Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Calcineurin B homologous protein 1

Gene

Chp1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Calcium-binding protein involved in different processes such as regulation of vesicular trafficking, plasma membrane Na+/H+ exchanger and gene transcription. Involved in the constitutive exocytic membrane traffic. Mediates the association between microtubules and membrane-bound organelles of the endoplasmic reticulum and Golgi apparatus and is also required for the targeting and fusion of transcytotic vesicles (TCV) with the plasma membrane. Functions as an integral cofactor in cell pH regulation by controlling plasma membrane-type Na+/H+ exchange activity. Affects the pH sensitivity of SLC9A1/NHE1 by increasing its sensitivity at acidic pH. Required for the stabilization and localization of SLC9A1/NHE1 at the plasma membrane. Inhibits serum- and GTPase-stimulated Na+/H+ exchange. Plays a role as an inhibitor of ribosomal RNA transcription by repressing the nucleolar UBF1 transcriptional activity. May sequester UBF1 in the nucleoplasm and limit its translocation to the nucleolus. Associates to the ribosomal gene promoter. Acts as a negative regulator of the calcineurin/NFAT signaling pathway. Inhibits NFAT nuclear translocation and transcriptional activity by suppressing the calcium-dependent calcineurin phosphatase activity. Also negatively regulates the kinase activity of the apoptosis-induced kinase STK17B. Inhibits both STK17B auto- and substrate-phosphorylations in a calcium-dependent manner.6 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Calcium bindingi123 – 134121Add
BLAST
Calcium bindingi164 – 175122Add
BLAST

GO - Molecular functioni

  • calcium-dependent protein binding Source: UniProtKB
  • calcium ion binding Source: RGD
  • kinase binding Source: UniProtKB
  • microtubule binding Source: UniProtKB
  • protein kinase inhibitor activity Source: UniProtKB-KW
  • transporter activity Source: UniProtKB

GO - Biological processi

  • calcium ion regulated exocytosis Source: RGD
  • calcium-mediated signaling Source: RGD
  • cellular response to acidic pH Source: UniProtKB
  • cytoplasmic microtubule organization Source: UniProtKB
  • membrane docking Source: UniProtKB
  • membrane fusion Source: UniProtKB
  • membrane organization Source: UniProtKB
  • microtubule bundle formation Source: UniProtKB
  • negative regulation of calcineurin-NFAT signaling cascade Source: UniProtKB
  • negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • negative regulation of phosphatase activity Source: UniProtKB
  • negative regulation of protein autophosphorylation Source: UniProtKB
  • negative regulation of protein import into nucleus Source: UniProtKB
  • negative regulation of protein kinase activity Source: UniProtKB
  • negative regulation of protein phosphorylation Source: UniProtKB
  • negative regulation of protein ubiquitination Source: UniProtKB
  • positive regulation of protein glycosylation Source: UniProtKB
  • positive regulation of protein targeting to membrane Source: UniProtKB
  • positive regulation of protein transport Source: UniProtKB
  • positive regulation of sodium:proton antiporter activity Source: UniProtKB
  • protein export from nucleus Source: UniProtKB
  • protein oligomerization Source: UniProtKB
  • protein stabilization Source: UniProtKB
  • regulation of intracellular pH Source: UniProtKB
  • regulation of neuron death Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Protein kinase inhibitor

Keywords - Biological processi

Protein transport, Transport

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-RNO-2160916. Hyaluronan uptake and degradation.

Names & Taxonomyi

Protein namesi
Recommended name:
Calcineurin B homologous protein 1
Alternative name(s):
Calcineurin B-like protein
Calcium-binding protein CHP
Calcium-binding protein p22
EF-hand calcium-binding domain-containing protein p22
Gene namesi
Name:Chp1
Synonyms:Chp
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 3

Organism-specific databases

RGDi620447. Chp1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: RGD
  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum-Golgi intermediate compartment Source: UniProtKB-SubCell
  • extracellular exosome Source: Ensembl
  • focal adhesion Source: Ensembl
  • Golgi membrane Source: UniProtKB
  • microtubule cytoskeleton Source: UniProtKB
  • nucleus Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • transport vesicle Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Endoplasmic reticulum, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi134 – 1341E → A: Inhibits calcium-mediated conformational changes. Loss of transcytotic targeting/fusion function. Reduces association with membranes. Does not affect microtubule formation. 2 Publications
Mutagenesisi138 – 1381V → A: Predominantly located in the cytoplasm; when associated with A-139. Predominantly located in the nucleus; when associated with A-139; A-179 and A-180. 1 Publication
Mutagenesisi139 – 1391L → A: Predominantly located in the cytoplasm; when associated with A-138. Predominantly located in the nucleus; when associated with A-138; A-179 and A-180. 1 Publication
Mutagenesisi143 – 1431V → A: Predominantly located in the cytoplasm; when associated with A-145 and A-147. Predominantly located in the nucleus; when associated with A-145; A-147; A-183 and A-185. 2 Publications
Mutagenesisi145 – 1451V → A: Predominantly located in the cytoplasm; when associated with A-143 and A-147. Predominantly located in the nucleus; when associated with A-143; A-147; A-183 and A-185. 2 Publications
Mutagenesisi147 – 1471I → A: Predominantly located in the cytoplasm; when associated with A-143 and A-145. Predominantly located in the nucleus; when associated with A-143; A-145; A-183 and A-185. 2 Publications
Mutagenesisi179 – 1791V → A: Predominantly located in the cytoplasm; when associated with A-180. Predominantly located in the nucleus; when associated with A-138; A-139 and A-180. 1 Publication
Mutagenesisi180 – 1801L → A: Predominantly located in the cytoplasm; when associated with A-179. Predominantly located in the nucleus; when associated with A-138; A-139 and A-179. 1 Publication
Mutagenesisi183 – 1831V → A: Predominantly located in the cytoplasm; when associated with A-185. Predominantly located in the nucleus; when associated with A-143; A-145; A-147 and A-185. 2 Publications
Mutagenesisi185 – 1851V → A: Predominantly located in the cytoplasm; when associated with A-183. Predominantly located in the nucleus; when associated with A-143; A-145; A-147 and A-183. 2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 195194Calcineurin B homologous protein 1PRO_0000073846Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycineBy similarity

Post-translational modificationi

Phosphorylated; decreased phosphorylation is associated with an increase in SLC9A1/NHE1 Na+/H+ exchange activity. Phosphorylation occurs in serum-dependent manner. The phosphorylation state may regulate the binding to SLC9A1/NHE1 (By similarity).By similarity
N-myristoylation is required for its association with microtubules and interaction with GAPDH, but not for the constitutive association to membranes. Both N-myristoylation and calcium-mediated conformational changes are essential in exocytic traffic.

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

PaxDbiP61023.
PRIDEiP61023.

PTM databases

PhosphoSiteiP61023.

Expressioni

Tissue specificityi

Expressed in liver and kidney (at protein level). Ubiquitously expressed. Expressed in the brain, lung, testes, kidney, spleen and heart.3 Publications

Gene expression databases

GenevisibleiP61023. RN.

Interactioni

Subunit structurei

Interacts with PPP3CA. Interacts with SLC9A1/NHE1 (via the juxtamembrane region of the cytoplasmic C-terminal domain); the interaction occurs at the plasma membrane in a calcium-dependent manner and at a domain that is critical for growth factor stimulation of the exchanger (By similarity). Monomer. Interacts with STK17B; the interaction occurs in a calcium-independent manner and induces the translocation of CHP1 from the Golgi to the nucleus. Interacts with GAPDH; the interaction is direct, occurs in a N-myristoylation-dependent manner and facilitates the ability of CHP1 to bind microtubules. Interacts with KIF1B (via the C-terminal end of the kinesin-motor domain); the interaction occurs in a calcium-dependent manner. Associates (via C-terminal domain) with microtubules; the association occurs with polymerized microtubules during the cell cycle in a myristoylation- and calcium-independent manner and is enhanced by GAPDH.By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GAPDHP464062EBI-917838,EBI-2750726From a different organism.
GapdhP047973EBI-917838,EBI-349219
Kif1bO88658-14EBI-917838,EBI-6143515
Stk17bQ91XS86EBI-917838,EBI-77460

GO - Molecular functioni

  • calcium-dependent protein binding Source: UniProtKB
  • kinase binding Source: UniProtKB
  • microtubule binding Source: UniProtKB

Protein-protein interaction databases

IntActiP61023. 11 interactions.
MINTiMINT-1786138.
STRINGi10116.ENSRNOP00000053243.

Structurei

Secondary structure

1
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi4 – 74Combined sources
Helixi11 – 2111Combined sources
Helixi25 – 3814Combined sources
Beta strandi43 – 464Combined sources
Helixi49 – 535Combined sources
Helixi55 – 584Combined sources
Helixi63 – 686Combined sources
Helixi80 – 889Combined sources
Helixi111 – 12212Combined sources
Beta strandi127 – 1304Combined sources
Helixi132 – 14211Combined sources
Helixi149 – 16315Combined sources
Beta strandi165 – 1728Combined sources
Helixi173 – 1786Combined sources
Turni179 – 1824Combined sources
Helixi185 – 1873Combined sources
Helixi189 – 1957Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2CT9X-ray2.20A/B1-195[»]
ProteinModelPortaliP61023.
SMRiP61023. Positions 1-195.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP61023.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini26 – 6136EF-hand 1PROSITE-ProRule annotationAdd
BLAST
Domaini71 – 10636EF-hand 2PROSITE-ProRule annotationAdd
BLAST
Domaini110 – 14536EF-hand 3PROSITE-ProRule annotationAdd
BLAST
Domaini151 – 18636EF-hand 4PROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi2 – 65Necessary for association with microtubule and interaction with GAPDH
Motifi138 – 14710Nuclear export signal 1
Motifi176 – 18510Nuclear export signal 2

Sequence similaritiesi

Contains 4 EF-hand domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0034. Eukaryota.
COG5126. LUCA.
GeneTreeiENSGT00760000119179.
HOGENOMiHOG000233019.
HOVERGENiHBG105307.
InParanoidiP61023.
KOiK17610.
OMAiFQPISRV.
OrthoDBiEOG78M035.
PhylomeDBiP61023.
TreeFamiTF354284.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
[Graphical view]
PfamiPF13499. EF-hand_7. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 2 hits.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiPS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 3 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P61023-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGSRASTLLR DEELEEIKKE TGFSHSQITR LYSRFTSLDK GENGTLSRED
60 70 80 90 100
FQRIPELAIN PLGDRIINAF FSEGEDQVNF RGFMRTLAHF RPIEDNEKSK
110 120 130 140 150
DVNGPEPLNS RSNKLHFAFR LYDLDKDDKI SRDELLQVLR MMVGVNISDE
160 170 180 190
QLGSIADRTI QEADQDGDSA ISFTEFVKVL EKVDVEQKMS IRFLH
Length:195
Mass (Da):22,432
Last modified:January 23, 2007 - v2
Checksum:i7B803EF0ABED829E
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U39875 mRNA. Translation: AAB04146.1.
AB070350 mRNA. Translation: BAB63369.1.
BC062029 mRNA. Translation: AAH62029.1.
RefSeqiNP_077053.1. NM_024139.2.
UniGeneiRn.11041.

Genome annotation databases

EnsembliENSRNOT00000056405; ENSRNOP00000053243; ENSRNOG00000004742.
GeneIDi64152.
KEGGirno:64152.
UCSCiRGD:620447. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U39875 mRNA. Translation: AAB04146.1.
AB070350 mRNA. Translation: BAB63369.1.
BC062029 mRNA. Translation: AAH62029.1.
RefSeqiNP_077053.1. NM_024139.2.
UniGeneiRn.11041.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2CT9X-ray2.20A/B1-195[»]
ProteinModelPortaliP61023.
SMRiP61023. Positions 1-195.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP61023. 11 interactions.
MINTiMINT-1786138.
STRINGi10116.ENSRNOP00000053243.

PTM databases

PhosphoSiteiP61023.

Proteomic databases

PaxDbiP61023.
PRIDEiP61023.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000056405; ENSRNOP00000053243; ENSRNOG00000004742.
GeneIDi64152.
KEGGirno:64152.
UCSCiRGD:620447. rat.

Organism-specific databases

CTDi11261.
RGDi620447. Chp1.

Phylogenomic databases

eggNOGiKOG0034. Eukaryota.
COG5126. LUCA.
GeneTreeiENSGT00760000119179.
HOGENOMiHOG000233019.
HOVERGENiHBG105307.
InParanoidiP61023.
KOiK17610.
OMAiFQPISRV.
OrthoDBiEOG78M035.
PhylomeDBiP61023.
TreeFamiTF354284.

Enzyme and pathway databases

ReactomeiR-RNO-2160916. Hyaluronan uptake and degradation.

Miscellaneous databases

EvolutionaryTraceiP61023.
NextBioi612777.
PROiP61023.

Gene expression databases

GenevisibleiP61023. RN.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
[Graphical view]
PfamiPF13499. EF-hand_7. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 2 hits.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiPS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 3 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A novel Ca2+-binding protein, p22, is required for constitutive membrane traffic."
    Barroso M.R., Bernd K.K., Dewitt N.D., Chang A., Mills K., Sztul E.S.
    J. Biol. Chem. 271:10183-10187(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION IN EXOCYTIC MEMBRANE TRAFFIC, CALCIUM-BINDING, MUTAGENESIS OF GLU-134, TISSUE SPECIFICITY.
    Tissue: Liver.
  2. "A serine/threonine kinase which causes apoptosis-like cell death interacts with a calcineurin B-like protein capable of binding Na+/H+ exchanger."
    Matsumoto M., Miyake Y., Nagita M., Inoue H., Shitakubo D., Takemoto K., Ohtsuka C., Murakami H., Nakamura N., Kanazawa H.
    J. Biochem. 130:217-225(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH STK17B.
    Tissue: Brain.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Prostate.
  4. "The EF-hand Ca(2+)-binding protein p22 associates with microtubules in an N-myristoylation-dependent manner."
    Timm S., Titus B., Bernd K., Barroso M.
    Mol. Biol. Cell 10:3473-3488(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: ASSOCIATION WITH MICROTUBULES, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  5. "KIF1Bbeta2, capable of interacting with CHP, is localized to synaptic vesicles."
    Nakamura N., Miyake Y., Matsushita M., Tanaka S., Inoue H., Kanazawa H.
    J. Biochem. 132:483-491(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH KIF1B, SUBCELLULAR LOCATION.
  6. "The apoptosis-inducing protein kinase DRAK2 is inhibited in a calcium-dependent manner by the calcium-binding protein CHP."
    Kuwahara H., Kamei J., Nakamura N., Matsumoto M., Inoue H., Kanazawa H.
    J. Biochem. 134:245-250(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS STK17B KINASE INHIBITOR, INTERACTION WITH STK17B.
  7. "Two nuclear export signals specify the cytoplasmic localization of calcineurin B homologous protein 1."
    Nagita M., Inoue H., Nakamura N., Kanazawa H.
    J. Biochem. 134:919-925(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, NUCLEAR EXPORT SIGNALS, MUTAGENESIS OF VAL-138; LEU-139; VAL-143; VAL-145; ILE-147; VAL-179; LEU-180; VAL-183 AND VAL-185.
  8. "Interactions among p22, glyceraldehyde-3-phosphate dehydrogenase and microtubules."
    Andrade J., Pearce S.T., Zhao H., Barroso M.
    Biochem. J. 384:327-336(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH GAPDH, ASSOCIATION WITH MICROTUBULES, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  9. "The EF-hand Ca2+-binding protein p22 plays a role in microtubule and endoplasmic reticulum organization and dynamics with distinct Ca2+-binding requirements."
    Andrade J., Zhao H., Titus B., Timm Pearce S., Barroso M.
    Mol. Biol. Cell 15:481-496(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF GLU-134.
  10. "Nuclear-localized calcineurin homologous protein CHP1 interacts with upstream binding factor and inhibits ribosomal RNA synthesis."
    Jimenez-Vidal M., Srivastava J., Putney L.K., Barber D.L.
    J. Biol. Chem. 285:36260-36266(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN TRANSCRIPTION REGULATION, SUBCELLULAR LOCATION, MUTAGENESIS OF VAL-143; VAL-145; ILE-147; VAL-183 AND VAL-185.
  11. "Dual functional significance of calcineurin homologous protein 1 binding to Na(+)/H(+) exchanger isoform 1."
    Matsushita M., Tanaka H., Mitsui K., Kanazawa H.
    Am. J. Physiol. 301:C280-C288(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  12. "Crystallization and preliminary X-ray crystallographic analysis of rat calcineurin B homologous protein 1."
    Naoe Y., Arita K., Hashimoto H., Kanazawa H., Sato M., Shimizu T.
    Acta Crystallogr. F 61:612-613(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: PRELIMINARY X-RAY CRYSTALLOGRAPHY.
  13. "Structural characterization of calcineurin B homologous protein 1."
    Naoe Y., Arita K., Hashimoto H., Kanazawa H., Sato M., Shimizu T.
    J. Biol. Chem. 280:32372-32378(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH CALCIUM IONS, SUBUNIT.

Entry informationi

Entry nameiCHP1_RAT
AccessioniPrimary (citable) accession number: P61023
Secondary accession number(s): Q62877
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: January 23, 2007
Last modified: March 16, 2016
This is version 108 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.