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| | Figure A. ALA-RICH, Alanine-rich region profile: 224-274: score = 8.657.
Figure B. MYRISTYL, N-myristoylation site: 16-21: GSllAS, 31-36: GLprNT, 209-214: GTreSA, 314-319: GVvgAL, 326-331: GTpdSL, 341-346: GtdaSL; PKC-PHOSPHO-SITE, Protein kinase C phosphorylation site: 21-23: SgR, 78-80: SlK, 133-135: TmR, 335-337: SsR; CAMP-PHOSPHO-SITE, Camp-and-cGMP-dependent protein kinase phosphorylation site: 26-29: RRaS, 200-203: KRaT; CK2-PHOSPHO-SITE, Casein kinase II phosphorylation site: 78-81: SlkE, 156-159: SivD, 203-206: TvlE, 229-232: SeaE, 277-280: TvaE, 335-338: SsrD, 345-348: SldE; ASN-GLYCOSYLATION, N-glycosylation site: 96-99: NVTL, 154-157: NASI; AMIDATION, amidation site: 219-222: eGKK. |
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| Description | NP_038470; 356 aa.
Human SLP-2 is presented on chromosome 9p13. The sequence at the 5'-end of the mRNA is interesting for the presence of three potential ATG initiator sites, all sharing the same open reading frame however, commonly forms a 356 amino acid residue polypeptide with a predicted molecular weight of 38.5 kDa. Similar to other family members, SLP-2 as well as the stomatin from other species shares a characteristic NH2-terminal hydrophobic domain as well as a consensus cognate stomatin signature sequence that defines the stomatin gene family, however, it lacks the NH2-terminal hydrophobic domain (Wang et al., 2000). The SLP-2 protein contains an alanine-rich domain and a number of potential protein kinase C phosphorylation sites, cAMP-and-cGMP-dependent protein kinase phosphorylation sites and casein kinase II phosphorylation sites. |
| Expression | SLP-2 is widely expressed in many tissues and thought as a new component of the peripheral membrane skeleton. Especially, in the erythrocyte membrane, it also appears to exist at least partially as an oligomeric protein complex. The overexpression of SLP-2 can be found in many kinds of human tumors, such as esophageal squamous cell carcinoma, laryngeal squamous cell carcinoma, endometrial adenocarcinoma, and lung cancer. |
| Localisation | Predominantly on plasma membrane and in the cytoplasm. |
| Function | Human SLP-2 protein with unknown function, we hypothesize that SLP-2 may link stomatin or other integral membrane proteins to the peripheral cytoskeleton and thereby play a role in regulating ion channel conductances or the organization of sphingolipid and cholesterol-rich lipid rafts. Some recent results indicated that SLP-2 protein can significantly influence on multi-tumor progression, which allowed us to identify this unwell-known gene that maybe modulate invasion and metastasis of different cancers. |
| Homology | SLP-2 is one of the members of the Stomatin superfamily, among which identified vertebrate homologues are SLP-1, SLP-2, and SLP-3. SLP-1 is most abundant in brain and shares many similarities with UNC-24 (STOML1). SLP-3 is specifically expressed in olfactory sensory neurons (Seidel et al., 1998; Goldstein et al., 2003). |
| Entity | Various cancers |
| Note | SLP-2 has been shown to be over-expressed in a number of different cancers, including esophageal squamous cell carcinoma (ESCC), laryngeal squamous cell carcinoma (LSCC), endometrial adenocarcinoma (EAC), lung cancer (LC) and breast cancer (see below). |
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| Entity | Esophageal squamous cell carcinoma (ESCC) |
| Prognosis | As shown in human ESCC, a significant correlation exists between SLP-2 protein high expression and the depth of ESCC invasion (P=0.033) (Wang et al., 2009). Also, decreased cell growth and tumorigenesis in the antisense transfectants revealed that SLP-2 may be important in ESCC tumorigenesis (Zhang et al., 2006). |
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| Entity | Laryngeal squamous cell carcinoma (LSCC) |
| Prognosis | In addition, SLP-2 takes part in human LSCC malignant phenotype formation and development. High-level expression of SLP-2 protein could contribute to the prognostic characteristics of lymph node metastasis in human LSCC (Cao et al., 2007). |
| | |
| Entity | Breast cancer |
| Prognosis | High-level expression of SLP-2 protein shows a worse prognosis, including increase in tumor size, progress in clinical stage, and appearance of lymph node and/or distant metastasis and is associated with decreased overall survival (P=0.011). Moreover, SLP-2 can be strongly associated with another important prognostic factor, HER-2/neu protein expression, which shows that they may act as dependent prognostic factors to indicate poor prognosis (Cao et al., 2007). |
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| Entity | Endometrial adenocarcinoma |
| Prognosis | Similarly, SLP-2 is also overexpressed in human endometrial adenocarcinoma (EAC) at both mRNA and protein level. Sense transfection of SLP-2 in EAC cell line accelerated cell growth whereas the antisense transfection reduced cell growth in vitro (Cui et al., 2007). |
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| Entity | Lung cancer |
| Prognosis | At last, SLP-2 was overexpressed in human lung cancer (Zhang et al., 2006). High-level SLP-2 expression was significantly correlated with distant metastasis, decreased overall survival and disease-free survival. SLP-2 overexpression was an independent prognostic factor in multivariate analysis using the Cox regression model (p<0.05) (Chang et al., 2009). |
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| Entity | Mitochondrial component |
| Note | SLP-2 localizes in mitochondria, affects mitochondrial membrane potential (MMP) and ATP production. Hence, SLP-2 is a mitochondrial protein and therefore, functions in energy process by MMP maintenance, and subsequently affecting cell motility, proliferation and chemosensitivity (Wang et al., 2009). |
| | |
| Molecular cloning of hSLP-1, a novel human brain-specific member of the band 7/MEC-2 family similar to Caenorhabditis elegans UNC-24. |
| Seidel G, Prohaska R. |
| Gene. 1998 Dec 28;225(1-2):23-9. |
| PMID 9931417 |
| |
| Identification and characterization of human SLP-2, a novel homologue of stomatin (band 7.2b) present in erythrocytes and other tissues. |
| Wang Y, Morrow JS. |
| J Biol Chem. 2000 Mar 17;275(11):8062-71. |
| PMID 10713127 |
| |
| A novel member of the STOMATIN/EPB72/mec-2 family, stomatin-like 2 (STOML2), is ubiquitously expressed and localizes to HSA chromosome 9p13.1. |
| Owczarek CM, Treutlein HR, Portbury KJ, Gulluyan LM, Kola I, Hertzog PJ. |
| Cytogenet Cell Genet. 2001;92(3-4):196-203. |
| PMID 11435687 |
| |
| Cloning and characterization of SLP3: a novel member of the stomatin family expressed by olfactory receptor neurons. |
| Goldstein BJ, Kulaga HM, Reed RR. |
| J Assoc Res Otolaryngol. 2003 Mar;4(1):74-82. Epub 2002 Sep 23. |
| PMID 12239636 |
| |
| Stomatin-like protein 2 is overexpressed in cancer and involved in regulating cell growth and cell adhesion in human esophageal squamous cell carcinoma. |
| Zhang L, Ding F, Cao W, Liu Z, Liu W, Yu Z, Wu Y, Li W, Li Y, Liu Z. |
| Clin Cancer Res. 2006 Mar 1;12(5):1639-46. |
| PMID 16533792 |
| |
| High-level SLP-2 expression and HER-2/neu protein expression are associated with decreased breast cancer patient survival. |
| Cao W, Zhang B, Liu Y, Li H, Zhang S, Fu L, Niu Y, Ning L, Cao X, Liu Z, Sun B. |
| Am J Clin Pathol. 2007 Sep;128(3):430-6. |
| PMID 17709317 |
| |
| Prognostic significance of stomatin-like protein 2 overexpression in laryngeal squamous cell carcinoma: clinical, histologic, and immunohistochemistry analyses with tissue microarray. |
| Cao WF, Zhang LY, Liu MB, Tang PZ, Liu ZH, Sun BC. |
| Hum Pathol. 2007 May;38(5):747-52. Epub 2007 Feb 15. |
| PMID 17306333 |
| |
| Stomatin-like protein 2 is overexpressed and related to cell growth in human endometrial adenocarcinoma. |
| Cui Z, Zhang L, Hua Z, Cao W, Feng W, Liu Z. |
| Oncol Rep. 2007 Apr;17(4):829-33. |
| PMID 17342323 |
| |
| Downregulation of a mitochondria associated protein SLP-2 inhibits tumor cell motility, proliferation and enhances cell sensitivity to chemotherapeutic reagents. |
| Wang Y, Cao W, Yu Z, Liu Z. |
| Cancer Biol Ther. 2009 Sep;8(17):1651-8. Epub 2009 Sep 17. |
| PMID 19597348 |
| |
| SLP-2 overexpression is associated with tumour distant metastasis and poor prognosis in pulmonary squamous cell carcinoma. |
| Chang D, Ma K, Gong M, Cui Y, Liu ZH, Zhou XG, Zhou CN, Wang TY. |
| Biomarkers. 2010 Mar;15(2):104-10. |
| PMID 19839737 |
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| Written | 02-2010 | Wenfeng Cao, Liyong Zhang, Fang Ding, Zhumei Cui, Zhihua Liu |
| | State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China (WC, LZ, DF, ZL); Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China (WC); Department of Obstetrics and Gynecology, Affiliated Hospital of Medical College, Qingdao University, Qingdao 266011, China (ZC) |
