Glomulin (GLMN)
The protein contains 594 amino acids for an estimated molecular weight of 68208 Da.
Regulatory component of cullin-RING-based SCF (SKP1-Cullin-F-box protein) E3 ubiquitin-protein ligase complexes (PubMed:22405651, PubMed:22748924). Inhibits E3 ubiquitin ligase activity by binding to RBX1 (via RING domain) and inhibiting its interaction with the E2 ubiquitin-conjugating enzyme CDC34 (PubMed:22405651, PubMed:22748924). Inhibits RBX1-mediated neddylation of CUL1 (PubMed:22405651). Required for normal stability and normal cellular levels of key components of SCF ubiquitin ligase complexes, including FBXW7, RBX1, CUL1, CUL2, CUL3, CUL4A, and thereby contributes to the regulation of CCNE1 and MYC levels (By similarity). Essential for normal development of the vasculature (PubMed:11845407). Contributes to the regulation of RPS6KB1 phosphorylation (PubMed:11571281). (updated: Dec. 11, 2019)
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.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- 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.
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)
| Variant | Description |
|---|---|
| dbSNP:rs35258161 |
Biological Process
Cell surface receptor signaling pathway
Muscle cell differentiation
Negative regulation of cell population proliferation
Negative regulation of protein ubiquitination
Negative regulation of T cell proliferation
Neural tube closure
Positive regulation of cytokine production
Positive regulation of cytokine secretion
Positive regulation of interleukin-2 biosynthetic process
Positive regulation of interleukin-2 production
Positive regulation of phosphorylation
Regulation of gene expression, epigenetic
Regulation of proteasomal ubiquitin-dependent protein catabolic process
Vasculogenesis
The reference OMIM entry for this protein is 138000
Glomuvenous malformations; gvm
Venous malformations with glomus cells; vmglom
Glomus tumors, multiple
Glomangiomas, multiple
A number sign (#) is used with this entry because glomuvenous malformations can be caused by heterozygous mutation in the glomulin gene (601749) on chromosome 1p22.
CLINICAL FEATURES
Glomuvenous malformations, also known as 'venous malformations with glomus cells' or glomangiomas, are similar to mucocutaneous venous malformations (VMCM; 600195), but clinically are distinguishable: they have a cobble-stone appearance, they have a consistency harder than that of venous malformations, and they are painful on palpation (Brouillard et al., 2002). Histologically, GVMs are distinguishable by the presence of pathognomonic rounded cells (glomus cells) around the distended vein-like channels. The term glomus (Latin for ball) stems from the morphologically similar contractile cells of the Sucquet-Hoyer arteriovenous anastomoses in glomus bodies that are involved in cutaneous thermoregulation. Glomus cells in GVMs appear to be incompletely or improperly differentiated vascular smooth muscle cells, since they stain positively with smooth muscle cell alpha-actin (102620) and vimentin (193060). The genetic distinctness of glomuvenous malformations from mucocutaneous venous malformations is indicated by the fact that mutations have been found in the TIE2/TEK gene (600221) in mucocutaneous venous malformations and not in glomuvenous malformations. Glomus tumors are benign cutaneous neoplasms that are derived from specialized arteriovenous shunts that occur normally in many parts of the body. Gorlin et al. (1960) reported 5 affected members in 2 generations of a family. The lesions tend to resemble cavernous hemangiomas. The distinctive feature is the presence of multiple layers of glomus cells lining the blood-filled cavities. The tumors are present at birth or appear in the first 2 decades. Isolated glomus tumor usually develops later (at about age 33 years on the average), is more frequently subungual than is the case with multiple tumors, and has no particular familial occurrence. Reed (1970) presented a pedigree of 4 persons with multiple glomus tumors in 2 generations. Beasley et al. (1986) reported 4 cases in 3 generations. The 9-year-old proposita had had 6 soft, blue-black skin lesions from birth, on the forearm, thigh, and buttocks. All but one were raised. As pointed out by Boon et al. (1999), glomus tumors, or glomangiomas, are a clinical and radiologic subtype of venous malformations. Their pathognomonic characteristic is the presence of undifferentiated smooth muscle cells (glomus cells) surrounding convoluted venous channels. Although clinically they look like any venous malformation, they are more painful on palpation, only partially compressible, and usually not found in mucosa. In addition, familial aggregation is more common than in venous malformations generally, and several pedigrees showing autosomal dominant inheritance have been reported. Iqbal et al. (1998) estimated that penetrance rises from 70% at age 5 years to 100% by age 30 years.INHERITANCE
The inheritance of the cutaneous disorder discussed here is uncomplicated autosomal dominant with many instances of male-to-male transmission. It is not to be confused with multiple paragangliomata (168000), which is often referred to as glomus tumors.MAPPING
Boon et al. (1999) demonstrated that 5 families with inherited cutaneous venous malformations with glomus cells showed linkage to 1p22-p21 (lod score = 12.7 at recombination fraction = 0.00). They ... More on the omim web site
Jan. 22, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
Nov. 16, 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
Oct. 27, 2017: Protein entry updated
Automatic update: model status changed
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 138000 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed