UniProtKB - A0AVT1 (UBA6_HUMAN)
Protein
Ubiquitin-like modifier-activating enzyme 6
Gene
UBA6
Organism
Homo sapiens (Human)
Status
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 EC:6.2.1.45
: protein ubiquitination Pathwayi
This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.By similarityView all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 470 | ATP; via amide nitrogenBy similarity | 1 | |
Binding sitei | 497 | ATPBy similarity | 1 | |
Binding sitei | 508 | ATPBy similarity | 1 | |
Binding sitei | 521 | ATPBy similarity | 1 | |
Active sitei | 625 | Glycyl thioester intermediatePROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 569 – 570 | ATPBy similarity | 2 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- FAT10 activating enzyme activity Source: UniProtKB
- ubiquitin activating enzyme activity Source: GO_Central
GO - Biological processi
- amygdala development Source: Ensembl
- cellular response to DNA damage stimulus Source: GO_Central
- dendritic spine development Source: Ensembl
- hippocampus development Source: Ensembl
- learning Source: Ensembl
- locomotory behavior Source: Ensembl
- protein modification by small protein conjugation Source: GO_Central
- protein ubiquitination Source: UniProtKB
- ubiquitin-dependent protein catabolic process Source: UniProtKB
Keywordsi
Molecular function | Ligase |
Biological process | Ubl conjugation pathway |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 6.2.1.B9, 2681 |
PathwayCommonsi | A0AVT1 |
Reactomei | R-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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:25581, UBA6 |
MIMi | 611361, gene |
neXtProti | NX_A0AVT1 |
VEuPathDBi | HostDB:ENSG00000033178.12 |
Subcellular locationi
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 625 | C → A or S: Impairs ubiquitin activation. 2 Publications | 1 |
Organism-specific databases
DisGeNETi | 55236 |
OpenTargetsi | ENSG00000033178 |
PharmGKBi | PA162407690 |
Miscellaneous databases
Pharosi | A0AVT1, Tchem |
Chemistry databases
ChEMBLi | CHEMBL2321622 |
Genetic variation databases
BioMutai | UBA6 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000277797 | 1 – 1052 | Ubiquitin-like modifier-activating enzyme 6Add BLAST | 1052 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionineCombined sources | 1 | |
Modified residuei | 54 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 301 | PhosphoserineCombined sources | 1 | |
Modified residuei | 544 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 729 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 737 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | A0AVT1 |
jPOSTi | A0AVT1 |
MassIVEi | A0AVT1 |
MaxQBi | A0AVT1 |
PaxDbi | A0AVT1 |
PeptideAtlasi | A0AVT1 |
PRIDEi | A0AVT1 |
ProteomicsDBi | 26 [A0AVT1-1] 27 [A0AVT1-2] 28 [A0AVT1-3] 29 [A0AVT1-4] |
PTM databases
iPTMneti | A0AVT1 |
MetOSitei | A0AVT1 |
PhosphoSitePlusi | A0AVT1 |
SwissPalmi | A0AVT1 |
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
Bgeei | ENSG00000033178, Expressed in corpus callosum and 230 other tissues |
ExpressionAtlasi | A0AVT1, baseline and differential |
Genevisiblei | A0AVT1, HS |
Organism-specific databases
HPAi | ENSG00000033178, Low tissue specificity |
Interactioni
Subunit structurei
Binary interactionsi
A0AVT1
With | #Exp. | IntAct |
---|---|---|
HMBOX1 [Q6NT76] | 3 | EBI-5282516,EBI-2549423 |
Protein-protein interaction databases
BioGRIDi | 120529, 90 interactors |
DIPi | DIP-57633N |
IntActi | A0AVT1, 16 interactors |
MINTi | A0AVT1 |
STRINGi | 9606.ENSP00000313454 |
Chemistry databases
BindingDBi | A0AVT1 |
Miscellaneous databases
RNActi | A0AVT1, protein |
Family & Domainsi
Sequence similaritiesi
Belongs to the ubiquitin-activating E1 family.Curated
Phylogenomic databases
eggNOGi | KOG2012, Eukaryota |
GeneTreei | ENSGT00940000158826 |
HOGENOMi | CLU_002556_0_0_1 |
InParanoidi | A0AVT1 |
OMAi | CPATENT |
PhylomeDBi | A0AVT1 |
TreeFami | TF300586 |
Family and domain databases
Gene3Di | 1.10.10.2660, 1 hit 2.40.30.180, 1 hit 3.10.290.60, 1 hit 3.50.50.80, 1 hit |
InterProi | View protein in InterPro IPR032420, E1_4HB IPR032418, E1_FCCH IPR042302, E1_FCCH_sf IPR000594, ThiF_NAD_FAD-bd IPR018965, Ub-activating_enz_E1_C IPR042449, Ub-E1_IAD_1 IPR038252, UBA_E1_C_sf IPR019572, UBA_E1_Cys IPR042063, Ubi_acti_E1_SCCH IPR035985, Ubiquitin-activating_enz IPR018075, UBQ-activ_enz_E1 IPR000011, UBQ/SUMO-activ_enz_E1-like |
Pfami | View 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 |
PRINTSi | PR01849, UBIQUITINACT |
SMARTi | View protein in SMART SM00985, UBA_e1_C, 1 hit |
SUPFAMi | SSF69572, SSF69572, 2 hits |
TIGRFAMsi | TIGR01408, Ube1, 1 hit |
s (4+)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis 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 sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH0Y8S8 | H0Y8S8_HUMAN | Ubiquitin-like modifier-activating ... | UBA6 | 271 | Annotation score: | ||
H0Y9U5 | H0Y9U5_HUMAN | Ubiquitin-like modifier-activating ... | UBA6 | 88 | Annotation score: |
Sequence cautioni
The sequence BAA91824 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 14 | E → K in CAD89908 (PubMed:17974005).Curated | 1 | |
Sequence conflicti | 140 | V → A in CAD89908 (PubMed:17974005).Curated | 1 | |
Sequence conflicti | 197 | C → Y in BAC04463 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 234 | N → D in CAD89959 (PubMed:17974005).Curated | 1 | |
Sequence conflicti | 297 | V → A in BAC04463 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 645 | F → V in AAQ63403 (PubMed:15202508).Curated | 1 | |
Sequence conflicti | 803 | Q → H in BAA91824 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 821 | E → G in CAD89959 (PubMed:17974005).Curated | 1 | |
Sequence conflicti | 868 | L → P in CAD89908 (PubMed:17974005).Curated | 1 | |
Sequence conflicti | 905 | V → G in AAQ63403 (PubMed:15202508).Curated | 1 | |
Sequence conflicti | 909 | M → K in CAD89959 (PubMed:17974005).Curated | 1 | |
Sequence conflicti | 920 | A → V in BAB19785 (Ref. 3) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_030594 | 224 | A → T3 PublicationsCorresponds to variant dbSNP:rs10010188Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_023083 | 1 – 474 | Missing in isoform 2. 1 PublicationAdd BLAST | 474 | |
Alternative sequenceiVSP_023084 | 321 – 340 | APLEI…QEKYS → VNKHFAGLREAAESEMRISE in isoform 4. 1 PublicationAdd BLAST | 20 | |
Alternative sequenceiVSP_023085 | 341 – 1052 | Missing in isoform 4. 1 PublicationAdd BLAST | 712 | |
Alternative sequenceiVSP_023086 | 369 – 389 | PDVNA…GFLSP → VTIEIYGCPNICLLIHKCSV Y in isoform 3. 1 PublicationAdd BLAST | 21 | |
Alternative sequenceiVSP_023087 | 390 – 1052 | Missing in isoform 3. 1 PublicationAdd BLAST | 663 |
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 |
CCDSi | CCDS3516.1 [A0AVT1-1] |
RefSeqi | NP_060697.4, NM_018227.5 [A0AVT1-1] |
Genome annotation databases
Ensembli | ENST00000322244; ENSP00000313454; ENSG00000033178 [A0AVT1-1] ENST00000420827; ENSP00000399234; ENSG00000033178 [A0AVT1-3] |
GeneIDi | 55236 |
KEGGi | hsa:55236 |
UCSCi | uc003hdg.5, human [A0AVT1-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar 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 |
CCDSi | CCDS3516.1 [A0AVT1-1] |
RefSeqi | NP_060697.4, NM_018227.5 [A0AVT1-1] |
3D structure databases
SMRi | A0AVT1 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 120529, 90 interactors |
DIPi | DIP-57633N |
IntActi | A0AVT1, 16 interactors |
MINTi | A0AVT1 |
STRINGi | 9606.ENSP00000313454 |
Chemistry databases
BindingDBi | A0AVT1 |
ChEMBLi | CHEMBL2321622 |
PTM databases
iPTMneti | A0AVT1 |
MetOSitei | A0AVT1 |
PhosphoSitePlusi | A0AVT1 |
SwissPalmi | A0AVT1 |
Genetic variation databases
BioMutai | UBA6 |
Proteomic databases
EPDi | A0AVT1 |
jPOSTi | A0AVT1 |
MassIVEi | A0AVT1 |
MaxQBi | A0AVT1 |
PaxDbi | A0AVT1 |
PeptideAtlasi | A0AVT1 |
PRIDEi | A0AVT1 |
ProteomicsDBi | 26 [A0AVT1-1] 27 [A0AVT1-2] 28 [A0AVT1-3] 29 [A0AVT1-4] |
Protocols and materials databases
Antibodypediai | 24140, 275 antibodies |
DNASUi | 55236 |
Genome annotation databases
Ensembli | ENST00000322244; ENSP00000313454; ENSG00000033178 [A0AVT1-1] ENST00000420827; ENSP00000399234; ENSG00000033178 [A0AVT1-3] |
GeneIDi | 55236 |
KEGGi | hsa:55236 |
UCSCi | uc003hdg.5, human [A0AVT1-1] |
Organism-specific databases
CTDi | 55236 |
DisGeNETi | 55236 |
GeneCardsi | UBA6 |
HGNCi | HGNC:25581, UBA6 |
HPAi | ENSG00000033178, Low tissue specificity |
MIMi | 611361, gene |
neXtProti | NX_A0AVT1 |
OpenTargetsi | ENSG00000033178 |
PharmGKBi | PA162407690 |
VEuPathDBi | HostDB:ENSG00000033178.12 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2012, Eukaryota |
GeneTreei | ENSGT00940000158826 |
HOGENOMi | CLU_002556_0_0_1 |
InParanoidi | A0AVT1 |
OMAi | CPATENT |
PhylomeDBi | A0AVT1 |
TreeFami | TF300586 |
Enzyme and pathway databases
UniPathwayi | UPA00143 |
BRENDAi | 6.2.1.B9, 2681 |
PathwayCommonsi | A0AVT1 |
Reactomei | R-HSA-8866652, Synthesis of active ubiquitin: roles of E1 and E2 enzymes R-HSA-983168, Antigen processing: Ubiquitination & Proteasome degradation |
Miscellaneous databases
BioGRID-ORCSi | 55236, 230 hits in 871 CRISPR screens |
ChiTaRSi | UBA6, human |
GeneWikii | UBE1L2 |
GenomeRNAii | 55236 |
Pharosi | A0AVT1, Tchem |
PROi | PR:A0AVT1 |
RNActi | A0AVT1, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000033178, Expressed in corpus callosum and 230 other tissues |
ExpressionAtlasi | A0AVT1, baseline and differential |
Genevisiblei | A0AVT1, HS |
Family and domain databases
Gene3Di | 1.10.10.2660, 1 hit 2.40.30.180, 1 hit 3.10.290.60, 1 hit 3.50.50.80, 1 hit |
InterProi | View protein in InterPro IPR032420, E1_4HB IPR032418, E1_FCCH IPR042302, E1_FCCH_sf IPR000594, ThiF_NAD_FAD-bd IPR018965, Ub-activating_enz_E1_C IPR042449, Ub-E1_IAD_1 IPR038252, UBA_E1_C_sf IPR019572, UBA_E1_Cys IPR042063, Ubi_acti_E1_SCCH IPR035985, Ubiquitin-activating_enz IPR018075, UBQ-activ_enz_E1 IPR000011, UBQ/SUMO-activ_enz_E1-like |
Pfami | View 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 |
PRINTSi | PR01849, UBIQUITINACT |
SMARTi | View protein in SMART SM00985, UBA_e1_C, 1 hit |
SUPFAMi | SSF69572, SSF69572, 2 hits |
TIGRFAMsi | TIGR01408, Ube1, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | UBA6_HUMAN | |
Accessioni | A0AVT1Primary (citable) accession number: A0AVT1 Secondary accession number(s): A6N8M7 Q9NVC9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 20, 2007 |
Last sequence update: | November 28, 2006 | |
Last modified: | February 10, 2021 | |
This is version 138 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Human chromosome 4
Human chromosome 4: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families