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Protein

Calcineurin B homologous protein 1

Gene

CHP1

Organism
Homo sapiens (Human)
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.4 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi123 – 1341Add BLAST12
Calcium bindingi164 – 1752Add BLAST12

GO - Molecular functioni

  • calcium-dependent protein binding Source: UniProtKB
  • calcium ion binding Source: UniProtKB
  • kinase binding Source: UniProtKB
  • microtubule binding Source: UniProtKB
  • potassium channel regulator activity Source: ProtInc
  • protein kinase inhibitor activity Source: UniProtKB-KW
  • transporter activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Protein kinase inhibitor

Keywords - Biological processi

Protein transport, Transport

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000128949-MONOMER.
ReactomeiR-HSA-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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:17433. CHP1.

Subcellular locationi

  • Nucleus By similarity
  • Cytoplasm By similarity
  • Cytoplasmcytoskeleton By similarity
  • Endomembrane system By similarity
  • Endoplasmic reticulum-Golgi intermediate compartment By similarity
  • Endoplasmic reticulum By similarity
  • Cell membrane By similarity
  • Membrane By similarity; Lipid-anchor By similarity

  • Note: Localizes in cytoplasmic compartments in dividing cells. Localizes in the nucleus in quiescent cells. Exported from the nucleus to the cytoplasm through a nuclear export signal (NES) and CRM1-dependent pathway. May shuttle between nucleus and cytoplasm. Localizes with the microtubule-organizing center (MTOC) and extends toward the periphery along microtubules. Associates with membranes of the early secretory pathway in a GAPDH-independent, N-myristoylation- and calcium-dependent manner. Colocalizes with the mitotic spindle microtubules. Colocalizes with GAPDH along microtubules. Colocalizes with SLC9A1 at the reticulum endoplasmic and plasma membrane. Colocalizes with STK17B at the plasma membrane.By similarity

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Ensembl
  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum-Golgi intermediate compartment Source: UniProtKB-SubCell
  • extracellular exosome Source: UniProtKB
  • focal adhesion Source: UniProtKB
  • 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)DescriptionActionsGraphical viewLength
Mutagenesisi50D → A: Does not reduce calcium-binding, colocalization and interaction with SLC9A1. 1 Publication1
Mutagenesisi134E → A: Reduces calcium-binding and SLC9A1-dependent Na(+)/H(+) exchange activity. Does not reduce colocalization and interaction with SLC9A1. Reduces colocalization and interaction with SLC9A1; when associated with A-175. 1 Publication1
Mutagenesisi143V → A: Inhibits translocation to the cytoplasm; when associated with A-145; A-147; A-183 and A-185. 1 Publication1
Mutagenesisi145V → A: Inhibits translocation to the cytoplasm; when associated with A-143; A-147; A-183 and A-185. 1 Publication1
Mutagenesisi147I → A: Inhibits translocation to the cytoplasm; when associated with A-143; A-145; A-183 and A-185. 1 Publication1
Mutagenesisi175E → A: Reduces calcium-binding and SLC9A1-dependent Na(+)/H(+) exchange activity. Does not reduce colocalization and interaction with SLC9A1. Reduces colocalization and interaction with SLC9A1; when associated with A-134. 1 Publication1
Mutagenesisi183V → A: Inhibits translocation to the cytoplasm; when associated with A-143; A-145; A-147 and A-185. 1 Publication1
Mutagenesisi185V → A: Inhibits translocation to the cytoplasm; when associated with A-143; A-145; A-147 and A-183. 1 Publication1

Organism-specific databases

DisGeNETi11261.
OpenTargetsiENSG00000187446.

Polymorphism and mutation databases

BioMutaiCHP1.
DMDMi3023439.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00000738432 – 195Calcineurin B homologous protein 1Add BLAST194

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine1 Publication1

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/NHE1.1 Publication
Both N-myristoylation and calcium-mediated conformational changes are essential for its function in exocytic traffic (By similarity). N-myristoylation is required for its association with microtubules and interaction with GAPDH, but not for the constitutive association to membranes.By similarity

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

EPDiQ99653.
MaxQBiQ99653.
PaxDbiQ99653.
PeptideAtlasiQ99653.
PRIDEiQ99653.
TopDownProteomicsiQ99653.

2D gel databases

OGPiQ99653.

PTM databases

iPTMnetiQ99653.
PhosphoSitePlusiQ99653.
SwissPalmiQ99653.

Expressioni

Tissue specificityi

Ubiquitously expressed. Has been found in fetal eye, lung, liver, muscle, heart, kidney, thymus and spleen.1 Publication

Gene expression databases

BgeeiENSG00000187446.
ExpressionAtlasiQ99653. baseline and differential.
GenevisibleiQ99653. HS.

Organism-specific databases

HPAiHPA006616.

Interactioni

Subunit structurei

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 similarity). 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 similarity5 Publications

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi116421. 13 interactors.
IntActiQ99653. 15 interactors.
MINTiMINT-1375478.
STRINGi9606.ENSP00000335632.

Structurei

Secondary structure

1195
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi11 – 22Combined sources12
Helixi26 – 37Combined sources12
Turni38 – 41Combined sources4
Helixi48 – 51Combined sources4
Helixi57 – 59Combined sources3
Helixi64 – 70Combined sources7
Helixi80 – 88Combined sources9
Beta strandi95 – 98Combined sources4
Beta strandi107 – 109Combined sources3
Helixi111 – 122Combined sources12
Beta strandi127 – 130Combined sources4
Helixi132 – 143Combined sources12
Turni144 – 146Combined sources3
Helixi149 – 163Combined sources15
Beta strandi165 – 169Combined sources5
Beta strandi171 – 173Combined sources3
Helixi174 – 180Combined sources7
Helixi185 – 188Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2E30NMR-A1-195[»]
ProteinModelPortaliQ99653.
SMRiQ99653.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99653.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini26 – 61EF-hand 1PROSITE-ProRule annotationAdd BLAST36
Domaini66 – 101EF-hand 2PROSITE-ProRule annotationAdd BLAST36
Domaini110 – 145EF-hand 3PROSITE-ProRule annotationAdd BLAST36
Domaini151 – 186EF-hand 4PROSITE-ProRule annotationAdd BLAST36

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni143 – 185Necessary for nuclear export signalAdd BLAST43

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi2 – 6Necessary for association with microtubule and interaction with GAPDHBy similarity5
Motifi138 – 147Nuclear export signal 1By similarity10
Motifi176 – 185Nuclear export signal 2By similarity10

Sequence similaritiesi

Contains 4 EF-hand domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0034. Eukaryota.
COG5126. LUCA.
GeneTreeiENSGT00860000133729.
HOGENOMiHOG000233019.
HOVERGENiHBG105307.
InParanoidiQ99653.
KOiK17610.
OMAiKSKDQNG.
OrthoDBiEOG091G0LZ1.
PhylomeDBiQ99653.
TreeFamiTF354284.

Family and domain databases

CDDicd00051. EFh. 1 hit.
Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR002048. EF_hand_dom.
[Graphical view]
PfamiPF13499. EF-hand_7. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 2 hits.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiPS50222. EF_HAND_2. 3 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q99653-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGSRASTLLR DEELEEIKKE TGFSHSQITR LYSRFTSLDK GENGTLSRED
60 70 80 90 100
FQRIPELAIN PLGDRIINAF FPEGEDQVNF RGFMRTLAHF RPIEDNEKSK
110 120 130 140 150
DVNGPEPLNS RSNKLHFAFR LYDLDKDEKI SRDELLQVLR MMVGVNISDE
160 170 180 190
QLGSIADRTI QEADQDGDSA ISFTEFVKVL EKVDVEQKMS IRFLH
Length:195
Mass (Da):22,456
Last modified:January 23, 2007 - v3
Checksum:i8E82EEF0CA5E832F
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U61538 mRNA. Translation: AAB37770.1.
CR536539 mRNA. Translation: CAG38776.1.
CR542085 mRNA. Translation: CAG46882.1.
AK312582 mRNA. Translation: BAG35476.1.
CH471125 Genomic DNA. Translation: EAW92474.1.
BC031293 mRNA. Translation: AAH31293.1.
BC051815 mRNA. No translation available.
CCDSiCCDS10073.1.
RefSeqiNP_009167.1. NM_007236.4.
UniGeneiHs.406234.
Hs.745372.

Genome annotation databases

EnsembliENST00000334660; ENSP00000335632; ENSG00000187446.
GeneIDi11261.
KEGGihsa:11261.
UCSCiuc001znl.4. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U61538 mRNA. Translation: AAB37770.1.
CR536539 mRNA. Translation: CAG38776.1.
CR542085 mRNA. Translation: CAG46882.1.
AK312582 mRNA. Translation: BAG35476.1.
CH471125 Genomic DNA. Translation: EAW92474.1.
BC031293 mRNA. Translation: AAH31293.1.
BC051815 mRNA. No translation available.
CCDSiCCDS10073.1.
RefSeqiNP_009167.1. NM_007236.4.
UniGeneiHs.406234.
Hs.745372.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2E30NMR-A1-195[»]
ProteinModelPortaliQ99653.
SMRiQ99653.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116421. 13 interactors.
IntActiQ99653. 15 interactors.
MINTiMINT-1375478.
STRINGi9606.ENSP00000335632.

PTM databases

iPTMnetiQ99653.
PhosphoSitePlusiQ99653.
SwissPalmiQ99653.

Polymorphism and mutation databases

BioMutaiCHP1.
DMDMi3023439.

2D gel databases

OGPiQ99653.

Proteomic databases

EPDiQ99653.
MaxQBiQ99653.
PaxDbiQ99653.
PeptideAtlasiQ99653.
PRIDEiQ99653.
TopDownProteomicsiQ99653.

Protocols and materials databases

DNASUi11261.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000334660; ENSP00000335632; ENSG00000187446.
GeneIDi11261.
KEGGihsa:11261.
UCSCiuc001znl.4. human.

Organism-specific databases

CTDi11261.
DisGeNETi11261.
GeneCardsiCHP1.
HGNCiHGNC:17433. CHP1.
HPAiHPA006616.
MIMi606988. gene.
neXtProtiNX_Q99653.
OpenTargetsiENSG00000187446.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0034. Eukaryota.
COG5126. LUCA.
GeneTreeiENSGT00860000133729.
HOGENOMiHOG000233019.
HOVERGENiHBG105307.
InParanoidiQ99653.
KOiK17610.
OMAiKSKDQNG.
OrthoDBiEOG091G0LZ1.
PhylomeDBiQ99653.
TreeFamiTF354284.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000128949-MONOMER.
ReactomeiR-HSA-2160916. Hyaluronan uptake and degradation.

Miscellaneous databases

EvolutionaryTraceiQ99653.
GeneWikiiCHP_(gene).
GenomeRNAii11261.
PROiQ99653.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000187446.
ExpressionAtlasiQ99653. baseline and differential.
GenevisibleiQ99653. HS.

Family and domain databases

CDDicd00051. EFh. 1 hit.
Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR002048. EF_hand_dom.
[Graphical view]
PfamiPF13499. EF-hand_7. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 2 hits.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiPS50222. EF_HAND_2. 3 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCHP1_HUMAN
AccessioniPrimary (citable) accession number: Q99653
Secondary accession number(s): B2R6H9, Q6FHZ9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 166 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.