CABP2_HUMAN
ID CABP2_HUMAN Reviewed; 220 AA.
AC Q9NPB3;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 4.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Calcium-binding protein 2;
DE Short=CaBP2;
GN Name=CABP2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS L-CABP2 AND S-CABP2),
RP VARIANT GLN-94, AND MYRISTOYLATION AT GLY-2.
RC TISSUE=Retina;
RX PubMed=10625670; DOI=10.1074/jbc.275.2.1247;
RA Haeseleer F., Sokal I., Verlinde C.L.M.J., Erdjument-Bromage H., Tempst P.,
RA Pronin A.N., Benovic J.L., Fariss R.N., Palczewski K.;
RT "Five members of a novel Ca(2+)-binding protein (CABP) subfamily with
RT similarity to calmodulin.";
RL J. Biol. Chem. 275:1247-1260(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=11108966; DOI=10.1016/s0167-4889(00)00099-9;
RA Sokal I., Li N., Verlinde C.L.M.J., Haeseleer F., Baehr W., Palczewski K.;
RT "Ca(2+)-binding proteins in the retina: from discovery to etiology of human
RT disease.";
RL Biochim. Biophys. Acta 1498:233-251(2000).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=19338761; DOI=10.1016/j.bbrc.2009.01.177;
RA McCue H.V., Burgoyne R.D., Haynes L.P.;
RT "Membrane targeting of the EF-hand containing calcium-sensing proteins
RT CaBP7 and CaBP8.";
RL Biochem. Biophys. Res. Commun. 380:825-831(2009).
RN [5]
RP INVOLVEMENT IN DFNB93.
RX PubMed=22981119; DOI=10.1016/j.ajhg.2012.08.018;
RA Schrauwen I., Helfmann S., Inagaki A., Predoehl F., Tabatabaiefar M.A.,
RA Picher M.M., Sommen M., Seco C.Z., Oostrik J., Kremer H., Dheedene A.,
RA Claes C., Fransen E., Chaleshtori M.H., Coucke P., Lee A., Moser T.,
RA Van Camp G.;
RT "A mutation in CABP2, expressed in cochlear hair cells, causes autosomal-
RT recessive hearing impairment.";
RL Am. J. Hum. Genet. 91:636-645(2012).
RN [6]
RP VARIANT DFNB93 156-GLU--ARG-216 DEL, AND FUNCTION.
RX PubMed=28183797; DOI=10.1073/pnas.1617533114;
RA Picher M.M., Gehrt A., Meese S., Ivanovic A., Predoehl F., Jung S.,
RA Schrauwen I., Dragonetti A.G., Colombo R., Van Camp G., Strenzke N.,
RA Moser T.;
RT "Ca(2+)-binding protein 2 inhibits Ca(2+)-channel inactivation in mouse
RT inner hair cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:E1717-E1726(2017).
CC -!- FUNCTION: Required for sound encoding at inner hair cells (IHCs)
CC synapses, likely via inhibition of the inactivation of voltage-gated
CC calcium channel of type 1.3 (Cav1.3) in the IHCs (PubMed:28183797).
CC Required for the normal transfer of light signals through the retina
CC (By similarity). {ECO:0000250|UniProtKB:Q9JLK4,
CC ECO:0000269|PubMed:28183797}.
CC -!- INTERACTION:
CC Q9NPB3; Q8IZF2: ADGRF5; NbExp=3; IntAct=EBI-12011224, EBI-7600130;
CC Q9NPB3; Q8N6D5: ANKRD29; NbExp=3; IntAct=EBI-12011224, EBI-17439331;
CC Q9NPB3; Q5T686: AVPI1; NbExp=3; IntAct=EBI-12011224, EBI-8640233;
CC Q9NPB3; Q9H1P6: C20orf85; NbExp=3; IntAct=EBI-12011224, EBI-12155483;
CC Q9NPB3; Q6P5X5: C22orf39; NbExp=3; IntAct=EBI-12011224, EBI-7317823;
CC Q9NPB3; Q9H257-2: CARD9; NbExp=3; IntAct=EBI-12011224, EBI-11530605;
CC Q9NPB3; Q5JTJ3: COA6; NbExp=3; IntAct=EBI-12011224, EBI-2874677;
CC Q9NPB3; A0A0U1RQF7: DPEP2NB; NbExp=3; IntAct=EBI-12011224, EBI-18398199;
CC Q9NPB3; Q5JST6: EFHC2; NbExp=3; IntAct=EBI-12011224, EBI-2349927;
CC Q9NPB3; A6NEM1: GOLGA6L9; NbExp=3; IntAct=EBI-12011224, EBI-5916454;
CC Q9NPB3; Q96ED9-2: HOOK2; NbExp=3; IntAct=EBI-12011224, EBI-10961706;
CC Q9NPB3; P35452-2: HOXD12; NbExp=3; IntAct=EBI-12011224, EBI-17244356;
CC Q9NPB3; Q9BRK3: MXRA8; NbExp=3; IntAct=EBI-12011224, EBI-11721798;
CC Q9NPB3; Q9BU61: NDUFAF3; NbExp=3; IntAct=EBI-12011224, EBI-2114801;
CC Q9NPB3; O00746: NME4; NbExp=3; IntAct=EBI-12011224, EBI-744871;
CC Q9NPB3; Q9NPE3: NOP10; NbExp=3; IntAct=EBI-12011224, EBI-1642169;
CC Q9NPB3; Q9BRJ7: NUDT16L1; NbExp=3; IntAct=EBI-12011224, EBI-2949792;
CC Q9NPB3; P86480: PRR20D; NbExp=3; IntAct=EBI-12011224, EBI-12754095;
CC Q9NPB3; Q7Z3Z2: RD3; NbExp=3; IntAct=EBI-12011224, EBI-10257497;
CC Q9NPB3; Q8NCR6: SMRP1; NbExp=3; IntAct=EBI-12011224, EBI-10269322;
CC Q9NPB3; O43623: SNAI2; NbExp=3; IntAct=EBI-12011224, EBI-9876238;
CC Q9NPB3; Q9H0A9-2: SPATC1L; NbExp=3; IntAct=EBI-12011224, EBI-11995806;
CC Q9NPB3; Q96M29: TEKT5; NbExp=3; IntAct=EBI-12011224, EBI-10239812;
CC Q9NPB3; Q8TBB0: THAP6; NbExp=3; IntAct=EBI-12011224, EBI-3925505;
CC Q9NPB3; Q08117-2: TLE5; NbExp=3; IntAct=EBI-12011224, EBI-11741437;
CC Q9NPB3; P19237: TNNI1; NbExp=3; IntAct=EBI-12011224, EBI-746692;
CC Q9NPB3; Q9UPQ4-2: TRIM35; NbExp=3; IntAct=EBI-12011224, EBI-17716262;
CC Q9NPB3; Q9H9P5-5: UNKL; NbExp=3; IntAct=EBI-12011224, EBI-12817837;
CC Q9NPB3; Q8TAG6: VXN; NbExp=3; IntAct=EBI-12011224, EBI-12071548;
CC Q9NPB3; P52738: ZNF140; NbExp=3; IntAct=EBI-12011224, EBI-12069140;
CC Q9NPB3; Q68EA5: ZNF57; NbExp=3; IntAct=EBI-12011224, EBI-8490788;
CC Q9NPB3; Q6NX45: ZNF774; NbExp=3; IntAct=EBI-12011224, EBI-10251462;
CC Q9NPB3; A8K8V0: ZNF785; NbExp=3; IntAct=EBI-12011224, EBI-3925400;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:19338761}. Cell membrane
CC {ECO:0000269|PubMed:19338761}; Lipid-anchor
CC {ECO:0000269|PubMed:19338761}; Cytoplasmic side
CC {ECO:0000269|PubMed:19338761}. Golgi apparatus
CC {ECO:0000269|PubMed:19338761}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=L-CaBP2;
CC IsoId=Q9NPB3-1; Sequence=Displayed;
CC Name=S-CaBP2;
CC IsoId=Q9NPB3-2; Sequence=VSP_000734;
CC -!- TISSUE SPECIFICITY: Retina. {ECO:0000269|PubMed:11108966}.
CC -!- DISEASE: Deafness, autosomal recessive, 93 (DFNB93) [MIM:614899]: A
CC form of non-syndromic deafness characterized by stable, bilateral,
CC symmetric, prelingual moderate to severe deafness. Hearing impairment
CC is slightly more pronounced in the mid-frequencies, resulting in a
CC distinctive shallow U-shaped audiogram. {ECO:0000269|PubMed:22981119,
CC ECO:0000269|PubMed:28183797}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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DR EMBL; AF170811; AAF26283.1; -; Genomic_DNA.
DR EMBL; AF169154; AAF25788.1; -; mRNA.
DR EMBL; AP001184; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS8170.1; -. [Q9NPB3-1]
DR RefSeq; NP_001305425.1; NM_001318496.1.
DR RefSeq; NP_057450.2; NM_016366.2. [Q9NPB3-1]
DR AlphaFoldDB; Q9NPB3; -.
DR SMR; Q9NPB3; -.
DR BioGRID; 119560; 71.
DR IntAct; Q9NPB3; 33.
DR STRING; 9606.ENSP00000294288; -.
DR iPTMnet; Q9NPB3; -.
DR BioMuta; CABP2; -.
DR DMDM; 294862530; -.
DR MassIVE; Q9NPB3; -.
DR PaxDb; Q9NPB3; -.
DR PeptideAtlas; Q9NPB3; -.
DR PRIDE; Q9NPB3; -.
DR Antibodypedia; 67889; 119 antibodies from 15 providers.
DR DNASU; 51475; -.
DR Ensembl; ENST00000294288.5; ENSP00000294288.4; ENSG00000167791.14. [Q9NPB3-1]
DR Ensembl; ENST00000353903.9; ENSP00000312037.4; ENSG00000167791.14. [Q9NPB3-2]
DR GeneID; 51475; -.
DR KEGG; hsa:51475; -.
DR MANE-Select; ENST00000294288.5; ENSP00000294288.4; NM_016366.3; NP_057450.2.
DR UCSC; uc001omc.2; human. [Q9NPB3-1]
DR CTD; 51475; -.
DR DisGeNET; 51475; -.
DR GeneCards; CABP2; -.
DR HGNC; HGNC:1385; CABP2.
DR HPA; ENSG00000167791; Tissue enriched (retina).
DR MalaCards; CABP2; -.
DR MIM; 607314; gene.
DR MIM; 614899; phenotype.
DR neXtProt; NX_Q9NPB3; -.
DR OpenTargets; ENSG00000167791; -.
DR Orphanet; 90636; Autosomal recessive non-syndromic sensorineural deafness type DFNB.
DR PharmGKB; PA26001; -.
DR VEuPathDB; HostDB:ENSG00000167791; -.
DR eggNOG; KOG0027; Eukaryota.
DR GeneTree; ENSGT00940000159796; -.
DR HOGENOM; CLU_061288_2_2_1; -.
DR InParanoid; Q9NPB3; -.
DR OrthoDB; 1424914at2759; -.
DR PhylomeDB; Q9NPB3; -.
DR TreeFam; TF334804; -.
DR PathwayCommons; Q9NPB3; -.
DR Reactome; R-HSA-9662360; Sensory processing of sound by inner hair cells of the cochlea.
DR SignaLink; Q9NPB3; -.
DR BioGRID-ORCS; 51475; 17 hits in 1061 CRISPR screens.
DR GenomeRNAi; 51475; -.
DR Pharos; Q9NPB3; Tbio.
DR PRO; PR:Q9NPB3; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9NPB3; protein.
DR Bgee; ENSG00000167791; Expressed in mucosa of transverse colon and 13 other tissues.
DR ExpressionAtlas; Q9NPB3; baseline and differential.
DR Genevisible; Q9NPB3; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0005246; F:calcium channel regulator activity; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; TAS:ProtInc.
DR GO; GO:1901385; P:regulation of voltage-gated calcium channel activity; IBA:GO_Central.
DR GO; GO:0007605; P:sensory perception of sound; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0007601; P:visual perception; ISS:UniProtKB.
DR CDD; cd00051; EFh; 1.
DR InterPro; IPR015754; Ca-bd_2.
DR InterPro; IPR043582; CaBP1/2/4/5.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR PANTHER; PTHR45917; PTHR45917; 1.
DR PANTHER; PTHR45917:SF2; PTHR45917:SF2; 1.
DR Pfam; PF00036; EF-hand_1; 1.
DR Pfam; PF13499; EF-hand_7; 1.
DR SMART; SM00054; EFh; 3.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS00018; EF_HAND_1; 3.
DR PROSITE; PS50222; EF_HAND_2; 4.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Cell membrane; Cytoplasm; Deafness;
KW Disease variant; Golgi apparatus; Hearing; Lipoprotein; Membrane;
KW Metal-binding; Myristate; Non-syndromic deafness; Reference proteome;
KW Repeat; Sensory transduction; Vision.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..220
FT /note="Calcium-binding protein 2"
FT /id="PRO_0000073517"
FT DOMAIN 78..113
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 129..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 DOMAIN 189..220
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 1..45
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 25..39
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 91
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 93
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 95
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 97
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 102
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 171
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 BINDING 202
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 204
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 206
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 213
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:10625670"
FT VAR_SEQ 15..71
FT /note="Missing (in isoform S-CaBP2)"
FT /evidence="ECO:0000303|PubMed:10625670"
FT /id="VSP_000734"
FT VARIANT 94
FT /note="R -> Q (in dbSNP:rs2276118)"
FT /evidence="ECO:0000269|PubMed:10625670"
FT /id="VAR_063087"
FT VARIANT 156..216
FT /note="Missing (in DFNB93)"
FT /evidence="ECO:0000269|PubMed:28183797"
FT /id="VAR_080405"
SQ SEQUENCE 220 AA; 24482 MW; 9A0F0E7358A44F3A CRC64;
MGNCAKRPWR RGPKDPLQWL GSPPRGSCPS PSSSPKEQGD PAPGVQGYSV LNSLVGPACI
FLRPSIAATQ LDRELRPEEI EELQVAFQEF DRDRDGYIGC RELGACMRTL GYMPTEMELI
EISQQISGGK VDFEDFVELM GPKLLAETAD MIGVRELRDA FREFDTNGDG RISVGELRAA
LKALLGERLS QREVDEILQD VDLNGDGLVD FEEFVRMMSR
