PCP4_HUMAN
ID PCP4_HUMAN Reviewed; 62 AA.
AC P48539; A6NDJ9; Q6ICS4; Q93059;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Calmodulin regulator protein PCP4 {ECO:0000305};
DE AltName: Full=Brain-specific polypeptide PEP-19 {ECO:0000303|PubMed:8931698};
DE AltName: Full=Purkinje cell protein 4 {ECO:0000312|HGNC:HGNC:8742};
GN Name=PCP4 {ECO:0000303|PubMed:8914602, ECO:0000312|HGNC:HGNC:8742};
GN Synonyms=PEP19 {ECO:0000303|PubMed:21491429};
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].
RC TISSUE=Retina;
RX PubMed=8931698; DOI=10.1007/s004390050282;
RA Chen H.M., Bouras C., Antonarakis S.E.;
RT "Cloning of the cDNA for a human homolog of the rat PEP-19 gene and mapping
RT to chromosome 21q22.2-q22.3.";
RL Hum. Genet. 98:672-677(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=8914602; DOI=10.1007/bf02369907;
RA Cabin D.E., Gardiner K., Reeves R.H.;
RT "Molecular genetic characterization and comparative mapping of the human
RT PCP4 gene.";
RL Somat. Cell Mol. Genet. 22:167-175(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Fetal kidney;
RX PubMed=21491429; DOI=10.1002/cne.22651;
RA Mouton-Liger F., Thomas S., Rattenbach R., Magnol L., Larigaldie V.,
RA Ledru A., Herault Y., Verney C., Creau N.;
RT "PCP4 (PEP19) overexpression induces premature neuronal differentiation
RT associated with Ca(2+) /calmodulin-dependent kinase II-o activation in
RT mouse models of Down syndrome.";
RL J. Comp. Neurol. 519:2779-2802(2011).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Taudien S., Nordsiek G., Korenberg J., Drescher B., Weber J.,
RA Schattevoy R., Rosenthal A.;
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fetal brain;
RA Kang L., Zhang B., Zhou Y., Peng X., Yuan J., Qiang B.;
RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10830953; DOI=10.1038/35012518;
RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S.,
RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.;
RT "The DNA sequence of human chromosome 21.";
RL Nature 405:311-319(2000).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Adrenal cortex;
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 [11]
RP FUNCTION, INTERACTION WITH CALMODULIN, AND DOMAIN.
RX PubMed=19106096; DOI=10.1074/jbc.m808067200;
RA Kleerekoper Q.K., Putkey J.A.;
RT "PEP-19, an intrinsically disordered regulator of calmodulin signaling.";
RL J. Biol. Chem. 284:7455-7464(2009).
RN [12]
RP FUNCTION, MUTAGENESIS OF GLU-29; ASP-31; ASP-33; ASP-35; PRO-37 AND GLU-40,
RP AND REGION.
RX PubMed=23204517; DOI=10.1074/jbc.m112.411314;
RA Wang X., Xiong L.W., El Ayadi A., Boehning D., Putkey J.A.;
RT "The calmodulin regulator protein, PEP-19, sensitizes ATP-induced Ca2+
RT release.";
RL J. Biol. Chem. 288:2040-2048(2013).
RN [13] {ECO:0007744|PDB:2N77}
RP STRUCTURE BY NMR OF 3-62 IN COMPLEX WITH CALM1, FUNCTION, AND INTERACTION
RP WITH CALMODULIN.
RX PubMed=27876793; DOI=10.1038/ncomms13583;
RA Wang X., Putkey J.A.;
RT "PEP-19 modulates calcium binding to calmodulin by electrostatic
RT steering.";
RL Nat. Commun. 7:13583-13583(2016).
CC -!- FUNCTION: Functions as a modulator of calcium-binding by calmodulin.
CC Thereby, regulates calmodulin activity and the different processes it
CC controls (PubMed:19106096, PubMed:23204517, PubMed:27876793). For
CC instance, may play a role in neuronal differentiation through
CC activation of calmodulin-dependent kinase signaling pathways
CC (PubMed:21491429). {ECO:0000269|PubMed:19106096,
CC ECO:0000269|PubMed:21491429, ECO:0000269|PubMed:23204517,
CC ECO:0000269|PubMed:27876793}.
CC -!- SUBUNIT: Binds to both calcium-free and calcium-bound calmodulin. The
CC affinity for the calcium-bound form is 50-fold greater.
CC {ECO:0000269|PubMed:19106096, ECO:0000269|PubMed:27876793}.
CC -!- INTERACTION:
CC P48539; Q8TD86: CALML6; NbExp=3; IntAct=EBI-4287270, EBI-12041267;
CC P48539; Q9NYB0: TERF2IP; NbExp=2; IntAct=EBI-4287270, EBI-750109;
CC -!- DOMAIN: Mostly intrinsically disordered, with residual structure
CC localized to the IQ domain which mediates the interaction with
CC calmodulin. {ECO:0000269|PubMed:19106096}.
CC -!- SIMILARITY: Belongs to the PCP4 family. {ECO:0000305}.
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DR EMBL; X93349; CAA63724.1; -; mRNA.
DR EMBL; U53709; AAC00024.1; -; Genomic_DNA.
DR EMBL; U53707; AAC00024.1; JOINED; Genomic_DNA.
DR EMBL; U53708; AAC00024.1; JOINED; Genomic_DNA.
DR EMBL; U52969; AAB09033.1; -; mRNA.
DR EMBL; AM183336; CAJ70630.1; -; mRNA.
DR EMBL; AF064857; AAC23994.1; -; Genomic_DNA.
DR EMBL; AF416716; AAL16810.1; -; mRNA.
DR EMBL; AK289964; BAF82653.1; -; mRNA.
DR EMBL; CR450319; CAG29315.1; -; mRNA.
DR EMBL; AL163281; CAB90443.1; -; Genomic_DNA.
DR EMBL; CH471079; EAX09623.1; -; Genomic_DNA.
DR EMBL; BC013791; AAH13791.1; -; mRNA.
DR CCDS; CCDS33563.1; -.
DR RefSeq; NP_006189.2; NM_006198.2.
DR PDB; 2N77; NMR; -; B=3-62.
DR PDBsum; 2N77; -.
DR AlphaFoldDB; P48539; -.
DR BMRB; P48539; -.
DR SMR; P48539; -.
DR BioGRID; 111150; 50.
DR IntAct; P48539; 6.
DR STRING; 9606.ENSP00000329403; -.
DR iPTMnet; P48539; -.
DR PhosphoSitePlus; P48539; -.
DR BioMuta; PCP4; -.
DR DMDM; 3915800; -.
DR CPTAC; CPTAC-1263; -.
DR jPOST; P48539; -.
DR MassIVE; P48539; -.
DR PaxDb; P48539; -.
DR PeptideAtlas; P48539; -.
DR PRIDE; P48539; -.
DR ProteomicsDB; 55899; -.
DR Antibodypedia; 1604; 120 antibodies from 21 providers.
DR DNASU; 5121; -.
DR Ensembl; ENST00000328619.10; ENSP00000329403.5; ENSG00000183036.11.
DR GeneID; 5121; -.
DR KEGG; hsa:5121; -.
DR MANE-Select; ENST00000328619.10; ENSP00000329403.5; NM_006198.3; NP_006189.2.
DR UCSC; uc002yyp.4; human.
DR CTD; 5121; -.
DR DisGeNET; 5121; -.
DR GeneCards; PCP4; -.
DR HGNC; HGNC:8742; PCP4.
DR HPA; ENSG00000183036; Tissue enhanced (brain, seminal vesicle).
DR MIM; 601629; gene.
DR neXtProt; NX_P48539; -.
DR OpenTargets; ENSG00000183036; -.
DR PharmGKB; PA33087; -.
DR VEuPathDB; HostDB:ENSG00000183036; -.
DR eggNOG; ENOG502STZW; Eukaryota.
DR GeneTree; ENSGT00530000064267; -.
DR HOGENOM; CLU_202697_1_0_1; -.
DR InParanoid; P48539; -.
DR OMA; FQIDMDA; -.
DR OrthoDB; 1635294at2759; -.
DR PhylomeDB; P48539; -.
DR TreeFam; TF336068; -.
DR PathwayCommons; P48539; -.
DR SignaLink; P48539; -.
DR SIGNOR; P48539; -.
DR BioGRID-ORCS; 5121; 11 hits in 1037 CRISPR screens.
DR ChiTaRS; PCP4; human.
DR GeneWiki; PCP4; -.
DR GenomeRNAi; 5121; -.
DR Pharos; P48539; Tbio.
DR PRO; PR:P48539; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; P48539; protein.
DR Bgee; ENSG00000183036; Expressed in lateral nuclear group of thalamus and 168 other tissues.
DR ExpressionAtlas; P48539; baseline and differential.
DR Genevisible; P48539; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:CAFA.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IDA:UniProtKB.
DR GO; GO:0099004; P:calmodulin dependent kinase signaling pathway; IMP:UniProtKB.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IMP:UniProtKB.
DR DisProt; DP00592; -.
DR InterPro; IPR033236; PCP4.
DR PANTHER; PTHR15359:SF7; PTHR15359:SF7; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calmodulin-binding; Reference proteome.
FT CHAIN 1..62
FT /note="Calmodulin regulator protein PCP4"
FT /id="PRO_0000058306"
FT DOMAIN 39..62
FT /note="IQ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT REGION 1..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 28..40
FT /note="Acidic; binds calcium and is required for modulating
FT the calcium-binding kinetics of calmodulin"
FT /evidence="ECO:0000269|PubMed:23204517"
FT COMPBIAS 1..16
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 17..38
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 29
FT /note="E->A: No effect on the calmodulin modulator
FT function."
FT /evidence="ECO:0000269|PubMed:23204517"
FT MUTAGEN 31
FT /note="D->A: Decreased calmodulin modulator function."
FT /evidence="ECO:0000269|PubMed:23204517"
FT MUTAGEN 33
FT /note="D->A: Decreased calmodulin modulator function."
FT /evidence="ECO:0000269|PubMed:23204517"
FT MUTAGEN 35
FT /note="D->A: No effect on the calmodulin modulator
FT function."
FT /evidence="ECO:0000269|PubMed:23204517"
FT MUTAGEN 37
FT /note="P->G: Loss of the calmodulin modulator function."
FT /evidence="ECO:0000269|PubMed:23204517"
FT MUTAGEN 40
FT /note="E->A: Decreased calmodulin modulator function."
FT /evidence="ECO:0000269|PubMed:23204517"
FT CONFLICT 9
FT /note="A -> P (in Ref. 1; CAA63724)"
FT /evidence="ECO:0000305"
FT STRAND 34..36
FT /evidence="ECO:0007829|PDB:2N77"
FT HELIX 37..58
FT /evidence="ECO:0007829|PDB:2N77"
SQ SEQUENCE 62 AA; 6791 MW; 99ED306DE41BF29D CRC64;
MSERQGAGAT NGKDKTSGEN DGQKKVQEEF DIDMDAPETE RAAVAIQSQF RKFQKKKAGS
QS
