CHP1_HUMAN
ID CHP1_HUMAN Reviewed; 195 AA.
AC Q99653; B2R6H9; Q6FHZ9;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=Calcineurin B homologous protein 1;
DE AltName: Full=Calcineurin B-like protein;
DE AltName: Full=Calcium-binding protein CHP;
DE AltName: Full=Calcium-binding protein p22;
DE AltName: Full=EF-hand calcium-binding domain-containing protein p22;
GN Name=CHP1; Synonyms=CHP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION IN PH REGULATION, CALCIUM-BINDING,
RP INTERACTION WITH SLC9A1, PHOSPHORYLATION, AND TISSUE SPECIFICITY.
RC TISSUE=B-cell;
RX PubMed=8901634; DOI=10.1073/pnas.93.22.12631;
RA Lin X., Barber D.L.;
RT "A calcineurin homologous protein inhibits GTPase-stimulated Na-H
RT exchange.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:12631-12636(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
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 [6]
RP FUNCTION AS A CALCINEURIN INHIBITOR, AND INTERACTION WITH PPP3CA.
RX PubMed=10593895; DOI=10.1074/jbc.274.51.36125;
RA Lin X., Sikkink R.A., Rusnak F., Barber D.L.;
RT "Inhibition of calcineurin phosphatase activity by a calcineurin B
RT homologous protein.";
RL J. Biol. Chem. 274:36125-36131(1999).
RN [7]
RP FUNCTION, INTERACTION WITH SLC9A1, AND SUBCELLULAR LOCATION.
RX PubMed=11350981; DOI=10.1074/jbc.m100296200;
RA Pang T., Su X., Wakabayashi S., Shigekawa M.;
RT "Calcineurin homologous protein as an essential cofactor for Na+/H+
RT exchangers.";
RL J. Biol. Chem. 276:17367-17372(2001).
RN [8]
RP FUNCTION, INTERACTION WITH SLC9A1, SUBCELLULAR LOCATION, CALCIUM-BINDING,
RP AND MUTAGENESIS OF ASP-50; GLU-134 AND GLU-175.
RX PubMed=15035633; DOI=10.1021/bi0360004;
RA Pang T., Hisamitsu T., Mori H., Shigekawa M., Wakabayashi S.;
RT "Role of calcineurin B homologous protein in pH regulation by the Na+/H+
RT exchanger 1: tightly bound Ca2+ ions as important structural elements.";
RL Biochemistry 43:3628-3636(2004).
RN [9]
RP MUTAGENESIS OF VAL-143; VAL-145; ILE-147; VAL-183 AND VAL-185.
RX PubMed=20720019; DOI=10.1074/jbc.m110.165555;
RA Jimenez-Vidal M., Srivastava J., Putney L.K., Barber D.L.;
RT "Nuclear-localized calcineurin homologous protein CHP1 interacts with
RT upstream binding factor and inhibits ribosomal RNA synthesis.";
RL J. Biol. Chem. 285:36260-36266(2010).
RN [10]
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., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [13]
RP MYRISTOYLATION AT GLY-2, CLEAVAGE OF INITIATOR METHIONINE, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=25255805; DOI=10.1038/ncomms5919;
RA Thinon E., Serwa R.A., Broncel M., Brannigan J.A., Brassat U., Wright M.H.,
RA Heal W.P., Wilkinson A.J., Mann D.J., Tate E.W.;
RT "Global profiling of co- and post-translationally N-myristoylated proteomes
RT in human cells.";
RL Nat. Commun. 5:4919-4919(2014).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [15]
RP STRUCTURE BY NMR OF 1-195 IN COMPLEX WITH CALCIUM IONS AND SLC9A1.
RX PubMed=17050540; DOI=10.1074/jbc.m604092200;
RA Mishima M., Wakabayashi S., Kojima C.;
RT "Solution structure of the cytoplasmic region of Na+/H+ exchanger 1
RT complexed with essential cofactor calcineurin B homologous protein 1.";
RL J. Biol. Chem. 282:2741-2751(2007).
RN [16]
RP SUBCELLULAR LOCATION, INVOLVEMENT IN SPAX9, VARIANT SPAX9 LYS-19 DEL, AND
RP CHARACTERIZATION OF VARIANT SPAX9 LYS-19 DEL.
RX PubMed=29379881; DOI=10.1212/nxg.0000000000000209;
RA Mendoza-Ferreira N., Coutelier M., Janzen E., Hosseinibarkooie S.,
RA Loehr H., Schneider S., Milbradt J., Karakaya M., Riessland M., Pichlo C.,
RA Torres-Benito L., Singleton A., Zuchner S., Brice A., Durr A.,
RA Hammerschmidt M., Stevanin G., Wirth B.;
RT "Biallelic CHP1 mutation causes human autosomal recessive ataxia by
RT impairing NHE1 function.";
RL Neurol. Genet. 4:E209-E209(2018).
CC -!- FUNCTION: Calcium-binding protein involved in different processes such
CC as regulation of vesicular trafficking, plasma membrane Na(+)/H(+)
CC exchanger and gene transcription. Involved in the constitutive exocytic
CC membrane traffic. Mediates the association between microtubules and
CC membrane-bound organelles of the endoplasmic reticulum and Golgi
CC apparatus and is also required for the targeting and fusion of
CC transcytotic vesicles (TCV) with the plasma membrane. Functions as an
CC integral cofactor in cell pH regulation by controlling plasma membrane-
CC type Na(+)/H(+) exchange activity. Affects the pH sensitivity of
CC SLC9A1/NHE1 by increasing its sensitivity at acidic pH. Required for
CC the stabilization and localization of SLC9A1/NHE1 at the plasma
CC membrane. Inhibits serum- and GTPase-stimulated Na(+)/H(+) exchange.
CC Plays a role as an inhibitor of ribosomal RNA transcription by
CC repressing the nucleolar UBF1 transcriptional activity. May sequester
CC UBF1 in the nucleoplasm and limit its translocation to the nucleolus.
CC Associates to the ribosomal gene promoter. Acts as a negative regulator
CC of the calcineurin/NFAT signaling pathway. Inhibits NFAT nuclear
CC translocation and transcriptional activity by suppressing the calcium-
CC dependent calcineurin phosphatase activity. Also negatively regulates
CC the kinase activity of the apoptosis-induced kinase STK17B. Inhibits
CC both STK17B auto- and substrate-phosphorylations in a calcium-dependent
CC manner. {ECO:0000269|PubMed:10593895, ECO:0000269|PubMed:11350981,
CC ECO:0000269|PubMed:15035633, ECO:0000269|PubMed:8901634}.
CC -!- SUBUNIT: Monomer. Interacts with STK17B; the interaction occurs in a
CC calcium-independent manner and induces the translocation of CHP1 from
CC the Golgi to the nucleus. Interacts with GAPDH; the interaction is
CC direct, occurs in a N-myristoylation-dependent manner and facilitates
CC the ability of CHP1 to bind microtubules. Interacts with KIF1B (via the
CC C-terminal end of the kinesin-motor domain); the interaction occurs in
CC a calcium-dependent manner. Associates (via C-terminal domain) with
CC microtubules; the association occurs with polymerized microtubules
CC during the cell cycle in a myristoylation- and calcium-independent
CC manner and is enhanced by GAPDH (By similarity). Interacts with PPP3CA.
CC Interacts with SLC9A1/NHE1 (via the juxtamembrane region of the
CC cytoplasmic C-terminal domain); the interaction occurs at the plasma
CC membrane in a calcium-dependent manner and at a domain that is critical
CC for growth factor stimulation of the exchanger.
CC {ECO:0000250|UniProtKB:P61022, ECO:0000269|PubMed:10593895,
CC ECO:0000269|PubMed:11350981, ECO:0000269|PubMed:15035633,
CC ECO:0000269|PubMed:17050540, ECO:0000269|PubMed:8901634}.
CC -!- INTERACTION:
CC Q99653; P19634: SLC9A1; NbExp=3; IntAct=EBI-722721, EBI-743635;
CC Q99653; A0A142I5B9; Xeno; NbExp=2; IntAct=EBI-722721, EBI-20625235;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P61023}. Cytoplasm
CC {ECO:0000250|UniProtKB:P61023}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:P61023}. Endomembrane system
CC {ECO:0000250|UniProtKB:P61023}. Endoplasmic reticulum-Golgi
CC intermediate compartment {ECO:0000250|UniProtKB:P61023}. Endoplasmic
CC reticulum {ECO:0000250|UniProtKB:P61023}. Cell membrane
CC {ECO:0000269|PubMed:15035633, ECO:0000269|PubMed:29379881}. Membrane
CC {ECO:0000269|PubMed:11350981, ECO:0000269|PubMed:29379881}; Lipid-
CC anchor {ECO:0000269|PubMed:25255805}. Note=Localizes in cytoplasmic
CC compartments in dividing cells. Localizes in the nucleus in quiescent
CC cells. Exported from the nucleus to the cytoplasm through a nuclear
CC export signal (NES) and CRM1-dependent pathway. May shuttle between
CC nucleus and cytoplasm. Localizes with the microtubule-organizing center
CC (MTOC) and extends toward the periphery along microtubules. Associates
CC with membranes of the early secretory pathway in a GAPDH-independent,
CC N-myristoylation- and calcium-dependent manner. Colocalizes with the
CC mitotic spindle microtubules. Colocalizes with GAPDH along
CC microtubules. Colocalizes with SLC9A1 at the reticulum endoplasmic and
CC plasma membrane. Colocalizes with STK17B at the plasma membrane.
CC {ECO:0000250|UniProtKB:P61023}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Has been found in fetal
CC eye, lung, liver, muscle, heart, kidney, thymus and spleen.
CC {ECO:0000269|PubMed:8901634}.
CC -!- PTM: Phosphorylated; decreased phosphorylation is associated with an
CC increase in SLC9A1/NHE1 Na(+)/H(+) exchange activity. Phosphorylation
CC occurs in serum-dependent manner. The phosphorylation state may
CC regulate the binding to SLC9A1/NHE1. {ECO:0000269|PubMed:8901634}.
CC -!- PTM: Both N-myristoylation and calcium-mediated conformational changes
CC are essential for its function in exocytic traffic (By similarity). N-
CC myristoylation is required for its association with microtubules and
CC interaction with GAPDH, but not for the constitutive association to
CC membranes. {ECO:0000250}.
CC -!- DISEASE: Spastic ataxia 9, autosomal recessive (SPAX9) [MIM:618438]: An
CC autosomal recessive disorder characterized by onset of spastic ataxia
CC in the first years of life. Clinical features include motor neuropathy,
CC cerebellar atrophy, spastic paraparesis, intellectual disability, slow
CC ocular saccades, axial hypotonia, distal muscle weakness and atrophy,
CC and pyramidal symptoms, including hyperreflexia and extensor plantar
CC responses. {ECO:0000269|PubMed:29379881}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the calcineurin regulatory subunit family. CHP
CC subfamily. {ECO:0000305}.
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DR EMBL; U61538; AAB37770.1; -; mRNA.
DR EMBL; CR536539; CAG38776.1; -; mRNA.
DR EMBL; CR542085; CAG46882.1; -; mRNA.
DR EMBL; AK312582; BAG35476.1; -; mRNA.
DR EMBL; CH471125; EAW92474.1; -; Genomic_DNA.
DR EMBL; BC031293; AAH31293.1; -; mRNA.
DR EMBL; BC051815; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS10073.1; -.
DR RefSeq; NP_009167.1; NM_007236.4.
DR PDB; 2E30; NMR; -; A=1-195.
DR PDB; 7DSV; EM; 3.40 A; C/D=11-195.
DR PDB; 7DSX; EM; 3.50 A; C/D=11-195.
DR PDBsum; 2E30; -.
DR PDBsum; 7DSV; -.
DR PDBsum; 7DSX; -.
DR AlphaFoldDB; Q99653; -.
DR SMR; Q99653; -.
DR BioGRID; 116421; 89.
DR IntAct; Q99653; 35.
DR MINT; Q99653; -.
DR STRING; 9606.ENSP00000335632; -.
DR DrugBank; DB11093; Calcium citrate.
DR DrugBank; DB11348; Calcium Phosphate.
DR DrugBank; DB14481; Calcium phosphate dihydrate.
DR TCDB; 8.A.82.1.6; the calmodulin calcium binding protein (calmodulin) family.
DR iPTMnet; Q99653; -.
DR PhosphoSitePlus; Q99653; -.
DR SwissPalm; Q99653; -.
DR BioMuta; CHP1; -.
DR DMDM; 3023439; -.
DR OGP; Q99653; -.
DR EPD; Q99653; -.
DR jPOST; Q99653; -.
DR MassIVE; Q99653; -.
DR MaxQB; Q99653; -.
DR PaxDb; Q99653; -.
DR PeptideAtlas; Q99653; -.
DR PRIDE; Q99653; -.
DR ProteomicsDB; 78381; -.
DR TopDownProteomics; Q99653; -.
DR Antibodypedia; 1886; 239 antibodies from 26 providers.
DR DNASU; 11261; -.
DR Ensembl; ENST00000334660.10; ENSP00000335632.5; ENSG00000187446.12.
DR GeneID; 11261; -.
DR KEGG; hsa:11261; -.
DR MANE-Select; ENST00000334660.10; ENSP00000335632.5; NM_007236.5; NP_009167.1.
DR UCSC; uc001znl.4; human.
DR CTD; 11261; -.
DR DisGeNET; 11261; -.
DR GeneCards; CHP1; -.
DR HGNC; HGNC:17433; CHP1.
DR HPA; ENSG00000187446; Low tissue specificity.
DR MalaCards; CHP1; -.
DR MIM; 606988; gene.
DR MIM; 618438; phenotype.
DR neXtProt; NX_Q99653; -.
DR OpenTargets; ENSG00000187446; -.
DR VEuPathDB; HostDB:ENSG00000187446; -.
DR eggNOG; KOG0034; Eukaryota.
DR GeneTree; ENSGT00940000154629; -.
DR HOGENOM; CLU_061288_10_5_1; -.
DR InParanoid; Q99653; -.
DR OMA; HSFFADS; -.
DR OrthoDB; 1271942at2759; -.
DR PhylomeDB; Q99653; -.
DR TreeFam; TF354284; -.
DR PathwayCommons; Q99653; -.
DR Reactome; R-HSA-2160916; Hyaluronan uptake and degradation.
DR SignaLink; Q99653; -.
DR BioGRID-ORCS; 11261; 58 hits in 1074 CRISPR screens.
DR ChiTaRS; CHP1; human.
DR EvolutionaryTrace; Q99653; -.
DR GeneWiki; CHP_(gene); -.
DR GenomeRNAi; 11261; -.
DR Pharos; Q99653; Tbio.
DR PRO; PR:Q99653; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q99653; protein.
DR Bgee; ENSG00000187446; Expressed in colonic mucosa and 200 other tissues.
DR ExpressionAtlas; Q99653; baseline and differential.
DR Genevisible; Q99653; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; ISS:UniProtKB.
DR GO; GO:0015630; C:microtubule cytoskeleton; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0030133; C:transport vesicle; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0048306; F:calcium-dependent protein binding; IDA:UniProtKB.
DR GO; GO:0019900; F:kinase binding; ISS:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; ISS:UniProtKB.
DR GO; GO:0015459; F:potassium channel regulator activity; TAS:ProtInc.
DR GO; GO:0004860; F:protein kinase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0071468; P:cellular response to acidic pH; ISS:UniProtKB.
DR GO; GO:0031122; P:cytoplasmic microtubule organization; ISS:UniProtKB.
DR GO; GO:0022406; P:membrane docking; ISS:UniProtKB.
DR GO; GO:0061025; P:membrane fusion; ISS:UniProtKB.
DR GO; GO:0061024; P:membrane organization; ISS:UniProtKB.
DR GO; GO:0001578; P:microtubule bundle formation; ISS:UniProtKB.
DR GO; GO:0070885; P:negative regulation of calcineurin-NFAT signaling cascade; IDA:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:0010923; P:negative regulation of phosphatase activity; IDA:UniProtKB.
DR GO; GO:0031953; P:negative regulation of protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0042308; P:negative regulation of protein import into nucleus; IDA:UniProtKB.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; ISS:UniProtKB.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0071073; P:positive regulation of phospholipid biosynthetic process; IMP:FlyBase.
DR GO; GO:0060050; P:positive regulation of protein glycosylation; ISS:UniProtKB.
DR GO; GO:0090314; P:positive regulation of protein targeting to membrane; ISS:UniProtKB.
DR GO; GO:0051222; P:positive regulation of protein transport; ISS:UniProtKB.
DR GO; GO:0032417; P:positive regulation of sodium:proton antiporter activity; IDA:UniProtKB.
DR GO; GO:0006813; P:potassium ion transport; TAS:ProtInc.
DR GO; GO:0006611; P:protein export from nucleus; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR GO; GO:0051453; P:regulation of intracellular pH; IDA:UniProtKB.
DR GO; GO:1901214; P:regulation of neuron death; IMP:UniProtKB.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; TAS:ProtInc.
DR CDD; cd00051; EFh; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR002048; EF_hand_dom.
DR Pfam; PF13499; EF-hand_7; 1.
DR SMART; SM00054; EFh; 2.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS50222; EF_HAND_2; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Cell membrane; Cytoplasm; Cytoskeleton;
KW Disease variant; Endoplasmic reticulum; Lipoprotein; Membrane;
KW Metal-binding; Myristate; Neurodegeneration; Nucleus; Phosphoprotein;
KW Protein kinase inhibitor; Protein transport; Reference proteome; Repeat;
KW Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:25255805"
FT CHAIN 2..195
FT /note="Calcineurin B homologous protein 1"
FT /id="PRO_0000073843"
FT DOMAIN 26..61
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 66..101
FT /note="EF-hand 2"
FT /evidence="ECO:0000305"
FT DOMAIN 110..145
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 151..186
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 143..185
FT /note="Necessary for nuclear export signal"
FT MOTIF 2..6
FT /note="Necessary for association with microtubule and
FT interaction with GAPDH"
FT /evidence="ECO:0000250"
FT MOTIF 138..147
FT /note="Nuclear export signal 1"
FT /evidence="ECO:0000250"
FT MOTIF 176..185
FT /note="Nuclear export signal 2"
FT /evidence="ECO:0000250"
FT BINDING 123
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 125
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 127
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 129
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 134
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 164
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 166
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 168
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 175
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:25255805"
FT VARIANT 19
FT /note="Missing (in SPAX9; decreased protein solubility;
FT decreased protein location at the plasma membrane;
FT dbSNP:rs1310569366)"
FT /evidence="ECO:0000269|PubMed:29379881"
FT /id="VAR_083033"
FT MUTAGEN 50
FT /note="D->A: Does not reduce calcium-binding,
FT colocalization and interaction with SLC9A1."
FT /evidence="ECO:0000269|PubMed:15035633"
FT MUTAGEN 134
FT /note="E->A: Reduces calcium-binding and SLC9A1-dependent
FT Na(+)/H(+) exchange activity. Does not reduce
FT colocalization and interaction with SLC9A1. Reduces
FT colocalization and interaction with SLC9A1; when associated
FT with A-175."
FT /evidence="ECO:0000269|PubMed:15035633"
FT MUTAGEN 143
FT /note="V->A: Inhibits translocation to the cytoplasm; when
FT associated with A-145; A-147; A-183 and A-185."
FT /evidence="ECO:0000269|PubMed:20720019"
FT MUTAGEN 145
FT /note="V->A: Inhibits translocation to the cytoplasm; when
FT associated with A-143; A-147; A-183 and A-185."
FT /evidence="ECO:0000269|PubMed:20720019"
FT MUTAGEN 147
FT /note="I->A: Inhibits translocation to the cytoplasm; when
FT associated with A-143; A-145; A-183 and A-185."
FT /evidence="ECO:0000269|PubMed:20720019"
FT MUTAGEN 175
FT /note="E->A: Reduces calcium-binding and SLC9A1-dependent
FT Na(+)/H(+) exchange activity. Does not reduce
FT colocalization and interaction with SLC9A1. Reduces
FT colocalization and interaction with SLC9A1; when associated
FT with A-134."
FT /evidence="ECO:0000269|PubMed:15035633"
FT MUTAGEN 183
FT /note="V->A: Inhibits translocation to the cytoplasm; when
FT associated with A-143; A-145; A-147 and A-185."
FT /evidence="ECO:0000269|PubMed:20720019"
FT MUTAGEN 185
FT /note="V->A: Inhibits translocation to the cytoplasm; when
FT associated with A-143; A-145; A-147 and A-183."
FT /evidence="ECO:0000269|PubMed:20720019"
FT HELIX 17..20
FT /evidence="ECO:0007829|PDB:7DSV"
FT HELIX 25..39
FT /evidence="ECO:0007829|PDB:7DSV"
FT STRAND 40..47
FT /evidence="ECO:0007829|PDB:7DSV"
FT HELIX 48..52
FT /evidence="ECO:0007829|PDB:7DSV"
FT TURN 55..59
FT /evidence="ECO:0007829|PDB:7DSV"
FT HELIX 63..70
FT /evidence="ECO:0007829|PDB:7DSV"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:7DSV"
FT HELIX 80..88
FT /evidence="ECO:0007829|PDB:7DSV"
FT HELIX 95..99
FT /evidence="ECO:0007829|PDB:7DSV"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:7DSV"
FT HELIX 111..122
FT /evidence="ECO:0007829|PDB:7DSV"
FT STRAND 123..125
FT /evidence="ECO:0007829|PDB:7DSV"
FT STRAND 127..130
FT /evidence="ECO:0007829|PDB:2E30"
FT HELIX 132..142
FT /evidence="ECO:0007829|PDB:7DSV"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:7DSV"
FT HELIX 149..163
FT /evidence="ECO:0007829|PDB:7DSV"
FT STRAND 166..169
FT /evidence="ECO:0007829|PDB:7DSV"
FT HELIX 173..181
FT /evidence="ECO:0007829|PDB:7DSV"
FT HELIX 185..188
FT /evidence="ECO:0007829|PDB:7DSV"
SQ SEQUENCE 195 AA; 22456 MW; 8E82EEF0CA5E832F CRC64;
MGSRASTLLR DEELEEIKKE TGFSHSQITR LYSRFTSLDK GENGTLSRED FQRIPELAIN
PLGDRIINAF FPEGEDQVNF RGFMRTLAHF RPIEDNEKSK DVNGPEPLNS RSNKLHFAFR
LYDLDKDEKI SRDELLQVLR MMVGVNISDE QLGSIADRTI QEADQDGDSA ISFTEFVKVL
EKVDVEQKMS IRFLH
