E3 ubiquitin-protein ligase KCMF1 (KCMF1)
The protein contains 381 amino acids for an estimated molecular weight of 41945 Da.
Has intrinsic E3 ubiquitin ligase activity and promotes ubiquitination. (updated: March 4, 2015)
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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
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.
This protein is annotated as membranous in Gene Ontology.
(right-click above to access to more options from the contextual menu)
Cellular Component
Cytosol
Extracellular region
Ficolin-1-rich granule lumen
Plasma membrane
Synapse
The reference OMIM entry for this protein is 614719
Potassium channel modulatory factor 1; kcmf1
Differentially expressed in branching tubulogenesis 91; debt91
Basic fibroblast growth factor-induced gene in gastric cancer; figc
CLONING
Li et al. (2003) cloned 2 splice variants of mouse Kcmf1, which they called Debt91, from a mouse heart cDNA library. The deduced proteins contain 331 and 381 amino acids and differ at their N termini. The full-length protein is serine and threonine rich and has a cysteine- and histidine-rich N terminus that is predicted to form zinc fingers. It also has a bipartite nuclear localization signal, 3 possible glycosylation sites, and multiple potential phosphorylation sites. Northern blot analysis detected 2 transcripts in adult mouse heart, skeletal muscle, and kidney, but only the smaller transcript was expressed in liver and testis. No significant expression was detected in brain, spleen, and lung. The smaller transcript was highly expressed throughout mouse embryonic development, with high expression after day 15. Database analysis revealed high conservation of the DEBT91 protein among human, mouse, fly, snail, and worm, particularly at the N-terminal end. By differential screening for basic FGF (FGF2; 134920)-inducible genes in SNU-16 gastric cancer cells, followed by 5-prime and 3-prime RACE of a brain cDNA library, Jang (2004) cloned human KCMF1, which he called FIGC. The deduced 381-amino acid protein has a calculated molecular mass of 42 kD. It has an N-terminal C6H2-type RING finger domain and a proline-rich C terminus. The ring finger domain of FIGC has an acidic-rich spacer region. Northern blot analysis detected FIGC expression in human spleen, small intestine, ovary, peripheral blood, lung, skeletal muscle, kidney, and pancreas, with much lower expression in thymus, prostate, testis, colon, heart, brain, placenta, and liver.GENE FUNCTION
Jang (2004) found that basic FGF induced expression of FIGC in SNU-16 human gastric cancer cells. Recombinant FIGC functioned as a ubiquitin-protein ligase in the presence of ATP, ubiquitin (191339), recombinant rabbit E1 (see 314370), and the E2 enzyme UBCH5B (602962), resulting in FIGC polyubiquitination. Beilke et al. (2010) observed upregulated nuclear KCMF1 expression in pancreatic cancers and several other adenocarcinomas. Overexpression of KCMF1 in HEK293 cells resulted in elevated cell proliferation, migration, and formation of tumor nodules in vivo.MAPPING
Hartz (2012) mapped the KCMF1 gene to chromosome 2p11.2 based on the alignment of the KCMF1 sequence (GenBank GENBANK AF155652) with the genomic sequence (GRCh37). Li et al. (2003) mapped the mouse Kcmf1 gene to a region of chromosome 6 that shares homology of synteny with human chromosome 2p11.2.ANIMAL MODEL
Beilke et al. (2010) developed a line of mice with reduced Kcmf1 expression. Knockdown of Kcmf1 reduced development of TGF-alpha (TGFA; 190170)-dependent tumors compared with controls. ... More on the omim web site
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 614719 was added.