S-phase kinase-associated protein 1 (SKP1)
The protein contains 163 amino acids for an estimated molecular weight of 18658 Da.
Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component. SCF(BTRC) and SCF(FBXW11) direct ubiquitination of CTNNB1 and participate in Wnt signaling. SCF(FBXW11) directs ubiquitination of phosphorylated NFKBIA. SCF(BTRC) directs ubiquitination of NFKBIB, NFKBIE, ATF4, SMAD3, SMAD4, CDC25A, FBXO5, CEP68 and probably NFKB2 (PubMed:25704143). SCF(SKP2) directs ubiquitination of phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. SCF(SKP2) directs ubiquitination of ORC1, CDT1, RBL2, ELF4, CDKN1A, RAG2, FOXO1A, and probably MYC and TAL1. SCF(FBXW7) directs ubiquitination of cyclin E, NOTCH1 released notch intracellular domain (NICD), and probably PSEN1. SCF(FBXW2) directs ubiquitination of GCM1. SCF(FBXO32) directs ubiquitination of MYOD1. SCF(FBXO7) directs ubiquitination of BIRC2 and DLGAP5. SCF(FBXO33) directs ubiquitination of YBX1. SCF(FBXO11) directs ubiquitination of BCL6 and DTL but does not seem to direct ubiquitination of TP53. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription (updated: Jan. 31, 2018)
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.
- 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.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| dbSNP:rs11538034 |
Biological Process
Anaphase-promoting complex-dependent catabolic process
Cellular iron ion homeostasis
Circadian rhythm
Fc-epsilon receptor signaling pathway
G1/S transition of mitotic cell cycle
G2/M transition of mitotic cell cycle
Histone H2A monoubiquitination
Interleukin-1-mediated signaling pathway
Maintenance of protein location in nucleus
Mitotic cell cycle
Negative regulation of G2/M transition of mitotic cell cycle
NIK/NF-kappaB signaling
Notch signaling pathway
Obsolete positive regulation of ubiquitin-protein ligase activity involved in regulation of mitotic cell cycle transition
Obsolete regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle
Positive regulation of ubiquitin protein ligase activity
Post-translational protein modification
Proteasome-mediated ubiquitin-dependent protein catabolic process
Protein K48-linked ubiquitination
Protein polyubiquitination
Protein ubiquitination
Regulation of mitotic cell cycle phase transition
SCF complex assembly
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
Stimulatory C-type lectin receptor signaling pathway
Stress-activated MAPK cascade
T cell receptor signaling pathway
Viral process
Wnt signaling pathway
The reference OMIM entry for this protein is 601434
S-phase kinase-associated protein 1; skp1
S-phase kinase-associated protein 1a; skp1a
Cdk2/cyclin a-associated protein p19a
Organ of corti protein 2; ocp2
Transcription elongation factor b, 1-like; tceb1l
CLONING
Chen et al. (1995) cloned the gene encoding OCP2 from a guinea pig organ of Corti cDNA library. They reported significant sequence similarity with TCEB1 (600788), a subunit of transcription factor SIII (or elongin) that regulates the activity of the RNA polymerase II elongation complex. Immunohistochemical staining by Chen et al. (1995) confirmed that OCP2 is localized abundantly in nonsensory cells in the organ of Corti; in addition, it was detected at a lower concentration in vestibular sensory organs, as well as auditory and vestibular brainstem nuclei. The results suggested that OCP2 may be involved in transcription regulation for the development or maintenance of specialized functions of the inner ear. Sowden et al. (1995) characterized cDNAs isolated from both mouse and human embryo cDNA libraries and designated them Tceb1l and TCEB1L, respectively. Predicted amino acid sequence showed significant homology with TCEB1 (600788), the eukaryotic elongation factor, also called elongin C, which is a component of the SIII elongation complex. The TCEB1L gene is highly conserved throughout vertebrates. The TCEB1L gene showed a restricted pattern of expression in the early mouse embryo, where it is absent from the neurectoderm; later, Tceb1l was expressed in the caudal region of the neural tube, followed by widespread expression in many tissues, including the brain and spinal cord. Zhang et al. (1995) cloned and sequenced the p19/SKP1 gene. Liang et al. (1997) reported that the coding region of OCP2 (TCEB1L) is identical to that of p19.GENE FUNCTION
Zhang et al. (1995) found that p45/SKP2 (601436) appears to serve as a bridge between p19 and the CDK2 (116953)/cyclin A (123835) complex. Bai et al. (1996) cloned SKP1 and determined that it binds to cyclin F (CCNF; 600227), SKP2, and potentially to other regulatory proteins that may be involved in ubiquitin proteolysis. Binding occurs through a novel motif, termed the F box. The F box contains about 40 residues and, in approximately half of the F-box proteins identified by Bai et al. (1996), it was associated with leucine-rich regions (LRRs), as in SKP2, or with WD40 repeats, as in BTRC (603482). Maniatis (1999) reviewed the work of Winston et al. (1999) and others concerning the SCF (SKP1, CUL1 (603134), F-box protein) ubiquitin ligase complex. CUL1 acts as a scaffold for SKP1 and the F-box-containing BTRC protein in the SCF complex, which regulates the function of nuclear factor kappa-B (see 164011) and beta-catenin (see 116806). Matsuzawa and Reed (2001) elucidated a network of protein interactions in which SIAH1 (602212), SIP (606186), SKP1, and EBI (300196) collaborate in a pathway controlling beta-catenin levels, affecting activity of beta-catenin-dependent TCF (e.g., TCF1; 142410) and LEF (e.g., LEF1; 153245) transcription factors. Dias et al. (2002) found that CUL7 (609577) assembled an SCF-ROC1 (RBX1; 603814)-like E3 ligase complex containing SKP1, CUL7, FBX29 (FBXW8; 609073), and ROC1 in human embryonic kidney cells. CUL7 specifically interacted with SKP1-FBX29, but not with SKP1 alone. CUL7 did not interact with SKP1-beta-TRCP2 (FBXW11; 605651) or SKP1-SKP2. Immunoprecipitated CUL7-ROC1 complexes converted monomeric ubiquitin into high molecular mass ubiquitin conjugates when incubated with E1 (see UBE1C; 603172) and UBC5C (UBE2D3; 602963). Arai et al. (2003) found that mouse Cul7 formed a specific SCF-like complex with Skp1, Fbx29, Rbx1, and Fap68 (GL ... More on the omim web site
Feb. 10, 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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601434 was added.
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed