SRCH_HUMAN
ID SRCH_HUMAN Reviewed; 699 AA.
AC P23327; Q504Y6;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Sarcoplasmic reticulum histidine-rich calcium-binding protein;
DE Flags: Precursor;
GN Name=HRC; Synonyms=HCP;
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], AND VARIANTS.
RC TISSUE=Skeletal muscle;
RX PubMed=2037293; DOI=10.1016/0888-7543(91)90359-m;
RA Hofmann S.L., Topham M., Hsieh C.-L., Francke U.;
RT "cDNA and genomic cloning of HRC, a human sarcoplasmic reticulum protein,
RT and localization of the gene to human chromosome 19 and mouse chromosome
RT 7.";
RL Genomics 9:656-669(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skeletal muscle;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-333, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [5]
RP PHOSPHORYLATION AT THR-76; SER-119; SER-145; SER-358; SER-431; SER-494 AND
RP SER-567.
RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028;
RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J.,
RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N.,
RA Pinna L.A., Pagliarini D.J., Dixon J.E.;
RT "A single kinase generates the majority of the secreted phosphoproteome.";
RL Cell 161:1619-1632(2015).
CC -!- FUNCTION: May play a role in the regulation of calcium sequestration or
CC release in the SR of skeletal and cardiac muscle.
CC -!- INTERACTION:
CC P23327; P14923: JUP; NbExp=2; IntAct=EBI-9639760, EBI-702484;
CC P23327; Q32M78: ZNF699; NbExp=3; IntAct=EBI-9639760, EBI-10217363;
CC P23327; E9Q401: Ryr2; Xeno; NbExp=3; IntAct=EBI-9639760, EBI-643628;
CC -!- SUBCELLULAR LOCATION: Sarcoplasmic reticulum lumen.
CC -!- SIMILARITY: Belongs to the HRC family. {ECO:0000305}.
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DR EMBL; M60052; AAA88071.1; -; mRNA.
DR EMBL; BC069795; AAH69795.1; -; mRNA.
DR EMBL; BC069802; AAH69802.1; -; mRNA.
DR EMBL; BC094691; AAH94691.1; -; mRNA.
DR CCDS; CCDS12759.1; -.
DR PIR; A54660; A54660.
DR RefSeq; NP_002143.1; NM_002152.2.
DR AlphaFoldDB; P23327; -.
DR BioGRID; 109506; 8.
DR IntAct; P23327; 9.
DR STRING; 9606.ENSP00000252825; -.
DR GlyGen; P23327; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P23327; -.
DR PhosphoSitePlus; P23327; -.
DR BioMuta; HRC; -.
DR DMDM; 134873; -.
DR jPOST; P23327; -.
DR MassIVE; P23327; -.
DR MaxQB; P23327; -.
DR PaxDb; P23327; -.
DR PeptideAtlas; P23327; -.
DR PRIDE; P23327; -.
DR ProteomicsDB; 54080; -.
DR Antibodypedia; 1379; 88 antibodies from 19 providers.
DR DNASU; 3270; -.
DR Ensembl; ENST00000252825.9; ENSP00000252825.3; ENSG00000130528.12.
DR GeneID; 3270; -.
DR KEGG; hsa:3270; -.
DR MANE-Select; ENST00000252825.9; ENSP00000252825.3; NM_002152.3; NP_002143.1.
DR UCSC; uc002pmv.4; human.
DR CTD; 3270; -.
DR DisGeNET; 3270; -.
DR GeneCards; HRC; -.
DR HGNC; HGNC:5178; HRC.
DR HPA; ENSG00000130528; Group enriched (heart muscle, skeletal muscle, tongue).
DR MIM; 142705; gene.
DR neXtProt; NX_P23327; -.
DR OpenTargets; ENSG00000130528; -.
DR PharmGKB; PA29452; -.
DR VEuPathDB; HostDB:ENSG00000130528; -.
DR eggNOG; ENOG502S3MW; Eukaryota.
DR GeneTree; ENSGT00730000111459; -.
DR HOGENOM; CLU_023924_0_0_1; -.
DR InParanoid; P23327; -.
DR OMA; EHPHHVP; -.
DR OrthoDB; 618515at2759; -.
DR PhylomeDB; P23327; -.
DR TreeFam; TF344276; -.
DR PathwayCommons; P23327; -.
DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR SignaLink; P23327; -.
DR BioGRID-ORCS; 3270; 11 hits in 1079 CRISPR screens.
DR ChiTaRS; HRC; human.
DR GeneWiki; HRC_(gene); -.
DR GenomeRNAi; 3270; -.
DR Pharos; P23327; Tbio.
DR PRO; PR:P23327; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P23327; protein.
DR Bgee; ENSG00000130528; Expressed in apex of heart and 106 other tissues.
DR ExpressionAtlas; P23327; baseline and differential.
DR Genevisible; P23327; HS.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0033018; C:sarcoplasmic reticulum lumen; TAS:BHF-UCL.
DR GO; GO:0030018; C:Z disc; IDA:BHF-UCL.
DR GO; GO:0051117; F:ATPase binding; IPI:BHF-UCL.
DR GO; GO:0005509; F:calcium ion binding; IDA:BHF-UCL.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:BHF-UCL.
DR GO; GO:0006936; P:muscle contraction; TAS:ProtInc.
DR GO; GO:0045823; P:positive regulation of heart contraction; IGI:BHF-UCL.
DR GO; GO:0010460; P:positive regulation of heart rate; IGI:BHF-UCL.
DR GO; GO:1901899; P:positive regulation of relaxation of cardiac muscle; IGI:BHF-UCL.
DR GO; GO:1903169; P:regulation of calcium ion transmembrane transport; IGI:BHF-UCL.
DR GO; GO:0010881; P:regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion; TAS:BHF-UCL.
DR GO; GO:1901844; P:regulation of cell communication by electrical coupling involved in cardiac conduction; IGI:BHF-UCL.
DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; IGI:BHF-UCL.
DR GO; GO:0002027; P:regulation of heart rate; IMP:BHF-UCL.
DR GO; GO:0033135; P:regulation of peptidyl-serine phosphorylation; IGI:BHF-UCL.
DR GO; GO:0010880; P:regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; IGI:BHF-UCL.
DR GO; GO:0060314; P:regulation of ryanodine-sensitive calcium-release channel activity; IGI:BHF-UCL.
DR InterPro; IPR019552; Hist_rich_Ca-bd.
DR InterPro; IPR015666; HRC.
DR PANTHER; PTHR15054; PTHR15054; 1.
DR Pfam; PF10529; Hist_rich_Ca-bd; 6.
PE 1: Evidence at protein level;
KW Calcium; Phosphoprotein; Reference proteome; Repeat;
KW Sarcoplasmic reticulum; Signal.
FT SIGNAL 1..28
FT CHAIN 29..699
FT /note="Sarcoplasmic reticulum histidine-rich calcium-
FT binding protein"
FT /id="PRO_0000022414"
FT REPEAT 106..121
FT /note="2-1"
FT REPEAT 134..154
FT /note="2-2"
FT REPEAT 155..177
FT /note="2-3"
FT REPEAT 180..213
FT /note="1-1"
FT REPEAT 214..237
FT /note="2-4"
FT REPEAT 238..270
FT /note="1-2"
FT REPEAT 271..294
FT /note="2-5"
FT REPEAT 295..318
FT /note="1-3"
FT REPEAT 319..342
FT /note="2-6"
FT REPEAT 343..365
FT /note="1-4"
FT REGION 50..95
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 106..365
FT /note="4 X tandem repeats, acidic"
FT REGION 106..342
FT /note="6 X approximate tandem repeats"
FT REGION 127..617
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 627..673
FT /note="Metal-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 53..95
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 127..174
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 189..206
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 207..245
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 246..262
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 263..304
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 311..375
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 395..489
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 500..516
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 517..552
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 566..580
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 581..601
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 76
FT /note="Phosphothreonine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 119
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 145
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 333
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 358
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 431
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 494
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 567
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT VARIANT 43
FT /note="S -> N (in dbSNP:rs3745298)"
FT /id="VAR_021931"
FT VARIANT 96
FT /note="S -> A (in dbSNP:rs3745297)"
FT /id="VAR_005623"
FT VARIANT 204
FT /note="Missing"
FT /id="VAR_011622"
SQ SEQUENCE 699 AA; 80244 MW; 9922EEDF012C61DD CRC64;
MGHHRPWLHA SVLWAGVASL LLPPAMTQQL RGDGLGFRNR NNSTGVAGLS EEASAELRHH
LHSPRDHPDE NKDVSTENGH HFWSHPDREK EDEDVSKEYG HLLPGHRSQD HKVGDEGVSG
EEVFAEHGGQ ARGHRGHGSE DTEDSAEHRH HLPSHRSHSH QDEDEDEVVS SEHHHHILRH
GHRGHDGEDD EGEEEEEEEE EEEEASTEYG HQAHRHRGHG SEEDEDVSDG HHHHGPSHRH
QGHEEDDDDD DDDDDDDDDD DVSIEYRHQA HRHQGHGIEE DEDVSDGHHH RDPSHRHRSH
EEDDNDDDDV STEYGHQAHR HQDHRKEEVE AVSGEHHHHV PDHRHQGHRD EEEDEDVSTE
RWHQGPQHVH HGLVDEEEEE EEITVQFGHY VASHQPRGHK SDEEDFQDEY KTEVPHHHHH
RVPREEDEEV SAELGHQAPS HRQSHQDEET GHGQRGSIKE MSHHPPGHTV VKDRSHLRKD
DSEEEKEKEE DPGSHEEDDE SSEQGEKGTH HGSRDQEDEE DEEEGHGLSL NQEEEEEEDK
EEEEEEEDEE RREERAEVGA PLSPDHSEEE EEEEEGLEED EPRFTIIPNP LDRREEAGGA
SSEEESGEDT GPQDAQEYGN YQPGSLCGYC SFCNRCTECE SCHCDEENMG EHCDQCQHCQ
FCYLCPLVCE TVCAPGSYVD YFSSSLYQAL ADMLETPEP
