CABP4_HUMAN
ID CABP4_HUMAN Reviewed; 275 AA.
AC P57796; Q8N4Z2; Q8WWY5;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2002, sequence version 2.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Calcium-binding protein 4;
DE Short=CaBP4;
GN Name=CABP4;
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 [MRNA] (ISOFORM 1).
RC TISSUE=Retina;
RX PubMed=15452577; DOI=10.1038/nn1320;
RA Haeseleer F., Imanishi Y., Maeda T., Possin D.E., Maeda A., Lee A.,
RA Rieke F., Palczewski K.;
RT "Essential role of Ca2+-binding protein 4, a Cav1.4 channel regulator, in
RT photoreceptor synaptic function.";
RL Nat. Neurosci. 7:1079-1087(2004).
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP IDENTIFICATION.
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 [5]
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 [6]
RP VARIANT CRSD CYS-124.
RX PubMed=16960802; DOI=10.1086/508067;
RA Zeitz C., Kloeckener-Gruissem B., Forster U., Kohl S., Magyar I.,
RA Wissinger B., Matyas G., Borruat F.-X., Schorderet D.F., Zrenner E.,
RA Munier F.L., Berger W.;
RT "Mutations in CABP4, the gene encoding the Ca2+-binding protein 4, cause
RT autosomal recessive night blindness.";
RL Am. J. Hum. Genet. 79:657-667(2006).
CC -!- FUNCTION: Involved in normal synaptic function through regulation of
CC Ca(2+) influx and neurotransmitter release in photoreceptor synaptic
CC terminals and in auditory transmission. Modulator of CACNA1D and
CC CACNA1F, suppressing the calcium-dependent inactivation and shifting
CC the activation range to more hyperpolarized voltages (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Interacts with CACNA1F and CACNA1D (via IQ domain) in a
CC calcium independent manner. Interacts (via N-terminus) with UNC119.
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19338761}.
CC Presynapse {ECO:0000250|UniProtKB:Q8VHC5}. Note=Found in rod spherules
CC and cone pedicles of the presynapses from both types of photoreceptors.
CC {ECO:0000250|UniProtKB:Q8VHC5}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P57796-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P57796-2; Sequence=VSP_012700, VSP_012701;
CC -!- TISSUE SPECIFICITY: Expressed in retina and in the inner hair cells
CC (IHC) of the cochlea.
CC -!- PTM: Phosphorylated. Phosphorylation levels change with the light
CC conditions and regulate the activity (By similarity). {ECO:0000250}.
CC -!- DISEASE: Cone-rod synaptic disorder, congenital non-progressive (CRSD)
CC [MIM:610427]: A non-progressive retinal disorder characterized by
CC stable low vision, nystagmus, photophobia, a normal or near-normal
CC fundus appearance, and no night blindness.
CC {ECO:0000269|PubMed:16960802}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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DR EMBL; AY039217; AAK83462.1; -; mRNA.
DR EMBL; AC005849; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC033167; AAH33167.1; -; mRNA.
DR CCDS; CCDS73333.1; -. [P57796-2]
DR CCDS; CCDS8166.1; -. [P57796-1]
DR RefSeq; NP_001287824.1; NM_001300895.1. [P57796-2]
DR RefSeq; NP_001287825.1; NM_001300896.1. [P57796-2]
DR RefSeq; NP_660201.1; NM_145200.3. [P57796-1]
DR RefSeq; XP_011543485.1; XM_011545183.2. [P57796-2]
DR RefSeq; XP_016873514.1; XM_017018025.1. [P57796-2]
DR AlphaFoldDB; P57796; -.
DR SMR; P57796; -.
DR BioGRID; 121324; 8.
DR IntAct; P57796; 6.
DR STRING; 9606.ENSP00000324960; -.
DR iPTMnet; P57796; -.
DR PhosphoSitePlus; P57796; -.
DR BioMuta; CABP4; -.
DR DMDM; 20178284; -.
DR MassIVE; P57796; -.
DR PaxDb; P57796; -.
DR PeptideAtlas; P57796; -.
DR PRIDE; P57796; -.
DR ProteomicsDB; 57041; -. [P57796-1]
DR ProteomicsDB; 57042; -. [P57796-2]
DR Antibodypedia; 30420; 234 antibodies from 26 providers.
DR DNASU; 57010; -.
DR Ensembl; ENST00000325656.7; ENSP00000324960.5; ENSG00000175544.14. [P57796-1]
DR Ensembl; ENST00000438189.6; ENSP00000401555.2; ENSG00000175544.14. [P57796-2]
DR GeneID; 57010; -.
DR KEGG; hsa:57010; -.
DR MANE-Select; ENST00000325656.7; ENSP00000324960.5; NM_145200.5; NP_660201.1.
DR UCSC; uc001oln.4; human. [P57796-1]
DR CTD; 57010; -.
DR DisGeNET; 57010; -.
DR GeneCards; CABP4; -.
DR HGNC; HGNC:1386; CABP4.
DR HPA; ENSG00000175544; Tissue enriched (retina).
DR MalaCards; CABP4; -.
DR MIM; 608965; gene.
DR MIM; 610427; phenotype.
DR neXtProt; NX_P57796; -.
DR OpenTargets; ENSG00000175544; -.
DR Orphanet; 98784; Autosomal dominant nocturnal frontal lobe epilepsy.
DR Orphanet; 215; Congenital stationary night blindness.
DR PharmGKB; PA26003; -.
DR VEuPathDB; HostDB:ENSG00000175544; -.
DR eggNOG; KOG0027; Eukaryota.
DR GeneTree; ENSGT00940000161468; -.
DR HOGENOM; CLU_061288_2_2_1; -.
DR InParanoid; P57796; -.
DR OMA; KNPSRTR; -.
DR OrthoDB; 1340191at2759; -.
DR PhylomeDB; P57796; -.
DR TreeFam; TF334804; -.
DR PathwayCommons; P57796; -.
DR BioGRID-ORCS; 57010; 37 hits in 1065 CRISPR screens.
DR ChiTaRS; CABP4; human.
DR GenomeRNAi; 57010; -.
DR Pharos; P57796; Tbio.
DR PRO; PR:P57796; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P57796; protein.
DR Bgee; ENSG00000175544; Expressed in vena cava and 178 other tissues.
DR ExpressionAtlas; P57796; baseline and differential.
DR Genevisible; P57796; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005576; C:extracellular region; NAS:UniProtKB.
DR GO; GO:0045202; C:synapse; TAS:UniProtKB.
DR GO; GO:0043195; C:terminal bouton; TAS:UniProtKB.
DR GO; GO:0005246; F:calcium channel regulator activity; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; TAS:UniProtKB.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:UniProtKB.
DR GO; GO:0008594; P:photoreceptor cell morphogenesis; IEA:Ensembl.
DR GO; GO:0007602; P:phototransduction; IEA:Ensembl.
DR GO; GO:1901385; P:regulation of voltage-gated calcium channel activity; IBA:GO_Central.
DR GO; GO:0060040; P:retinal bipolar neuron differentiation; IEA:Ensembl.
DR GO; GO:0046549; P:retinal cone cell development; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; NAS:UniProtKB.
DR GO; GO:0007601; P:visual perception; IMP:UniProtKB.
DR CDD; cd00051; EFh; 1.
DR InterPro; IPR043582; CaBP1/2/4/5.
DR InterPro; IPR033014; CABP4.
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:SF4; PTHR45917:SF4; 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 projection; Cytoplasm; Disease variant;
KW Metal-binding; Phosphoprotein; Reference proteome; Repeat; Synapse.
FT CHAIN 1..275
FT /note="Calcium-binding protein 4"
FT /id="PRO_0000073521"
FT DOMAIN 129..164
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 183..200
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 206..241
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 243..275
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 1..112
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 54..77
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 142
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 144
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 146
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 148
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 153
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 219
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 221
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 223
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 225
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 230
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 256
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 258
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 260
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 262
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 267
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT MOD_RES 42
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VHC5"
FT VAR_SEQ 1..105
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_012700"
FT VAR_SEQ 106..122
FT /note="DAAQRTYGPLLNRVFGK -> MTEPWLALGTSWTLPLQ (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_012701"
FT VARIANT 124
FT /note="R -> C (in CRSD; dbSNP:rs121917828)"
FT /evidence="ECO:0000269|PubMed:16960802"
FT /id="VAR_029375"
SQ SEQUENCE 275 AA; 30433 MW; 1AEB49C93AD67DB7 CRC64;
MTTEQARGQQ GPNLAIGRQK PPAGVVTPKS DAEEPPLTRK RSKKERGLRG SRKRTGSSGE
QTGPEAPGSS NNPPSTGEGP AGAPPASPGP ASSRQSHRHR PDSLHDAAQR TYGPLLNRVF
GKDRELGPEE LDELQAAFEE FDTDRDGYIS HRELGDCMRT LGYMPTEMEL LEVSQHIKMR
MGGRVDFEEF VELIGPKLRE ETAHMLGVRE LRIAFREFDR DRDGRITVAE LREAVPALLG
EPLAGPELDE MLREVDLNGD GTVDFDEFVM MLSRH
