Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Mitotic spindle assembly checkpoint protein MAD2B

Gene

MAD2L2

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

Functioni

Adapter protein able to interact with different proteins and involved in different biological processes (PubMed:11459825, PubMed:11459826, PubMed:17719540, PubMed:17296730, PubMed:19443654, PubMed:29656893). Mediates the interaction between the error-prone DNA polymerase zeta catalytic subunit REV3L and the inserter polymerase REV1, thereby mediating the second polymerase switching in translesion DNA synthesis (PubMed:20164194). Translesion DNA synthesis releases the replication blockade of replicative polymerases, stalled in presence of DNA lesions (PubMed:20164194). Component of the shieldin complex, which plays an important role in repair of DNA double-stranded breaks (DSBs) (PubMed:29656893). During G1 and S phase of the cell cycle, the complex functions downstream of TP53BP1 to promote non-homologous end joining (NHEJ) and suppress DNA end resection (PubMed:29656893). Mediates various NHEJ-dependent processes including immunoglobulin class-switch recombination, and fusion of unprotected telomeres (PubMed:29656893). May also regulate another aspect of cellular response to DNA damage through regulation of the JNK-mediated phosphorylation and activation of the transcriptional activator ELK1 (PubMed:17296730). Inhibits the FZR1- and probably CDC20-mediated activation of the anaphase promoting complex APC thereby regulating progression through the cell cycle (PubMed:11459825, PubMed:17719540). Regulates TCF7L2-mediated gene transcription and may play a role in epithelial-mesenchymal transdifferentiation (PubMed:19443654).7 Publications

GO - Molecular functioni

  • JUN kinase binding Source: UniProtKB
  • RNA polymerase II activating transcription factor binding Source: BHF-UCL

GO - Biological processi

  • actin filament organization Source: BHF-UCL
  • cell division Source: UniProtKB-KW
  • DNA damage response, signal transduction resulting in transcription Source: UniProtKB
  • double-strand break repair Source: UniProtKB
  • error-prone translesion synthesis Source: Reactome
  • mitotic spindle assembly checkpoint Source: ProtInc
  • negative regulation of canonical Wnt signaling pathway Source: BHF-UCL
  • negative regulation of cell-cell adhesion mediated by cadherin Source: BHF-UCL
  • negative regulation of DNA binding transcription factor activity Source: BHF-UCL
  • negative regulation of double-strand break repair via homologous recombination Source: UniProtKB
  • negative regulation of epithelial to mesenchymal transition Source: BHF-UCL
  • negative regulation of protein catabolic process Source: UniProtKB
  • negative regulation of transcription by competitive promoter binding Source: BHF-UCL
  • negative regulation of transcription by RNA polymerase II Source: BHF-UCL
  • negative regulation of transcription regulatory region DNA binding Source: BHF-UCL
  • negative regulation of ubiquitin protein ligase activity Source: UniProtKB
  • positive regulation of double-strand break repair via nonhomologous end joining Source: UniProtKB
  • positive regulation of isotype switching Source: UniProtKB
  • positive regulation of peptidyl-serine phosphorylation Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • regulation of cell growth Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW

Keywordsi

Biological processCell cycle, Cell division, DNA damage, DNA repair, Mitosis, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-110312 Translesion synthesis by REV1
R-HSA-5655862 Translesion synthesis by POLK
R-HSA-5656121 Translesion synthesis by POLI
SIGNORiQ9UI95

Names & Taxonomyi

Protein namesi
Recommended name:
Mitotic spindle assembly checkpoint protein MAD2B
Alternative name(s):
Mitotic arrest deficient 2-like protein 2
Short name:
MAD2-like protein 2
REV7 homolog
Short name:
hREV7
Gene namesi
Name:MAD2L2
Synonyms:MAD2B, REV7
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000116670.14
HGNCiHGNC:6764 MAD2L2
MIMi604094 gene
neXtProtiNX_Q9UI95

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, Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Involvement in diseasei

Fanconi anemia, complementation group V (FANCV)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair.
See also OMIM:617243
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07798185V → E in FANCV; drastically reduced protein abundance. 1 PublicationCorresponds to variant dbSNP:rs1057517674Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi63Y → A: Alters interaction with REV3L. Loss of interaction with REV3L; when associated with A-171. 1 Publication1
Mutagenesisi124R → A: Induces structural changes that increase affinity for REV3L and REV1. No effect on interaction with REV1; when associated with A-171. 1 Publication1
Mutagenesisi171W → A: Alters interaction with REV3L and REV1. Loss of interaction with REV3L; when associated with A-63. No effect on interaction with REV1; when associated with A-124. 1 Publication1
Mutagenesisi186L → A: Significantly prevents interaction with REV1; no effect on interaction with REV3L. 1 Publication1
Mutagenesisi200Q → A: Significantly prevents interaction with REV1; no effect on interaction with REV3L. 1 Publication1
Mutagenesisi202Y → A: Significantly prevents interaction with REV1; no effect on interaction with REV3L. 1 Publication1

Keywords - Diseasei

Disease mutation, Fanconi anemia

Organism-specific databases

DisGeNETi10459
MalaCardsiMAD2L2
MIMi617243 phenotype
OpenTargetsiENSG00000116670
PharmGKBiPA398

Polymorphism and mutation databases

BioMutaiMAD2L2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001261191 – 211Mitotic spindle assembly checkpoint protein MAD2BAdd BLAST211

Proteomic databases

EPDiQ9UI95
MaxQBiQ9UI95
PaxDbiQ9UI95
PeptideAtlasiQ9UI95
PRIDEiQ9UI95
ProteomicsDBi84481
TopDownProteomicsiQ9UI95

PTM databases

iPTMnetiQ9UI95
PhosphoSitePlusiQ9UI95

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Gene expression databases

BgeeiENSG00000116670
CleanExiHS_MAD2L2
ExpressionAtlasiQ9UI95 baseline and differential
GenevisibleiQ9UI95 HS

Organism-specific databases

HPAiCAB008110
HPA024176

Interactioni

Subunit structurei

Homooligomer (Probable). Heterodimer with REV3L (PubMed:10660610, PubMed:11485998). This dimer forms the minimal DNA polymerase zeta complex (Pol-zeta2), with REV3L bearing DNA polymerase catalytic activity, although its activity is very low in this context (PubMed:11485998). Component of the tetrameric Pol-zeta complex (Pol-zeta4), which consists of REV3L, MAD2L2, POLD2 and POLD3; Pol-zeta4 is the fully active form of DNA polymerase zeta (PubMed:24449906). Component of the shieldin complex, consisting of SHLD1, SHLD2, SHLD3 and MAD2L2/REV7 (PubMed:29656893). Within the complex, SHLD2 forms a scaffold which interacts with a SHLD3-MAD2L2 subcomplex via its N-terminus, and with SHLD1 via its C-terminus (PubMed:29656893). Interacts with REV1 (PubMed:11485998, PubMed:20164194). Interacts with ADAM9 (PubMed:10527948). Interacts with CHAMP1 (PubMed:21063390). Interacts with FZR1 (in complex with the anaphase promoting complex APC) (PubMed:11459825, PubMed:11459826). Interacts with CDC20; PubMed:11459825 could not detect the interaction (PubMed:11459826). Interacts with RAN (PubMed:19753112). Interacts with ELK1; the interaction is direct and recruits MAD2L2 to ELK1-specific promoters (PubMed:17296730). May interact with the JNK kinases MAPK8 and/or MAPK9 to stimulate ELK1 phosphorylation and transcriptional activity upon DNA damage (PubMed:17296730). Interacts with TCF7L2; prevents its binding to promoters and negatively modulates its transcriptional activity (PubMed:19443654). Interacts with YY1AP1 (PubMed:17541814). Interacts with S.flexneri protein ipaB; prevents the interaction of MAD2L2 with FZR1 and CDC20 resulting in an activation of the anaphase-promoting complex APC and a cell cycle arrest (PubMed:17719540). Interacts with PRCC; the interaction is direct (PubMed:11717438). Interacts with POGZ (PubMed:20850016).Curated16 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • JUN kinase binding Source: UniProtKB
  • RNA polymerase II activating transcription factor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi115722, 67 interactors
CORUMiQ9UI95
IntActiQ9UI95, 54 interactors
MINTiQ9UI95
STRINGi9606.ENSP00000235310

Structurei

Secondary structure

1211
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi13 – 33Combined sources21
Helixi39 – 41Combined sources3
Beta strandi42 – 47Combined sources6
Beta strandi50 – 55Combined sources6
Helixi58 – 76Combined sources19
Beta strandi80 – 88Combined sources9
Beta strandi90 – 92Combined sources3
Beta strandi94 – 103Combined sources10
Turni106 – 111Combined sources6
Helixi115 – 131Combined sources17
Helixi133 – 135Combined sources3
Beta strandi145 – 152Combined sources8
Helixi157 – 163Combined sources7
Beta strandi171 – 173Combined sources3
Helixi176 – 179Combined sources4
Beta strandi182 – 193Combined sources12
Beta strandi198 – 207Combined sources10

3D structure databases

ProteinModelPortaliQ9UI95
SMRiQ9UI95
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UI95

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini13 – 203HORMAPROSITE-ProRule annotationAdd BLAST191

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni21 – 155Mediates interaction with REV1 and REV3L and homodimerizationAdd BLAST135
Regioni150 – 211Mediates interaction with ipaBAdd BLAST62

Phylogenomic databases

eggNOGiKOG3186 Eukaryota
ENOG4111I7Q LUCA
GeneTreeiENSGT00500000044946
HOGENOMiHOG000231083
HOVERGENiHBG052443
InParanoidiQ9UI95
KOiK13728
PhylomeDBiQ9UI95
TreeFamiTF101085

Family and domain databases

Gene3Di3.30.900.10, 1 hit
InterProiView protein in InterPro
IPR003511 HORMA_dom
IPR036570 HORMA_dom_sf
PfamiView protein in Pfam
PF02301 HORMA, 1 hit
SUPFAMiSSF56019 SSF56019, 1 hit
PROSITEiView protein in PROSITE
PS50815 HORMA, 1 hit

Sequencei

Sequence statusi: Complete.

Q9UI95-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTTLTRQDLN FGQVVADVLC EFLEVAVHLI LYVREVYPVG IFQKRKKYNV
60 70 80 90 100
PVQMSCHPEL NQYIQDTLHC VKPLLEKNDV EKVVVVILDK EHRPVEKFVF
110 120 130 140 150
EITQPPLLSI SSDSLLSHVE QLLRAFILKI SVCDAVLDHN PPGCTFTVLV
160 170 180 190 200
HTREAATRNM EKIQVIKDFP WILADEQDVH MHDPRLIPLK TMTSDILKMQ
210
LYVEERAHKG S
Length:211
Mass (Da):24,334
Last modified:January 11, 2001 - v2
Checksum:i1DE6353EF7D650B9
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti17D → A in AAD30290 (PubMed:10366450).Curated1
Sequence conflicti96E → D in AAF20267 (Ref. 2) Curated1
Sequence conflicti199M → V in AAF20267 (Ref. 2) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07798185V → E in FANCV; drastically reduced protein abundance. 1 PublicationCorresponds to variant dbSNP:rs1057517674Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF072933 mRNA Translation: AAD41647.1
AF080398 mRNA Translation: AAF20267.1
AF139365 mRNA Translation: AAD30290.1
AF157482 mRNA Translation: AAF34357.1
AK027327 mRNA Translation: BAG51305.1
AK094316 mRNA Translation: BAG52858.1
DQ017900 Genomic DNA Translation: AAY26393.1
AL031731 Genomic DNA No translation available.
CH471130 Genomic DNA Translation: EAW71697.1
BC015244 mRNA Translation: AAH15244.1
CCDSiCCDS134.1
RefSeqiNP_001120797.1, NM_001127325.1
NP_006332.3, NM_006341.3
XP_011538809.1, XM_011540507.1
UniGeneiHs.19400

Genome annotation databases

EnsembliENST00000235310; ENSP00000235310; ENSG00000116670
ENST00000376667; ENSP00000365855; ENSG00000116670
ENST00000376692; ENSP00000365882; ENSG00000116670
GeneIDi10459
KEGGihsa:10459
UCSCiuc001asp.4 human

Similar proteinsi

Entry informationi

Entry nameiMD2L2_HUMAN
AccessioniPrimary (citable) accession number: Q9UI95
Secondary accession number(s): B3KNE3
, Q5TGW7, Q9UNA7, Q9Y6I6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: January 11, 2001
Last modified: July 18, 2018
This is version 156 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 1
    Human chromosome 1: 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

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health