CHP3_MOUSE
ID CHP3_MOUSE Reviewed; 214 AA.
AC Q9JKL5; Q32Q85; Q8VCN1;
DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Calcineurin B homologous protein 3;
DE AltName: Full=Tescalcin;
DE Short=TE-1;
DE Short=TSC;
GN Name=Tesc; Synonyms=Chp3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=CD-1; TISSUE=Embryonic gonad;
RX PubMed=11145610; DOI=10.1210/endo.142.1.7882;
RA Perera E.M., Martin H., Seeherunvong T., Kos L., Hughes I.A., Hawkins J.R.,
RA Berkovitz G.D.;
RT "Tescalcin, a novel gene encoding a putative EF-hand Ca(2+)-binding
RT protein, Col9a3, and renin are expressed in the mouse testis during the
RT early stages of gonadal differentiation.";
RL Endocrinology 142:455-463(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Kidney, and Mammary tumor;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION AS A CALCINEURIN INHIBITOR, HOMODIMERIZATION, MAGNESIUM-BINDING,
RP CALCIUM-BINDING, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS
RP OF ASP-123.
RX PubMed=14661968; DOI=10.1021/bi034870f;
RA Gutierrez-Ford C., Levay K., Gomes A.V., Perera E.M., Som T., Kim Y.M.,
RA Benovic J.L., Berkovitz G.D., Slepak V.Z.;
RT "Characterization of tescalcin, a novel EF-hand protein with a single Ca2+-
RT binding site: metal-binding properties, localization in tissues and cells,
RT and effect on calcineurin.";
RL Biochemistry 42:14553-14565(2003).
RN [4]
RP TISSUE SPECIFICITY.
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 [5]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=19345287; DOI=10.1016/j.gep.2009.03.004;
RA Bao Y., Hudson Q.J., Perera E.M., Akan L., Tobet S.A., Smith C.A.,
RA Sinclair A.H., Berkovitz G.D.;
RT "Expression and evolutionary conservation of the tescalcin gene during
RT development.";
RL Gene Expr. Patterns 9:273-281(2009).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP ABSENCE OF FUNCTION IN MEGAKARYOCYTE DEVELOPMENT, AND DISRUPTION PHENOTYPE.
RX PubMed=22285131; DOI=10.1016/j.yexcr.2012.01.009;
RA Ukarapong S., Bao Y., Perera E.M., Berkovitz G.D.;
RT "Megakaryocyte development is normal in mice with targeted disruption of
RT Tescalcin.";
RL Exp. Cell Res. 318:662-669(2012).
CC -!- FUNCTION: Functions as an integral cofactor in cell pH regulation by
CC controlling plasma membrane-type Na(+)/H(+) exchange activity. Promotes
CC the maturation, transport, cell surface stability and exchange activity
CC of SLC9A1/NHE1 at the plasma membrane. Promotes the induction of
CC hematopoietic stem cell differentiation toward megakaryocytic lineage.
CC Essential for the coupling of ERK cascade activation with the
CC expression of ETS family genes in megakaryocytic differentiation. Also
CC involved in granulocytic differentiation in a ERK-dependent manner.
CC Inhibits the phosphatase activity of calcineurin.
CC {ECO:0000269|PubMed:14661968}.
CC -!- SUBUNIT: Monomer (PubMed:14661968). Homodimer; disulfide-linked
CC (PubMed:14661968). Interacts with SLC9A1/NHE1; the interaction enables
CC an optimal Na(+)/H(+) exchange activity (By similarity).
CC {ECO:0000250|UniProtKB:Q96BS2, ECO:0000269|PubMed:14661968}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14661968}. Cytoplasm
CC {ECO:0000269|PubMed:14661968}. Membrane {ECO:0000250|UniProtKB:Q96BS2};
CC Lipid-anchor {ECO:0000250|UniProtKB:Q96BS2}. Cell membrane
CC {ECO:0000250|UniProtKB:Q96BS2}. Cell projection, lamellipodium
CC {ECO:0000269|PubMed:14661968}. Cell projection, ruffle membrane
CC {ECO:0000269|PubMed:14661968}. Note=Colocalizes with SLC9A1 at the cell
CC membrane. {ECO:0000250|UniProtKB:Q96BS2}.
CC -!- TISSUE SPECIFICITY: Expressed in embryonic, newborn and adult testis,
CC but not in prepubertal testis. Expressed in the embryonic testis during
CC testis determination but is not expressed at any time in the embryonic
CC ovary. In embryonic testis, expression is restricted to the testis
CC cords and is seen in both Sertoli cells and germ cells. Expression is
CC excluded from the myoid cells which surround the cords. Expressed in
CC the embryonic adrenal after the initial stages of differentiation.
CC Expressed at a lower level in the embryonic brain, heart and lung but
CC not in liver or gut. May be expressed at a very low level in the
CC embryonic kidney. In the embryonic brain, expressed in the nasal
CC placode and in fibers extending from the olfactory epithelium to the
CC primordial olfactory bulb. In adults, expressed in the heart, and
CC weakly in the brain and kidney. Highly expressed in terminally
CC differentiated megakaryocytes (at protein level). Not detected in fetal
CC liver cells (at protein level). {ECO:0000269|PubMed:11145610,
CC ECO:0000269|PubMed:14661968, ECO:0000269|PubMed:17717601,
CC ECO:0000269|PubMed:19345287}.
CC -!- DEVELOPMENTAL STAGE: Expression is first detected in the male gonad at
CC 11.5 dpc, peaks at 14.5 dpc, declines slightly by 15.5 dpc, and
CC continues to at least 17.5 dpc. {ECO:0000269|PubMed:11145610}.
CC -!- DOMAIN: Binds calcium via its EF-hands. Calcium-binding mediates a
CC conformational change. Can also bind magnesium.
CC -!- DISRUPTION PHENOTYPE: According PubMed:22285131, mice show a normal
CC number of megakaryocytes and platelets. {ECO:0000269|PubMed:22285131}.
CC -!- SIMILARITY: Belongs to the calcineurin regulatory subunit family. CHP
CC subfamily. {ECO:0000305}.
CC -!- CAUTION: The region of SLC9A1/NHE1 that interacts with CHP3 is
CC conflicting: In human, interaction with SLC9A1/NHE1 has been reported
CC via residues 507-549, the juxtamembrane region of the cytoplasmic C-
CC terminus. However, another publication has reported interaction with
CC SLC9A1/NHE1 via residues 637-820, the region of the cytoplasmic C-
CC terminus more distal to the membrane. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF234783; AAF40439.1; -; mRNA.
DR EMBL; BC019492; AAH19492.1; -; mRNA.
DR EMBL; BC107679; AAI07680.1; -; mRNA.
DR CCDS; CCDS19608.1; -.
DR RefSeq; NP_067319.2; NM_021344.3.
DR AlphaFoldDB; Q9JKL5; -.
DR SMR; Q9JKL5; -.
DR BioGRID; 208338; 2.
DR STRING; 10090.ENSMUSP00000031304; -.
DR iPTMnet; Q9JKL5; -.
DR PhosphoSitePlus; Q9JKL5; -.
DR SwissPalm; Q9JKL5; -.
DR EPD; Q9JKL5; -.
DR MaxQB; Q9JKL5; -.
DR PaxDb; Q9JKL5; -.
DR PRIDE; Q9JKL5; -.
DR ProteomicsDB; 281467; -.
DR Antibodypedia; 45432; 180 antibodies from 24 providers.
DR DNASU; 57816; -.
DR Ensembl; ENSMUST00000031304; ENSMUSP00000031304; ENSMUSG00000029359.
DR GeneID; 57816; -.
DR KEGG; mmu:57816; -.
DR UCSC; uc008zgc.1; mouse.
DR CTD; 54997; -.
DR MGI; MGI:1930803; Tesc.
DR VEuPathDB; HostDB:ENSMUSG00000029359; -.
DR eggNOG; KOG0034; Eukaryota.
DR GeneTree; ENSGT00940000155845; -.
DR HOGENOM; CLU_061288_10_0_1; -.
DR InParanoid; Q9JKL5; -.
DR OMA; EIETRMH; -.
DR OrthoDB; 1271942at2759; -.
DR PhylomeDB; Q9JKL5; -.
DR TreeFam; TF354284; -.
DR BioGRID-ORCS; 57816; 1 hit in 75 CRISPR screens.
DR PRO; PR:Q9JKL5; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q9JKL5; protein.
DR Bgee; ENSMUSG00000029359; Expressed in facial nucleus and 210 other tissues.
DR ExpressionAtlas; Q9JKL5; baseline and differential.
DR Genevisible; Q9JKL5; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030027; C:lamellipodium; IDA:HGNC-UCL.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:HGNC-UCL.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0001726; C:ruffle; IDA:HGNC-UCL.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IDA:HGNC-UCL.
DR GO; GO:0000287; F:magnesium ion binding; IDA:HGNC-UCL.
DR GO; GO:0019212; F:phosphatase inhibitor activity; IDA:HGNC-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0004860; F:protein kinase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0071300; P:cellular response to retinoic acid; ISS:UniProtKB.
DR GO; GO:0006883; P:cellular sodium ion homeostasis; ISO:MGI.
DR GO; GO:0008584; P:male gonad development; IEP:UniProtKB.
DR GO; GO:0030219; P:megakaryocyte differentiation; IEP:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0030854; P:positive regulation of granulocyte differentiation; ISS:UniProtKB.
DR GO; GO:0045654; P:positive regulation of megakaryocyte differentiation; ISS:UniProtKB.
DR GO; GO:0032417; P:positive regulation of sodium:proton antiporter activity; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISS:UniProtKB.
DR GO; GO:0051604; P:protein maturation; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0033628; P:regulation of cell adhesion mediated by integrin; ISS:UniProtKB.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR SMART; SM00054; EFh; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS50222; EF_HAND_2; 1.
PE 1: Evidence at protein level;
KW Calcium; Cell membrane; Cell projection; Cytoplasm; Differentiation;
KW Disulfide bond; Lipoprotein; Membrane; Metal-binding; Myristate; Nucleus;
KW Protein kinase inhibitor; Protein transport; Reference proteome; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q96BS2"
FT CHAIN 2..214
FT /note="Calcineurin B homologous protein 3"
FT /id="PRO_0000073860"
FT DOMAIN 110..145
FT /note="EF-hand"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 123
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 125
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 127
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 129
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 134
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250|UniProtKB:Q96BS2"
FT MUTAGEN 123
FT /note="D->A: Abolishes calcium-binding. Does not alter
FT subcellular localization and does not prevent inhibition of
FT calcineurin activity."
FT /evidence="ECO:0000269|PubMed:14661968"
FT CONFLICT 85
FT /note="F -> L (in Ref. 1; AAF40439)"
FT /evidence="ECO:0000305"
FT CONFLICT 97
FT /note="P -> S (in Ref. 2; AAI07680)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 214 AA; 24600 MW; 015CFF4379DC1F0E CRC64;
MGAAHSASEE VRELEGKTGF SSDQIEQLHR RFKQLSGDQP TIRKENFNNV PDLELNPIRS
KIVRAFFDNR NLRKGSSGLA DEINFEDFLT IMSYFRPIDT TLGEEQVELS RKEKLKFLFH
MYDSDSDGRI TLEEYRNVVE ELLSGNPHIE KESARSIADG AMMEAASVCV GQMEPDQVYE
GITFEDFLKI WQGIDIETKM HIRFLNMETI ALCH
