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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 a 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)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri154 – 23683SP-RING-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

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

GO - Biological processi

  • cell division Source: UniProtKB-KW
  • cellular senescence Source: UniProtKB
  • double-strand break repair via homologous recombination Source: UniProtKB
  • mitotic nuclear division Source: UniProtKB-KW
  • positive regulation of maintenance of mitotic sister chromatid cohesion Source: UniProtKB
  • positive regulation of mitotic metaphase/anaphase transition Source: UniProtKB
  • protein sumoylation Source: Reactome
  • telomere maintenance via recombination Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Cell cycle, Cell division, DNA damage, DNA recombination, DNA repair, Mitosis, Ubl conjugation pathway

Keywords - Ligandi

Metal-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

HGNCiHGNC:26513. NSMCE2.

Subcellular locationi

  • Nucleus 1 Publication
  • Chromosometelomere 1 Publication
  • NucleusPML body 1 Publication

  • Note: Localizes to PML nuclear bodies in ALT cell lines.1 Publication

GO - Cellular componenti

  • chromosome, telomeric region Source: UniProtKB
  • nucleoplasm Source: Reactome
  • nucleus Source: HPA
  • PML body Source: UniProtKB
  • Smc5-Smc6 complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleus, Telomere

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi169 – 1691C → A: Induces a strong decrease in SUMO ligase activity. 1 Publication
Mutagenesisi185 – 1851C → A: Induces a strong decrease in SUMO ligase activity. 1 Publication
Mutagenesisi187 – 1871H → A: Induces a strong decrease in SUMO ligase activity. 1 Publication
Mutagenesisi210 – 2101C → A: Induces a strong decrease in SUMO ligase activity. 1 Publication
Mutagenesisi215 – 2151C → A: Induces a strong decrease in SUMO ligase activity. 1 Publication

Organism-specific databases

PharmGKBiPA142672355.

Polymorphism and mutation databases

BioMutaiNSMCE2.
DMDMi122064623.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 247247E3 SUMO-protein ligase NSE2PRO_0000270939Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineCombined sources
Modified residuei116 – 1161PhosphoserineCombined sources

Post-translational modificationi

Sumoylated, possibly via autosumoylation.2 Publications

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ96MF7.
MaxQBiQ96MF7.
PaxDbiQ96MF7.
PeptideAtlasiQ96MF7.
PRIDEiQ96MF7.

PTM databases

iPTMnetiQ96MF7.

Expressioni

Gene expression databases

BgeeiQ96MF7.
CleanExiHS_NSMCE2.
ExpressionAtlasiQ96MF7. baseline and differential.
GenevisibleiQ96MF7. HS.

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

WithEntry#Exp.IntActNotes
SMC6Q96SB83EBI-2557388,EBI-605415
TXLNAP402223EBI-2557388,EBI-359793

Protein-protein interaction databases

BioGridi130282. 29 interactions.
IntActiQ96MF7. 13 interactions.
STRINGi9606.ENSP00000287437.

Structurei

Secondary structure

1
247
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni170 – 1723Combined sources
Beta strandi177 – 1859Combined sources
Beta strandi188 – 1903Combined sources
Helixi191 – 20212Combined sources
Turni203 – 2053Combined sources
Helixi222 – 2243Combined sources
Beta strandi225 – 2273Combined sources
Helixi229 – 23911Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2YU4NMR-A167-247[»]
ProteinModelPortaliQ96MF7.
SMRiQ96MF7. Positions 161-247.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96MF7.

Family & Domainsi

Sequence similaritiesi

Belongs to the NSE2 family.Curated
Contains 1 SP-RING-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri154 – 23683SP-RING-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG2979. Eukaryota.
COG5627. LUCA.
GeneTreeiENSGT00390000013961.
HOGENOMiHOG000063700.
HOVERGENiHBG082059.
InParanoidiQ96MF7.
OMAiIESKHRR.
PhylomeDBiQ96MF7.
TreeFamiTF324383.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR026846. Nse2(Mms21).
IPR004181. Znf_MIZ.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PANTHERiPTHR21330. PTHR21330. 1 hit.
PfamiPF11789. zf-Nse. 1 hit.
[Graphical view]
PROSITEiPS51044. ZF_SP_RING. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti108 – 1081F → L in BAB71338 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti27 – 271L → F in a breast cancer sample; somatic mutation. 1 Publication
VAR_036327
Natural varianti66 – 661V → A.
Corresponds to variant rs11542104 [ dbSNP | Ensembl ].
VAR_050537

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_005250876.3.
XP_011515276.1. XM_011516974.1.
XP_011515277.1. XM_011516975.1.
UniGeneiHs.388297.

Genome annotation databases

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

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

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_005250876.3.
XP_011515276.1. XM_011516974.1.
XP_011515277.1. XM_011516975.1.
UniGeneiHs.388297.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2YU4NMR-A167-247[»]
ProteinModelPortaliQ96MF7.
SMRiQ96MF7. Positions 161-247.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi130282. 29 interactions.
IntActiQ96MF7. 13 interactions.
STRINGi9606.ENSP00000287437.

PTM databases

iPTMnetiQ96MF7.

Polymorphism and mutation databases

BioMutaiNSMCE2.
DMDMi122064623.

Proteomic databases

EPDiQ96MF7.
MaxQBiQ96MF7.
PaxDbiQ96MF7.
PeptideAtlasiQ96MF7.
PRIDEiQ96MF7.

Protocols and materials databases

DNASUi286053.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi286053.
GeneCardsiNSMCE2.
HGNCiHGNC:26513. NSMCE2.
neXtProtiNX_Q96MF7.
PharmGKBiPA142672355.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2979. Eukaryota.
COG5627. LUCA.
GeneTreeiENSGT00390000013961.
HOGENOMiHOG000063700.
HOVERGENiHBG082059.
InParanoidiQ96MF7.
OMAiIESKHRR.
PhylomeDBiQ96MF7.
TreeFamiTF324383.

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiNSMCE2. human.
EvolutionaryTraceiQ96MF7.
GenomeRNAii286053.
PROiQ96MF7.

Gene expression databases

BgeeiQ96MF7.
CleanExiHS_NSMCE2.
ExpressionAtlasiQ96MF7. baseline and differential.
GenevisibleiQ96MF7. HS.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR026846. Nse2(Mms21).
IPR004181. Znf_MIZ.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PANTHERiPTHR21330. PTHR21330. 1 hit.
PfamiPF11789. zf-Nse. 1 hit.
[Graphical view]
PROSITEiPS51044. ZF_SP_RING. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Skeletal muscle.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Cervix.
  3. "Human MMS21/NSE2 is a SUMO ligase required for DNA repair."
    Potts P.R., Yu H.
    Mol. Cell. Biol. 25:7021-7032(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUMOYLATION, INTERACTION WITH SMC5 AND SMC6, MUTAGENESIS OF CYS-169; CYS-185; HIS-187; CYS-210 AND CYS-215.
  4. "Human SMC5/6 complex promotes sister chromatid homologous recombination by recruiting the SMC1/3 cohesin complex to double-strand breaks."
    Potts P.R., Porteus M.H., Yu H.
    EMBO J. 25:3377-3388(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  5. "The SMC5/6 complex maintains telomere length in ALT cancer cells through SUMOylation of telomere-binding proteins."
    Potts P.R., Yu H.
    Nat. Struct. Mol. Biol. 14:581-590(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  6. "Identification of the proteins, including MAGEG1, that make up the human SMC5-6 protein complex."
    Taylor E.M., Copsey A.C., Hudson J.J., Vidot S., Lehmann A.R.
    Mol. Cell. Biol. 28:1197-1206(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, INTERACTION WITH NSMCE1, IDENTIFICATION IN THE SMC5-SMC6 COMPLEX, SUMOYLATION.
  7. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  8. "SMC5 and MMS21 are required for chromosome cohesion and mitotic progression."
    Behlke-Steinert S., Touat-Todeschini L., Skoufias D.A., Margolis R.L.
    Cell Cycle 8:2211-2218(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  10. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
    Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
    Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  11. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  12. "Toward a comprehensive characterization of a human cancer cell phosphoproteome."
    Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., Mohammed S.
    J. Proteome Res. 12:260-271(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-116, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma and Erythroleukemia.
  13. "Solution structure of the SP-RING domain in non-SMC element 2 homolog (MMS21, S. cerevisiae)."
    RIKEN structural genomics initiative (RSGI)
    Submitted (OCT-2007) to the PDB data bank
    Cited for: STRUCTURE BY NMR OF 168-247.
  14. Cited for: VARIANT [LARGE SCALE ANALYSIS] PHE-27.

Entry informationi

Entry nameiNSE2_HUMAN
AccessioniPrimary (citable) accession number: Q96MF7
Secondary accession number(s): Q8N549
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 9, 2007
Last sequence update: January 9, 2007
Last modified: July 6, 2016
This is version 113 of the entry and version 2 of the sequence. [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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.