C-Jun-amino-terminal kinase-interacting protein 4 (SPAG9)
The protein contains 1321 amino acids for an estimated molecular weight of 146205 Da.
The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module (PubMed:14743216). Regulates lysosomal positioning by acting as an adapter protein which links PIP4P1-positive lysosomes to the dynein-dynactin complex (PubMed:29146937). Assists PIKFYVE selective functionality in microtubule-based endosome-to-TGN trafficking (By similarity). (updated: Oct. 7, 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.
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
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.
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| Variant | Description |
|---|---|
| dbSNP:rs9896965 |
Biological Process
Activation of JUN kinase activity
Lysosome localization
Muscle cell differentiation
Negative regulation of dendrite extension
Negative regulation of neuron differentiation
Negative regulation of protein homodimerization activity
Negative regulation of protein phosphorylation
Positive regulation of cell migration
Positive regulation of muscle cell differentiation
Positive regulation of neuron differentiation
Protein homooligomerization
Retrograde transport, endosome to Golgi
Spermatogenesis
Striated muscle cell differentiation
Vesicle-mediated transport
The reference OMIM entry for this protein is 605430
Sperm-associated antigen 9; spag9
Sunday driver, drosophila, homolog of, 1; syd1
Protein highly expressed in testis; phet
Kiaa0516
CLONING
Shankar et al. (1998) cloned SPAG9 from a human testis cDNA library using antibodies against sperm proteins showing surface localization as probe. The deduced 766-amino acid protein has a calculated molecular mass of 84 kD and contains a large N-terminal extracellular domain, a short transmembrane helical domain, and a cytoplasmic domain. There are 6 putative N-glycosylation sites, several putative phosphorylation sites for cAMP/cGMP-dependent protein kinase, protein kinase C, and casein kinase II, and 10 putative myristoylation sites. There is also a leucine zipper motif, with 6 leucine repeats, that may aid in dimerization since there is no upstream basic domain characteristic of DNA binding proteins. Northern blot analysis detected testis-restricted expression of a 3-kb SPAG9 transcript. In situ hybridization of human testis sections revealed SPAG9 on round spermatids of stages I, II, and III of the human seminiferous cycle. Immunohistochemical staining showed that SPAG9 is exclusively associated with elongated spermatids and not with round spermatids, indicating posttranscriptional delay in expression. Analysis of the cDNA revealed 3 putative hairpin loop structures at key positions within the open reading frame that could stabilize the mRNA in vivo. Bowman et al. (2000) identified a broadly conserved membrane-associated protein, which they termed 'sunday driver' (syd), required for the functional interaction of kinesin I (see 148760) with axonal cargo in Drosophila. Mutations in syd and the axonal transport motor kinesin I were found to cause similar phenotypes in Drosophila, including aberrant accumulations of axonal cargoes. By searching genomic and EST sequence databases for proteins similar to syd, Bowman et al. (2000) obtained full-length cDNAs encoding human SYD1 and mouse Syd2, as well as partial cDNAs encoding human SYD2 (605431) and mouse Syd1. Human SYD1 is 69% similar to mouse Syd2 and 55% similar to Drosophila syd. The predicted SYD proteins have a transmembrane region flanked by an N-terminal domain containing 2 coiled-coil regions and a C-terminal domain containing a conserved hydrophobic core. GFP-tagged mouse Syd2 localized to tubulovesicular structures that costained for kinesin I and a marker of the secretory pathway. By immunoscreening a liver cell line cDNA library with systemic sclerosis (see 181750) serum, Yasuoka et al. (2003) identified a partial cDNA encoding PHET. RT-PCR detected PHET expression in testis only. Serum autoantibodies to a recombinant PHET fragment were detected in 8% of systemic sclerosis patients, but were not present in systemic lupus erythematosus (SLE; 152700) patients or healthy controls. In systemic sclerosis patients, anti-PHET autoantibodies were associated with diffuse cutaneous or lung disease. RT-PCR analysis detected increased PHET expression in systemic sclerosis patient fibroblasts compared with controls. Immunofluorescence microscopy demonstrated more intense cytoplasmic staining for PHET in patient fibroblasts. Yasuoka et al. (2003) concluded that PHET is a testicular antigenic variant of SPAG9 that is overexpressed in systemic sclerosis patient dermal fibroblasts.GENE FUNCTION
By coimmunoprecipitation analysis, Bowman et al. (2000) found that Syd2 forms a complex with kinesin I in vivo. Yeast 2-hybrid analysis and in vitro interaction studies revealed that Syd2 directly binds kinesin I via the tetratricopeptide repeat (TPR) domain of kinesin li ... More on the omim web site
Oct. 20, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
June 7, 2019: 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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 605430 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed