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 27-MAR-2024, entry version 176. 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. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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. DR RefSeq; XP_016873514.1; XM_017018025.1. DR AlphaFoldDB; P57796; -. DR SMR; P57796; -. DR BioGRID; 121324; 10. 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; 9606-ENSP00000324960; -. DR PeptideAtlas; P57796; -. DR ProteomicsDB; 57041; -. [P57796-1] DR ProteomicsDB; 57042; -. [P57796-2] DR Antibodypedia; 30420; 257 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 AGR; HGNC:1386; -. DR CTD; 57010; -. DR DisGeNET; 57010; -. DR GeneCards; CABP4; -. DR GeneReviews; 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; 143520at2759; -. DR PhylomeDB; P57796; -. DR TreeFam; TF334804; -. DR PathwayCommons; P57796; -. DR BioGRID-ORCS; 57010; 41 hits in 1143 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 179 other cell types or tissues. DR ExpressionAtlas; P57796; baseline and differential. 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: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 Gene3D; 1.10.238.10; EF-hand; 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; CALCIUM-BINDING PROTEIN 1-RELATED; 1. DR PANTHER; PTHR45917:SF4; CALCIUM-BINDING PROTEIN 4; 1. DR Pfam; PF00036; EF-hand_1; 1. DR Pfam; PF13499; EF-hand_7; 1. DR SMART; SM00054; EFh; 3. DR SUPFAM; SSF47473; EF-hand; 1. DR PROSITE; PS00018; EF_HAND_1; 3. DR PROSITE; PS50222; EF_HAND_2; 4. DR Genevisible; P57796; HS. 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 //