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Protein

Non-structural maintenance of chromosomes element 3 homolog

Gene

NSMCE3

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

Functioni

Component of the SMC5-SMC6 complex, a complex involved in repair of DNA double-strand breaks by homologous recombination (PubMed:20864041, PubMed:27427983). 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). In vitro enhances ubiquitin ligase activity of NSMCE1. Proposed to act through recruitment and/or stabilization of the Ubl-conjugating enzyme (E2) at the E3:substrate complex (PubMed:20864041). May be a growth suppressor that facilitates the entry of the cell into cell cycle arrest (By similarity).By similarity2 Publications

GO - Molecular functioni

  • protein dimerization activity Source: UniProtKB

GO - Biological processi

  • cellular response to hydroxyurea Source: UniProtKB
  • cellular response to radiation Source: UniProtKB
  • cellular response to UV Source: UniProtKB
  • DNA recombination Source: UniProtKB-KW
  • DNA repair Source: UniProtKB
  • positive regulation of protein ubiquitination Source: UniProtKB
  • regulation of growth Source: UniProtKB-KW

Keywordsi

Molecular functionTumor antigen
Biological processDNA damage, DNA recombination, DNA repair, Growth regulation, Ubl conjugation pathway

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Non-structural maintenance of chromosomes element 3 homolog
Short name:
Non-SMC element 3 homolog
Alternative name(s):
Hepatocellular carcinoma-associated protein 4
MAGE-G1 antigen
Melanoma-associated antigen G1
Necdin-like protein 2
Gene namesi
Name:NSMCE3Imported
Synonyms:HCA4, MAGEG1, NDNL2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:7677. NSMCE3.

Subcellular locationi

GO - Cellular componenti

  • chromosome, telomeric region Source: UniProtKB-SubCell
  • cytoplasm Source: UniProtKB-SubCell
  • nucleoplasm Source: Reactome
  • Smc5-Smc6 complex Source: UniProtKB

Keywords - Cellular componenti

Chromosome, Cytoplasm, Nucleus, Telomere

Pathology & Biotechi

Involvement in diseasei

Lung disease, immunodeficiency, and chromosome breakage syndrome (LICS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive chromosome breakage syndrome associated with severe, fatal lung disease in early childhood, following viral pneumonia. LICS is characterized by combined T and B-cell immunodeficiency. Some patients may have mild dysmorphic features.
See also OMIM:617241
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_078021209P → L in LICS; creates novel endoproteolytic cleavage sites compared to wild-type; loss of interaction with NSMCE4; loss of interaction with NSMCE1. 1 Publication1
Natural variantiVAR_078022264L → F in LICS; no loss of protein stability; loss of interaction with NSMCE4; decreased interaction with NSMCE1; decreased association with the SMC5-SMC6 complex; decreased DNA repair. 1 PublicationCorresponds to variant dbSNP:rs199905054Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi96 – 97LL → AA: Decreases interaction with NSMCE1, no effect on interaction with NSMCE4A, abolishes in vitro promotion of NSMCE1 ubiquitin ligase activity. 1 Publication2
Mutagenesisi180M → A: Abolishes interaction with EID3. 1 Publication1
Mutagenesisi181I → A: Abolishes interaction with EID3. 1 Publication1
Mutagenesisi185L → A: Abolishes interaction with EID3. 1 Publication1
Mutagenesisi266F → A: Abolishes interaction with EID3. 1 Publication1
Mutagenesisi270V → A: Abolishes interaction with EID3. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi56160.
MIMi617241. phenotype.
OpenTargetsiENSG00000185115.
PharmGKBiPA31480.

Polymorphism and mutation databases

BioMutaiNDNL2.
DMDMi46396494.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001567331 – 304Non-structural maintenance of chromosomes element 3 homologAdd BLAST304

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei57PhosphoserineCombined sources1
Modified residuei60PhosphoserineCombined sources1
Modified residuei64PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ96MG7.
MaxQBiQ96MG7.
PaxDbiQ96MG7.
PeptideAtlasiQ96MG7.
PRIDEiQ96MG7.

PTM databases

iPTMnetiQ96MG7.
PhosphoSitePlusiQ96MG7.

Miscellaneous databases

PMAP-CutDBiQ96MG7.

Expressioni

Tissue specificityi

Ubiquitous.1 Publication

Gene expression databases

BgeeiENSG00000185115.
CleanExiHS_NDNL2.
GenevisibleiQ96MG7. HS.

Interactioni

Subunit structurei

Component of the SMC5-SMC6 complex which consists at least of SMC5, SMC6, NSMCE2, NSMCE1, NSMCE4A or EID3 and NSMCE3. NSMCE1, NSMCE4A or EID3 and NSMCE3 probably form a subcomplex that bridges the head domains of the SMC5:SMC6 heterodimer (PubMed:18086888). Interacts with PJA1 (PubMed:20864041). Interacts with E2F1 (via C-terminus) (By similarity). Interacts with NGFR (via C-terminus) (By similarity). Interacts with NSMCE1 (PubMed:18086888, PubMed:21364888, PubMed:20864041, PubMed:27427983). Interacts with NSMCE4 (PubMed:20864041, PubMed:27427983). Interacts with SMC6 (PubMed:18086888). Interacts with EID3 (PubMed:21364888).By similarity4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • protein dimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi121094. 19 interactors.
IntActiQ96MG7. 6 interactors.
MINTiMINT-2814584.
STRINGi9606.ENSP00000330694.

Structurei

Secondary structure

1304
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi82 – 102Combined sources21
Helixi108 – 114Combined sources7
Helixi117 – 122Combined sources6
Helixi123 – 138Combined sources16
Beta strandi140 – 146Combined sources7
Beta strandi150 – 156Combined sources7
Turni166 – 169Combined sources4
Helixi174 – 188Combined sources15
Turni189 – 191Combined sources3
Helixi195 – 204Combined sources10
Helixi220 – 230Combined sources11
Beta strandi232 – 236Combined sources5
Beta strandi247 – 249Combined sources3
Helixi252 – 255Combined sources4
Helixi260 – 271Combined sources12
Beta strandi275 – 277Combined sources3
Helixi278 – 293Combined sources16

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5HVQX-ray2.92D78-294[»]
5WY5X-ray2.92B78-294[»]
ProteinModelPortaliQ96MG7.
SMRiQ96MG7.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96MG7.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini85 – 285MAGEPROSITE-ProRule annotationAdd BLAST201

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni78 – 304Interaction with NSMCE1Add BLAST227

Phylogenomic databases

eggNOGiKOG4562. Eukaryota.
ENOG4111S70. LUCA.
GeneTreeiENSGT00760000118824.
HOGENOMiHOG000231161.
HOVERGENiHBG006315.
InParanoidiQ96MG7.
OMAiQWGPRTN.
OrthoDBiEOG091G0TJ0.
PhylomeDBiQ96MG7.
TreeFamiTF328505.

Family and domain databases

InterProiView protein in InterPro
IPR002190. MHD_dom.
PfamiView protein in Pfam
PF01454. MAGE. 1 hit.
SMARTiView protein in SMART
SM01373. MAGE. 1 hit.
PROSITEiView protein in PROSITE
PS50838. MAGE. 1 hit.

Sequencei

Sequence statusi: Complete.

Q96MG7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLQKPRNRGR SGGQAERDRD WSHSGNPGAS RAGEDARVLR DGFAEEAPST
60 70 80 90 100
SRGPGGSQGS QGPSPQGARR AQAAPAVGPR SQKQLELKVS ELVQFLLIKD
110 120 130 140 150
QKKIPIKRAD ILKHVIGDYK DIFPDLFKRA AERLQYVFGY KLVELEPKSN
160 170 180 190 200
TYILINTLEP VEEDAEMRGD QGTPTTGLLM IVLGLIFMKG NTIKETEAWD
210 220 230 240 250
FLRRLGVYPT KKHLIFGDPK KLITEDFVRQ RYLEYRRIPH TDPVDYEFQW
260 270 280 290 300
GPRTNLETSK MKVLKFVAKV HNQDPKDWPA QYCEALADEE NRARPQPSGP

APSS
Length:304
Mass (Da):34,308
Last modified:December 1, 2001 - v1
Checksum:iC00E2FB2D2CCED7B
GO

Sequence cautioni

The sequence BAB84964 differs from that shown. Reason: Frameshift at position 290.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_078021209P → L in LICS; creates novel endoproteolytic cleavage sites compared to wild-type; loss of interaction with NSMCE4; loss of interaction with NSMCE1. 1 Publication1
Natural variantiVAR_078022264L → F in LICS; no loss of protein stability; loss of interaction with NSMCE4; decreased interaction with NSMCE1; decreased association with the SMC5-SMC6 complex; decreased DNA repair. 1 PublicationCorresponds to variant dbSNP:rs199905054Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF490510 mRNA. Translation: AAM08357.1.
AK056957 mRNA. Translation: BAB71325.1.
BC041166 mRNA. Translation: AAH41166.2.
BC053999 mRNA. Translation: AAH53999.1.
AK074138 mRNA. Translation: BAB84964.1. Frameshift.
AF320911 Genomic DNA. Translation: AAG38607.1.
CCDSiCCDS10023.1.
RefSeqiNP_619649.1. NM_138704.3.
UniGeneiHs.94011.

Genome annotation databases

EnsembliENST00000332303; ENSP00000330694; ENSG00000185115.
ENST00000631973; ENSP00000487893; ENSG00000282130.
GeneIDi56160.
KEGGihsa:56160.
UCSCiuc001zco.4. human.

Similar proteinsi

Entry informationi

Entry nameiNSE3_HUMAN
AccessioniPrimary (citable) accession number: Q96MG7
Secondary accession number(s): Q8IW16, Q8TEI6, Q9H214
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: December 1, 2001
Last modified: August 30, 2017
This is version 132 of the entry and version 1 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 15
    Human chromosome 15: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references