GRAN_HUMAN
ID GRAN_HUMAN Reviewed; 217 AA.
AC P28676; B2R5X3; Q53TB5; Q59EP3;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 2.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Grancalcin;
GN Name=GCA; Synonyms=GCL;
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], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Neutrophil;
RX PubMed=1737748; DOI=10.1016/s0021-9258(19)50675-5;
RA Boyhan A., Casimir C.M., French J.K., Teahan C.G., Segal A.W.;
RT "Molecular cloning and characterization of grancalcin, a novel EF-hand
RT calcium-binding protein abundant in neutrophils and monocytes.";
RL J. Biol. Chem. 267:2928-2933(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-80.
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Urinary bladder;
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 [7]
RP PROTEIN SEQUENCE OF 15-27; 109-125 AND 146-175, SUBUNIT, CALCIUM-BINDING,
RP AND SUBCELLULAR LOCATION.
RC TISSUE=Neutrophil;
RX PubMed=1530588; DOI=10.1042/bj2860549;
RA Teahan C.G., Totty N.F., Segal A.W.;
RT "Isolation and characterization of grancalcin, a novel 28 kDa EF-hand
RT calcium-binding protein from human neutrophils.";
RL Biochem. J. 286:549-554(1992).
RN [8]
RP INTERACTION WITH LCP1.
RX PubMed=11279160; DOI=10.1074/jbc.m100965200;
RA Lollike K., Johnsen A.H., Durussel I., Borregaard N., Cox J.A.;
RT "Biochemical characterization of the penta-EF-hand protein grancalcin and
RT identification of L-plastin as a binding partner.";
RL J. Biol. Chem. 276:17762-17769(2001).
RN [9]
RP INTERACTION WITH SRI.
RX PubMed=12804766; DOI=10.1016/s0014-5793(03)00518-0;
RA Hansen C., Tarabykina S., la Cour J.M., Lollike K., Berchtold M.W.;
RT "The PEF family proteins sorcin and grancalcin interact in vivo and in
RT vitro.";
RL FEBS Lett. 545:151-154(2003).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 53-217.
RX PubMed=10903868; DOI=10.1006/jmbi.2000.3925;
RA Jia J., Han Q., Borregaard N., Lollike K., Cygler M.;
RT "Crystal structure of human grancalcin, a member of the penta-EF-hand
RT protein family.";
RL J. Mol. Biol. 300:1271-1281(2000).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 53-217 IN COMPLEX WITH CALCIUM,
RP AND SUBUNIT.
RX PubMed=11717497; DOI=10.1107/s0907444901016511;
RA Jia J., Borregaard N., Lollike K., Cygler M.;
RT "Structure of Ca(2+)-loaded human grancalcin.";
RL Acta Crystallogr. D 57:1843-1849(2001).
CC -!- FUNCTION: Calcium-binding protein that may play a role in the adhesion
CC of neutrophils to fibronectin. May play a role in the formation of
CC focal adhesions.
CC -!- SUBUNIT: Homodimer. Interacts with SRI and LCP1.
CC {ECO:0000269|PubMed:11279160, ECO:0000269|PubMed:11717497,
CC ECO:0000269|PubMed:12804766, ECO:0000269|PubMed:1530588}.
CC -!- INTERACTION:
CC P28676; Q8NFV4-4: ABHD11; NbExp=3; IntAct=EBI-947242, EBI-12318443;
CC P28676; P54253: ATXN1; NbExp=4; IntAct=EBI-947242, EBI-930964;
CC P28676; Q9NP55: BPIFA1; NbExp=3; IntAct=EBI-947242, EBI-953896;
CC P28676; Q5SWW7: C10orf55; NbExp=3; IntAct=EBI-947242, EBI-12809220;
CC P28676; Q9H6J7-2: C11orf49; NbExp=3; IntAct=EBI-947242, EBI-13328871;
CC P28676; Q13137: CALCOCO2; NbExp=3; IntAct=EBI-947242, EBI-739580;
CC P28676; Q9H4Y5: GSTO2; NbExp=3; IntAct=EBI-947242, EBI-10194609;
CC P28676; P42858: HTT; NbExp=3; IntAct=EBI-947242, EBI-466029;
CC P28676; P43361: MAGEA8; NbExp=9; IntAct=EBI-947242, EBI-10182930;
CC P28676; P28070: PSMB4; NbExp=3; IntAct=EBI-947242, EBI-603350;
CC P28676; Q13077: TRAF1; NbExp=3; IntAct=EBI-947242, EBI-359224;
CC P28676; Q12933: TRAF2; NbExp=3; IntAct=EBI-947242, EBI-355744;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:1530588,
CC ECO:0000269|PubMed:1737748}. Cytoplasmic granule membrane
CC {ECO:0000269|PubMed:1737748, ECO:0000305|PubMed:1530588}; Peripheral
CC membrane protein; Cytoplasmic side. Note=Primarily cytosolic in the
CC absence of calcium or magnesium ions. Relocates to granules and other
CC membranes in response to elevated calcium and magnesium levels.
CC {ECO:0000269|PubMed:1737748}.
CC -!- TISSUE SPECIFICITY: Detected in neutrophils and macrophages (at protein
CC level). Highly expressed in bone marrow. {ECO:0000269|PubMed:1737748}.
CC -!- MISCELLANEOUS: This protein has been shown to bind calcium with high
CC affinity.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD93005.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; M81637; AAA58498.1; -; mRNA.
DR EMBL; AK312349; BAG35270.1; -; mRNA.
DR EMBL; AB209768; BAD93005.1; ALT_INIT; mRNA.
DR EMBL; AC010876; AAX93138.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX11350.1; -; Genomic_DNA.
DR EMBL; BC005214; AAH05214.1; -; mRNA.
DR CCDS; CCDS2218.1; -.
DR PIR; A42578; A42578.
DR RefSeq; NP_036330.1; NM_012198.4.
DR PDB; 1F4O; X-ray; 2.50 A; A/B=53-217.
DR PDB; 1F4Q; X-ray; 1.90 A; A/B=53-217.
DR PDB; 1K94; X-ray; 1.70 A; A/B=53-217.
DR PDB; 1K95; X-ray; 1.90 A; A=53-217.
DR PDBsum; 1F4O; -.
DR PDBsum; 1F4Q; -.
DR PDBsum; 1K94; -.
DR PDBsum; 1K95; -.
DR AlphaFoldDB; P28676; -.
DR SMR; P28676; -.
DR BioGRID; 117333; 49.
DR CORUM; P28676; -.
DR DIP; DIP-41437N; -.
DR IntAct; P28676; 29.
DR STRING; 9606.ENSP00000394842; -.
DR DrugBank; DB11093; Calcium citrate.
DR DrugBank; DB11348; Calcium Phosphate.
DR DrugBank; DB14481; Calcium phosphate dihydrate.
DR iPTMnet; P28676; -.
DR PhosphoSitePlus; P28676; -.
DR BioMuta; GCA; -.
DR DMDM; 1170014; -.
DR EPD; P28676; -.
DR jPOST; P28676; -.
DR MassIVE; P28676; -.
DR MaxQB; P28676; -.
DR PaxDb; P28676; -.
DR PeptideAtlas; P28676; -.
DR PRIDE; P28676; -.
DR ProteomicsDB; 54491; -.
DR Antibodypedia; 33752; 135 antibodies from 26 providers.
DR DNASU; 25801; -.
DR Ensembl; ENST00000437150.7; ENSP00000394842.2; ENSG00000115271.11.
DR GeneID; 25801; -.
DR KEGG; hsa:25801; -.
DR MANE-Select; ENST00000437150.7; ENSP00000394842.2; NM_012198.5; NP_036330.1.
DR UCSC; uc002ucg.4; human.
DR CTD; 25801; -.
DR DisGeNET; 25801; -.
DR GeneCards; GCA; -.
DR HGNC; HGNC:15990; GCA.
DR HPA; ENSG00000115271; Tissue enriched (bone).
DR MIM; 607030; gene.
DR neXtProt; NX_P28676; -.
DR OpenTargets; ENSG00000115271; -.
DR PharmGKB; PA28602; -.
DR VEuPathDB; HostDB:ENSG00000115271; -.
DR eggNOG; KOG0037; Eukaryota.
DR GeneTree; ENSGT00940000153979; -.
DR InParanoid; P28676; -.
DR OMA; DSMWTYF; -.
DR OrthoDB; 1330600at2759; -.
DR PhylomeDB; P28676; -.
DR TreeFam; TF314682; -.
DR PathwayCommons; P28676; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; P28676; -.
DR BioGRID-ORCS; 25801; 9 hits in 1076 CRISPR screens.
DR ChiTaRS; GCA; human.
DR EvolutionaryTrace; P28676; -.
DR GeneWiki; GCA_(gene); -.
DR GenomeRNAi; 25801; -.
DR Pharos; P28676; Tbio.
DR PRO; PR:P28676; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P28676; protein.
DR Bgee; ENSG00000115271; Expressed in monocyte and 190 other tissues.
DR ExpressionAtlas; P28676; baseline and differential.
DR Genevisible; P28676; HS.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0061025; P:membrane fusion; TAS:ProtInc.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR Pfam; PF13833; EF-hand_8; 1.
DR SMART; SM00054; EFh; 2.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS50222; EF_HAND_2; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Cytoplasm; Direct protein sequencing; Membrane;
KW Metal-binding; Reference proteome; Repeat.
FT CHAIN 1..217
FT /note="Grancalcin"
FT /id="PRO_0000073721"
FT DOMAIN 48..83
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 89..122
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 119..154
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 155..180
FT /note="EF-hand 4"
FT /evidence="ECO:0000305"
FT BINDING 65
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 69
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 71
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 132
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 134
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 136
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 138
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 143
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT VARIANT 80
FT /note="S -> A (in dbSNP:rs17783344)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_048657"
FT CONFLICT 166
FT /note="R -> D (in Ref. 7; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 54..62
FT /evidence="ECO:0007829|PDB:1K94"
FT HELIX 63..65
FT /evidence="ECO:0007829|PDB:1K94"
FT HELIX 70..80
FT /evidence="ECO:0007829|PDB:1K94"
FT TURN 81..85
FT /evidence="ECO:0007829|PDB:1K94"
FT HELIX 91..101
FT /evidence="ECO:0007829|PDB:1K94"
FT STRAND 106..109
FT /evidence="ECO:0007829|PDB:1F4O"
FT HELIX 111..131
FT /evidence="ECO:0007829|PDB:1K94"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:1F4Q"
FT STRAND 138..140
FT /evidence="ECO:0007829|PDB:1F4Q"
FT HELIX 141..150
FT /evidence="ECO:0007829|PDB:1K94"
FT HELIX 157..167
FT /evidence="ECO:0007829|PDB:1K94"
FT STRAND 169..171
FT /evidence="ECO:0007829|PDB:1F4O"
FT STRAND 172..174
FT /evidence="ECO:0007829|PDB:1F4Q"
FT HELIX 175..193
FT /evidence="ECO:0007829|PDB:1K94"
FT STRAND 201..206
FT /evidence="ECO:0007829|PDB:1K94"
FT HELIX 207..215
FT /evidence="ECO:0007829|PDB:1K94"
SQ SEQUENCE 217 AA; 24010 MW; 88CA4DDF835AFFE4 CRC64;
MAYPGYGGGF GNFSIQVPGM QMGQPVPETG PAILLDGYSG PAYSDTYSSA GDSVYTYFSA
VAGQDGEVDA EELQRCLTQS GINGTYSPFS LETCRIMIAM LDRDHTGKMG FNAFKELWAA
LNAWKENFMT VDQDGSGTVE HHELRQAIGL MGYRLSPQTL TTIVKRYSKN GRIFFDDYVA
CCVKLRALTD FFRKRDHLQQ GSANFIYDDF LQGTMAI
