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    UBA1 ubiquitin like modifier activating enzyme 1 [ Homo sapiens (human) ]

    Gene ID: 7317, updated on 10-Dec-2024

    Summary

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    Official Symbol
    UBA1provided by HGNC
    Official Full Name
    ubiquitin like modifier activating enzyme 1provided by HGNC
    Primary source
    HGNC:HGNC:12469
    See related
    Ensembl:ENSG00000130985 MIM:314370; AllianceGenome:HGNC:12469
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    A1S9; A1ST; GXP1; UBE1; A1S9T; AMCX1; POC20; SMAX2; UBA1A; UBE1X; VEXAS; CFAP124
    Summary
    The protein encoded by this gene catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation. This gene complements an X-linked mouse temperature-sensitive defect in DNA synthesis, and thus may function in DNA repair. It is part of a gene cluster on chromosome Xp11.23. Alternatively spliced transcript variants that encode the same protein have been described. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in thyroid (RPKM 27.6), brain (RPKM 26.8) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See UBA1 in Genome Data Viewer
    Location:
    Xp11.3
    Exon count:
    32
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (47190847..47215128)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (46600543..46624827)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (47050246..47074527)

    Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29582 Neighboring gene NADH:ubiquinone oxidoreductase subunit B11 Neighboring gene RNA binding motif protein 10 Neighboring gene ITPK1 pseudogene 1 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chrX:47037923-47039122 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29583 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chrX:47050393-47050933 Neighboring gene ReSE screen-validated silencer GRCh37_chrX:47053068-47053256 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20798 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chrX:47057593-47058792 Neighboring gene uncharacterized LOC105373194 Neighboring gene inactivation escape 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20799 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29586 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29587 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chrX:47078167-47078806 Neighboring gene cyclin dependent kinase 16 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:47087788-47088288 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:47088289-47088789 Neighboring gene CRISPRi-FlowFISH-validated HDAC6 regulatory element 1 Neighboring gene ubiquitin specific peptidase 11

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Identification of UBA1 as the causative gene of an X-linked non-Kennedy spinal-bulbar muscular atrophy. Khani M, et al. Eur J Neurol, 2022 Dec. PMID 35996994
    2. Pleiotropic effects of ATP.Mg2+ binding in the catalytic cycle of ubiquitin-activating enzyme. Tokgöz Z, et al. J Biol Chem, 2006 May 26. PMID 16595681
    3. Impaired nucleotide excision repair upon macrophage differentiation is corrected by E1 ubiquitin-activating enzyme. Nouspikel T, et al. Proc Natl Acad Sci U S A, 2006 Oct 31. PMID 17060614, Free PMC Article
    4. An update on VEXAS syndrome. Al-Hakim A, et al. Expert Rev Clin Immunol, 2023 Feb. PMID 36537591
    5. Rare missense and synonymous variants in UBE1 are associated with X-linked infantile spinal muscular atrophy. Ramser J, et al. Am J Hum Genet, 2008 Jan. PMID 18179898, Free PMC Article

    See all (329) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Molecular and clinical presentation of UBA1-mutated myelodysplastic syndromes.
      Title: Molecular and clinical presentation of UBA1-mutated myelodysplastic syndromes.
    2. VEXAS-Defining UBA1 Somatic Variants in 245,368 Diverse Individuals in the NIH All Of Us Cohort.
      Title: VEXAS-Defining UBA1 Somatic Variants in 245,368 Diverse Individuals in the NIH All Of Us Cohort.
    3. A comprehensive prognostic and immune infiltration analysis of UBA1 in pan-cancer: A computational analysis and in vitro experiments.
      Title: A comprehensive prognostic and immune infiltration analysis of UBA1 in pan-cancer: A computational analysis and in vitro experiments.
    4. Shared and distinct mechanisms of UBA1 inactivation across different diseases.
      Title: Shared and distinct mechanisms of UBA1 inactivation across different diseases.
    5. Acetylated Ubiquitin Modulates the Catalytic Activity of the E1 Enzyme Uba1.
      Title: Acetylated Ubiquitin Modulates the Catalytic Activity of the E1 Enzyme Uba1.
    6. Clonal haematopoiesis and UBA1 mutations in individuals with biopsy-proven giant cell arteritis and population-based controls.
      Title: Clonal haematopoiesis and UBA1 mutations in individuals with biopsy-proven giant cell arteritis and population-based controls.
    7. Dynamic monitoring of UBA1 somatic mutations in patients with relapsing polychondritis.
      Title: Dynamic monitoring of UBA1 somatic mutations in patients with relapsing polychondritis.
    8. Clinical and genetic features of Japanese cases of MDS associated with VEXAS syndrome.
      Title: Clinical and genetic features of Japanese cases of MDS associated with VEXAS syndrome.
    9. An update on VEXAS syndrome.
      Title: An update on VEXAS syndrome.
    10. Absence of NLRP3 somatic mutations and VEXAS-related UBA1 mutations in a large cohort of patients with Schnitzler syndrome.
      Title: Absence of NLRP3 somatic mutations and VEXAS-related UBA1 mutations in a large cohort of patients with Schnitzler syndrome.
    Submit: New GeneRIF Correction See all GeneRIFs (45)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Infantile-onset X-linked spinal muscular atrophy
    MedGen: C1844934 OMIM: 301830 GeneReviews: Spinal Muscular Atrophy, X-Linked Infantile
    		Compare labs
    VEXAS syndrome
    MedGen: C5435753 OMIM: 301054 GeneReviews: Not available
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat Ubiquitination of HIV-1 Tat by Hdm2 requires ubiquitin-activating enzyme E1 PubMed
    Vif vif HIV-1 is dependent on UBA1 (lysine at position 48, UbK48) for A3G degradation; results suggest that UbK48 is the primary ubiquitin conjugate needed for A3G degradation PubMed
    integrase gag-pol HIV-1 IN is identified to have a physical interaction with ubiquitin-like modifier activating enzyme 1 (UBA1) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC4781

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables RNA binding HDA PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ubiquitin activating enzyme activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables ubiquitin activating enzyme activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables ubiquitin activating enzyme activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables ubiquitin activating enzyme activity TAS
    Traceable Author Statement
    more info
    		  
    Process Evidence Code Pubs
    involved_in DNA damage response IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in DNA damage response IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein ubiquitination IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein ubiquitination IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein ubiquitination TAS
    Traceable Author Statement
    more info
    		  
    involved_in ubiquitin-dependent protein catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoplasm IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    colocalizes_with desmosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    colocalizes_with endosome membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in extracellular exosome HDA PubMed 
    colocalizes_with heterochromatin IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    colocalizes_with lysosomal membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleus HDA PubMed 
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    colocalizes_with rough endoplasmic reticulum membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    ubiquitin-like modifier-activating enzyme 1
    Names
    A1S9T and BN75 temperature sensitivity complementing
    POC20 centriolar protein homolog
    UBA1, ubiquitin-activating enzyme E1 homolog A
    testicular secretory protein Li 63
    NP_003325.2
    NP_695012.1
    XP_005272706.1
    XP_011542256.1
    XP_016885266.1
    XP_016885267.1
    XP_016885269.1
    XP_047298376.1
    XP_047298377.1
    XP_047298378.1
    XP_047298379.1
    XP_047298380.1
    XP_047298381.1
    XP_054183662.1
    XP_054183663.1
    XP_054183664.1
    XP_054183665.1
    XP_054183666.1
    XP_054183667.1
    XP_054183668.1
    XP_054183669.1
    XP_054183670.1
    XP_054183671.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_009161.1 RefSeqGene

      Range
      8030..29329
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_003334.4 → NP_003325.2  ubiquitin-like modifier-activating enzyme 1

      See identical proteins and their annotated locations for NP_003325.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript. Variants 1 and 2 encode the same protein.
      Source sequence(s)
      BC013041, BI547207, M58028
      Consensus CDS
      CCDS14275.1
      UniProtKB/Swiss-Prot
      P22314, Q5JRR8, Q96E13
      UniProtKB/TrEMBL
      A0A024R1A3
      Related
      ENSP00000338413.6, ENST00000335972.11
      Conserved Domains (4) summary
      cd01490
      Location:470 → 1011
      Ube1_repeat2; Ubiquitin activating enzyme (E1), repeat 2. E1, a highly conserved small protein present universally in eukaryotic cells, is part of cascade to attach ubiquitin (Ub) covalently to substrate proteins. This cascade consists of activating (E1), conjugating ...
      cd01491
      Location:54 → 436
      Ube1_repeat1; Ubiquitin activating enzyme (E1), repeat 1. E1, a highly conserved small protein present universally in eukaryotic cells, is part of cascade to attach ubiquitin (Ub) covalently to substrate proteins. This cascade consists of activating (E1), conjugating ...
      TIGR01408
      Location:49 → 1055
      Ube1; ubiquitin-activating enzyme E1
      pfam16191
      Location:302 → 366
      E1_4HB; Ubiquitin-activating enzyme E1 four-helix bundle

    2. NM_153280.3 → NP_695012.1  ubiquitin-like modifier-activating enzyme 1

      See identical proteins and their annotated locations for NP_695012.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 encode the same protein.
      Source sequence(s)
      BC013041, BG703038
      Consensus CDS
      CCDS14275.1
      UniProtKB/Swiss-Prot
      P22314, Q5JRR8, Q96E13
      UniProtKB/TrEMBL
      A0A024R1A3
      Related
      ENSP00000366568.4, ENST00000377351.8
      Conserved Domains (4) summary
      cd01490
      Location:470 → 1011
      Ube1_repeat2; Ubiquitin activating enzyme (E1), repeat 2. E1, a highly conserved small protein present universally in eukaryotic cells, is part of cascade to attach ubiquitin (Ub) covalently to substrate proteins. This cascade consists of activating (E1), conjugating ...
      cd01491
      Location:54 → 436
      Ube1_repeat1; Ubiquitin activating enzyme (E1), repeat 1. E1, a highly conserved small protein present universally in eukaryotic cells, is part of cascade to attach ubiquitin (Ub) covalently to substrate proteins. This cascade consists of activating (E1), conjugating ...
      TIGR01408
      Location:49 → 1055
      Ube1; ubiquitin-activating enzyme E1
      pfam16191
      Location:302 → 366
      E1_4HB; Ubiquitin-activating enzyme E1 four-helix bundle

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000023.11 Reference GRCh38.p14 Primary Assembly

      Range
      47190847..47215128
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047442425.1 → XP_047298381.1  ubiquitin-like modifier-activating enzyme 1 isoform X6

      UniProtKB/Swiss-Prot
      P22314, Q5JRR8, Q96E13
      UniProtKB/TrEMBL
      A0A024R1A3

    2. XM_017029777.2 → XP_016885266.1  ubiquitin-like modifier-activating enzyme 1 isoform X1

    3. XM_047442420.1 → XP_047298376.1  ubiquitin-like modifier-activating enzyme 1 isoform X1

    4. XM_047442421.1 → XP_047298377.1  ubiquitin-like modifier-activating enzyme 1 isoform X3

    5. XM_005272649.2 → XP_005272706.1  ubiquitin-like modifier-activating enzyme 1 isoform X5

      See identical proteins and their annotated locations for XP_005272706.1

      Conserved Domains (4) summary
      cd01490
      Location:476 → 1017
      Ube1_repeat2; Ubiquitin activating enzyme (E1), repeat 2. E1, a highly conserved small protein present universally in eukaryotic cells, is part of cascade to attach ubiquitin (Ub) covalently to substrate proteins. This cascade consists of activating (E1), conjugating ...
      cd01491
      Location:60 → 442
      Ube1_repeat1; Ubiquitin activating enzyme (E1), repeat 1. E1, a highly conserved small protein present universally in eukaryotic cells, is part of cascade to attach ubiquitin (Ub) covalently to substrate proteins. This cascade consists of activating (E1), conjugating ...
      TIGR01408
      Location:55 → 1061
      Ube1; ubiquitin-activating enzyme E1
      pfam16191
      Location:308 → 372
      E1_4HB; Ubiquitin-activating enzyme E1 four-helix bundle

    6. XM_047442422.1 → XP_047298378.1  ubiquitin-like modifier-activating enzyme 1 isoform X3

    7. XM_047442423.1 → XP_047298379.1  ubiquitin-like modifier-activating enzyme 1 isoform X5

    8. XM_011543954.2 → XP_011542256.1  ubiquitin-like modifier-activating enzyme 1 isoform X4

      Conserved Domains (4) summary
      cd01490
      Location:484 → 1025
      Ube1_repeat2; Ubiquitin activating enzyme (E1), repeat 2. E1, a highly conserved small protein present universally in eukaryotic cells, is part of cascade to attach ubiquitin (Ub) covalently to substrate proteins. This cascade consists of activating (E1), conjugating ...
      cd01491
      Location:68 → 450
      Ube1_repeat1; Ubiquitin activating enzyme (E1), repeat 1. E1, a highly conserved small protein present universally in eukaryotic cells, is part of cascade to attach ubiquitin (Ub) covalently to substrate proteins. This cascade consists of activating (E1), conjugating ...
      TIGR01408
      Location:63 → 1069
      Ube1; ubiquitin-activating enzyme E1
      pfam16191
      Location:316 → 380
      E1_4HB; Ubiquitin-activating enzyme E1 four-helix bundle

    9. XM_017029778.3 → XP_016885267.1  ubiquitin-like modifier-activating enzyme 1 isoform X2

      Conserved Domains (4) summary
      cd01490
      Location:498 → 1039
      Ube1_repeat2; Ubiquitin activating enzyme (E1), repeat 2. E1, a highly conserved small protein present universally in eukaryotic cells, is part of cascade to attach ubiquitin (Ub) covalently to substrate proteins. This cascade consists of activating (E1), conjugating ...
      cd01491
      Location:82 → 464
      Ube1_repeat1; Ubiquitin activating enzyme (E1), repeat 1. E1, a highly conserved small protein present universally in eukaryotic cells, is part of cascade to attach ubiquitin (Ub) covalently to substrate proteins. This cascade consists of activating (E1), conjugating ...
      TIGR01408
      Location:77 → 1083
      Ube1; ubiquitin-activating enzyme E1
      pfam16191
      Location:330 → 394
      E1_4HB; Ubiquitin-activating enzyme E1 four-helix bundle

    10. XM_017029780.2 → XP_016885269.1  ubiquitin-like modifier-activating enzyme 1 isoform X6

      UniProtKB/Swiss-Prot
      P22314, Q5JRR8, Q96E13
      UniProtKB/TrEMBL
      A0A024R1A3
      Conserved Domains (4) summary
      cd01490
      Location:470 → 1011
      Ube1_repeat2; Ubiquitin activating enzyme (E1), repeat 2. E1, a highly conserved small protein present universally in eukaryotic cells, is part of cascade to attach ubiquitin (Ub) covalently to substrate proteins. This cascade consists of activating (E1), conjugating ...
      cd01491
      Location:54 → 436
      Ube1_repeat1; Ubiquitin activating enzyme (E1), repeat 1. E1, a highly conserved small protein present universally in eukaryotic cells, is part of cascade to attach ubiquitin (Ub) covalently to substrate proteins. This cascade consists of activating (E1), conjugating ...
      TIGR01408
      Location:49 → 1055
      Ube1; ubiquitin-activating enzyme E1
      pfam16191
      Location:302 → 366
      E1_4HB; Ubiquitin-activating enzyme E1 four-helix bundle

    11. XM_047442424.1 → XP_047298380.1  ubiquitin-like modifier-activating enzyme 1 isoform X6

      UniProtKB/Swiss-Prot
      P22314, Q5JRR8, Q96E13
      UniProtKB/TrEMBL
      A0A024R1A3

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060947.1 Alternate T2T-CHM13v2.0

      Range
      46600543..46624827
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054327687.1 → XP_054183662.1  ubiquitin-like modifier-activating enzyme 1 isoform X1

    2. XM_054327688.1 → XP_054183663.1  ubiquitin-like modifier-activating enzyme 1 isoform X1

    3. XM_054327690.1 → XP_054183665.1  ubiquitin-like modifier-activating enzyme 1 isoform X3

    4. XM_054327693.1 → XP_054183668.1  ubiquitin-like modifier-activating enzyme 1 isoform X5

    5. XM_054327691.1 → XP_054183666.1  ubiquitin-like modifier-activating enzyme 1 isoform X3

    6. XM_054327694.1 → XP_054183669.1  ubiquitin-like modifier-activating enzyme 1 isoform X5

    7. XM_054327692.1 → XP_054183667.1  ubiquitin-like modifier-activating enzyme 1 isoform X4

    8. XM_054327689.1 → XP_054183664.1  ubiquitin-like modifier-activating enzyme 1 isoform X2

    9. XM_054327696.1 → XP_054183671.1  ubiquitin-like modifier-activating enzyme 1 isoform X6

      UniProtKB/Swiss-Prot
      P22314, Q5JRR8, Q96E13
      UniProtKB/TrEMBL
      A0A024R1A3

    10. XM_054327695.1 → XP_054183670.1  ubiquitin-like modifier-activating enzyme 1 isoform X6

      UniProtKB/Swiss-Prot
      P22314, Q5JRR8, Q96E13
      UniProtKB/TrEMBL
      A0A024R1A3
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P22314.3 GenPept UniProtKB/Swiss-Prot:P22314

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