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STOML2 (stomatin (EPB72)-like 2)
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)
Published in Atlas Database: February 2010
Online updated version : http://AtlasGeneticsOncology.org/Genes/STOML2ID44346ch9p13.html
DOI: 10.4267/2042/44911
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2010 Atlas of Genetics and Cytogenetics in Oncology and Haematology
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.
Identity
Other names: HSPC108, SLP-2
HGNC (Hugo): STOML2
Location: 9p13.3
DNA/RNA
Description
The gene encoding SLP-2 was 3250 bp long and
consisted of ten exons interrupted by nine introns.
Transcription
There are 5 transcripts in this gene. However, a single
1.3 kb mRNA transcript encoding SLP-2 was
ubiquitously expressed, and the translation length is
356 residues (Owczarek et al., 2001).
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.
Pseudogene
No known pseudogenes.
Protein
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
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(12)
Localisation
Predominantly on plasma membrane and in the
cytoplasm.
1118
STOML2 (stomatin (EPB72)-like 2)
Cao W, et al.
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-cGMPdependent 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; ASNGLYCOSYLATION, N-glycosylation site: 96-99: NVTL, 154-157: NASI; AMIDATION, amidation site: 219-222: eGKK.
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).
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.
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).
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).
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).
Mutations
Breast cancer
No mutations have been reported for SLP-2. Mutation
detection of SLP-2 exons was done using PCR and
automated sequencing with 30 patient-matched human
esophageal cancer tissues. No mutation was found
within the open-reading frame of SLP-2 after
sequencing results were aligned by the procedure
SeqMan of DNAStar software (Zhang et al., 2006).
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).
Implicated in
Various cancers
Note
SLP-2 has been shown to be over-expressed in a
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(12)
1119
STOML2 (stomatin (EPB72)-like 2)
Cao W, et al.
Owczarek CM, Treutlein HR, Portbury KJ, Gulluyan LM, Kola I,
Hertzog PJ. A novel member of the STOMATIN/EPB72/mec-2
family, stomatin-like 2 (STOML2), is ubiquitously expressed
and localizes to HSA chromosome 9p13.1. Cytogenet Cell
Genet. 2001;92(3-4):196-203
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).
Goldstein BJ, Kulaga HM, Reed RR. Cloning and
characterization of SLP3: a novel member of the stomatin
family expressed by olfactory receptor neurons. J Assoc Res
Otolaryngol. 2003 Mar;4(1):74-82
Zhang L, Ding F, Cao W, Liu Z, Liu W, Yu Z, Wu Y, Li W, Li Y,
Liu Z. Stomatin-like protein 2 is overexpressed in cancer and
involved in regulating cell growth and cell adhesion in human
esophageal squamous cell carcinoma. Clin Cancer Res. 2006
Mar 1;12(5):1639-46
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).
Cao W, Zhang B, Liu Y, Li H, Zhang S, Fu L, Niu Y, Ning L,
Cao X, Liu Z, Sun B. High-level SLP-2 expression and HER2/neu protein expression are associated with decreased breast
cancer patient survival. Am J Clin Pathol. 2007
Sep;128(3):430-6
Cao WF, Zhang LY, Liu MB, Tang PZ, Liu ZH, Sun BC.
Prognostic
significance
of
stomatin-like
protein
2
overexpression in laryngeal squamous cell carcinoma: clinical,
histologic, and immunohistochemistry analyses with tissue
microarray. Hum Pathol. 2007 May;38(5):747-52
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).
Cui Z, Zhang L, Hua Z, Cao W, Feng W, Liu Z. Stomatin-like
protein 2 is overexpressed and related to cell growth in human
endometrial adenocarcinoma. Oncol Rep. 2007 Apr;17(4):82933
References
Wang Y, Cao W, Yu Z, Liu Z. Downregulation of a
mitochondria associated protein SLP-2 inhibits tumor cell
motility, proliferation and enhances cell sensitivity to
chemotherapeutic reagents. Cancer Biol Ther. 2009
Sep;8(17):1651-8
Seidel G, Prohaska R. Molecular cloning of hSLP-1, a novel
human brain-specific member of the band 7/MEC-2 family
similar to Caenorhabditis elegans UNC-24. Gene. 1998 Dec
28;225(1-2):23-9
Chang D, Ma K, Gong M, Cui Y, Liu ZH, Zhou XG, Zhou CN,
Wang TY. SLP-2 overexpression is associated with tumour
distant metastasis and poor prognosis in pulmonary squamous
cell carcinoma. Biomarkers. 2010 Mar;15(2):104-10
Wang Y, Morrow JS. Identification and characterization of
human SLP-2, a novel homologue of stomatin (band 7.2b)
present in erythrocytes and other tissues. J Biol Chem. 2000
Mar 17;275(11):8062-71
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(12)
This article should be referenced as such:
Cao W, Zhang L, Ding F, Cui Z, Liu Z. STOML2 (stomatin
(EPB72)-like 2). Atlas Genet Cytogenet Oncol Haematol. 2010;
14(12):1118-1120.
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