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

Summary

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

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_000008.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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	Compare labs

EBI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D8S371 (e-PCR)
- UniSTS:16660

SHGC-33154 (e-PCR)
- UniSTS:810

D8S1461 (e-PCR), detects polymorphism
- UniSTS:15984

A009A17 (e-PCR)
- UniSTS:39545

D8S1688 (e-PCR)
- UniSTS:154245

G20371 (e-PCR)
- UniSTS:50582

A005O09 (e-PCR)
- UniSTS:50583

D8S1571E (e-PCR)
- UniSTS:153764

RH36327 (e-PCR)
- UniSTS:49586

RH11704 (e-PCR)
- UniSTS:20157

RH36272 (e-PCR)
- UniSTS:73927

SHGC-154637 (e-PCR)
- UniSTS:178151

SHGC-56887 (e-PCR)
- UniSTS:59882

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

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

NG_053069.1 RefSeqGene

Range

5043..280303

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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
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

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
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

NC_000008.11 Reference GRCh38.p14 Primary Assembly

Range

125091860..125367120

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/Swiss-Prot

Q8N549, Q96MF7
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
XM_047421705.1 → XP_047277661.1 E3 SUMO-protein ligase NSE2 isoform X2

UniProtKB/Swiss-Prot

Q8N549, Q96MF7
XM_047421703.1 → XP_047277659.1 E3 SUMO-protein ligase NSE2 isoform X2

UniProtKB/Swiss-Prot

Q8N549, Q96MF7
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
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
XM_047421704.1 → XP_047277660.1 E3 SUMO-protein ligase NSE2 isoform X4

UniProtKB/TrEMBL

E5RHW9

Related

ENSP00000429612.1, ENST00000517532.5
XM_017013332.3 → XP_016868821.1 E3 SUMO-protein ligase NSE2 isoform X3
XM_017013330.3 → XP_016868819.1 E3 SUMO-protein ligase NSE2 isoform X1

Alternate T2T-CHM13v2.0

Genomic

NC_060932.1 Alternate T2T-CHM13v2.0

Range

126225519..126500604

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/Swiss-Prot

Q8N549, Q96MF7
XM_054360308.1 → XP_054216283.1 E3 SUMO-protein ligase NSE2 isoform X2

UniProtKB/Swiss-Prot

Q8N549, Q96MF7
XM_054360310.1 → XP_054216285.1 E3 SUMO-protein ligase NSE2 isoform X2

UniProtKB/Swiss-Prot

Q8N549, Q96MF7
XM_054360309.1 → XP_054216284.1 E3 SUMO-protein ligase NSE2 isoform X2

UniProtKB/Swiss-Prot

Q8N549, Q96MF7
XM_054360306.1 → XP_054216281.1 E3 SUMO-protein ligase NSE2 isoform X2

UniProtKB/Swiss-Prot

Q8N549, Q96MF7
XM_054360307.1 → XP_054216282.1 E3 SUMO-protein ligase NSE2 isoform X2

UniProtKB/Swiss-Prot

Q8N549, Q96MF7
XM_054360313.1 → XP_054216288.1 E3 SUMO-protein ligase NSE2 isoform X4

UniProtKB/TrEMBL

E5RHW9
XM_054360312.1 → XP_054216287.1 E3 SUMO-protein ligase NSE2 isoform X3
XM_054360305.1 → XP_054216280.1 E3 SUMO-protein ligase NSE2 isoform X1