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Protein

Ubiquitin-like modifier-activating enzyme 5

Gene

UBA5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

GO - Biological processi

  • cyclic threonylcarbamoyladenosine biosynthetic process Source: GO_Central
  • 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

HGNCiHGNC:23230. UBA5.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: GO_Central
  • intracellular membrane-bounded organelle Source: HPA
  • nucleus Source: UniProtKB-SubCell

Keywords - Cellular componenti

Cytoplasm, 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:rs774318611Ensembl.1
Natural variantiVAR_07715457M → V in EIEE44; reduces UFM1 activating enzyme activity; reduces UFM1-DDRGK1 formation. 1 PublicationCorresponds to variant dbSNP:rs532178791Ensembl.1
Natural variantiVAR_077155168G → E in EIEE44; abolishes UFM1 activating enzyme activity. 1 Publication1
Natural variantiVAR_077156260V → M in EIEE44; reduces UFM1 activating enzyme activity. 1 Publication1
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:rs114925667Ensembl.1
Natural variantiVAR_077159389D → Y in EIEE44; no effect on UFM1 activating enzyme activity. 1 Publication1
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_077157310K → E in SCAR24; does not affect cytoplasm localization; decreased protein stability; does not affect interaction with UFM1. 1 Publication1

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

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.

PTM databases

iPTMnetiQ9GZZ9.
PhosphoSitePlusiQ9GZZ9.
SwissPalmiQ9GZZ9.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiENSG00000081307.
CleanExiHS_UBA5.
ExpressionAtlasiQ9GZZ9. baseline and differential.
GenevisibleiQ9GZZ9. HS.

Organism-specific databases

HPAiHPA017235.

Interactioni

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi122964. 82 interactors.
IntActiQ9GZZ9. 54 interactors.
MINTiMINT-1475093.
STRINGi9606.ENSP00000348565.

Structurei

Secondary structure

1404
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi70 – 73Combined sources4
Beta strandi75 – 79Combined sources5
Helixi83 – 95Combined sources13
Beta strandi98 – 103Combined sources6
Helixi120 – 122Combined sources3
Helixi127 – 138Combined sources12
Beta strandi142 – 147Combined sources6
Helixi154 – 166Combined sources13
Beta strandi167 – 170Combined sources4
Beta strandi176 – 180Combined sources5
Helixi185 – 198Combined sources14
Beta strandi202 – 207Combined sources6
Beta strandi211 – 219Combined sources9
Turni221 – 223Combined sources3
Beta strandi229 – 231Combined sources3
Helixi247 – 274Combined sources28
Beta strandi281 – 286Combined sources6
Turni287 – 290Combined sources4
Helixi306 – 317Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3GUCX-ray2.25A/B57-329[»]
3H8VX-ray2.00A/B57-329[»]
5HKHX-ray2.55B338-346[»]
5IAAX-ray1.85A/B57-346[»]
5L95X-ray2.10A/B68-346[»]
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.
GeneTreeiENSGT00810000125467.
HOGENOMiHOG000256352.
HOVERGENiHBG056496.
InParanoidiQ9GZZ9.
KOiK12164.
OMAiYTVPQKQ.
OrthoDBiEOG090B08Y1.
PhylomeDBiQ9GZZ9.
TreeFamiTF314168.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiView protein in InterPro
IPR029752. D-isomer_DH_CS1.
IPR016040. NAD(P)-bd_dom.
IPR000594. ThiF_NAD_FAD-bd.
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

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

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:rs774318611Ensembl.1
Natural variantiVAR_07715457M → V in EIEE44; reduces UFM1 activating enzyme activity; reduces UFM1-DDRGK1 formation. 1 PublicationCorresponds to variant dbSNP:rs532178791Ensembl.1
Natural variantiVAR_077155168G → E in EIEE44; abolishes UFM1 activating enzyme activity. 1 Publication1
Natural variantiVAR_077156260V → M in EIEE44; reduces UFM1 activating enzyme activity. 1 Publication1
Natural variantiVAR_077157310K → E in SCAR24; does not affect cytoplasm localization; decreased protein stability; does not affect interaction with UFM1. 1 Publication1
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:rs114925667Ensembl.1
Natural variantiVAR_077159389D → Y in EIEE44; no effect on UFM1 activating enzyme activity. 1 Publication1

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

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3GUCX-ray2.25A/B57-329[»]
3H8VX-ray2.00A/B57-329[»]
5HKHX-ray2.55B338-346[»]
5IAAX-ray1.85A/B57-346[»]
5L95X-ray2.10A/B68-346[»]
ProteinModelPortaliQ9GZZ9.
SMRiQ9GZZ9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122964. 82 interactors.
IntActiQ9GZZ9. 54 interactors.
MINTiMINT-1475093.
STRINGi9606.ENSP00000348565.

Chemistry databases

ChEMBLiCHEMBL2016429.

PTM databases

iPTMnetiQ9GZZ9.
PhosphoSitePlusiQ9GZZ9.
SwissPalmiQ9GZZ9.

Polymorphism and mutation databases

BioMutaiUBA5.
DMDMi74733510.

Proteomic databases

EPDiQ9GZZ9.
MaxQBiQ9GZZ9.
PaxDbiQ9GZZ9.
PeptideAtlasiQ9GZZ9.
PRIDEiQ9GZZ9.

Protocols and materials databases

DNASUi79876.
Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi79876.
GeneCardsiUBA5.
HGNCiHGNC:23230. UBA5.
HPAiHPA017235.
MIMi610552. gene.
617132. phenotype.
617133. phenotype.
neXtProtiNX_Q9GZZ9.
OpenTargetsiENSG00000081307.
PharmGKBiPA162407661.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2336. Eukaryota.
COG0476. LUCA.
GeneTreeiENSGT00810000125467.
HOGENOMiHOG000256352.
HOVERGENiHBG056496.
InParanoidiQ9GZZ9.
KOiK12164.
OMAiYTVPQKQ.
OrthoDBiEOG090B08Y1.
PhylomeDBiQ9GZZ9.
TreeFamiTF314168.

Enzyme and pathway databases

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

Miscellaneous databases

EvolutionaryTraceiQ9GZZ9.
GeneWikiiUBE1DC1.
GenomeRNAii79876.
PROiQ9GZZ9.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000081307.
CleanExiHS_UBA5.
ExpressionAtlasiQ9GZZ9. baseline and differential.
GenevisibleiQ9GZZ9. HS.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiView protein in InterPro
IPR029752. D-isomer_DH_CS1.
IPR016040. NAD(P)-bd_dom.
IPR000594. ThiF_NAD_FAD-bd.
PfamiView protein in Pfam
PF00899. ThiF. 1 hit.
SUPFAMiSSF69572. SSF69572. 1 hit.
ProtoNetiSearch...

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: February 15, 2017
This is version 149 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

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.