CHP2_RAT
ID CHP2_RAT Reviewed; 196 AA.
AC Q810D1;
DT 05-SEP-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Calcineurin B homologous protein 2;
DE Short=Chp-2;
GN Name=Chp2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH SLC9A1, SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RX PubMed=12576672; DOI=10.1248/bpb.26.148;
RA Inoue H., Nakamura Y., Nagita M., Takai T., Masuda M., Nakamura N.,
RA Kanazawa H.;
RT "Calcineurin homologous protein isoform 2 (CHP2), Na+/H+ exchangers-binding
RT protein, is expressed in intestinal epithelium.";
RL Biol. Pharm. Bull. 26:148-155(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Functions as an integral cofactor in cell pH regulation by
CC controlling plasma membrane-type Na(+)/H(+) exchange activity. Binds to
CC and activates SLC9A1/NHE1 in a serum-independent manner, thus
CC increasing pH and protecting cells from serum deprivation-induced
CC death. Also plays a role in the regulation of cell proliferation and
CC tumor growth by increasing the phosphatase activity of PPP3CA in a
CC calcium-dependent manner. Activator of the calcineurin/NFAT signaling
CC pathway. Involved in the cytoplasmic translocation of the transcription
CC factor NFATC3 to the nucleus (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with PPP3CA. Interacts with SLC9A1/NHE1; the
CC interaction occurs in a calcium-dependent manner (By similarity).
CC Interacts with SLC9A1/NHE1. {ECO:0000250, ECO:0000269|PubMed:12576672}.
CC -!- INTERACTION:
CC Q810D1; P26431: Slc9a1; NbExp=2; IntAct=EBI-6146708, EBI-77471;
CC Q810D1; P26433: Slc9a3; NbExp=3; IntAct=EBI-6146708, EBI-961694;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12576672}. Nucleus
CC {ECO:0000269|PubMed:12576672}. Cell membrane
CC {ECO:0000269|PubMed:12576672}. Note=Exported from the nucleus to the
CC cytoplasm through a nuclear export signal (NES) pathway. May shuttle
CC between nucleus and cytoplasm (By similarity). Predominantly localized
CC in a juxtanuclear region. Colocalizes with SLC9A3 in the juxtanuclear
CC region and at the plasma membrane. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in brain, lungs, stomach and intestines
CC (at protein level). Strongly expressed in the epithelial layer on the
CC small intestinal luminal side. {ECO:0000269|PubMed:12576672}.
CC -!- SIMILARITY: Belongs to the calcineurin regulatory subunit family. CHP
CC subfamily. {ECO:0000305}.
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DR EMBL; AB086189; BAC66507.1; -; mRNA.
DR EMBL; AABR03005739; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH473956; EDM17558.1; -; Genomic_DNA.
DR RefSeq; NP_877402.1; NM_182738.1.
DR RefSeq; XP_008757968.1; XM_008759746.2.
DR RefSeq; XP_017444695.1; XM_017589206.1.
DR AlphaFoldDB; Q810D1; -.
DR SMR; Q810D1; -.
DR IntAct; Q810D1; 5.
DR STRING; 10116.ENSRNOP00000025832; -.
DR iPTMnet; Q810D1; -.
DR PhosphoSitePlus; Q810D1; -.
DR PaxDb; Q810D1; -.
DR GeneID; 308965; -.
DR KEGG; rno:308965; -.
DR UCSC; RGD:727796; rat.
DR CTD; 63928; -.
DR RGD; 727796; Chp2.
DR VEuPathDB; HostDB:ENSRNOG00000019112; -.
DR eggNOG; KOG0034; Eukaryota.
DR HOGENOM; CLU_061288_10_5_1; -.
DR InParanoid; Q810D1; -.
DR OMA; YHRFQAL; -.
DR OrthoDB; 1271942at2759; -.
DR PhylomeDB; Q810D1; -.
DR TreeFam; TF354284; -.
DR PRO; PR:Q810D1; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Proteomes; UP000234681; Chromosome 1.
DR Bgee; ENSRNOG00000019112; Expressed in duodenum and 19 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; TAS:RGD.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005730; C:nucleolus; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; TAS:RGD.
DR GO; GO:0071277; P:cellular response to calcium ion; ISS:UniProtKB.
DR GO; GO:0006883; P:cellular sodium ion homeostasis; TAS:RGD.
DR GO; GO:0070886; P:positive regulation of calcineurin-NFAT signaling cascade; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0010922; P:positive regulation of phosphatase activity; ISS:UniProtKB.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; ISS:UniProtKB.
DR GO; GO:0032417; P:positive regulation of sodium:proton antiporter activity; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0030641; P:regulation of cellular pH; TAS:RGD.
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; 2.
DR PROSITE; PS50222; EF_HAND_2; 3.
PE 1: Evidence at protein level;
KW Calcium; Cell membrane; Cytoplasm; Lipoprotein; Membrane; Metal-binding;
KW Myristate; Nucleus; Phosphoprotein; Protein transport; Reference proteome;
KW Repeat; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000255"
FT CHAIN 2..196
FT /note="Calcineurin B homologous protein 2"
FT /id="PRO_0000419115"
FT DOMAIN 26..61
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 111..146
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 152..187
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT MOTIF 137..148
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT BINDING 124
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 126
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 128
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 130
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 135
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 165
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 167
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 169
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 176
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT MOD_RES 27
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 196 AA; 22486 MW; 00B49EE6E9D2EFEE CRC64;
MGSRSSHVAL IPDVDQIRRE TGFSQASLLR LYHRFQALDR EEKGFLSRLD LQQIGALAVN
PLGDRIIDSF FPNGSQRVYF AGFARVLAYF RPIDEDDATL RDPKQPEPLN SRMNKLRFAF
QLYDLDRDGK ISRNEMLQVL RLMVGVQVTD EQLESITDRT VQEADEDGDG AVSFLEFAKS
LEKMNIEQKM SIRILK
