNP:rs532178791EnsemblClinVar.1
Natural variantiVAR_077155168G → E in EIEE44; abolishes UFM1 activating enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs886039761EnsemblClinVar.1
Natural variantiVAR_077156260V → M in EIEE44; reduces UFM1 activating enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs886039759EnsemblClinVar.1
Natural variantiVAR_077158371A → T in EIEE44; reduces UFM1 activating enzyme activity; reduces UFM1 activating enzyme activity; reduces UFM1-DDRGK1 formation. 2 PublicationsCorresponds to variant dbSNP:rs114925667EnsemblClinVar.1
Natural variantiVAR_077159389D → Y in EIEE44; no effect on UFM1 activating enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs886039760EnsemblClinVar.1
Spinocerebellar ataxia, autosomal recessive, 24 (SCAR24)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR24 patients manifest gait instability and speech difficulties with onset in childhood. Clinical features include gait and limb ataxia, dysarthria, nystagmus, cataracts, and cerebellar atrophy on brain imaging.
See also OMIM:617133
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_080409246 – 404Missing in SCAR24; delocalizes protein to the nucleus; activates degradation through the ubiquitin proteasome pathway; decreases protein stability; disrupts interaction with UFM1. Add BLAST159
Natural variantiVAR_077157310K → E in SCAR24; does not affect cytoplasm localization; decreases protein stability; does not affect interaction with UFM1. 1 PublicationCorresponds to variant dbSNP:rs886039762Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi250C → S: Forms a stable intermediate complex. 2 Publications1

Keywords - Diseasei

Disease mutation, Epilepsy, Mental retardation, Neurodegeneration

Organism-specific databases

DisGeNETi79876
MalaCardsiUBA5
MIMi617132 phenotype
617133 phenotype
OpenTargetsiENSG00000081307
PharmGKBiPA162407661

Chemistry databases

ChEMBLiCHEMBL2016429

Polymorphism and mutation databases

BioMutaiUBA5
DMDMi74733510

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001949701 – 404Ubiquitin-like modifier-activating enzyme 5Add BLAST404

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei45PhosphoserineCombined sources1
Modified residuei358PhosphoserineCombined sources1
Modified residuei393PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9GZZ9
MaxQBiQ9GZZ9
PaxDbiQ9GZZ9
PeptideAtlasiQ9GZZ9
PRIDEiQ9GZZ9
ProteomicsDBi80189
80190 [Q9GZZ9-2]

PTM databases

iPTMnetiQ9GZZ9
PhosphoSitePlusiQ9GZZ9
SwissPalmiQ9GZZ9

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiENSG00000081307 Expressed in 220 organ(s), highest expression level in body of pancreas
CleanExiHS_UBA5
ExpressionAtlasiQ9GZZ9 baseline and differential
GenevisibleiQ9GZZ9 HS

Organism-specific databases

HPAiHPA017235

Interactioni

Subunit structurei

Interacts (via C-terminus) with UFC1 (PubMed:17825256). Interacts with UFM1 (PubMed:26872069).2 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi122964, 85 interactors
ELMiQ9GZZ9
IntActiQ9GZZ9, 54 interactors
MINTiQ9GZZ9
STRINGi9606.ENSP00000348565

Structurei

Secondary structure

1404
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9GZZ9
SMRiQ9GZZ9
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9GZZ9

Family & Domainsi

Sequence similaritiesi

Belongs to the ubiquitin-activating E1 family. UBA5 subfamily.Sequence analysis

Phylogenomic databases

eggNOGiKOG2336 Eukaryota
COG0476 LUCA
GeneTreeiENSGT00920000149149
HOGENOMiHOG000256352
HOVERGENiHBG056496
InParanoidiQ9GZZ9
KOiK12164
OMAiETHNYNI
OrthoDBiEOG091G0BHP
PhylomeDBiQ9GZZ9
TreeFamiTF314168

Family and domain databases

InterProiView protein in InterPro
IPR029752 D-isomer_DH_CS1
IPR000594 ThiF_NAD_FAD-bd
IPR035985 Ubiquitin-activating_enz
PfamiView protein in Pfam
PF00899 ThiF, 1 hit
SUPFAMiSSF69572 SSF69572, 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 6 potential isoforms that are computationally mapped.iShow all

Isoform 1 (identifier: Q9GZZ9-1) [UniParc]FASTAAdd to basket
Also known as: UBE1DC1A

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
MAESVERLQQ RVQELERELA QERSLQVPRS GDGGGGRVRI EKMSSEVVDS
60 70 80 90 100
NPYSRLMALK RMGIVSDYEK IRTFAVAIVG VGGVGSVTAE MLTRCGIGKL
110 120 130 140 150
LLFDYDKVEL ANMNRLFFQP HQAGLSKVQA AEHTLRNINP DVLFEVHNYN
160 170 180 190 200
ITTVENFQHF MDRISNGGLE EGKPVDLVLS CVDNFEARMT INTACNELGQ
210 220 230 240 250
TWMESGVSEN AVSGHIQLII PGESACFACA PPLVVAANID EKTLKREGVC
260 270 280 290 300
AASLPTTMGV VAGILVQNVL KFLLNFGTVS FYLGYNAMQD FFPTMSMKPN
310 320 330 340 350
PQCDDRNCRK QQEEYKKKVA ALPKQEVIQE EEEIIHEDNE WGIELVSEVS
360 370 380 390 400
EEELKNFSGP VPDLPEGITV AYTIPKKQED SVTELTVEDS GESLEDLMAK

MKNM
Length:404
Mass (Da):44,863
Last modified:March 1, 2001 - v1
Checksum:i02F0F64FEAA1E880
GO
Isoform 2 (identifier: Q9GZZ9-2) [UniParc]FASTAAdd to basket
Also known as: UBE1DC1B

The sequence of this isoform differs from the canonical sequence as follows:
     1-56: Missing.

Show »
Length:348
Mass (Da):38,537
Checksum:i127B3CB48EB035B1
GO

Computationally mapped potential isoform sequencesi

There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E7EWE1E7EWE1_HUMAN
Ubiquitin-like modifier-activating ...
UBA5
347Annotation score:
E7EQ61E7EQ61_HUMAN
Ubiquitin-like modifier-activating ...
UBA5
377Annotation score:
D6RJC9D6RJC9_HUMAN
Ubiquitin-like modifier-activating ...
UBA5
64Annotation score:
C9J5W5C9J5W5_HUMAN
Ubiquitin-like modifier-activating ...
UBA5
108Annotation score:
C9J0F6C9J0F6_HUMAN
Ubiquitin-like modifier-activating ...
UBA5
79Annotation score:
C9JRV9C9JRV9_HUMAN
Ubiquitin-like modifier-activating ...
UBA5
110Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti403N → S in BAB55199 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07715355R → H in EIEE44; reduces UFM1 activating enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs774318611EnsemblClinVar.1
Natural variantiVAR_07715457M → V in EIEE44; reduces UFM1 activating enzyme activity; reduces UFM1-DDRGK1 formation. 1 PublicationCorresponds to variant dbSNP:rs532178791EnsemblClinVar.1
Natural variantiVAR_077155168G → E in EIEE44; abolishes UFM1 activating enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs886039761EnsemblClinVar.1
Natural variantiVAR_080409246 – 404Missing in SCAR24; delocalizes protein to the nucleus; activates degradation through the ubiquitin proteasome pathway; decreases protein stability; disrupts interaction with UFM1. Add BLAST159
Natural variantiVAR_077156260V → M in EIEE44; reduces UFM1 activating enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs886039759EnsemblClinVar.1
Natural variantiVAR_077157310K → E in SCAR24; does not affect cytoplasm localization; decreases protein stability; does not affect interaction with UFM1. 1 PublicationCorresponds to variant dbSNP:rs886039762Ensembl.1
Natural variantiVAR_077158371A → T in EIEE44; reduces UFM1 activating enzyme activity; reduces UFM1 activating enzyme activity; reduces UFM1-DDRGK1 formation. 2 PublicationsCorresponds to variant dbSNP:rs114925667EnsemblClinVar.1
Natural variantiVAR_077159389D → Y in EIEE44; no effect on UFM1 activating enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs886039760EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0385281 – 56Missing in isoform 2. CuratedAdd BLAST56

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB154406 mRNA Translation: BAD15375.1
AY253672 mRNA Translation: AAP79600.1
AL136757 mRNA Translation: CAB66691.1
AK026904 mRNA Translation: BAB15587.1
AK027563 mRNA Translation: BAB55199.1
AC020632 Genomic DNA No translation available.
CH471052 Genomic DNA Translation: EAW79192.1
CH471052 Genomic DNA Translation: EAW79189.1
CH471052 Genomic DNA Translation: EAW79191.1
BC009737 mRNA Translation: AAH09737.1
CCDSiCCDS3076.1 [Q9GZZ9-1]
CCDS3077.1 [Q9GZZ9-2]
RefSeqiNP_001307139.1, NM_001320210.1 [Q9GZZ9-2]
NP_001308167.1, NM_001321238.1
NP_001308168.1, NM_001321239.1
NP_079094.1, NM_024818.4 [Q9GZZ9-1]
NP_938143.1, NM_198329.3 [Q9GZZ9-2]
UniGeneiHs.170737

Genome annotation databases

EnsembliENST00000264991; ENSP00000264991; ENSG00000081307 [Q9GZZ9-2]
ENST00000356232; ENSP00000348565; ENSG00000081307 [Q9GZZ9-1]
ENST00000494238; ENSP00000418807; ENSG00000081307 [Q9GZZ9-2]
GeneIDi79876
KEGGihsa:79876
UCSCiuc003epa.5 human [Q9GZZ9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiUBA5_HUMAN
AccessioniPrimary (citable) accession number: Q9GZZ9
Secondary accession number(s): A6NJL3, D3DNC8, Q96ST1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 27, 2005
Last sequence update: March 1, 2001
Last modified: September 12, 2018
This is version 164 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again