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Protein

E3 SUMO-protein ligase NSE2

Gene

NSMCE2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

E3 SUMO-protein ligase component of the SMC5-SMC6 complex, a complex involved in DNA double-strand break repair by homologous recombination. Is not be required for the stability of the complex. The complex may promote sister chromatid homologous recombination by recruiting the SMC1-SMC3 cohesin complex to double-strand breaks. The complex is required for telomere maintenance via recombination in ALT (alternative lengthening of telomeres) cell lines and mediates sumoylation of shelterin complex (telosome) components which is proposed to lead to shelterin complex disassembly in ALT-associated PML bodies (APBs). Acts as an E3 ligase mediating SUMO attachment to various proteins such as SMC6L1 and TRAX, the shelterin complex subunits TERF1, TERF2, TINF2 and TERF2IP, and maybe the cohesin components RAD21 and STAG2. Required for recruitment of telomeres to PML nuclear bodies. SUMO protein-ligase activity is required for the prevention of DNA damage-induced apoptosis by facilitating DNA repair, and for formation of APBs in ALT cell lines. Required for sister chromatid cohesion during prometaphase and mitotic progression.4 Publications

Pathwayi: protein sumoylation

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

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri154 – 236SP-RING-typePROSITE-ProRule annotationAdd BLAST83

GO - Molecular functioni

  • ligase activity Source: UniProtKB-KW
  • SUMO transferase activity Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • cell cycle Source: UniProtKB-KW
  • cell division Source: UniProtKB-KW
  • cellular senescence Source: UniProtKB
  • double-strand break repair via homologous recombination Source: UniProtKB
  • positive regulation of maintenance of mitotic sister chromatid cohesion Source: UniProtKB
  • positive regulation of mitotic metaphase/anaphase transition Source: UniProtKB
  • telomere maintenance via recombination Source: UniProtKB

Keywordsi

Molecular functionLigase
Biological processCell cycle, Cell division, DNA damage, DNA recombination, DNA repair, Mitosis, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-3108214. SUMOylation of DNA damage response and repair proteins.
UniPathwayiUPA00886.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 SUMO-protein ligase NSE2 (EC:6.3.2.-)
Alternative name(s):
MMS21 homolog
Short name:
hMMS21
Non-structural maintenance of chromosomes element 2 homolog
Short name:
Non-SMC element 2 homolog
Gene namesi
Name:NSMCE2
Synonyms:C8orf36, MMS21
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000156831.7.
HGNCiHGNC:26513. NSMCE2.

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

Keywords - Cellular componenti

Chromosome, Nucleus, Telomere

Pathology & Biotechi

Involvement in diseasei

Seckel syndrome 10 (SCKL10)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of Seckel syndrome, a rare autosomal recessive disorder characterized by proportionate dwarfism of prenatal onset associated with low birth weight, growth retardation, severe microcephaly with a bird-headed like appearance, and mental retardation.
See also OMIM:617253

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi169C → A: Induces a strong decrease in SUMO ligase activity. 1 Publication1
Mutagenesisi185C → A: Induces a strong decrease in SUMO ligase activity. 1 Publication1
Mutagenesisi187H → A: Induces a strong decrease in SUMO ligase activity. 1 Publication1
Mutagenesisi210C → A: Induces a strong decrease in SUMO ligase activity. 1 Publication1
Mutagenesisi215C → A: Induces a strong decrease in SUMO ligase activity. 1 Publication1

Keywords - Diseasei

Dwarfism, Mental retardation

Organism-specific databases

DisGeNETi286053.
MalaCardsiNSMCE2.
MIMi617253. phenotype.
OpenTargetsiENSG00000156831.
PharmGKBiPA142672355.

Polymorphism and mutation databases

BioMutaiNSMCE2.
DMDMi122064623.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002709391 – 247E3 SUMO-protein ligase NSE2Add BLAST247

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Cross-linki90Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki107Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei116PhosphoserineCombined sources1
Cross-linki125Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki130Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Post-translational modificationi

Sumoylated, possibly via autosumoylation.2 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ96MF7.
MaxQBiQ96MF7.
PaxDbiQ96MF7.
PeptideAtlasiQ96MF7.
PRIDEiQ96MF7.

PTM databases

iPTMnetiQ96MF7.
PhosphoSitePlusiQ96MF7.

Expressioni

Gene expression databases

BgeeiENSG00000156831.
CleanExiHS_NSMCE2.
ExpressionAtlasiQ96MF7. baseline and differential.
GenevisibleiQ96MF7. HS.

Organism-specific databases

HPAiHPA051614.
HPA065734.

Interactioni

Subunit structurei

Component of the SMC5-SMC6 complex which consists at least of SMC5, SMC6, NSMCE2, NSMCE1, NSMCE4A or EID3 and NSMCE3.1 Publication

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi130282. 29 interactors.
IntActiQ96MF7. 15 interactors.
STRINGi9606.ENSP00000287437.

Structurei

Secondary structure

1247
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni170 – 172Combined sources3
Beta strandi177 – 185Combined sources9
Beta strandi188 – 190Combined sources3
Helixi191 – 202Combined sources12
Turni203 – 205Combined sources3
Helixi222 – 224Combined sources3
Beta strandi225 – 227Combined sources3
Helixi229 – 239Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2YU4NMR-A167-247[»]
ProteinModelPortaliQ96MF7.
SMRiQ96MF7.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96MF7.

Family & Domainsi

Sequence similaritiesi

Belongs to the NSE2 family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri154 – 236SP-RING-typePROSITE-ProRule annotationAdd BLAST83

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG2979. Eukaryota.
COG5627. LUCA.
GeneTreeiENSGT00390000013961.
HOGENOMiHOG000063700.
HOVERGENiHBG082059.
InParanoidiQ96MF7.
OMAiMIESKHR.
OrthoDBiEOG091G11GG.
PhylomeDBiQ96MF7.
TreeFamiTF324383.

Family and domain databases

CDDicd16651. SPL-RING_NSE2. 1 hit.
Gene3Di3.30.40.10. 1 hit.
InterProiView protein in InterPro
IPR026846. Nse2(Mms21).
IPR004181. Znf_MIZ.
IPR013083. Znf_RING/FYVE/PHD.
PANTHERiPTHR21330. PTHR21330. 1 hit.
PfamiView protein in Pfam
PF11789. zf-Nse. 1 hit.
PROSITEiView protein in PROSITE
PS51044. ZF_SP_RING. 1 hit.

Sequencei

Sequence statusi: Complete.

Q96MF7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPGRSSSNSG STGFISFSGV ESALSSLKNF QACINSGMDT ASSVALDLVE
60 70 80 90 100
SQTEVSSEYS MDKAMVEFAT LDRQLNHYVK AVQSTINHVK EERPEKIPDL
110 120 130 140 150
KLLVEKKFLA LQSKNSDADF QNNEKFVQFK QQLKELKKQC GLQADREADG
160 170 180 190 200
TEGVDEDIIV TQSQTNFTCP ITKEEMKKPV KNKVCGHTYE EDAIVRMIES
210 220 230 240
RQKRKKKAYC PQIGCSHTDI RKSDLIQDEA LRRAIENHNK KRHRHSE
Length:247
Mass (Da):27,932
Last modified:January 9, 2007 - v2
Checksum:i24D945C8F16F58F8
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti108F → L in BAB71338 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03632727L → F in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_05053766V → A. Corresponds to variant dbSNP:rs11542104Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK057002 mRNA. Translation: BAB71338.1.
BC032797 mRNA. Translation: AAH32797.1.
CCDSiCCDS6356.1.
RefSeqiNP_775956.1. NM_173685.2.
XP_005250932.1. XM_005250875.2.
XP_005250933.1. XM_005250876.4.
XP_011515276.1. XM_011516974.2.
XP_011515277.1. XM_011516975.1.
XP_016868820.1. XM_017013331.1.
UniGeneiHs.388297.

Genome annotation databases

EnsembliENST00000287437; ENSP00000287437; ENSG00000156831.
ENST00000522563; ENSP00000430668; ENSG00000156831.
GeneIDi286053.
KEGGihsa:286053.
UCSCiuc003yrw.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNSE2_HUMAN
AccessioniPrimary (citable) accession number: Q96MF7
Secondary accession number(s): Q8N549
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 9, 2007
Last sequence update: January 9, 2007
Last modified: September 27, 2017
This is version 122 of the entry and version 2 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families