MMS19 nucleotide excision repair protein homolog (MMS19)
The protein contains 1030 amino acids for an estimated molecular weight of 113290 Da.
Key component of the cytosolic iron-sulfur protein assembly (CIA) complex, a multiprotein complex that mediates the incorporation of iron-sulfur cluster into apoproteins specifically involved in DNA metabolism and genomic integrity (PubMed:29848660). In the CIA complex, MMS19 acts as an adapter between early-acting CIA components and a subset of cellular target iron-sulfur proteins such as ERCC2/XPD, FANCJ and RTEL1, thereby playing a key role in nucleotide excision repair (NER), homologous recombination-mediated double-strand break DNA repair, DNA replication and RNA polymerase II (POL II) transcription (PubMed:22678362, PubMed:22678361, PubMed:29225034, PubMed:23585563). As part of the mitotic spindle-associated MMXD complex, plays a role in chromosome segregation, probably by facilitating iron-sulfur (Fe-S) cluster assembly into ERCC2/XPD (PubMed:20797633). Together with CIAO2, facilitates the transfer of Fe-S clusters to the motor protein KIF4A, which ensures proper localization of KIF4A to mitotic machinery components to promote the progression of mitosis (PubMed:29848660). Indirectly acts as a transcriptional coactivator of estrogen receptor (ER), via its role in iron-sulfur insertion into some component of the TFIIH-machinery (PubMed:11279242). (updated: June 17, 2020)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
(right-click above to access to more options from the contextual menu)
Biological Process
Cellular response to DNA damage stimulus
Chromosome segregation
DNA metabolic process
DNA repair
Iron-sulfur cluster assembly
Nucleotide-excision repair
Phosphorelay signal transduction system
Positive regulation of double-strand break repair via homologous recombination
Positive regulation of transcription, DNA-templated
Protein maturation by iron-sulfur cluster transfer
Response to hormone
Small molecule metabolic process
Transcription, DNA-templated
The reference OMIM entry for this protein is 614777
Mms19 nucleotide excision repair, s. cerevisiae, homolog of; mms19
Mms19-like protein; mms19l
DESCRIPTION
MMS19 has a critical role in the biogenesis of multiple Fe-S proteins that function in genomic stability, RNA polymerase II function, and telomere length regulation (Stehling et al., 2012; Gari et al., 2012).CLONING
By searching databases for sequences similar to S. cerevisiae Mms19, followed by RT-PCR and screening of a HeLa cell cDNA library, Seroz et al. (2000) cloned MMS19. The deduced 1,030-amino acid protein has a calculated molecular mass of 113 kD. MMS19 has an alanine- and leucine-rich N terminus and several putative phosphorylation sites. Northern blot analysis detected a 4-kb transcript in HeLa cells and in all mouse tissues examined, with highest expression in testis. By RT-PCR of HeLa cells and testis cDNA libraries, and 5-prime RACE, Queimado et al. (2001) cloned 7 splice variants of MMS19. Two major transcripts differ in their 5-prime UTRs and encode an identical full-length protein of 1,030 amino acids. Other transcripts differ in splicing of 5-prime exons and encode proteins that are 43, 158, or 201 amino acids shorter at their N-terminal ends. Full-length MMS19 contains 2 conserved globular domains. The N-terminal globular domain has a highly conserved sequence of about 120 amino acids; a shorter globular region at the C terminus contains 4 tightly spaced HEAT repeats that are predicted to form tandem bihelical structures and function as scaffolds for assembly of other protein subunits. Northern blot analysis detected variable expression of major transcripts at 3.9 and 4.8 in all human tissues examined. Each band appeared to be a heterogeneous collection of alternatively spliced forms, and the difference in size appeared to be due to use of alternate polyadenylation signals. Queimado et al. (2001) also cloned Mms19 splice variants from mouse. The deduced full-length mouse protein contains 1,031 amino acids and shares 90% sequence identity with full-length human MMS19. Wu et al. (2001) independently cloned MMS19 from a placenta cDNA library. The deduced protein contains 1,030 amino acids. Northern blot analysis detected a 4-kb MMS19 transcript in all cancer cell lines and human tissues examined. Immunofluorescence analysis localized MMS19 to the nucleus of HeLa cells. Hatfield et al. (2006) identified 3 conserved domains in the full-length MMS19 protein, which they called domains A, B, and C. The approximately 160-amino acid N-terminal A domain is followed immediately by the B domain with 2 highly conserved motifs; the C domain constitutes the C-terminal HEAT repeats. Alternative splicing deletes the A domain and/or motif 1 of the B domain. Hatfield et al. (2006) also identified MMS19 splice variants that lack exon 24, in addition to various other 5-prime exons, and these transcripts encode 3 different proteins lacking domain C. RT-PCR detected transcripts lacking exon 24 in all normal tissues examined; however, full-length MMS19 represented 80 to 90% of all MMS19 transcripts.GENE FUNCTION
By coimmunoprecipitation of HeLa cell lysates, Seroz et al. (2000) found that MMS19 interacted specifically with the transcription factor IIH (TFIIH) helicase subunits XPB (ERCC3; 133510) and XPD (ERCC2; 126340). Queimado et al. (2001) found that expression of MMS19 complemented ultraviolet (UV) radiation sensitivity and thermosensitivity, but not methionine auxotrophy, in Mms19 mutant yeast. Using yeast 2-hybrid analysis, Wu et al. (2001) found that the basic helix-loop-helix (bHLH)-PAS ... More on the omim web site
June 29, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Dec. 10, 2018: Protein entry updated
Automatic update: model status changed
Nov. 16, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
April 12, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 614777 was added.