RBCC

Full text data of TMEM97

TMEM97 (MAC30) [Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Transmembrane protein 97 (Protein MAC30)

UniProt Q5BJF2
ID TMM97_HUMAN Reviewed; 176 AA.
AC Q5BJF2; B4DS02; Q07823;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
read moreDT 12-APR-2005, sequence version 1.
DT 22-JAN-2014, entry version 66.
DE RecName: Full=Transmembrane protein 97;
DE AltName: Full=Protein MAC30;
GN Name=TMEM97; Synonyms=MAC30;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=7694637;
RA Murphy M., Pykett M.J., Harnish P., Zang K.D., George D.L.;
RT "Identification and characterization of genes differentially expressed
RT in meningiomas.";
RL Cell Growth Differ. 4:715-722(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=15375745;
RA Kayed H., Kleeff J., Ding J., Hammer J., Giese T., Zentgraf H.,
RA Buchler M.W., Friess H.;
RT "Expression analysis of MAC30 in human pancreatic cancer and tumors of
RT the gastrointestinal tract.";
RL Histol. Histopathol. 19:1021-1031(2004).
RN [5]
RP INDUCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=18070364; DOI=10.1186/1471-2407-7-223;
RA Wilcox C.B., Feddes G.O., Willett-Brozick J.E., Hsu L.C., DeLoia J.A.,
RA Baysal B.E.;
RT "Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes
RT in normal ovarian surface epithelial cells treated with progesterone:
RT implications for pathogenesis of ovarian cancer.";
RL BMC Cancer 7:223-223(2007).
RN [6]
RP FUNCTION, INTERACTION WITH NPC1, AND SUBCELLULAR LOCATION.
RX PubMed=19583955; DOI=10.1016/j.cmet.2009.05.009;
RA Bartz F., Kern L., Erz D., Zhu M., Gilbert D., Meinhof T., Wirkner U.,
RA Erfle H., Muckenthaler M., Pepperkok R., Runz H.;
RT "Identification of cholesterol-regulating genes by targeted RNAi
RT screening.";
RL Cell Metab. 10:63-75(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Plays a role as a regulator of cellular cholesterol
CC homeostasis.
CC -!- SUBUNIT: Interacts with NPC1.
CC -!- SUBCELLULAR LOCATION: Nucleus membrane. Rough endoplasmic
CC reticulum. Cell membrane. Lysosome. Membrane; Multi-pass membrane
CC protein (Potential). Note=Localized in sterol-depleted cells at
CC cell membrane and in lysosomes.
CC -!- TISSUE SPECIFICITY: Widely expressed in normal tissues. Expressed
CC in pancreatic, renal, breast, colon, ovarian surface epithelial
CC (OSE) cells and meningioma cancers. Expressed in ovarian cancer;
CC expression is reduced relative to OSE cells.
CC -!- INDUCTION: Up-regulated in ovarian surface epithelial (OSE) cells
CC with progesterone.
CC -!- SIMILARITY: Belongs to the TMEM97 family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA16188.1; Type=Frameshift; Positions=5;
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DR EMBL; L19183; AAA16188.1; ALT_FRAME; mRNA.
DR EMBL; AK299511; BAG61464.1; -; mRNA.
DR EMBL; BC091504; AAH91504.1; -; mRNA.
DR PIR; I65744; I65744.
DR RefSeq; NP_055388.2; NM_014573.2.
DR UniGene; Hs.199695; -.
DR ProteinModelPortal; Q5BJF2; -.
DR STRING; 9606.ENSP00000226230; -.
DR PhosphoSite; Q5BJF2; -.
DR DMDM; 74736009; -.
DR PaxDb; Q5BJF2; -.
DR PRIDE; Q5BJF2; -.
DR Ensembl; ENST00000226230; ENSP00000226230; ENSG00000109084.
DR Ensembl; ENST00000576254; ENSP00000461068; ENSG00000262046.
DR GeneID; 27346; -.
DR KEGG; hsa:27346; -.
DR UCSC; uc002hat.3; human.
DR CTD; 27346; -.
DR GeneCards; GC17P026647; -.
DR HGNC; HGNC:28106; TMEM97.
DR HPA; HPA044795; -.
DR MIM; 612912; gene.
DR neXtProt; NX_Q5BJF2; -.
DR PharmGKB; PA143485635; -.
DR eggNOG; NOG16760; -.
DR HOGENOM; HOG000031140; -.
DR HOVERGEN; HBG079913; -.
DR InParanoid; Q5BJF2; -.
DR OMA; LFMLRSP; -.
DR ChiTaRS; TMEM97; human.
DR GenomeRNAi; 27346; -.
DR NextBio; 50434; -.
DR PRO; PR:Q5BJF2; -.
DR ArrayExpress; Q5BJF2; -.
DR Bgee; Q5BJF2; -.
DR CleanEx; HS_TMEM97; -.
DR Genevestigator; Q5BJF2; -.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005791; C:rough endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; IDA:UniProtKB.
DR GO; GO:0001558; P:regulation of cell growth; NAS:UniProtKB.
DR InterPro; IPR016964; Transmembrane_6/97.
DR Pfam; PF10914; DUF2781; 1.
DR PIRSF; PIRSF031032; TMP_97_prd; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Complete proteome; Endoplasmic reticulum; Lysosome;
KW Membrane; Nucleus; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1 176 Transmembrane protein 97.
FT /FTId=PRO_0000254567.
FT TOPO_DOM 1 9 Cytoplasmic (Potential).
FT TRANSMEM 10 30 Helical; (Potential).
FT TOPO_DOM 31 68 Extracellular (Potential).
FT TRANSMEM 69 89 Helical; (Potential).
FT TOPO_DOM 90 99 Cytoplasmic (Potential).
FT TRANSMEM 100 120 Helical; (Potential).
FT TOPO_DOM 121 140 Extracellular (Potential).
FT TRANSMEM 141 161 Helical; (Potential).
FT TOPO_DOM 162 176 Cytoplasmic (Potential).
FT CONFLICT 5 5 A -> S (in Ref. 1; AAA16188).
FT CONFLICT 34 34 L -> V (in Ref. 1; AAA16188).
FT CONFLICT 113 113 P -> L (in Ref. 1; AAA16188).
SQ SEQUENCE 176 AA; 20848 MW; 685248D421877F84 CRC64;
MGAPATRRCV EWLLGLYFLS HIPITLFMDL QAVLPRELYP VEFRNLLKWY AKEFKDPLLQ
EPPAWFKSFL FCELVFQLPF FPIATYAFLK GSCKWIRTPA IIYSVHTMTT LIPILSTFLF
EDFSKASGFK GQRPETLHER LTLVSVYAPY LLIPFILLIF MLRSPYYKYE EKRKKK
//

MIM 612912
*RECORD*
*FIELD* NO
612912
*FIELD* TI
*612912 TRANSMEMBRANE PROTEIN 97; TMEM97
;;MAC30
*FIELD* TX

DESCRIPTION

TMEM97 is a conserved integral membrane protein that plays a role in
read morecontrolling cellular cholesterol levels (Bartz et al., 2009).

CLONING

Using a phage subtraction library to identify genes expressed in normal
leptomeningeal cells but not in a meningioma cell line, followed by
RT-PCR, Murphy et al. (1993) cloned TMEM97, which they called MAC30.
Northern blot analysis detected transcripts of about 2.3 and 2.8 kb in
normal leptomeningeal cells and in a cell line derived from these cells.

Using differential display RT-PCR to identify genes expressed in fetal
but not adult liver, Malhotra et al. (1999) obtained a partial MAC30
clone. Northern blot analysis detected transcripts of about 2.3 and 2.8
kb in 10-, 16-, and 20-week fetal liver, but not in adult liver.

Using real-time quantitative PCR, Kayed et al. (2004) found variable
MAC30 expression in all normal human tissues examined, with highest
expression in testis and stomach and lowest expression in thyroid,
thymus, and adipose tissue. In situ hybridization detected MAC30 in
normal pancreatic acini, islets, and large ducts. Immunohistochemical
analysis showed MAC30 protein in the cytoplasm of peripheral pancreatic
islet cells, in endothelial and smooth muscle cells of blood vessels,
and in nerves, monocytes, and fibroblasts. In esophagus, MAC30 was
detected in cytoplasm of mucosal cells, particularly in the superficial
and intermediate epithelial layers. Gastric submucosa and muscularis and
normal colonic epithelium exhibited staining patterns similar to that of
esophagus.

Bartz et al. (2009) reported that the full-length 176-amino acid TMEM97
protein contains an N-terminal signal peptide and 4 transmembrane
domains.

GENE FUNCTION

Murphy et al. (1993) found that MAC30 expression was downregulated in
meningiomas and Schwann cell tumors compared with normal leptomeningeal
cells.

Kayed et al. (2004) found that expression of MAC30 was significantly
increased in breast and colon cancers and significantly decreased in
pancreatic and renal cancers compared with normal tissue.

Using microarray analysis, Wilcox et al. (2007) found that TMEM97 and
several genes regulating cholesterol and lipid homeostasis were
upregulated in cultured ovarian surface epithelial (OSE) cells treated
with progesterone. TMEM97 was the most highly upregulated gene
identified. Real-time quantitative RT-PCR analysis showed that TMEM97
expression was downregulated in ovarian cancer cells relative to normal
OSE cells. Database analysis suggested that expression of TMEM97 is
coregulated with that of cholesterol biosynthesis genes in normal human
tissues. Wilcox et al. (2007) proposed that TMEM97 may play a role in
cholesterol and lipid metabolism.

Using genomewide expression profiling and RT-PCR, Bartz et al. (2009)
found that TMEM97 was upregulated to an extent similar to that of LDL
receptor (LDLR; 606945) following sterol depletion in HeLa cells. TMEM97
expression was also upregulated following knockdown of LDLR via small
interfering RNA (siRNA). Bartz et al. (2009) identified a sterol
regulatory element-1 (SRE1) consensus sequence upstream of the TMEM97
transcription initiation site, and siRNA-mediated knockdown of SREBP2
(SREBF2; 600481) suppressed TMEM97 expression in sterol-depleted cells.
Knockdown of TMEM97 via siRNA reduced the number of LDL-containing
endosomes in HeLa cells and reduced cellular uptake of radiolabeled
cholesterol. Restoration of TMEM97 expression rescued cellular
cholesterol levels in TMEM97-knockdown cells. Fluorescence-tagged TMEM97
localized to the endoplasmic reticulum in control HeLa cells, but it
redistributed to perinuclear and plasma membrane lysosomal vesicles in
sterol-depleted cells. TMEM97 coimmunoprecipitated with NPC1 (607623), a
cholesterol-binding protein essential for efficient lysosomal
cholesterol export. Interaction between TMEM97 and NPC1 was inversely
proportional to cellular sterol content. Bartz et al. (2009) concluded
that TMEM97 is an SREBP target gene that localizes to lysosomes under
sterol depletion, directly or indirectly binds NPC1, and contributes to
the regulation of cellular cholesterol levels.

MAPPING

Using a rodent/human somatic cell hybrid panel and a somatic cell hybrid
containing a t(11;17) translocation, Murphy et al. (1993) mapped the
TMEM97 gene to chromosome 17q21-qter. Kayed et al. (2004) stated that
the TMEM97 gene maps to chromosome 17q11.2.

*FIELD* RF
1. Bartz, F.; Kern, L.; Erz, D.; Zhu, M.; Gilbert, D.; Meinhof, T.;
Wirkner, U.; Erfle, H.; Muckenthaler, M.; Pepperkok, R.; Runz, H.
: Identification of cholesterol-regulating genes by targeted RNAi
screening. Cell Metab. 10: 63-75, 2009.

2. Kayed, H.; Kleeff, J.; Ding, J.; Hammer, J.; Giese, T.; Zentgraf,
H.; Buchler, M. W.; Friess, H.: Expression analysis of MAC30 in human
pancreatic cancer and tumors of the gastrointestinal tract. Histol.
Histopath. 19: 1021-1031, 2004.

3. Malhotra, K.; Leuhrsen, K. R.; Costello, L. L.; Raich, T. J.; Sim,
K.; Foltz, L.; Davidson, S.; Xu, H.; Chen, A.; Yamanishi, D. T.; Lindemann,
G. W.; Cain, C. A.; Madlansacay, M. R.; Hashima, S. M.; Pham, T. L.;
Mahoney, W.; Schueler, P. A.: Identification of differentially expressed
mRNAs in human fetal liver across gestation. Nucleic Acids Res. 27:
839-847, 1999.

4. Murphy, M.; Pykett, M. J.; Harnish, P.; Zang, K. D.; George, D.
L.: Identification and characterization of genes differentially expressed
in meningiomas. Cell Growth Differ. 4: 715-722, 1993.

5. Wilcox, C. B.; Feddes, G. O.; Willett-Brozick, J. E.; Hsu, L.-C.;
DeLoia, J. A.; Baysal, B. E.: Coordinate up-regulation of TMEM97
and cholesterol biosynthesis genes in normal ovarian surface epithelial
cells treated with progesterone: implications for pathogenesis of
ovarian cancer. BMC Cancer 7: 223, 2007. Note: Electronic Article.

*FIELD* CD
Patricia A. Hartz: 7/16/2009

*FIELD* ED
terry: 09/16/2010
mgross: 7/16/2009

RBCC Red Blood Cell Collection

Full text data of TMEM97