CIB1_SHEEP
ID CIB1_SHEEP Reviewed; 191 AA.
AC B1A8Z2;
DT 19-MAR-2014, integrated into UniProtKB/Swiss-Prot.
DT 08-APR-2008, sequence version 1.
DT 03-AUG-2022, entry version 74.
DE RecName: Full=Calcium and integrin-binding protein 1;
DE AltName: Full=Calmyrin;
GN Name=CIB1;
OS Ovis aries (Sheep).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Ovis.
OX NCBI_TaxID=9940;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=18989754; DOI=10.1007/s11033-008-9383-4;
RA Yu Y., Song X., Du L., Wang C.;
RT "Molecular characterization of the sheep CIB1 gene.";
RL Mol. Biol. Rep. 36:1799-1809(2009).
CC -!- FUNCTION: Calcium-binding protein that plays a role in the regulation
CC of numerous cellular processes, such as cell differentiation, cell
CC division, cell proliferation, cell migration, thrombosis, angiogenesis,
CC cardiac hypertrophy and apoptosis. Involved in bone marrow
CC megakaryocyte differentiation by negatively regulating thrombopoietin-
CC mediated signaling pathway. Participates in the endomitotic cell cycle
CC of megakaryocyte, a form of mitosis in which both karyokinesis and
CC cytokinesis are interrupted. Plays a role in integrin signaling by
CC negatively regulating alpha-IIb/beta3 activation in thrombin-stimulated
CC megakaryocytes preventing platelet aggregation. Up-regulates PTK2/FAK1
CC activity, and is also needed for the recruitment of PTK2/FAK1 to focal
CC adhesions; it thus appears to play an important role in focal adhesion
CC formation. Positively regulates cell migration on fibronectin in a
CC CDC42-dependent manner, the effect being negatively regulated by PAK1.
CC Functions as a negative regulator of stress activated MAP kinase (MAPK)
CC signaling pathways. Down-regulates inositol 1,4,5-trisphosphate
CC receptor-dependent calcium signaling. Involved in sphingosine kinase
CC SPHK1 translocation to the plasma membrane in a N-myristoylation-
CC dependent manner preventing TNF-alpha-induced apoptosis. Regulates
CC serine/threonine-protein kinase PLK3 activity for proper completion of
CC cell division progression. Plays a role in microtubule (MT) dynamics
CC during neuronal development; disrupts the MT depolymerization activity
CC of STMN2 attenuating NGF-induced neurite outgrowth and the MT
CC reorganization at the edge of lamellipodia. Promotes cardiomyocyte
CC hypertrophy via activation of the calcineurin/NFAT signaling pathway.
CC Stimulates calcineurin PPP3R1 activity by mediating its anchoring to
CC the sarcolemma. In ischemia-induced (pathological or adaptive)
CC angiogenesis, stimulates endothelial cell proliferation, migration and
CC microvessel formation by activating the PAK1 and ERK1/ERK2 signaling
CC pathway. Promotes also cancer cell survival and proliferation. May
CC regulate cell cycle and differentiation of spermatogenic germ cells,
CC and/or differentiation of supporting Sertoli cells (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Monomer. Interacts with the heterodimeric integrin alpha-
CC IIb/beta3 (ITGA2B-ITGB3). Interacts with ITGA2B (via cytoplasmic
CC domain); the interaction is direct and calcium-dependent. Interacts
CC with the protein kinases PLK2/SNK and PRKDC (via the region immediately
CC upstream of the kinase domain). Interacts with PLK3; the interaction
CC inhibits PLK3 kinase activity. Interacts with PSEN2. Interacts (via C-
CC terminus) with F8. Interacts with NBR1 (via C-terminus). Interacts with
CC FEZ1 (via C-terminus). Interacts with UBR5 (via C-terminus); the
CC interaction is sensitive to DNA damage, and may target CIB1 for
CC ubiquitin-mediated degradation. Interacts with IFI6; the interaction is
CC direct. Interacts with BCL2. Interacts with ITPR3; the interaction
CC occurs in a calcium dependent manner. Interacts with PTK2/FAK1.
CC Interacts with MAP3K5; the interaction inhibits MAP3K5 activation by
CC phosphorylation, and its subsequent interaction with TRAF2. Interacts
CC (via C-terminal region) with STMN2 (via the N-terminal region); the
CC interaction is direct, occurs in a calcium-dependent manner and
CC attenuates the STMN2-induced neurite outgrowth inhibition. Interacts
CC with SPHK1, the interaction occurs in a calcium-dependent manner.
CC Interacts with ITGA2B (via C-terminal cytoplasmic tail); the
CC interaction occurs upon platelet aggregation and is
CC stabilized/increased in a calcium and magnesium-dependent manner.
CC Interacts with PAK1 (via N-terminal region); the interaction is direct
CC and occurs in a calcium-dependent manner. Interacts with RAC3 (via C-
CC terminal region); the interaction induces their association with the
CC cytoskeleton upon alpha-IIb/beta3 integrin-mediated adhesion. Interacts
CC with ITGA5 and ITGAV. Interacts with MYO1C. Interacts with ITGA2B (via
CC C-terminal cytoplasmic tail region). Interacts (via C-terminal region)
CC with PPP3R1; the interaction increases upon cardiomyocytes hypertrophy.
CC Interacts with CACNA1C; the interaction increases upon cardiomyocytes
CC hypertrophy. Interacts with TAS1R2 (via C-terminus); this interaction
CC is independent of the myristoylation state of CIB1 (By similarity).
CC Interacts and forms a complex with TMC6 and TMC8 (By similarity).
CC {ECO:0000250, ECO:0000250|UniProtKB:Q99828}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:Q99828}; Lipid-
CC anchor {ECO:0000250|UniProtKB:Q99828}. Cell membrane, sarcolemma
CC {ECO:0000250|UniProtKB:Q99828}. Cell membrane
CC {ECO:0000250|UniProtKB:Q99828}. Apical cell membrane
CC {ECO:0000250|UniProtKB:Q99828}. Cell projection, ruffle membrane
CC {ECO:0000250|UniProtKB:Q99828}. Cell projection, filopodium tip
CC {ECO:0000250|UniProtKB:Q99828}. Cell projection, growth cone
CC {ECO:0000250|UniProtKB:Q99828}. Cell projection, lamellipodium
CC {ECO:0000250|UniProtKB:Q99828}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q99828}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:Q99828}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250|UniProtKB:Q99828}.
CC Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:Q99828}. Nucleus
CC {ECO:0000250|UniProtKB:Q99828}. Cell projection, neuron projection
CC {ECO:0000250|UniProtKB:Q99828}. Perikaryon
CC {ECO:0000250|UniProtKB:Q99828}. Note=Colocalized with PPP3R1 at the
CC cell membrane of cardiomyocytes in the hypertrophic heart (By
CC similarity). Colocalized with NBR1 to the perinuclear region.
CC Colocalizes with TAS1R2 in apical regions of taste receptor cells.
CC Colocalized with RAC3 in the perinuclear area and at the cell
CC periphery. Colocalized with PAK1 within membrane ruffles during cell
CC spreading upon readhesion to fibronectin. Redistributed to the
CC cytoskeleton upon platelet aggregation. Translocates from the cytosol
CC to the plasma membrane in a calcium-dependent manner. Colocalized with
CC PLK3 at centrosomes in ductal breast carcinoma cells. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed strongly in testis. Expressed weakly in
CC liver, kidney and spleen. {ECO:0000269|PubMed:18989754}.
CC -!- DOMAIN: The EF-hands may also bind magnesium ions in the presence of
CC high Mg(2+) levels and low Ca(2+) levels. {ECO:0000250}.
CC -!- MISCELLANEOUS: The binding of either calcium or magnesium significantly
CC increases the structural stability of the protein in comparison to apo-
CC CIB (calcium- and magnesium-free form). {ECO:0000250}.
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DR EMBL; EU430744; ABZ91971.1; -; mRNA.
DR EMBL; EU499336; ACD39827.1; -; Genomic_DNA.
DR RefSeq; NP_001108237.1; NM_001114765.1.
DR AlphaFoldDB; B1A8Z2; -.
DR SMR; B1A8Z2; -.
DR STRING; 9940.ENSOARP00000013003; -.
DR Ensembl; ENSOART00000013190; ENSOARP00000013001; ENSOARG00000012128.
DR Ensembl; ENSOART00020021641; ENSOARP00020017922; ENSOARG00020014063.
DR GeneID; 100141300; -.
DR KEGG; oas:100141300; -.
DR CTD; 10519; -.
DR eggNOG; KOG0034; Eukaryota.
DR HOGENOM; CLU_061288_6_1_1; -.
DR OrthoDB; 1271942at2759; -.
DR Proteomes; UP000002356; Chromosome 18.
DR Bgee; ENSOARG00000012128; Expressed in descending colon and 53 other tissues.
DR ExpressionAtlas; B1A8Z2; baseline.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005813; C:centrosome; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0032433; C:filopodium tip; IEA:UniProtKB-SubCell.
DR GO; GO:0030426; C:growth cone; IEA:UniProtKB-SubCell.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042383; C:sarcolemma; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IEA:Ensembl.
DR GO; GO:0008427; F:calcium-dependent protein kinase inhibitor activity; IEA:Ensembl.
DR GO; GO:0030291; F:protein serine/threonine kinase inhibitor activity; IEA:Ensembl.
DR GO; GO:0043495; F:protein-membrane adaptor activity; IEA:Ensembl.
DR GO; GO:0031267; F:small GTPase binding; IEA:Ensembl.
DR GO; GO:0044325; F:transmembrane transporter binding; IEA:Ensembl.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IEA:Ensembl.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IEA:Ensembl.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl.
DR GO; GO:0031122; P:cytoplasmic microtubule organization; IEA:Ensembl.
DR GO; GO:0007113; P:endomitotic cell cycle; IEA:Ensembl.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0045653; P:negative regulation of megakaryocyte differentiation; IEA:Ensembl.
DR GO; GO:0007026; P:negative regulation of microtubule depolymerization; IEA:Ensembl.
DR GO; GO:0010977; P:negative regulation of neuron projection development; IEA:Ensembl.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IEA:Ensembl.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IEA:Ensembl.
DR GO; GO:0030220; P:platelet formation; IEA:Ensembl.
DR GO; GO:0070886; P:positive regulation of calcineurin-NFAT signaling cascade; IEA:Ensembl.
DR GO; GO:0033630; P:positive regulation of cell adhesion mediated by integrin; IEA:Ensembl.
DR GO; GO:0030307; P:positive regulation of cell growth; IEA:Ensembl.
DR GO; GO:0090050; P:positive regulation of cell migration involved in sprouting angiogenesis; IEA:Ensembl.
DR GO; GO:0001954; P:positive regulation of cell-matrix adhesion; IEA:Ensembl.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:2000256; P:positive regulation of male germ cell proliferation; IEA:Ensembl.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IEA:Ensembl.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IEA:Ensembl.
DR GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; IEA:Ensembl.
DR GO; GO:0090314; P:positive regulation of protein targeting to membrane; IEA:Ensembl.
DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; IEA:Ensembl.
DR GO; GO:0051302; P:regulation of cell division; IEA:Ensembl.
DR GO; GO:0002931; P:response to ischemia; IEA:Ensembl.
DR GO; GO:0007286; P:spermatid development; IEA:Ensembl.
DR GO; GO:0038163; P:thrombopoietin-mediated signaling pathway; IEA:Ensembl.
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; 2.
PE 2: Evidence at transcript level;
KW Angiogenesis; Apoptosis; Calcium; Cell adhesion; Cell cycle; Cell division;
KW Cell membrane; Cell projection; Cytoplasm; Cytoskeleton; Differentiation;
KW Integrin; Lipoprotein; Magnesium; Membrane; Metal-binding; Myristate;
KW Nucleus; Reference proteome; Repeat; Spermatogenesis.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000255"
FT CHAIN 2..191
FT /note="Calcium and integrin-binding protein 1"
FT /id="PRO_0000425743"
FT DOMAIN 103..138
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 148..183
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 116
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 118
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 120
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 122
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 161
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 163
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
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 172
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 191 AA; 21728 MW; C6E0C5FC56F6E589 CRC64;
MGGSGSRLSK ELLAEYQDLT FLTKQEILLA HRRFCELLPQ EHRSVEESLQ ARVSLEQILS
LPELKANPFK ERICKVFSTS PSRDSLSFED FLDLLSVFSD TATPDIKSHY AFRIFDFDDD
GTLNREDLSQ LVNCLTGESE DTRLSASEMK QLIDNILEES DIDRDGTINL SEFQHVISRS
PDFASSFKIV L
