Full text data of TESC
TESC
(CHP3)
[Confidence: low (only semi-automatic identification from reviews)]
Calcineurin B homologous protein 3 (Tescalcin; TSC)
Calcineurin B homologous protein 3 (Tescalcin; TSC)
UniProt
Q96BS2
ID CHP3_HUMAN Reviewed; 214 AA.
AC Q96BS2; F5H1Y5; Q9NWT9;
DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 19-JAN-2010, sequence version 3.
DT 22-JAN-2014, entry version 103.
DE RecName: Full=Calcineurin B homologous protein 3;
DE AltName: Full=Tescalcin;
DE Short=TSC;
GN Name=TESC; Synonyms=CHP3;
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] (ISOFORM 1), INTERACTION WITH SLC9A1,
RP CALCIUM-BINDING, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11696366; DOI=10.1016/S0014-5793(01)02986-6;
RA Mailaender J., Mueller-Esterl W., Dedio J.;
RT "Human homolog of mouse tescalcin associates with Na(+)/H(+) exchanger
RT type-1.";
RL FEBS Lett. 507:331-335(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Signet-ring cell carcinoma;
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 GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M.,
RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M.,
RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D.,
RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA Kucherlapati R., Weinstock G., Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
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 [6]
RP INTERACTION WITH SLC9A1.
RX PubMed=12809501; DOI=10.1021/bi027143d;
RA Li X., Liu Y., Kay C.M., Muller-Esterl W., Fliegel L.;
RT "The Na+/H+ exchanger cytoplasmic tail: structure, function, and
RT interactions with tescalcin.";
RL Biochemistry 42:7448-7456(2003).
RN [7]
RP MYRISTOYLATION AT GLY-2.
RX PubMed=14661968; DOI=10.1021/bi034870f;
RA Gutierrez-Ford C., Levay K., Gomes A.V., Perera E.M., Som T.,
RA Kim Y.M., Benovic J.L., Berkovitz G.D., Slepak V.Z.;
RT "Characterization of tescalcin, a novel EF-hand protein with a single
RT Ca2+-binding site: metal-binding properties, localization in tissues
RT and cells, and effect on calcineurin.";
RL Biochemistry 42:14553-14565(2003).
RN [8]
RP FUNCTION IN MEGAKARYOCYTIC DIFFERENTIATION, INDUCTION, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=17717601; DOI=10.1172/JCI27465;
RA Levay K., Slepak V.Z.;
RT "Tescalcin is an essential factor in megakaryocytic differentiation
RT associated with Ets family gene expression.";
RL J. Clin. Invest. 117:2672-2683(2007).
RN [9]
RP FUNCTION, INTERACTION WITH SLC9A1, AND SUBCELLULAR LOCATION.
RX PubMed=18321853; DOI=10.1074/jbc.M800267200;
RA Zaun H.C., Shrier A., Orlowski J.;
RT "Calcineurin B homologous protein 3 promotes the biosynthetic
RT maturation, cell surface stability, and optimal transport of the
RT Na+/H+ exchanger NHE1 isoform.";
RL J. Biol. Chem. 283:12456-12467(2008).
RN [10]
RP FUNCTION IN GRANULOCYTIC DIFFERENTIATION, INDUCTION, AND TISSUE
RP SPECIFICITY.
RX PubMed=20060826; DOI=10.1016/j.yexcr.2010.01.007;
RA Levay K., Slepak V.Z.;
RT "Up- or downregulation of tescalcin in HL-60 cells is associated with
RT their differentiation to either granulocytic or macrophage-like
RT lineage.";
RL Exp. Cell Res. 316:1254-1262(2010).
RN [11]
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: Functions as an integral cofactor in cell pH regulation
CC by controlling plasma membrane-type Na(+)/H(+) exchange activity.
CC Promotes the maturation, transport, cell surface stability and
CC exchange activity of SLC9A1/NHE1 at the plasma membrane. Promotes
CC the induction of hematopoietic stem cell differentiation toward
CC megakaryocytic lineage. Essential for the coupling of ERK cascade
CC activation with the expression of ETS family genes in
CC megakaryocytic differentiation. Also involved in granulocytic
CC differentiation in a ERK-dependent manner. Inhibits the
CC phosphatase activity of calcineurin.
CC -!- SUBUNIT: Monomer. Homodimer; disulfide-linked (By similarity).
CC Interacts with SLC9A1/NHE1 (via juxtamembrane region of the
CC cytoplasmic C-terminus); the interaction enable an optimal
CC Na(+)/H(+) exchange activity.
CC -!- INTERACTION:
CC Q9NP66:HMG20A; NbExp=2; IntAct=EBI-740653, EBI-740641;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Membrane (By
CC similarity). Cell membrane. Cell projection, lamellipodium (By
CC similarity). Cell projection, ruffle membrane (By similarity).
CC Note=Colocalizes with SLC9A1 at the plasma membrane.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q96BS2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96BS2-2; Sequence=VSP_035518, VSP_035519;
CC Name=3;
CC IsoId=Q96BS2-3; Sequence=VSP_045287;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed in mature megakaryocytes and
CC polymorphonuclear granulocytes (at protein level). Abundantly
CC expressed in heart. Also expressed at a lower level in adult
CC testis and salivary gland, and in the placenta.
CC -!- DEVELOPMENTAL STAGE: Strongly up-regulated in K562 cells treated
CC by PMA to promote megakaryocytic differentiation, but not when
CC treated by DMSO to promote granulocytic differentiation or by
CC hemin to promote erythroid differentiation (at protein level).
CC -!- INDUCTION: Up-regulated during granulocytic differentiation in a
CC ERK-dependent manner (is mediated by activation of ERK) (at
CC protein level). Up-regulated during the differentiation and
CC maturation of primary megakaryocytes. Down-regulated during
CC monocytic-macrophage differentiation in a ERK-dependent manner.
CC -!- DOMAIN: Binds calcium via its EF-hands. Calcium-binding mediates a
CC conformational change. Can also bind magnesium (By similarity).
CC -!- SIMILARITY: Belongs to the calcineurin regulatory subunit family.
CC CHP subfamily.
CC -!- SIMILARITY: Contains 1 EF-hand domain.
CC -!- CAUTION: Although PubMed:12809501 reports that TESC results in a
CC decrease in transporter activity of human SLC9A1, studies with rat
CC SLC9A1 (PubMed:18321853) show that TESC-binding results in the
CC maturation and accumulation of SLC9A1 at the cell surface.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA91288.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=EAW98101.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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DR EMBL; AF443207; AAL35615.1; -; mRNA.
DR EMBL; AK000614; BAA91288.1; ALT_INIT; mRNA.
DR EMBL; AC026368; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471054; EAW98101.1; ALT_INIT; Genomic_DNA.
DR EMBL; BC015221; AAH15221.1; -; mRNA.
DR EMBL; BQ949772; -; NOT_ANNOTATED_CDS; mRNA.
DR RefSeq; NP_001161797.1; NM_001168325.1.
DR RefSeq; NP_060369.3; NM_017899.3.
DR UniGene; Hs.525709; -.
DR ProteinModelPortal; Q96BS2; -.
DR SMR; Q96BS2; 9-214.
DR IntAct; Q96BS2; 4.
DR MINT; MINT-1477844; -.
DR STRING; 9606.ENSP00000376328; -.
DR PhosphoSite; Q96BS2; -.
DR DMDM; 284018160; -.
DR PaxDb; Q96BS2; -.
DR PRIDE; Q96BS2; -.
DR DNASU; 54997; -.
DR Ensembl; ENST00000335209; ENSP00000334785; ENSG00000088992.
DR Ensembl; ENST00000470612; ENSP00000432716; ENSG00000088992.
DR Ensembl; ENST00000541210; ENSP00000445689; ENSG00000088992.
DR GeneID; 54997; -.
DR KEGG; hsa:54997; -.
DR UCSC; uc021rem.1; human.
DR CTD; 54997; -.
DR GeneCards; GC12M117477; -.
DR HGNC; HGNC:26065; TESC.
DR HPA; HPA053200; -.
DR MIM; 611585; gene.
DR neXtProt; NX_Q96BS2; -.
DR PharmGKB; PA143485630; -.
DR eggNOG; COG5126; -.
DR HOGENOM; HOG000233019; -.
DR HOVERGEN; HBG105313; -.
DR InParanoid; Q96BS2; -.
DR KO; K17612; -.
DR OrthoDB; EOG7NSB38; -.
DR ChiTaRS; TESC; human.
DR GenomeRNAi; 54997; -.
DR NextBio; 58314; -.
DR PRO; PR:Q96BS2; -.
DR ArrayExpress; Q96BS2; -.
DR Bgee; Q96BS2; -.
DR CleanEx; HS_TESC; -.
DR Genevestigator; Q96BS2; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0001726; C:ruffle; ISS:UniProtKB.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0019212; F:phosphatase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0004860; F:protein kinase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0071300; P:cellular response to retinoic acid; IDA:UniProtKB.
DR GO; GO:0008584; P:male gonad development; IEA:Ensembl.
DR GO; GO:0030219; P:megakaryocyte differentiation; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell proliferation; IMP:UniProtKB.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; IEA:GOC.
DR GO; GO:0030854; P:positive regulation of granulocyte differentiation; IDA:UniProtKB.
DR GO; GO:0045654; P:positive regulation of megakaryocyte differentiation; IMP:UniProtKB.
DR GO; GO:0032417; P:positive regulation of sodium:hydrogen antiporter activity; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-dependent; IMP:UniProtKB.
DR GO; GO:0051604; P:protein maturation; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IDA:UniProtKB.
DR GO; GO:0072661; P:protein targeting to plasma membrane; IDA:UniProtKB.
DR GO; GO:0033628; P:regulation of cell adhesion mediated by integrin; IMP:UniProtKB.
DR Gene3D; 1.10.238.10; -; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR Pfam; PF13405; EF-hand_6; 1.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS50222; EF_HAND_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Cell membrane; Cell projection;
KW Complete proteome; Cytoplasm; Differentiation; Disulfide bond;
KW Lipoprotein; Membrane; Metal-binding; Myristate; Nucleus;
KW Protein kinase inhibitor; Protein transport; Reference proteome;
KW Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 214 Calcineurin B homologous protein 3.
FT /FTId=PRO_0000073859.
FT DOMAIN 110 145 EF-hand.
FT CA_BIND 123 134 By similarity.
FT LIPID 2 2 N-myristoyl glycine.
FT VAR_SEQ 43 69 Missing (in isoform 3).
FT /FTId=VSP_045287.
FT VAR_SEQ 139 163 VEELLSGNPHIEKESARSIADGAMM -> KWSRSCCRETLT
FT SRRSPLAPSPTGP (in isoform 2).
FT /FTId=VSP_035518.
FT VAR_SEQ 164 214 Missing (in isoform 2).
FT /FTId=VSP_035519.
FT CONFLICT 209 211 TMA -> NMG (in Ref. 5; BQ949772).
SQ SEQUENCE 214 AA; 24750 MW; AB3DBE6EA3EB5E60 CRC64;
MGAAHSASEE VRELEGKTGF SSDQIEQLHR RFKQLSGDQP TIRKENFNNV PDLELNPIRS
KIVRAFFDNR NLRKGPSGLA DEINFEDFLT IMSYFRPIDT TMDEEQVELS RKEKLRFLFH
MYDSDSDGRI TLEEYRNVVE ELLSGNPHIE KESARSIADG AMMEAASVCM GQMEPDQVYE
GITFEDFLKI WQGIDIETKM HVRFLNMETM ALCH
//
ID CHP3_HUMAN Reviewed; 214 AA.
AC Q96BS2; F5H1Y5; Q9NWT9;
DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 19-JAN-2010, sequence version 3.
DT 22-JAN-2014, entry version 103.
DE RecName: Full=Calcineurin B homologous protein 3;
DE AltName: Full=Tescalcin;
DE Short=TSC;
GN Name=TESC; Synonyms=CHP3;
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] (ISOFORM 1), INTERACTION WITH SLC9A1,
RP CALCIUM-BINDING, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11696366; DOI=10.1016/S0014-5793(01)02986-6;
RA Mailaender J., Mueller-Esterl W., Dedio J.;
RT "Human homolog of mouse tescalcin associates with Na(+)/H(+) exchanger
RT type-1.";
RL FEBS Lett. 507:331-335(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Signet-ring cell carcinoma;
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 GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M.,
RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M.,
RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D.,
RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA Kucherlapati R., Weinstock G., Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
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 [6]
RP INTERACTION WITH SLC9A1.
RX PubMed=12809501; DOI=10.1021/bi027143d;
RA Li X., Liu Y., Kay C.M., Muller-Esterl W., Fliegel L.;
RT "The Na+/H+ exchanger cytoplasmic tail: structure, function, and
RT interactions with tescalcin.";
RL Biochemistry 42:7448-7456(2003).
RN [7]
RP MYRISTOYLATION AT GLY-2.
RX PubMed=14661968; DOI=10.1021/bi034870f;
RA Gutierrez-Ford C., Levay K., Gomes A.V., Perera E.M., Som T.,
RA Kim Y.M., Benovic J.L., Berkovitz G.D., Slepak V.Z.;
RT "Characterization of tescalcin, a novel EF-hand protein with a single
RT Ca2+-binding site: metal-binding properties, localization in tissues
RT and cells, and effect on calcineurin.";
RL Biochemistry 42:14553-14565(2003).
RN [8]
RP FUNCTION IN MEGAKARYOCYTIC DIFFERENTIATION, INDUCTION, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=17717601; DOI=10.1172/JCI27465;
RA Levay K., Slepak V.Z.;
RT "Tescalcin is an essential factor in megakaryocytic differentiation
RT associated with Ets family gene expression.";
RL J. Clin. Invest. 117:2672-2683(2007).
RN [9]
RP FUNCTION, INTERACTION WITH SLC9A1, AND SUBCELLULAR LOCATION.
RX PubMed=18321853; DOI=10.1074/jbc.M800267200;
RA Zaun H.C., Shrier A., Orlowski J.;
RT "Calcineurin B homologous protein 3 promotes the biosynthetic
RT maturation, cell surface stability, and optimal transport of the
RT Na+/H+ exchanger NHE1 isoform.";
RL J. Biol. Chem. 283:12456-12467(2008).
RN [10]
RP FUNCTION IN GRANULOCYTIC DIFFERENTIATION, INDUCTION, AND TISSUE
RP SPECIFICITY.
RX PubMed=20060826; DOI=10.1016/j.yexcr.2010.01.007;
RA Levay K., Slepak V.Z.;
RT "Up- or downregulation of tescalcin in HL-60 cells is associated with
RT their differentiation to either granulocytic or macrophage-like
RT lineage.";
RL Exp. Cell Res. 316:1254-1262(2010).
RN [11]
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: Functions as an integral cofactor in cell pH regulation
CC by controlling plasma membrane-type Na(+)/H(+) exchange activity.
CC Promotes the maturation, transport, cell surface stability and
CC exchange activity of SLC9A1/NHE1 at the plasma membrane. Promotes
CC the induction of hematopoietic stem cell differentiation toward
CC megakaryocytic lineage. Essential for the coupling of ERK cascade
CC activation with the expression of ETS family genes in
CC megakaryocytic differentiation. Also involved in granulocytic
CC differentiation in a ERK-dependent manner. Inhibits the
CC phosphatase activity of calcineurin.
CC -!- SUBUNIT: Monomer. Homodimer; disulfide-linked (By similarity).
CC Interacts with SLC9A1/NHE1 (via juxtamembrane region of the
CC cytoplasmic C-terminus); the interaction enable an optimal
CC Na(+)/H(+) exchange activity.
CC -!- INTERACTION:
CC Q9NP66:HMG20A; NbExp=2; IntAct=EBI-740653, EBI-740641;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Membrane (By
CC similarity). Cell membrane. Cell projection, lamellipodium (By
CC similarity). Cell projection, ruffle membrane (By similarity).
CC Note=Colocalizes with SLC9A1 at the plasma membrane.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q96BS2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96BS2-2; Sequence=VSP_035518, VSP_035519;
CC Name=3;
CC IsoId=Q96BS2-3; Sequence=VSP_045287;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed in mature megakaryocytes and
CC polymorphonuclear granulocytes (at protein level). Abundantly
CC expressed in heart. Also expressed at a lower level in adult
CC testis and salivary gland, and in the placenta.
CC -!- DEVELOPMENTAL STAGE: Strongly up-regulated in K562 cells treated
CC by PMA to promote megakaryocytic differentiation, but not when
CC treated by DMSO to promote granulocytic differentiation or by
CC hemin to promote erythroid differentiation (at protein level).
CC -!- INDUCTION: Up-regulated during granulocytic differentiation in a
CC ERK-dependent manner (is mediated by activation of ERK) (at
CC protein level). Up-regulated during the differentiation and
CC maturation of primary megakaryocytes. Down-regulated during
CC monocytic-macrophage differentiation in a ERK-dependent manner.
CC -!- DOMAIN: Binds calcium via its EF-hands. Calcium-binding mediates a
CC conformational change. Can also bind magnesium (By similarity).
CC -!- SIMILARITY: Belongs to the calcineurin regulatory subunit family.
CC CHP subfamily.
CC -!- SIMILARITY: Contains 1 EF-hand domain.
CC -!- CAUTION: Although PubMed:12809501 reports that TESC results in a
CC decrease in transporter activity of human SLC9A1, studies with rat
CC SLC9A1 (PubMed:18321853) show that TESC-binding results in the
CC maturation and accumulation of SLC9A1 at the cell surface.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA91288.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=EAW98101.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC -----------------------------------------------------------------------
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DR EMBL; AF443207; AAL35615.1; -; mRNA.
DR EMBL; AK000614; BAA91288.1; ALT_INIT; mRNA.
DR EMBL; AC026368; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471054; EAW98101.1; ALT_INIT; Genomic_DNA.
DR EMBL; BC015221; AAH15221.1; -; mRNA.
DR EMBL; BQ949772; -; NOT_ANNOTATED_CDS; mRNA.
DR RefSeq; NP_001161797.1; NM_001168325.1.
DR RefSeq; NP_060369.3; NM_017899.3.
DR UniGene; Hs.525709; -.
DR ProteinModelPortal; Q96BS2; -.
DR SMR; Q96BS2; 9-214.
DR IntAct; Q96BS2; 4.
DR MINT; MINT-1477844; -.
DR STRING; 9606.ENSP00000376328; -.
DR PhosphoSite; Q96BS2; -.
DR DMDM; 284018160; -.
DR PaxDb; Q96BS2; -.
DR PRIDE; Q96BS2; -.
DR DNASU; 54997; -.
DR Ensembl; ENST00000335209; ENSP00000334785; ENSG00000088992.
DR Ensembl; ENST00000470612; ENSP00000432716; ENSG00000088992.
DR Ensembl; ENST00000541210; ENSP00000445689; ENSG00000088992.
DR GeneID; 54997; -.
DR KEGG; hsa:54997; -.
DR UCSC; uc021rem.1; human.
DR CTD; 54997; -.
DR GeneCards; GC12M117477; -.
DR HGNC; HGNC:26065; TESC.
DR HPA; HPA053200; -.
DR MIM; 611585; gene.
DR neXtProt; NX_Q96BS2; -.
DR PharmGKB; PA143485630; -.
DR eggNOG; COG5126; -.
DR HOGENOM; HOG000233019; -.
DR HOVERGEN; HBG105313; -.
DR InParanoid; Q96BS2; -.
DR KO; K17612; -.
DR OrthoDB; EOG7NSB38; -.
DR ChiTaRS; TESC; human.
DR GenomeRNAi; 54997; -.
DR NextBio; 58314; -.
DR PRO; PR:Q96BS2; -.
DR ArrayExpress; Q96BS2; -.
DR Bgee; Q96BS2; -.
DR CleanEx; HS_TESC; -.
DR Genevestigator; Q96BS2; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0001726; C:ruffle; ISS:UniProtKB.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0019212; F:phosphatase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0004860; F:protein kinase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0071300; P:cellular response to retinoic acid; IDA:UniProtKB.
DR GO; GO:0008584; P:male gonad development; IEA:Ensembl.
DR GO; GO:0030219; P:megakaryocyte differentiation; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell proliferation; IMP:UniProtKB.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; IEA:GOC.
DR GO; GO:0030854; P:positive regulation of granulocyte differentiation; IDA:UniProtKB.
DR GO; GO:0045654; P:positive regulation of megakaryocyte differentiation; IMP:UniProtKB.
DR GO; GO:0032417; P:positive regulation of sodium:hydrogen antiporter activity; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-dependent; IMP:UniProtKB.
DR GO; GO:0051604; P:protein maturation; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IDA:UniProtKB.
DR GO; GO:0072661; P:protein targeting to plasma membrane; IDA:UniProtKB.
DR GO; GO:0033628; P:regulation of cell adhesion mediated by integrin; IMP:UniProtKB.
DR Gene3D; 1.10.238.10; -; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR Pfam; PF13405; EF-hand_6; 1.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS50222; EF_HAND_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Cell membrane; Cell projection;
KW Complete proteome; Cytoplasm; Differentiation; Disulfide bond;
KW Lipoprotein; Membrane; Metal-binding; Myristate; Nucleus;
KW Protein kinase inhibitor; Protein transport; Reference proteome;
KW Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 214 Calcineurin B homologous protein 3.
FT /FTId=PRO_0000073859.
FT DOMAIN 110 145 EF-hand.
FT CA_BIND 123 134 By similarity.
FT LIPID 2 2 N-myristoyl glycine.
FT VAR_SEQ 43 69 Missing (in isoform 3).
FT /FTId=VSP_045287.
FT VAR_SEQ 139 163 VEELLSGNPHIEKESARSIADGAMM -> KWSRSCCRETLT
FT SRRSPLAPSPTGP (in isoform 2).
FT /FTId=VSP_035518.
FT VAR_SEQ 164 214 Missing (in isoform 2).
FT /FTId=VSP_035519.
FT CONFLICT 209 211 TMA -> NMG (in Ref. 5; BQ949772).
SQ SEQUENCE 214 AA; 24750 MW; AB3DBE6EA3EB5E60 CRC64;
MGAAHSASEE VRELEGKTGF SSDQIEQLHR RFKQLSGDQP TIRKENFNNV PDLELNPIRS
KIVRAFFDNR NLRKGPSGLA DEINFEDFLT IMSYFRPIDT TMDEEQVELS RKEKLRFLFH
MYDSDSDGRI TLEEYRNVVE ELLSGNPHIE KESARSIADG AMMEAASVCM GQMEPDQVYE
GITFEDFLKI WQGIDIETKM HVRFLNMETM ALCH
//
MIM
611585
*RECORD*
*FIELD* NO
611585
*FIELD* TI
*611585 TESCALCIN, MOUSE, HOMOLOG OF; TESC
;;TSC
*FIELD* TX
CLONING
Using differential display analysis, Perera et al. (2001) cloned Tesc
read morefrom embryonic mouse testis. The deduced 214-amino acid protein has a
central EF-hand Ca(2+)-binding domain, several phosphorylation sites,
and an N-myristoylation site. Northern blot analysis of adult mouse
tissues detected strong expression of Tesc in heart only. RT-PCR
detected Tesc expression in mouse testis beginning at 11.5 days
postcoitum, with peak expression at 14.5 days postcoitum. Weaker
expression was detected in adult testis and ovary, and Tesc was also
expressed in testis devoid of germ cells. In situ hybridization revealed
Tesc in the developing sex cord of testis, but not in ovary.
Using the cytosolic C-terminal domain of the Na+/H+ exchanger NHE1
(SLC9A1; 107310) as bait in a yeast 2-hybrid screen, Mailander et al.
(2001) cloned human TSC from a placenta cDNA library. The deduced
214-amino acid protein, which shares 96.7% identity with mouse Tsc,
contains a central EF-hand Ca(2+)-binding domain and an N-myristoylation
site. Northern blot analysis detected a 1.3-kb transcript highly
expressed in heart and weakly expressed in adult testis and salivary
gland. PCR analysis detected TSC expression in placenta. Overexpressed
epitope-labeled TSC localized to the cytosol and lamellipodia of mouse
fibroblasts.
Levay and Slepak (2007) stated that TESC is expressed in primary human
blood cells and hematopoietic cell lines and that mouse Tesc is
expressed in adult heart, brain, stomach, and bone marrow and in fetal
liver.
GENE FUNCTION
Using protein pull-down assays and coimmunoprecipitation analysis,
Mailander et al. (2001) confirmed that TESC interacted with the
C-terminal domain of NHE1. A calcium overlay assay showed that TSC bound
calcium.
Levay and Slepak (2007) showed that expression of TESC was upregulated
during differentiation and maturation of mouse primary megakaryocytes
and upon phorbol ester-induced differentiation of human K562 cells. TESC
upregulation required sustained signaling through the ERK (see MAPK3;
601795) pathway. Overexpression of TESC in K562 cells initiated events
of megakaryocytic differentiation, including expression of specific cell
surface antigens, inhibition of cell proliferation, and
polyploidization. Conversely, knockdown of TESC in primary CD34
(142230)-positive hematopoietic progenitors and cell lines by RNA
interference suppressed megakaryocytic differentiation. In cells lacking
TESC, expression of the transcription factors FLI1 (193067), ETS1
(164720), and ETS2 (164740), but not GATA1 (305371) or MAFB (608968),
was blocked. Levay and Slepak (2007) concluded that TESC is essential
for coupling ERK signaling with expression of ETS family genes during
megakaryocytic differentiation.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the TESC
gene to chromosome 12 (TMAP RH91363).
Perera et al. (2001) mapped the mouse Tesc gene to distal chromosome 5F.
*FIELD* RF
1. Levay, K.; Slepak, V. Z.: Tescalcin is an essential factor in
megakaryocytic differentiation associated with Ets family gene expression. J.
Clin. Invest. 117: 2672-2683, 2007.
2. Mailander, J.; Muller-Esterl, W.; Dedio, J.: Human homolog of
mouse tescalcin associates with Na+/H+ exchanger type-1. FEBS Lett. 507:
331-335, 2001.
3. Perera, E. M.; Martin, H.; Seeherunvong, T.; Kos, L.; Hughes, I.
A.; Hawkins, J. R.; Berkovitz, G. D.: Tescalcin, a novel gene encoding
a putative EF-hand Ca(2+)-binding protein, Col9a3, and renin are expressed
in the mouse testis during the early stages of gonadal differentiation. Endocrinology 142:
455-463, 2001.
*FIELD* CD
Patricia A. Hartz: 11/6/2007
*FIELD* ED
mgross: 11/06/2007
*RECORD*
*FIELD* NO
611585
*FIELD* TI
*611585 TESCALCIN, MOUSE, HOMOLOG OF; TESC
;;TSC
*FIELD* TX
CLONING
Using differential display analysis, Perera et al. (2001) cloned Tesc
read morefrom embryonic mouse testis. The deduced 214-amino acid protein has a
central EF-hand Ca(2+)-binding domain, several phosphorylation sites,
and an N-myristoylation site. Northern blot analysis of adult mouse
tissues detected strong expression of Tesc in heart only. RT-PCR
detected Tesc expression in mouse testis beginning at 11.5 days
postcoitum, with peak expression at 14.5 days postcoitum. Weaker
expression was detected in adult testis and ovary, and Tesc was also
expressed in testis devoid of germ cells. In situ hybridization revealed
Tesc in the developing sex cord of testis, but not in ovary.
Using the cytosolic C-terminal domain of the Na+/H+ exchanger NHE1
(SLC9A1; 107310) as bait in a yeast 2-hybrid screen, Mailander et al.
(2001) cloned human TSC from a placenta cDNA library. The deduced
214-amino acid protein, which shares 96.7% identity with mouse Tsc,
contains a central EF-hand Ca(2+)-binding domain and an N-myristoylation
site. Northern blot analysis detected a 1.3-kb transcript highly
expressed in heart and weakly expressed in adult testis and salivary
gland. PCR analysis detected TSC expression in placenta. Overexpressed
epitope-labeled TSC localized to the cytosol and lamellipodia of mouse
fibroblasts.
Levay and Slepak (2007) stated that TESC is expressed in primary human
blood cells and hematopoietic cell lines and that mouse Tesc is
expressed in adult heart, brain, stomach, and bone marrow and in fetal
liver.
GENE FUNCTION
Using protein pull-down assays and coimmunoprecipitation analysis,
Mailander et al. (2001) confirmed that TESC interacted with the
C-terminal domain of NHE1. A calcium overlay assay showed that TSC bound
calcium.
Levay and Slepak (2007) showed that expression of TESC was upregulated
during differentiation and maturation of mouse primary megakaryocytes
and upon phorbol ester-induced differentiation of human K562 cells. TESC
upregulation required sustained signaling through the ERK (see MAPK3;
601795) pathway. Overexpression of TESC in K562 cells initiated events
of megakaryocytic differentiation, including expression of specific cell
surface antigens, inhibition of cell proliferation, and
polyploidization. Conversely, knockdown of TESC in primary CD34
(142230)-positive hematopoietic progenitors and cell lines by RNA
interference suppressed megakaryocytic differentiation. In cells lacking
TESC, expression of the transcription factors FLI1 (193067), ETS1
(164720), and ETS2 (164740), but not GATA1 (305371) or MAFB (608968),
was blocked. Levay and Slepak (2007) concluded that TESC is essential
for coupling ERK signaling with expression of ETS family genes during
megakaryocytic differentiation.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the TESC
gene to chromosome 12 (TMAP RH91363).
Perera et al. (2001) mapped the mouse Tesc gene to distal chromosome 5F.
*FIELD* RF
1. Levay, K.; Slepak, V. Z.: Tescalcin is an essential factor in
megakaryocytic differentiation associated with Ets family gene expression. J.
Clin. Invest. 117: 2672-2683, 2007.
2. Mailander, J.; Muller-Esterl, W.; Dedio, J.: Human homolog of
mouse tescalcin associates with Na+/H+ exchanger type-1. FEBS Lett. 507:
331-335, 2001.
3. Perera, E. M.; Martin, H.; Seeherunvong, T.; Kos, L.; Hughes, I.
A.; Hawkins, J. R.; Berkovitz, G. D.: Tescalcin, a novel gene encoding
a putative EF-hand Ca(2+)-binding protein, Col9a3, and renin are expressed
in the mouse testis during the early stages of gonadal differentiation. Endocrinology 142:
455-463, 2001.
*FIELD* CD
Patricia A. Hartz: 11/6/2007
*FIELD* ED
mgross: 11/06/2007