STAM-binding protein (STAMBP)
The protein contains 424 amino acids for an estimated molecular weight of 48077 Da.
Zinc metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains. Does not cleave 'Lys-48'-linked polyubiquitin chains (By similarity). Plays a role in signal transduction for cell growth and MYC induction mediated by IL-2 and GM-CSF. Potentiates BMP (bone morphogenetic protein) signaling by antagonizing the inhibitory action of SMAD6 and SMAD7. Has a key role in regulation of cell surface receptor-mediated endocytosis and ubiquitin-dependent sorting of receptors to lysosomes. Endosomal localization of STAMBP is required for efficient EGFR degradation but not for its internalization (By similarity). Involved in the negative regulation of PI3K-AKT-mTOR and RAS-MAP signaling pathways. (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.
- 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.
- 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.
Biological Process
Mitotic cytokinesis
Negative regulation of neuron apoptotic process
Negative regulation of phosphatidylinositol 3-kinase signaling
Negative regulation of Ras protein signal transduction
Positive regulation of cell population proliferation
Protein deubiquitination
Protein K63-linked deubiquitination
Receptor signaling pathway via JAK-STAT
The reference OMIM entry for this protein is 606247
Stam-binding protein; stambp
Associated molecule with the sh3 domain of stam; amsh
DESCRIPTION
The STAMBP gene encodes a deubiquitinating (DUB) isopeptidase that has a key role in cell surface receptor-mediated endocytosis and sorting (summary by McDonell et al., 2013).CLONING
Signal-transducing adaptor molecule (STAM; 601899) acts downstream of interleukin-2 (IL2; 147680)-induced signaling through JAK3 (600173). It also interacts with JAK2 (147796) after granulocyte-macrophage colony-stimulating factor (GMCSF; 138960) stimulation. STAM contains an SH3 domain that is required for induction of MYC (190080) and cell growth. By Far Western screening of an activated peripheral blood leukocyte cDNA library to identify cDNAs binding to the SH3 domain of STAM, Tanaka et al. (1999) obtained a cDNA encoding AMSH. The deduced 424-amino acid protein contains 2 potential SH3-binding domains (PxxP motifs), a JAB1 (604850) subdomain homologous (JSH) region, and a putative bipartite nuclear localization signal. Northern blot analysis revealed ubiquitous expression of a 2.1-kb AMSH transcript. Using in situ hybridization and Northern blot analysis, Ishii et al. (2001) observed that Amsh was expressed diffusely in both mantle and ventricular layers throughout the mouse brain at embryonic day 14. By postnatal day 10, Amsh expression was localized to the olfactory bulb, cerebral cortex, hippocampus, and cerebellum. In transfected COS-7 cells, Kikuchi et al. (2003) found that fluorescence-tagged AMSH was expressed diffusely in the cytoplasm and in a punctate pattern surrounding the nuclear membrane.GENE FUNCTION
By immunoprecipitation and immunoblot analysis, Tanaka et al. (1999) showed that the SH3 domain of STAM was required for AMSH binding at the PxxP motif at pro227 to pro231. Mutation analysis indicated that MYC induction and cell growth were eliminated in the presence of exogenous AMSH lacking the 190 C-terminal residues. Tanaka et al. (1999) concluded that the STAM-AMSH complex plays a critical role in signaling for MYC induction and cell cycle progression downstream of JAK3 and JAK2 after IL2 or GMCSF stimulation. Using RNF11 (612598) as bait in a yeast 2-hybrid screen of a human ovary cDNA library, Li and Seth (2004) showed that human RNF11 interacted with several proteins, including AMSH. The interaction of RNF11 with AMSH was independent of the RNF11 RING finger domain and PY motif. AMSH was ubiquitinated by the E3 ubiquitin ligase SMURF2 (605532) in the presence of RNF11, and reduction in the steady-state level of AMSH required both RNF11 and SMURF2. Li and Seth (2004) concluded that RNF11 recruits AMSH to SMURF2 for ubiquitination, leading to its degradation by the 26S proteasome. Using several protein interaction assays, Tsang et al. (2006) showed that AMSH interacted directly with the ESCRT-III components CHMP1B (606486) and CHMP3 (VPS24; 610052). The 3 proteins partially colocalized with M6PR (154540) on late endosomal membranes. Kikuchi et al. (2003) found that both the nuclear localization signal and the MPN domain of AMSH are required for its nuclear localization. Coimmunoprecipitation analysis of transfected 293T cells showed that epitope-tagged AMSH bound STAM, STAM2 (606244), and GRB2 (108355).MAPPING
Using FISH, Tanaka et al. (1999) mapped the STAMBP gene to 2p13-p12.MOLECULAR GENETICS
In 10 patients from 9 families with microcephaly-capillary malformation syndrome (MICCAP; 614261), McDonell et al. (2013) identified biallelic mutations in the STAMBP gene ( ... 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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 606247 was added.
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed