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Protein

Ubiquitin-like modifier-activating enzyme 6

Gene

UBA6

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

Functioni

Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP. Specific for ubiquitin, does not activate ubiquitin-like peptides. Differs from UBE1 in its specificity for substrate E2 charging. Does not charge cell cycle E2s, such as CDC34. Essential for embryonic development. Required for UBD/FAT10 conjugation. Isoform 2 may play a key role in ubiquitin system and may influence spermatogenesis and male fertility.3 Publications

Catalytic activityi

ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine = AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine.By similarity

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.By similarity
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei470ATP; via amide nitrogenBy similarity1
Binding sitei497ATPBy similarity1
Binding sitei508ATPBy similarity1
Binding sitei521ATPBy similarity1
Active sitei625Glycyl thioester intermediatePROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi569 – 570ATPBy similarity2

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • FAT10 activating enzyme activity Source: UniProtKB
  • ubiquitin activating enzyme activity Source: UniProtKB-EC

GO - Biological processi

Keywordsi

Molecular functionLigase
Biological processUbl conjugation pathway
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi6.2.1.B9 2681
ReactomeiR-HSA-8866652 Synthesis of active ubiquitin: roles of E1 and E2 enzymes
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin-like modifier-activating enzyme 6 (EC:6.2.1.45By similarity)
Short name:
Ubiquitin-activating enzyme 6
Alternative name(s):
Monocyte protein 4
Short name:
MOP-4
Ubiquitin-activating enzyme E1-like protein 2
Short name:
E1-L2
Gene namesi
Name:UBA6
Synonyms:MOP4, UBE1L2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000033178.12
HGNCiHGNC:25581 UBA6
MIMi611361 gene
neXtProtiNX_A0AVT1

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi625C → A or S: Impairs ubiquitin activation. 2 Publications1

Organism-specific databases

OpenTargetsiENSG00000033178
PharmGKBiPA162407690

Chemistry databases

ChEMBLiCHEMBL2321622

Polymorphism and mutation databases

BioMutaiUBA6

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002777971 – 1052Ubiquitin-like modifier-activating enzyme 6Add BLAST1052

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei54PhosphothreonineCombined sources1
Modified residuei301PhosphoserineCombined sources1
Modified residuei544N6-acetyllysineCombined sources1
Modified residuei729N6-acetyllysineBy similarity1
Modified residuei737PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiA0AVT1
MaxQBiA0AVT1
PaxDbiA0AVT1
PRIDEiA0AVT1
ProteomicsDBi26
27 [A0AVT1-2]
28 [A0AVT1-3]
29 [A0AVT1-4]

PTM databases

iPTMnetiA0AVT1
PhosphoSitePlusiA0AVT1

Expressioni

Tissue specificityi

Widely expressed. Isoform 2 is predominantly expressed in testis with higher expression in adult testis than in fetal testis.2 Publications

Gene expression databases

BgeeiENSG00000033178 Expressed in 214 organ(s), highest expression level in corpus callosum
ExpressionAtlasiA0AVT1 baseline and differential
GenevisibleiA0AVT1 HS

Organism-specific databases

HPAiHPA037001

Interactioni

Subunit structurei

Forms a thioester with UBD in cells stimulated with tumor necrosis factor-alpha (TNFa) and interferon-gamma (IFNg) (PubMed:17889673, PubMed:25422469).2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
HMBOX1Q6NT763EBI-5282516,EBI-2549423

Protein-protein interaction databases

BioGridi120529, 78 interactors
DIPiDIP-57633N
IntActiA0AVT1, 5 interactors
MINTiA0AVT1
STRINGi9606.ENSP00000313454

Chemistry databases

BindingDBiA0AVT1

Structurei

3D structure databases

ProteinModelPortaliA0AVT1
SMRiA0AVT1
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the ubiquitin-activating E1 family.Curated

Phylogenomic databases

eggNOGiKOG2012 Eukaryota
COG0476 LUCA
GeneTreeiENSGT00390000016689
HOVERGENiHBG054199
InParanoidiA0AVT1
KOiK10699
OMAiHSLEGCF
OrthoDBiEOG091G0130
PhylomeDBiA0AVT1
TreeFamiTF300586

Family and domain databases

Gene3Di3.10.290.60, 1 hit
InterProiView protein in InterPro
IPR032420 E1_4HB
IPR032418 E1_FCCH
IPR000594 ThiF_NAD_FAD-bd
IPR018965 Ub-activating_enz_E1_C
IPR038252 UBA_E1_C_sf
IPR019572 UBA_E1_Cys
IPR035985 Ubiquitin-activating_enz
IPR018075 UBQ-activ_enz_E1
IPR000011 UBQ/SUMO-activ_enz_E1-like
PfamiView protein in Pfam
PF16191 E1_4HB, 1 hit
PF16190 E1_FCCH, 1 hit
PF09358 E1_UFD, 1 hit
PF00899 ThiF, 2 hits
PF10585 UBA_e1_thiolCys, 1 hit
PRINTSiPR01849 UBIQUITINACT
SMARTiView protein in SMART
SM00985 UBA_e1_C, 1 hit
SUPFAMiSSF69572 SSF69572, 2 hits
TIGRFAMsiTIGR01408 Ube1, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: A0AVT1-1) [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
MEGSEPVAAH QGEEASCSSW GTGSTNKNLP IMSTASVEID DALYSRQRYV
60 70 80 90 100
LGDTAMQKMA KSHVFLSGMG GLGLEIAKNL VLAGIKAVTI HDTEKCQAWD
110 120 130 140 150
LGTNFFLSED DVVNKRNRAE AVLKHIAELN PYVHVTSSSV PFNETTDLSF
160 170 180 190 200
LDKYQCVVLT EMKLPLQKKI NDFCRSQCPP IKFISADVHG IWSRLFCDFG
210 220 230 240 250
DEFEVLDTTG EEPKEIFISN ITQANPGIVT CLENHPHKLE TGQFLTFREI
260 270 280 290 300
NGMTGLNGSI QQITVISPFS FSIGDTTELE PYLHGGIAVQ VKTPKTVFFE
310 320 330 340 350
SLERQLKHPK CLIVDFSNPE APLEIHTAML ALDQFQEKYS RKPNVGCQQD
360 370 380 390 400
SEELLKLATS ISETLEEKPD VNADIVHWLS WTAQGFLSPL AAAVGGVASQ
410 420 430 440 450
EVLKAVTGKF SPLCQWLYLE AADIVESLGK PECEEFLPRG DRYDALRACI
460 470 480 490 500
GDTLCQKLQN LNIFLVGCGA IGCEMLKNFA LLGVGTSKEK GMITVTDPDL
510 520 530 540 550
IEKSNLNRQF LFRPHHIQKP KSYTAADATL KINSQIKIDA HLNKVCPTTE
560 570 580 590 600
TIYNDEFYTK QDVIITALDN VEARRYVDSR CLANLRPLLD SGTMGTKGHT
610 620 630 640 650
EVIVPHLTES YNSHRDPPEE EIPFCTLKSF PAAIEHTIQW ARDKFESSFS
660 670 680 690 700
HKPSLFNKFW QTYSSAEEVL QKIQSGHSLE GCFQVIKLLS RRPRNWSQCV
710 720 730 740 750
ELARLKFEKY FNHKALQLLH CFPLDIRLKD GSLFWQSPKR PPSPIKFDLN
760 770 780 790 800
EPLHLSFLQN AAKLYATVYC IPFAEEDLSA DALLNILSEV KIQEFKPSNK
810 820 830 840 850
VVQTDETARK PDHVPISSED ERNAIFQLEK AILSNEATKS DLQMAVLSFE
860 870 880 890 900
KDDDHNGHID FITAASNLRA KMYSIEPADR FKTKRIAGKI IPAIATTTAT
910 920 930 940 950
VSGLVALEMI KVTGGYPFEA YKNCFLNLAI PIVVFTETTE VRKTKIRNGI
960 970 980 990 1000
SFTIWDRWTV HGKEDFTLLD FINAVKEKYG IEPTMVVQGV KMLYVPVMPG
1010 1020 1030 1040 1050
HAKRLKLTMH KLVKPTTEKK YVDLTVSFAP DIDGDEDLPG PPVRYYFSHD

TD
Length:1,052
Mass (Da):117,970
Last modified:November 28, 2006 - v1
Checksum:i9F9C70EABA750A71
GO
Isoform 2 (identifier: A0AVT1-2) [UniParc]FASTAAdd to basket
Also known as: nUBE1L

The sequence of this isoform differs from the canonical sequence as follows:
     1-474: Missing.

Show »
Length:578
Mass (Da):65,757
Checksum:i33FDBFF4EA8AADF0
GO
Isoform 3 (identifier: A0AVT1-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     369-389: PDVNADIVHWLSWTAQGFLSP → VTIEIYGCPNICLLIHKCSVY
     390-1052: Missing.

Show »
Length:389
Mass (Da):43,216
Checksum:iE4534BE50710EF6C
GO
Isoform 4 (identifier: A0AVT1-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     321-340: APLEIHTAMLALDQFQEKYS → VNKHFAGLREAAESEMRISE
     341-1052: Missing.

Show »
Length:340
Mass (Da):37,693
Checksum:iB73DEE549B7E7143
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0Y8S8H0Y8S8_HUMAN
Ubiquitin-like modifier-activating ...
UBA6
271Annotation score:
H0Y9U5H0Y9U5_HUMAN
Ubiquitin-like modifier-activating ...
UBA6
88Annotation score:

Sequence cautioni

The sequence BAA91824 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti14E → K in CAD89908 (PubMed:17974005).Curated1
Sequence conflicti140V → A in CAD89908 (PubMed:17974005).Curated1
Sequence conflicti197C → Y in BAC04463 (PubMed:14702039).Curated1
Sequence conflicti234N → D in CAD89959 (PubMed:17974005).Curated1
Sequence conflicti297V → A in BAC04463 (PubMed:14702039).Curated1
Sequence conflicti645F → V in AAQ63403 (PubMed:15202508).Curated1
Sequence conflicti803Q → H in BAA91824 (PubMed:14702039).Curated1
Sequence conflicti821E → G in CAD89959 (PubMed:17974005).Curated1
Sequence conflicti868L → P in CAD89908 (PubMed:17974005).Curated1
Sequence conflicti905V → G in AAQ63403 (PubMed:15202508).Curated1
Sequence conflicti909M → K in CAD89959 (PubMed:17974005).Curated1
Sequence conflicti920A → V in BAB19785 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_030594224A → T3 PublicationsCorresponds to variant dbSNP:rs10010188Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0230831 – 474Missing in isoform 2. 1 PublicationAdd BLAST474
Alternative sequenceiVSP_023084321 – 340APLEI…QEKYS → VNKHFAGLREAAESEMRISE in isoform 4. 1 PublicationAdd BLAST20
Alternative sequenceiVSP_023085341 – 1052Missing in isoform 4. 1 PublicationAdd BLAST712
Alternative sequenceiVSP_023086369 – 389PDVNA…GFLSP → VTIEIYGCPNICLLIHKCSV Y in isoform 3. 1 PublicationAdd BLAST21
Alternative sequenceiVSP_023087390 – 1052Missing in isoform 3. 1 PublicationAdd BLAST663

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY359880 mRNA Translation: AAQ63403.1
EF623993 mRNA Translation: ABR25253.1
AB014773 mRNA Translation: BAB19785.1
AK001670 mRNA Translation: BAA91824.1 Different initiation.
AK094969 mRNA Translation: BAC04463.1
AK314371 mRNA Translation: BAG37000.1
AL832015 mRNA Translation: CAD89908.1
AL832458 mRNA Translation: CAD89959.1
AC079880 Genomic DNA No translation available.
AC096720 Genomic DNA Translation: AAY40999.1
BC031637 mRNA Translation: AAH31637.1
BC126484 mRNA Translation: AAI26485.1
BC126486 mRNA Translation: AAI26487.1
CCDSiCCDS3516.1 [A0AVT1-1]
RefSeqiNP_060697.4, NM_018227.5 [A0AVT1-1]
UniGeneiHs.212774

Genome annotation databases

EnsembliENST00000322244; ENSP00000313454; ENSG00000033178 [A0AVT1-1]
ENST00000420827; ENSP00000399234; ENSG00000033178 [A0AVT1-3]
GeneIDi55236
KEGGihsa:55236
UCSCiuc003hdg.5 human [A0AVT1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY359880 mRNA Translation: AAQ63403.1
EF623993 mRNA Translation: ABR25253.1
AB014773 mRNA Translation: BAB19785.1
AK001670 mRNA Translation: BAA91824.1 Different initiation.
AK094969 mRNA Translation: BAC04463.1
AK314371 mRNA Translation: BAG37000.1
AL832015 mRNA Translation: CAD89908.1
AL832458 mRNA Translation: CAD89959.1
AC079880 Genomic DNA No translation available.
AC096720 Genomic DNA Translation: AAY40999.1
BC031637 mRNA Translation: AAH31637.1
BC126484 mRNA Translation: AAI26485.1
BC126486 mRNA Translation: AAI26487.1
CCDSiCCDS3516.1 [A0AVT1-1]
RefSeqiNP_060697.4, NM_018227.5 [A0AVT1-1]
UniGeneiHs.212774

3D structure databases

ProteinModelPortaliA0AVT1
SMRiA0AVT1
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120529, 78 interactors
DIPiDIP-57633N
IntActiA0AVT1, 5 interactors
MINTiA0AVT1
STRINGi9606.ENSP00000313454

Chemistry databases

BindingDBiA0AVT1
ChEMBLiCHEMBL2321622

PTM databases

iPTMnetiA0AVT1
PhosphoSitePlusiA0AVT1

Polymorphism and mutation databases

BioMutaiUBA6

Proteomic databases

EPDiA0AVT1
MaxQBiA0AVT1
PaxDbiA0AVT1
PRIDEiA0AVT1
ProteomicsDBi26
27 [A0AVT1-2]
28 [A0AVT1-3]
29 [A0AVT1-4]

Protocols and materials databases

DNASUi55236
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000322244; ENSP00000313454; ENSG00000033178 [A0AVT1-1]
ENST00000420827; ENSP00000399234; ENSG00000033178 [A0AVT1-3]
GeneIDi55236
KEGGihsa:55236
UCSCiuc003hdg.5 human [A0AVT1-1]

Organism-specific databases

CTDi55236
EuPathDBiHostDB:ENSG00000033178.12
GeneCardsiUBA6
H-InvDBiHIX0031574
HIX0120163
HGNCiHGNC:25581 UBA6
HPAiHPA037001
MIMi611361 gene
neXtProtiNX_A0AVT1
OpenTargetsiENSG00000033178
PharmGKBiPA162407690
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2012 Eukaryota
COG0476 LUCA
GeneTreeiENSGT00390000016689
HOVERGENiHBG054199
InParanoidiA0AVT1
KOiK10699
OMAiHSLEGCF
OrthoDBiEOG091G0130
PhylomeDBiA0AVT1
TreeFamiTF300586

Enzyme and pathway databases

UniPathwayi
UPA00143

BRENDAi6.2.1.B9 2681
ReactomeiR-HSA-8866652 Synthesis of active ubiquitin: roles of E1 and E2 enzymes
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation

Miscellaneous databases

ChiTaRSiUBA6 human
GeneWikiiUBE1L2
GenomeRNAii55236
PROiPR:A0AVT1
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000033178 Expressed in 214 organ(s), highest expression level in corpus callosum
ExpressionAtlasiA0AVT1 baseline and differential
GenevisibleiA0AVT1 HS

Family and domain databases

Gene3Di3.10.290.60, 1 hit
InterProiView protein in InterPro
IPR032420 E1_4HB
IPR032418 E1_FCCH
IPR000594 ThiF_NAD_FAD-bd
IPR018965 Ub-activating_enz_E1_C
IPR038252 UBA_E1_C_sf
IPR019572 UBA_E1_Cys
IPR035985 Ubiquitin-activating_enz
IPR018075 UBQ-activ_enz_E1
IPR000011 UBQ/SUMO-activ_enz_E1-like
PfamiView protein in Pfam
PF16191 E1_4HB, 1 hit
PF16190 E1_FCCH, 1 hit
PF09358 E1_UFD, 1 hit
PF00899 ThiF, 2 hits
PF10585 UBA_e1_thiolCys, 1 hit
PRINTSiPR01849 UBIQUITINACT
SMARTiView protein in SMART
SM00985 UBA_e1_C, 1 hit
SUPFAMiSSF69572 SSF69572, 2 hits
TIGRFAMsiTIGR01408 Ube1, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiUBA6_HUMAN
AccessioniPrimary (citable) accession number: A0AVT1
Secondary accession number(s): A6N8M7
, B2RAV3, Q4W5K0, Q6UV21, Q86T78, Q86TC7, Q8N5T3, Q8N9E4, Q9H3T7, Q9NVC9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: November 28, 2006
Last modified: November 7, 2018
This is version 122 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

Complete proteome, Reference proteome

Documents

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