ICAL_HUMAN
ID ICAL_HUMAN Reviewed; 708 AA.
AC P20810; B7Z468; G5E946; G5E9D3; O95360; Q05DE8; Q7Z4K0; Q96D08; Q9H1Z5;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 4.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Calpastatin;
DE AltName: Full=Calpain inhibitor;
DE AltName: Full=Sperm BS-17 component;
GN Name=CAST;
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), AND VARIANTS SER-408 AND GLY-592.
RX PubMed=2577276; DOI=10.3109/14756368909030363;
RA Asada K., Ishino Y., Shimada M., Shimojo T., Endo M., Kimizuka F., Kato I.,
RA Maki M., Hatanaka M., Murachi T.;
RT "cDNA cloning of human calpastatin: sequence homology among human, pig, and
RT rabbit calpastatins.";
RL J. Enzym. Inhib. 3:49-56(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC TISSUE=Testis;
RX PubMed=11978196;
RA Zhu H., Zhou Z.-M., Li J.-M., Zhu H., Cheng L.-J., Shan Y.-X., Yin L.-L.,
RA Sha J.H.;
RT "Cloning and characterization of a novel isoform of calpastatin in human
RT adult testis.";
RL Acta Pharmacol. Sin. 23:450-454(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 10).
RC TISSUE=Tongue;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING
RP (ISOFORMS 6 AND 7).
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [6]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1-319 (ISOFORM 5).
RC TISSUE=Lung, and Skin;
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-479 (ISOFORM 8), AND VARIANT
RP SER-408.
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-283 (ISOFORM 1), AND ALTERNATIVE SPLICING.
RC TISSUE=Lung;
RX PubMed=1569094; DOI=10.1016/s0021-9258(18)42463-5;
RA Lee W.J., Ma H., Takano E., Yang H.Q., Hatanaka M., Maki M.;
RT "Molecular diversity in amino-terminal domains of human calpastatin by exon
RT skipping.";
RL J. Biol. Chem. 267:8437-8442(1992).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 101-317.
RX PubMed=2553724; DOI=10.1016/s0021-9258(19)47235-9;
RA Maki M., Bagci H., Hamaguchi K., Ueda M., Murachi T., Hatanaka M.;
RT "Inhibition of calpain by a synthetic oligopeptide corresponding to an exon
RT of the human calpastatin gene.";
RL J. Biol. Chem. 264:18866-18869(1989).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 125-283 (ISOFORMS 2/3).
RX PubMed=2407243; DOI=10.1016/0006-291x(90)91035-q;
RA Uemori T., Shimojo T., Asada K., Asano T., Kimizuka F., Kato I., Maki M.,
RA Hatanaka M., Murachi T., Hanzawa H., Arata Y.;
RT "Characterization of a functional domain of human calpastatin.";
RL Biochem. Biophys. Res. Commun. 166:1485-1493(1990).
RN [12]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 153-708 (ISOFORMS 2/3), SEQUENCE REVISION,
RP AND VARIANT SER-408.
RA Wang L.F.;
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 523-708 (ISOFORMS 1/2/3/4).
RC TISSUE=Testis;
RX PubMed=7951045;
RA Wang L.F., Wei S.G., Miao S.Y., Liu Q.Y., Koide S.S.;
RT "Calpastatin gene in human testis.";
RL Biochem. Mol. Biol. Int. 33:245-252(1994).
RN [14]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 425-708 (ISOFORMS 1/2/3/4).
RC TISSUE=Placenta;
RX PubMed=7706496; DOI=10.1172/jci117870;
RA Despres N., Talbot G., Plouffe B., Boire G., Menard H.A.;
RT "Detection and expression of a cDNA clone that encodes a polypeptide
RT containing two inhibitory domains of human calpastatin and its recognition
RT by rheumatoid arthritis sera.";
RL J. Clin. Invest. 95:1891-1896(1995).
RN [15]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 244-708 (ISOFORMS 1/2/3/4), AND VARIANT
RP SER-408.
RC TISSUE=Placenta;
RA El-Amine M., Talbot G., Despres N., Asselin C., Boire G., Menard H.A.;
RL Submitted (JUL-1995) to the EMBL/GenBank/DDBJ databases.
RN [16]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 636-708 (ISOFORMS 1/2/3/4).
RA Rochdi M.D., El-Amine M., Menard H.A.;
RT "New calpastatin 3' UTR.";
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [17]
RP PHOSPHORYLATION.
RX PubMed=1995645; DOI=10.1016/s0021-9258(19)67888-9;
RA Adachi Y., Ishida-Takahashi A., Takahashi C., Takano E., Murachi T.,
RA Hatanaka M.;
RT "Phosphorylation and subcellular distribution of calpastatin in human
RT hematopoietic system cells.";
RL J. Biol. Chem. 266:3968-3972(1991).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-243; SER-364; SER-366 AND
RP SER-373, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-133; SER-575 AND SER-577,
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11 (ISOFORMS 10; 5; 6; 7 AND
RP 9), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [22]
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 [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-133; SER-373; SER-440;
RP SER-563; SER-575 AND SER-577, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-133; SER-440; SER-516;
RP SER-527; SER-575 AND SER-577, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [25]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-32, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [26]
RP INVOLVEMENT IN PLACK.
RX PubMed=25683118; DOI=10.1016/j.ajhg.2014.12.026;
RA Lin Z., Zhao J., Nitoiu D., Scott C.A., Plagnol V., Smith F.J.,
RA Wilson N.J., Cole C., Schwartz M.E., McLean W.H., Wang H., Feng C., Duo L.,
RA Zhou E.Y., Ren Y., Dai L., Chen Y., Zhang J., Xu X., O'Toole E.A.,
RA Kelsell D.P., Yang Y.;
RT "Loss-of-function mutations in CAST cause peeling skin, leukonychia, acral
RT punctate keratoses, cheilitis, and knuckle pads.";
RL Am. J. Hum. Genet. 96:440-447(2015).
RN [27]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-32, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
CC -!- FUNCTION: Specific inhibition of calpain (calcium-dependent cysteine
CC protease). Plays a key role in postmortem tenderization of meat and
CC have been proposed to be involved in muscle protein degradation in
CC living tissue.
CC -!- INTERACTION:
CC P20810; P16333: NCK1; NbExp=2; IntAct=EBI-1268770, EBI-389883;
CC P20810; O35505: CACNA1C; Xeno; NbExp=2; IntAct=EBI-1268770, EBI-9084208;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=10;
CC Comment=Additional isoforms seem to exist.;
CC Name=1;
CC IsoId=P20810-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P20810-2; Sequence=VSP_000744;
CC Name=3;
CC IsoId=P20810-3; Sequence=VSP_000741, VSP_000744;
CC Name=4;
CC IsoId=P20810-4; Sequence=VSP_000742, VSP_000743;
CC Name=5;
CC IsoId=P20810-5; Sequence=VSP_038037, VSP_000744;
CC Name=6;
CC IsoId=P20810-6; Sequence=VSP_038038;
CC Name=7;
CC IsoId=P20810-7; Sequence=VSP_038038, VSP_000743;
CC Name=8;
CC IsoId=P20810-8; Sequence=VSP_000742;
CC Name=9;
CC IsoId=P20810-9; Sequence=VSP_047393;
CC Name=10;
CC IsoId=P20810-10; Sequence=VSP_038037;
CC -!- DOMAIN: Each of the four flexible inhibitory domains can inhibit one
CC calcium-bound calpain molecule by occupying both sides of the active
CC site. {ECO:0000250}.
CC -!- PTM: The N-terminus is blocked.
CC -!- DISEASE: Peeling skin with leukonychia, acral punctate keratoses,
CC cheilitis, and knuckle pads (PLACK) [MIM:616295]: An autosomal
CC recessive disease characterized by generalized, continuous shedding of
CC the outer layers of the epidermis, leukonychia, acral punctate
CC keratosis, cheilitis, knuckle pads with multiple hyperkeratotic
CC micropapules involving the interphalangeal joints, and palmoplantar
CC keratoderma. {ECO:0000269|PubMed:25683118}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the protease inhibitor I27 (calpastatin) family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH16066.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
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DR EMBL; D16217; BAA03747.1; -; mRNA.
DR EMBL; D50827; BAA09438.1; -; mRNA.
DR EMBL; AF327443; AAG48151.1; -; mRNA.
DR EMBL; BT009783; AAP88785.1; -; mRNA.
DR EMBL; AK296919; BAH12454.1; -; mRNA.
DR EMBL; AC008906; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC020900; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC104125; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KC877037; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471084; EAW96068.1; -; Genomic_DNA.
DR EMBL; CH471084; EAW96071.1; -; Genomic_DNA.
DR EMBL; CH471084; EAW96075.1; -; Genomic_DNA.
DR EMBL; BC013579; AAH13579.1; -; mRNA.
DR EMBL; BC016066; AAH16066.1; ALT_SEQ; mRNA.
DR EMBL; AL832349; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; M86258; AAB59398.1; -; mRNA.
DR EMBL; M28230; AAA52066.1; -; Genomic_DNA.
DR EMBL; M28227; AAA52066.1; JOINED; Genomic_DNA.
DR EMBL; M28228; AAA52066.1; JOINED; Genomic_DNA.
DR EMBL; M28229; AAA52066.1; JOINED; Genomic_DNA.
DR EMBL; M33328; AAA52296.1; -; mRNA.
DR EMBL; U26724; AAC50136.2; -; mRNA.
DR EMBL; S73329; AAB32311.1; -; mRNA.
DR EMBL; U38525; AAA80684.1; -; mRNA.
DR EMBL; U31345; AAB60371.1; -; mRNA.
DR EMBL; U31346; AAB60372.1; -; mRNA.
DR EMBL; AF095891; AAD09102.1; -; mRNA.
DR CCDS; CCDS4082.1; -. [P20810-8]
DR CCDS; CCDS43344.1; -. [P20810-10]
DR CCDS; CCDS54882.1; -. [P20810-9]
DR CCDS; CCDS54883.1; -. [P20810-2]
DR PIR; A38091; A38091.
DR RefSeq; NP_001035905.1; NM_001042440.4. [P20810-9]
DR RefSeq; NP_001035906.1; NM_001042441.2. [P20810-7]
DR RefSeq; NP_001035907.1; NM_001042442.2. [P20810-10]
DR RefSeq; NP_001035908.1; NM_001042443.2. [P20810-1]
DR RefSeq; NP_001035909.1; NM_001042444.2. [P20810-4]
DR RefSeq; NP_001271141.1; NM_001284212.3.
DR RefSeq; NP_001317560.1; NM_001330631.1. [P20810-2]
DR RefSeq; NP_001741.4; NM_001750.6. [P20810-6]
DR RefSeq; NP_775083.1; NM_173060.4. [P20810-8]
DR RefSeq; XP_006714759.1; XM_006714696.3.
DR RefSeq; XP_006714764.1; XM_006714701.3.
DR RefSeq; XP_006714766.1; XM_006714703.3.
DR RefSeq; XP_006714767.1; XM_006714704.3.
DR RefSeq; XP_016865402.1; XM_017009913.1.
DR AlphaFoldDB; P20810; -.
DR SMR; P20810; -.
DR BioGRID; 107281; 64.
DR IntAct; P20810; 30.
DR MINT; P20810; -.
DR STRING; 9606.ENSP00000379157; -.
DR DrugBank; DB11638; Artenimol.
DR DrugBank; DB01373; Calcium.
DR MEROPS; I27.001; -.
DR MEROPS; I27.002; -.
DR MEROPS; I27.003; -.
DR MEROPS; I27.004; -.
DR GlyGen; P20810; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P20810; -.
DR MetOSite; P20810; -.
DR PhosphoSitePlus; P20810; -.
DR BioMuta; CAST; -.
DR DMDM; 126302556; -.
DR CPTAC; CPTAC-1023; -.
DR CPTAC; CPTAC-1024; -.
DR EPD; P20810; -.
DR jPOST; P20810; -.
DR MassIVE; P20810; -.
DR MaxQB; P20810; -.
DR PeptideAtlas; P20810; -.
DR PRIDE; P20810; -.
DR ProteomicsDB; 33826; -.
DR ProteomicsDB; 33906; -.
DR ProteomicsDB; 53796; -. [P20810-1]
DR ProteomicsDB; 53797; -. [P20810-2]
DR ProteomicsDB; 53798; -. [P20810-3]
DR ProteomicsDB; 53799; -. [P20810-4]
DR ProteomicsDB; 53800; -. [P20810-5]
DR ProteomicsDB; 53801; -. [P20810-6]
DR ProteomicsDB; 53802; -. [P20810-7]
DR ProteomicsDB; 6573; -.
DR TopDownProteomics; P20810-5; -. [P20810-5]
DR Antibodypedia; 4008; 423 antibodies from 33 providers.
DR DNASU; 831; -.
DR Ensembl; ENST00000309190.9; ENSP00000312523.5; ENSG00000153113.24. [P20810-8]
DR Ensembl; ENST00000338252.7; ENSP00000343421.3; ENSG00000153113.24. [P20810-2]
DR Ensembl; ENST00000341926.7; ENSP00000339914.3; ENSG00000153113.24. [P20810-1]
DR Ensembl; ENST00000395812.6; ENSP00000379157.2; ENSG00000153113.24. [P20810-9]
DR Ensembl; ENST00000395813.5; ENSP00000379158.2; ENSG00000153113.24. [P20810-1]
DR Ensembl; ENST00000508830.5; ENSP00000425721.1; ENSG00000153113.24. [P20810-6]
DR Ensembl; ENST00000510756.6; ENSP00000422176.2; ENSG00000153113.24. [P20810-4]
DR Ensembl; ENST00000674984.1; ENSP00000501713.1; ENSG00000153113.24. [P20810-10]
DR Ensembl; ENST00000675033.1; ENSP00000501659.1; ENSG00000153113.24. [P20810-4]
DR Ensembl; ENST00000675179.1; ENSP00000501872.1; ENSG00000153113.24. [P20810-6]
DR GeneID; 831; -.
DR KEGG; hsa:831; -.
DR MANE-Select; ENST00000675179.1; ENSP00000501872.1; NM_001750.7; NP_001741.4. [P20810-6]
DR UCSC; uc003klt.4; human. [P20810-1]
DR CTD; 831; -.
DR DisGeNET; 831; -.
DR GeneCards; CAST; -.
DR HGNC; HGNC:1515; CAST.
DR HPA; ENSG00000153113; Low tissue specificity.
DR MalaCards; CAST; -.
DR MIM; 114090; gene.
DR MIM; 616295; phenotype.
DR neXtProt; NX_P20810; -.
DR OpenTargets; ENSG00000153113; -.
DR Orphanet; 444138; Peeling skin-leukonychia-acral punctate keratoses-cheilitis-knuckle pads syndrome.
DR PharmGKB; PA26098; -.
DR VEuPathDB; HostDB:ENSG00000153113; -.
DR eggNOG; ENOG502RHIZ; Eukaryota.
DR GeneTree; ENSGT00390000002993; -.
DR InParanoid; P20810; -.
DR OMA; IKEKDHT; -.
DR OrthoDB; 203890at2759; -.
DR PhylomeDB; P20810; -.
DR TreeFam; TF332525; -.
DR PathwayCommons; P20810; -.
DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix.
DR Reactome; R-HSA-8862803; Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models.
DR SignaLink; P20810; -.
DR SIGNOR; P20810; -.
DR BioGRID-ORCS; 831; 20 hits in 1082 CRISPR screens.
DR ChiTaRS; CAST; human.
DR GeneWiki; Calpastatin; -.
DR GenomeRNAi; 831; -.
DR Pharos; P20810; Tbio.
DR PRO; PR:P20810; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P20810; protein.
DR Bgee; ENSG00000153113; Expressed in calcaneal tendon and 208 other tissues.
DR ExpressionAtlas; P20810; baseline and differential.
DR Genevisible; P20810; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:BHF-UCL.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0016020; C:membrane; IDA:BHF-UCL.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0010859; F:calcium-dependent cysteine-type endopeptidase inhibitor activity; IMP:CAFA.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; TAS:ProtInc.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0097340; P:inhibition of cysteine-type endopeptidase activity; IMP:CAFA.
DR GO; GO:2000675; P:negative regulation of type B pancreatic cell apoptotic process; IDA:BHF-UCL.
DR GO; GO:1990709; P:presynaptic active zone organization; TAS:ARUK-UCL.
DR DisProt; DP00196; -.
DR InterPro; IPR026998; Calpastatin.
DR InterPro; IPR001259; Prot_inh_calpain.
DR PANTHER; PTHR10077; PTHR10077; 1.
DR Pfam; PF00748; Calpain_inhib; 4.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Isopeptide bond;
KW Palmoplantar keratoderma; Phosphoprotein; Protease inhibitor;
KW Reference proteome; Repeat; Thiol protease inhibitor; Ubl conjugation.
FT CHAIN 1..708
FT /note="Calpastatin"
FT /id="PRO_0000147632"
FT REPEAT 170..222
FT /note="Inhibitory domain 1"
FT REPEAT 304..356
FT /note="Inhibitory domain 2"
FT REPEAT 446..499
FT /note="Inhibitory domain 3"
FT REPEAT 583..636
FT /note="Inhibitory domain 4"
FT REGION 1..187
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 212..404
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 416..527
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 543..708
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 32..66
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 67..92
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 170..185
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 273..287
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 306..394
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 437..497
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 543..559
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 561..650
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 690..708
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 50
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P51125"
FT MOD_RES 87
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51125"
FT MOD_RES 133
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 135
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P27321"
FT MOD_RES 222
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51125"
FT MOD_RES 243
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 364
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 366
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 373
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 440
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 516
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 527
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 563
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 575
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 577
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT CROSSLNK 32
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..105
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11978196"
FT /id="VSP_000741"
FT VAR_SEQ 1..62
FT /note="MNPTETKAIPVSQQMEGPHLPNKKKHKKQAVKTEPEKKSQSTKLSVVHEKKS
FT QEGKPKEHTE -> MSQPGQKPAASPRPRRAAAARRTHEHVSEKTSESPSKPGEKKGSD
FT EKKAASLGSSQSSRTYAGGTASATKVSASSGATSKSSSMNPTETKAVKTEPEKKSQSTK
FT (in isoform 9)"
FT /evidence="ECO:0000305"
FT /id="VSP_047393"
FT VAR_SEQ 1..29
FT /note="MNPTETKAIPVSQQMEGPHLPNKKKHKKQ -> MSQPGQKPAASPRPRRAAA
FT ARRTHEHVSEKTSESPSKPGEKKGSDEKKAASLGSSQSSRTYAGGTASATKVSASSGAT
FT SKSSSMNPTETK (in isoform 5 and isoform 10)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_038037"
FT VAR_SEQ 1
FT /note="M -> MSQPGQKPAASPRPRRAAAARRTHEHVSEKTSESPSKPGEKKGSDEK
FT KAASLGSSQSSRTYAGGTASATKVSASSGATSKSSSM (in isoform 6 and
FT isoform 7)"
FT /evidence="ECO:0000305"
FT /id="VSP_038038"
FT VAR_SEQ 9..30
FT /note="Missing (in isoform 4 and isoform 8)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17974005, ECO:0000303|Ref.3"
FT /id="VSP_000742"
FT VAR_SEQ 44..62
FT /note="Missing (in isoform 4 and isoform 7)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.3"
FT /id="VSP_000743"
FT VAR_SEQ 212..224
FT /note="Missing (in isoform 2, isoform 3 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:11978196,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_000744"
FT VARIANT 380
FT /note="E -> K (in dbSNP:rs1643702)"
FT /id="VAR_030741"
FT VARIANT 408
FT /note="C -> S (in dbSNP:rs754615)"
FT /evidence="ECO:0000269|PubMed:17974005,
FT ECO:0000269|PubMed:2577276, ECO:0000269|Ref.12,
FT ECO:0000269|Ref.15"
FT /id="VAR_022686"
FT VARIANT 537
FT /note="A -> V (in dbSNP:rs4948)"
FT /id="VAR_030742"
FT VARIANT 592
FT /note="E -> G"
FT /evidence="ECO:0000269|PubMed:2577276"
FT /id="VAR_005298"
FT CONFLICT 467
FT /note="R -> L (in Ref. 12; AAC50136)"
FT /evidence="ECO:0000305"
FT CONFLICT 486..488
FT /note="VKD -> GKE (in Ref. 12; AAC50136)"
FT /evidence="ECO:0000305"
FT CONFLICT 543
FT /note="V -> L (in Ref. 12; AAC50136)"
FT /evidence="ECO:0000305"
FT CONFLICT 562
FT /note="Missing (in Ref. 15; AAB60371)"
FT /evidence="ECO:0000305"
FT CONFLICT 651
FT /note="I -> V (in Ref. 16; AAD09102)"
FT /evidence="ECO:0000305"
FT MOD_RES P20810-5:11
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES P20810-6:11
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES P20810-7:11
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES P20810-9:11
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES P20810-10:11
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
SQ SEQUENCE 708 AA; 76573 MW; 2DB0C14B860E89C7 CRC64;
MNPTETKAIP VSQQMEGPHL PNKKKHKKQA VKTEPEKKSQ STKLSVVHEK KSQEGKPKEH
TEPKSLPKQA SDTGSNDAHN KKAVSRSAEQ QPSEKSTEPK TKPQDMISAG GESVAGITAI
SGKPGDKKKE KKSLTPAVPV ESKPDKPSGK SGMDAALDDL IDTLGGPEET EEENTTYTGP
EVSDPMSSTY IEELGKREVT IPPKYRELLA KKEGITGPPA DSSKPIGPDD AIDALSSDFT
CGSPTAAGKK TEKEESTEVL KAQSAGTVRS AAPPQEKKRK VEKDTMSDQA LEALSASLGT
RQAEPELDLR SIKEVDEAKA KEEKLEKCGE DDETIPSEYR LKPATDKDGK PLLPEPEEKP
KPRSESELID ELSEDFDRSE CKEKPSKPTE KTEESKAAAP APVSEAVCRT SMCSIQSAPP
EPATLKGTVP DDAVEALADS LGKKEADPED GKPVMDKVKE KAKEEDREKL GEKEETIPPD
YRLEEVKDKD GKPLLPKESK EQLPPMSEDF LLDALSEDFS GPQNASSLKF EDAKLAAAIS
EVVSQTPAST TQAGAPPRDT SQSDKDLDDA LDKLSDSLGQ RQPDPDENKP MEDKVKEKAK
AEHRDKLGER DDTIPPEYRH LLDDNGQDKP VKPPTKKSED SKKPADDQDP IDALSGDLDS
CPSTTETSQN TAKDKCKKAA SSSKAPKNGG KAKDSAKTTE ETSKPKDD
