CHP1_MOUSE
ID CHP1_MOUSE Reviewed; 195 AA.
AC P61022; Q62877; Q6ZWQ8;
DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 153.
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;
DE AltName: Full=Sid 470;
DE AltName: Full=p24;
GN Name=Chp1; Synonyms=Chp, Sid470;
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].
RA Seki N., Hattori A., Hayashi A., Kozuma S., Muramatsu M., Saito T.;
RT "Mouse calcium binding protein p22.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=BALB/cJ, C57BL/6J, and NOD;
RC TISSUE=Corpora quadrigemina, Liver, Mammary gland, Placenta, and Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Corpora quadrigemina;
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 [4]
RP INTERACTION WITH SLC9A1.
RX PubMed=8967452; DOI=10.1152/ajpcell.1996.270.5.c1493;
RA Goss G., Orlowski J., Grinstein S.;
RT "Coimmunoprecipitation of a 24-kDa protein with NHE1, the ubiquitous
RT isoform of the Na+/H+ exchanger.";
RL Am. J. Physiol. 270:C1493-C1502(1996).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
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).
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 membranes. 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 (By similarity). {ECO:0000250|UniProtKB:Q99653}.
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. Interacts with PPP3CA. Interacts with
CC SLC9A1/NHE1 (via the juxtamembrane region of the cytoplasmic C-terminal
CC domain); the interaction occurs at the plasma membrane in a calcium-
CC dependent manner and at a domain that is critical for growth factor
CC stimulation of the exchanger (By similarity). Interacts with
CC SLC9A1/NHE1. {ECO:0000250|UniProtKB:Q99653,
CC ECO:0000269|PubMed:8967452}.
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:0000250|UniProtKB:P61023}. Membrane
CC {ECO:0000250|UniProtKB:Q99653}; Lipid-anchor
CC {ECO:0000250|UniProtKB:Q99653}. 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 -!- 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 (By similarity). {ECO:0000250}.
CC -!- PTM: Both N-myristoylation and calcium-mediated conformational changes
CC are essential for its function in exocytic traffic. N-myristoylation is
CC required for its association with microtubules and interaction with
CC GAPDH, but not for the constitutive association to membranes (By
CC similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the calcineurin regulatory subunit family. CHP
CC subfamily. {ECO:0000305}.
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DR EMBL; AB025217; BAA84688.1; -; mRNA.
DR EMBL; AK005067; BAB23791.1; -; mRNA.
DR EMBL; AK045920; BAC32532.1; -; mRNA.
DR EMBL; AK156588; BAE33769.1; -; mRNA.
DR EMBL; AK166219; BAE38637.1; -; mRNA.
DR EMBL; AK167179; BAE39314.1; -; mRNA.
DR EMBL; AK167720; BAE39762.1; -; mRNA.
DR EMBL; AK168284; BAE40230.1; -; mRNA.
DR EMBL; AK169146; BAE40925.1; -; mRNA.
DR EMBL; BC054733; AAH54733.1; -; mRNA.
DR EMBL; BC064784; AAH64784.1; -; mRNA.
DR CCDS; CCDS16604.1; -.
DR RefSeq; NP_062743.1; NM_019769.3.
DR AlphaFoldDB; P61022; -.
DR SMR; P61022; -.
DR BioGRID; 207952; 5.
DR STRING; 10090.ENSMUSP00000014221; -.
DR iPTMnet; P61022; -.
DR PhosphoSitePlus; P61022; -.
DR EPD; P61022; -.
DR jPOST; P61022; -.
DR MaxQB; P61022; -.
DR PaxDb; P61022; -.
DR PeptideAtlas; P61022; -.
DR PRIDE; P61022; -.
DR ProteomicsDB; 281671; -.
DR Antibodypedia; 1886; 239 antibodies from 26 providers.
DR Ensembl; ENSMUST00000014221; ENSMUSP00000014221; ENSMUSG00000014077.
DR GeneID; 56398; -.
DR KEGG; mmu:56398; -.
DR UCSC; uc008ltw.1; mouse.
DR CTD; 11261; -.
DR MGI; MGI:1927185; Chp1.
DR VEuPathDB; HostDB:ENSMUSG00000014077; -.
DR eggNOG; KOG0034; Eukaryota.
DR GeneTree; ENSGT00940000154629; -.
DR HOGENOM; CLU_061288_10_5_1; -.
DR InParanoid; P61022; -.
DR OMA; HSFFADS; -.
DR OrthoDB; 1271942at2759; -.
DR PhylomeDB; P61022; -.
DR TreeFam; TF354284; -.
DR Reactome; R-MMU-2160916; Hyaluronan uptake and degradation.
DR BioGRID-ORCS; 56398; 17 hits in 76 CRISPR screens.
DR ChiTaRS; Chp1; mouse.
DR PRO; PR:P61022; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P61022; protein.
DR Bgee; ENSMUSG00000014077; Expressed in seminal vesicle and 259 other tissues.
DR ExpressionAtlas; P61022; baseline and differential.
DR Genevisible; P61022; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
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:0000139; C:Golgi membrane; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IPI:MGI.
DR GO; GO:0015630; C:microtubule cytoskeleton; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0030133; C:transport vesicle; ISS:UniProtKB.
DR GO; GO:1990351; C:transporter complex; IDA:MGI.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0048306; F:calcium-dependent protein binding; ISS:UniProtKB.
DR GO; GO:0019900; F:kinase binding; ISS:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; ISS:UniProtKB.
DR GO; GO:0004860; F:protein kinase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0015385; F:sodium:proton antiporter activity; IMP:MGI.
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; ISS:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0010923; P:negative regulation of phosphatase activity; ISS: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; ISS: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; ISO:MGI.
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; ISS:UniProtKB.
DR GO; GO:0051259; P:protein complex oligomerization; ISO:MGI.
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; ISS:UniProtKB.
DR GO; GO:1901214; P:regulation of neuron death; ISO:MGI.
DR GO; GO:0006906; P:vesicle fusion; ISO:MGI.
DR GO; GO:0006903; P:vesicle targeting; ISO:MGI.
DR CDD; cd00051; EFh; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
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; PS00018; EF_HAND_1; 1.
DR PROSITE; PS50222; EF_HAND_2; 3.
PE 1: Evidence at protein level;
KW Calcium; Cell membrane; Cytoplasm; Cytoskeleton; Endoplasmic reticulum;
KW Lipoprotein; Membrane; Metal-binding; Myristate; Nucleus; Phosphoprotein;
KW Protein kinase inhibitor; Protein transport; Reference proteome; Repeat;
KW Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q99653"
FT CHAIN 2..195
FT /note="Calcineurin B homologous protein 1"
FT /id="PRO_0000073844"
FT DOMAIN 26..61
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 71..106
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 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="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 125
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 127
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 129
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 134
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
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:0000250|UniProtKB:Q99653"
SQ SEQUENCE 195 AA; 22432 MW; 7B803EF0ABED829E CRC64;
MGSRASTLLR DEELEEIKKE TGFSHSQITR LYSRFTSLDK GENGTLSRED FQRIPELAIN
PLGDRIINAF FSEGEDQVNF RGFMRTLAHF RPIEDNEKSK DVNGPEPLNS RSNKLHFAFR
LYDLDKDDKI SRDELLQVLR MMVGVNISDE QLGSIADRTI QEADQDGDSA ISFTEFVKVL
EKVDVEQKMS IRFLH
