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NSMCE2 NSE2 (MMS21) homolog, SMC5-SMC6 complex SUMO ligase [ Homo sapiens (human) ]

Gene ID: 286053, updated on 2-Nov-2024

Summary

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Official Symbol
NSMCE2provided by HGNC
Official Full Name
NSE2 (MMS21) homolog, SMC5-SMC6 complex SUMO ligaseprovided by HGNC
Primary source
HGNC:HGNC:26513
See related
Ensembl:ENSG00000156831 MIM:617246; AllianceGenome:HGNC:26513
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
NSE2; MMS21; ZMIZ7; C8orf36
Summary
This gene encodes a member of a family of E3 small ubiquitin-related modifier (SUMO) ligases that mediates the attachment of a SUMO protein to proteins involved in nuclear transport, transcription, chromosome segregation and DNA repair. The encoded protein is part of the structural maintenance of chromosomes (SMC) 5/6 complex which plays a key role genome maintenance, facilitating chromosome segregation and suppressing mitotic recombination. A knockout of the orthologous mouse gene is lethal prior to embryonic day 10.5. Naturally occurring mutations in this gene, that abolish the SUMO ligase activity, are associated with primordial dwarfism and extreme insulin resistance. [provided by RefSeq, Mar 2017]
Expression
Ubiquitous expression in bone marrow (RPKM 2.5), lymph node (RPKM 2.3) and 25 other tissues See more
Orthologs
mouse all
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Genomic context

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See NSMCE2 in Genome Data Viewer
Location:
8q24.13
Exon count:
13
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 8 NC_000008.11 (125091860..125367120)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 8 NC_060932.1 (126225519..126500604)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 8 NC_000008.10 (126104102..126379362)

Chromosome 8 - NC_000008.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19516 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27898 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr8:126043836-126045035 Neighboring gene WASHC5 antisense RNA 1 Neighboring gene squalene epoxidase Neighboring gene WASH complex subunit 5 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19517 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27899 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27900 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27901 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27902 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27903 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr8:126201101-126202300 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27904 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27905 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27906 Neighboring gene HNF1 motif-containing MPRA enhancer 31 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27907 Neighboring gene Sharpr-MPRA regulatory region 6874 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27908 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27909 Neighboring gene RNA, 7SL, cytoplasmic 329, pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:126312861-126313361 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27910 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:126346157-126346974 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:126389339-126389905 Neighboring gene Sharpr-MPRA regulatory region 8491 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:126398994-126399684 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:126400790-126401290 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:126401291-126401791 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:126416953-126417640 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:126417641-126418327 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:126427297-126428194 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:126428195-126429092 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27913 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:126433597-126434098 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:126434099-126434598 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19518 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27914 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27915 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19519 Neighboring gene Sharpr-MPRA regulatory region 8664 Neighboring gene MPRA-validated peak7163 silencer Neighboring gene tribbles pseudokinase 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:126513538-126514038 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27916 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27917 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr8:126525111-126526310 Neighboring gene TRIB1 associated lncRNA Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:126533553-126534054 Neighboring gene ReSE screen-validated silencer GRCh37_chr8:126544853-126545039 Neighboring gene long intergenic non-protein coding RNA 2964

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 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. Effects of Nephrolithiasis on Serum DNase (Deoxyribonuclease I and II) Activity and E3 SUMO-Protein Ligase NSE2 (NSMCE2) in Malaysian Individuals. Yusof F, et al. Biomed Environ Sci, 2015 Sep. PMID 26464253
  2. The Yin and Yang of the MMS21-SMC5/6 SUMO ligase complex in homologous recombination. Potts PR. DNA Repair (Amst), 2009 Apr 5. PMID 19217832
  3. NSMCE2, a novel super-enhancer-regulated gene, is linked to poor prognosis and therapy resistance in breast cancer. Di Benedetto C, et al. BMC Cancer, 2022 Oct 12. PMID 36224576, Free PMC Article
  4. The SUMO pathway: emerging mechanisms that shape specificity, conjugation and recognition. Gareau JR, et al. Nat Rev Mol Cell Biol, 2010 Dec. PMID 21102611, Free PMC Article
  5. Rescue of collapsed replication forks is dependent on NSMCE2 to prevent mitotic DNA damage. Pond KW, et al. PLoS Genet, 2019 Feb. PMID 30735491, Free PMC Article

See all (57) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. NSMCE2, a novel super-enhancer-regulated gene, is linked to poor prognosis and therapy resistance in breast cancer.
    Title: NSMCE2, a novel super-enhancer-regulated gene, is linked to poor prognosis and therapy resistance in breast cancer.
  2. We demonstrate that Topo2a is SUMOylated in an ICRF193-dependent manner by NSE2 at a novel non-canonical site (K1520) and that K1520 sumoylation is required for chromosome segregation but not the G2 arrest.
    Title: A genome-wide RNAi screen identifies the SMC5/6 complex as a non-redundant regulator of a Topo2a-dependent G2 arrest.
  3. Study the fate of collapsed replication forks generated by prolonged hydroxyurea treatment in NSMCE2-deficient cells. Double strand breaks accumulate during rescue by converging forks in normal cells but not in NSMCE2-deficient cells. Un-rescued forks persist into mitosis, leading to increased mitotic DNA damage.
    Title: Rescue of collapsed replication forks is dependent on NSMCE2 to prevent mitotic DNA damage.
  4. Absence of NSMCE2 affects survival upon topoisomerase II inhibitor etoposide-induced DNA double-strand breaks double-strand breaks.
    Title: Non-SMC Element 2 (NSMCE2) of the SMC5/6 Complex Helps to Resolve Topological Stress.
  5. our study identified novel PVT1-NSMCE2 and CCDC26-NSMCE2 fusion genes that may play functional roles in leukemia.
    Title: 8q24 amplified segments involve novel fusion genes between NSMCE2 and long noncoding RNAs in acute myelogenous leukemia.
  6. support a role for NSMCE2 in recovery from DNA damage and raise the possibility that loss of its function produces dwarfism through reduced tolerance of replicative stress
    Title: Hypomorphism in human NSMCE2 linked to primordial dwarfism and insulin resistance.
  7. show that the Smc5/6 subunit Mms21 sumoylates multiple lysines of the cohesin subunit Scc1
    Title: Scc1 sumoylation by Mms21 promotes sister chromatid recombination through counteracting Wapl.
  8. Studies indicate that Nse1 may function as a ubiquitin ligase, and is targeted to chromatin through its interaction with the Smc5/6 complex.
    Title: The Nse2/Mms21 SUMO ligase of the Smc5/6 complex in the maintenance of genome stability.
  9. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
    Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
  10. MMS21 dependent sumoylation is integral and important to the cohesion mechanism and mitotic progression and that this function appears to be independent of SMC6.
    Title: SMC5 and MMS21 are required for chromosome cohesion and mitotic progression.
Submit: New GeneRIF Correction See all GeneRIFs (12)

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
Seckel syndrome 10
MedGen: C4310647 OMIM: 617253 GeneReviews: Not available
not available

EBI GWAS Catalog

Description
C9orf72 and UNC13A are shared risk loci for ALS and FTD: A genome-wide meta-analysis.
EBI GWAS Catalog
Genome-wide association of lipid-lowering response to statins in combined study populations.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

  • FLJ32440

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables SUMO ligase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables SUMO transferase activity EXP
Inferred from Experiment
more info
 PubMed 
enables SUMO transferase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables zinc ion binding IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in cell division IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular senescence IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in chromatin looping NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in double-strand break repair via homologous recombination IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in double-strand break repair via homologous recombination IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in double-strand break repair via homologous recombination NAS
Non-traceable Author Statement
more info
 PubMed 
NOT involved_in double-strand break repair via nonhomologous end joining IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of maintenance of mitotic sister chromatid cohesion IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of mitotic metaphase/anaphase transition IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein sumoylation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein sumoylation IEA
Inferred from Electronic Annotation
more info
  
involved_in protein sumoylation NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in protein sumoylation TAS
Traceable Author Statement
more info
  
involved_in regulation of telomere maintenance NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in telomere maintenance via recombination IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
located_in PML body IDA
Inferred from Direct Assay
more info
 PubMed 
part_of Smc5-Smc6 complex IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of Smc5-Smc6 complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of Smc5-Smc6 complex NAS
Non-traceable Author Statement
more info
 PubMed 
located_in chromosome, telomeric region IDA
Inferred from Direct Assay
more info
 PubMed 
located_in chromosome, telomeric region NAS
Non-traceable Author Statement
more info
 PubMed 
located_in nuclear body IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
E3 SUMO-protein ligase NSE2
Names
E3 SUMO-protein transferase NSE2
NSMCE2/PVT1 fusion
PVT1/NSMCE2 fusion
methyl methanesulfonate sensitivity gene 21
non-SMC element 2, MMS21 homolog
non-structural maintenance of chromosomes element 2 homolog
zinc finger, MIZ-type containing 7
NP_001336414.1
NP_001336415.1
NP_001336416.1
NP_775956.1
XP_011515276.1
XP_011515277.1
XP_016868819.1
XP_016868820.1
XP_016868821.1
XP_024302898.1
XP_047277658.1
XP_047277659.1
XP_047277660.1
XP_047277661.1
XP_054216280.1
XP_054216281.1
XP_054216282.1
XP_054216283.1
XP_054216284.1
XP_054216285.1
XP_054216286.1
XP_054216287.1
XP_054216288.1

NCBI Reference Sequences (RefSeq)

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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_053069.1 RefSeqGene

    Range
    5043..280303
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001349485.2 → NP_001336414.1  E3 SUMO-protein ligase NSE2 isoform 1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate exon in the 5' UTR compared to variant 1. Variants 1-3 encode the same isoform (1).
    Source sequence(s)
    AC084083, AC126366
    Consensus CDS
    CCDS6356.1
    UniProtKB/Swiss-Prot
    Q8N549, Q96MF7
    Related
    ENSP00000430668.1, ENST00000522563.6
    Conserved Domains (1) summary
    cd16651
    Location:167 → 237
    SPL-RING_NSE2; SPL-RING finger found in E3 SUMO-protein ligase NSE2 and similar proteins

  2. NM_001349486.2 → NP_001336415.1  E3 SUMO-protein ligase NSE2 isoform 1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) uses an alternate slice site in the 5' UTR compared to variant 1. Variants 1-3 encode the same isoform (1).
    Source sequence(s)
    AC084083, AC126366
    Consensus CDS
    CCDS6356.1
    UniProtKB/Swiss-Prot
    Q8N549, Q96MF7
    Conserved Domains (1) summary
    cd16651
    Location:167 → 237
    SPL-RING_NSE2; SPL-RING finger found in E3 SUMO-protein ligase NSE2 and similar proteins

  3. NM_001349487.2 → NP_001336416.1  E3 SUMO-protein ligase NSE2 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks several exons and its 3' terminal exon extends past a splice site that is used in variant 1. This results in a novel 3' coding region and 3' UTR, compared to variant 1. It encodes isoform 2 which is shorter and has a distinct C-terminus, compared to isoform 1.
    Source sequence(s)
    AC126366, BM993808
    Consensus CDS
    CCDS87625.1
    UniProtKB/TrEMBL
    A0A087WTZ8, E5RIM1
    Related
    ENSP00000478256.1, ENST00000520866.5

  4. NM_173685.4 → NP_775956.1  E3 SUMO-protein ligase NSE2 isoform 1

    See identical proteins and their annotated locations for NP_775956.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longer isoform (1). Variants 1-3 encode the same isoform (1).
    Source sequence(s)
    BC032797, CB217595
    Consensus CDS
    CCDS6356.1
    UniProtKB/Swiss-Prot
    Q8N549, Q96MF7
    Related
    ENSP00000287437.3, ENST00000287437.8
    Conserved Domains (1) summary
    cd16651
    Location:167 → 237
    SPL-RING_NSE2; SPL-RING finger found in E3 SUMO-protein ligase NSE2 and similar proteins

RNA

  1. NR_146191.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) uses an alternate splice site and contains an alternate exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AC084083, AC126366

  2. NR_146192.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) lacks several exons, contains an exon, and its 3' terminal exon extends past a splice site that is used in variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AC126366, BM993808

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_000008.11 Reference GRCh38.p14 Primary Assembly

    Range
    125091860..125367120
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017013331.2 → XP_016868820.1  E3 SUMO-protein ligase NSE2 isoform X2

    UniProtKB/Swiss-Prot
    Q8N549, Q96MF7
    Conserved Domains (1) summary
    cd16651
    Location:167 → 237
    SPL-RING_NSE2; SPL-RING finger found in E3 SUMO-protein ligase NSE2 and similar proteins

  2. XM_047421702.1 → XP_047277658.1  E3 SUMO-protein ligase NSE2 isoform X2

    UniProtKB/Swiss-Prot
    Q8N549, Q96MF7

  3. XM_011516974.3 → XP_011515276.1  E3 SUMO-protein ligase NSE2 isoform X2

    See identical proteins and their annotated locations for XP_011515276.1

    UniProtKB/Swiss-Prot
    Q8N549, Q96MF7
    Conserved Domains (1) summary
    cd16651
    Location:167 → 237
    SPL-RING_NSE2; SPL-RING finger found in E3 SUMO-protein ligase NSE2 and similar proteins

  4. XM_047421705.1 → XP_047277661.1  E3 SUMO-protein ligase NSE2 isoform X2

    UniProtKB/Swiss-Prot
    Q8N549, Q96MF7

  5. XM_047421703.1 → XP_047277659.1  E3 SUMO-protein ligase NSE2 isoform X2

    UniProtKB/Swiss-Prot
    Q8N549, Q96MF7

  6. XM_024447130.2 → XP_024302898.1  E3 SUMO-protein ligase NSE2 isoform X2

    UniProtKB/Swiss-Prot
    Q8N549, Q96MF7
    Conserved Domains (1) summary
    cd16651
    Location:167 → 237
    SPL-RING_NSE2; SPL-RING finger found in E3 SUMO-protein ligase NSE2 and similar proteins

  7. XM_011516975.3 → XP_011515277.1  E3 SUMO-protein ligase NSE2 isoform X2

    See identical proteins and their annotated locations for XP_011515277.1

    UniProtKB/Swiss-Prot
    Q8N549, Q96MF7
    Conserved Domains (1) summary
    cd16651
    Location:167 → 237
    SPL-RING_NSE2; SPL-RING finger found in E3 SUMO-protein ligase NSE2 and similar proteins

  8. XM_047421704.1 → XP_047277660.1  E3 SUMO-protein ligase NSE2 isoform X4

    Related
    ENSP00000429612.1, ENST00000517532.5

  9. XM_017013332.3 → XP_016868821.1  E3 SUMO-protein ligase NSE2 isoform X3

  10. XM_017013330.3 → XP_016868819.1  E3 SUMO-protein ligase NSE2 isoform X1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060932.1 Alternate T2T-CHM13v2.0

    Range
    126225519..126500604
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054360311.1 → XP_054216286.1  E3 SUMO-protein ligase NSE2 isoform X2

    UniProtKB/Swiss-Prot
    Q8N549, Q96MF7

  2. XM_054360308.1 → XP_054216283.1  E3 SUMO-protein ligase NSE2 isoform X2

    UniProtKB/Swiss-Prot
    Q8N549, Q96MF7

  3. XM_054360310.1 → XP_054216285.1  E3 SUMO-protein ligase NSE2 isoform X2

    UniProtKB/Swiss-Prot
    Q8N549, Q96MF7

  4. XM_054360309.1 → XP_054216284.1  E3 SUMO-protein ligase NSE2 isoform X2

    UniProtKB/Swiss-Prot
    Q8N549, Q96MF7

  5. XM_054360306.1 → XP_054216281.1  E3 SUMO-protein ligase NSE2 isoform X2

    UniProtKB/Swiss-Prot
    Q8N549, Q96MF7

  6. XM_054360307.1 → XP_054216282.1  E3 SUMO-protein ligase NSE2 isoform X2

    UniProtKB/Swiss-Prot
    Q8N549, Q96MF7

  7. XM_054360313.1 → XP_054216288.1  E3 SUMO-protein ligase NSE2 isoform X4

  8. XM_054360312.1 → XP_054216287.1  E3 SUMO-protein ligase NSE2 isoform X3

  9. XM_054360305.1 → XP_054216280.1  E3 SUMO-protein ligase NSE2 isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q96MF7.2 GenPept UniProtKB/Swiss-Prot:Q96MF7

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