CYTC_HUMAN
ID CYTC_HUMAN Reviewed; 146 AA.
AC P01034; B2R5J9; D3DW42; Q6FGW9;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1988, sequence version 1.
DT 03-AUG-2022, entry version 231.
DE RecName: Full=Cystatin-C;
DE AltName: Full=Cystatin-3;
DE AltName: Full=Gamma-trace;
DE AltName: Full=Neuroendocrine basic polypeptide;
DE AltName: Full=Post-gamma-globulin;
DE Flags: Precursor;
GN Name=CST3;
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=Placenta;
RX PubMed=3495457; DOI=10.1016/0014-5793(87)80695-6;
RA Abrahamson M., Grubb A., Olafsson I., Lundwall A.;
RT "Molecular cloning and sequence analysis of cDNA coding for the precursor
RT of the human cysteine proteinase inhibitor cystatin C.";
RL FEBS Lett. 216:229-233(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARMD11 THR-25.
RX PubMed=2764935; DOI=10.1016/0006-291x(89)90818-8;
RA Saitoh E., Sabatini L.M., Eddy R.L., Shows T.B., Azen E.A., Isemura S.,
RA Sanada K.;
RT "The human cystatin C gene (CST3) is a member of the cystatin gene family
RT which is localized on chromosome 20.";
RL Biochem. Biophys. Res. Commun. 162:1324-1331(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT AMYL6 GLN-94.
RC TISSUE=Brain;
RX PubMed=2541223; DOI=10.1084/jem.169.5.1771;
RA Levy E., Lopez-Otin C., Ghiso J., Geltner D., Frangione B.;
RT "Stroke in Icelandic patients with hereditary amyloid angiopathy is related
RT to a mutation in the cystatin C gene, an inhibitor of cysteine proteases.";
RL J. Exp. Med. 169:1771-1778(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Leukocyte;
RX PubMed=2363674; DOI=10.1042/bj2680287;
RA Abrahamson M., Olafsson I., Palsdottir A., Ulvsbaeck M., Lundwall A.,
RA Jensson O., Grubb A.;
RT "Structure and expression of the human cystatin C gene.";
RL Biochem. J. 268:287-294(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Synovial cell;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [9]
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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 PROTEIN SEQUENCE OF 27-146.
RX PubMed=6283552; DOI=10.1073/pnas.79.9.3024;
RA Grubb A., Loefberg H.;
RT "Human gamma-trace, a basic microprotein: amino acid sequence and presence
RT in the adenohypophysis.";
RL Proc. Natl. Acad. Sci. U.S.A. 79:3024-3027(1982).
RN [12]
RP PROTEIN SEQUENCE OF 27-76.
RX PubMed=6365094; DOI=10.1016/0006-291x(84)91073-8;
RA Brzin J., Popovic T., Turk V.;
RT "Human cystatin, a new protein inhibitor of cysteine proteinases.";
RL Biochem. Biophys. Res. Commun. 118:103-109(1984).
RN [13]
RP PROTEIN SEQUENCE OF 27-73.
RX PubMed=6662498; DOI=10.1515/bchm2.1983.364.2.1487;
RA Turk V., Brzin J., Longer M., Ritonja A., Eropkin M., Borchart U.,
RA Machleidt W.;
RT "Protein inhibitors of cysteine proteinases. III. Amino-acid sequence of
RT cystatin from chicken egg white.";
RL Hoppe-Seyler's Z. Physiol. Chem. 364:1487-1496(1983).
RN [14]
RP PROTEIN SEQUENCE OF 27-41.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [15]
RP DISULFIDE BONDS.
RA Grubb A., Loefberg H., Barrett A.J.;
RT "The disulphide bridges of human cystatin C (gamma-trace) and chicken
RT cystatin.";
RL FEBS Lett. 170:370-374(1984).
RN [16]
RP TISSUE SPECIFICITY.
RX PubMed=15274116; DOI=10.1002/pmic.200300799;
RA Sanchez J.C., Guillaume E., Lescuyer P., Allard L., Carrette O., Scherl A.,
RA Burgess J., Corthals G.L., Burkhard P.R., Hochstrasser D.F.;
RT "Cystatin C as a potential cerebrospinal fluid marker for the diagnosis of
RT Creutzfeldt-Jakob disease.";
RL Proteomics 4:2229-2233(2004).
RN [17]
RP MUTAGENESIS OF ALA-25.
RX PubMed=16635487; DOI=10.1016/j.exer.2006.01.030;
RA Ratnayaka A., Paraoan L., Spiller D.G., Hiscott P., Nelson G., White M.R.,
RA Grierson I.;
RT "A dual Golgi- and mitochondria-localised Ala25Ser precursor cystatin C: an
RT additional tool for characterising intracellular mis-localisation leading
RT to increased AMD susceptibility.";
RL Exp. Eye Res. 84:1135-1139(2007).
RN [18]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS], STRUCTURE OF CARBOHYDRATES, AND
RP CHARACTERIZATION OF VARIANT ARMD11 THR-25.
RC TISSUE=Cerebrospinal fluid;
RX PubMed=19838169; DOI=10.1038/nmeth.1392;
RA Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G.,
RA Larson G.;
RT "Enrichment of glycopeptides for glycan structure and attachment site
RT identification.";
RL Nat. Methods 6:809-811(2009).
RN [19]
RP DISULFIDE BONDS, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND MASS
RP SPECTROMETRY.
RC TISSUE=Saliva;
RX PubMed=20189825; DOI=10.1016/j.jasms.2010.01.025;
RA Ryan C.M., Souda P., Halgand F., Wong D.T., Loo J.A., Faull K.F.,
RA Whitelegge J.P.;
RT "Confident assignment of intact mass tags to human salivary cystatins using
RT top-down Fourier-transform ion cyclotron resonance mass spectrometry.";
RL J. Am. Soc. Mass Spectrom. 21:908-917(2010).
RN [20]
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 [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22905912; DOI=10.1021/pr300539b;
RA Rosenow A., Noben J.P., Jocken J., Kallendrusch S., Fischer-Posovszky P.,
RA Mariman E.C., Renes J.;
RT "Resveratrol-induced changes of the human adipocyte secretion profile.";
RL J. Proteome Res. 11:4733-4743(2012).
RN [22]
RP PHOSPHORYLATION AT SER-43.
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).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 27-146.
RX PubMed=11276250; DOI=10.1038/86188;
RA Janowski R., Kozak M., Jankowska E., Grzonka Z., Grubb A., Abrahamson M.,
RA Jaskolski M.;
RT "Human cystatin C, an amyloidogenic protein, dimerizes through three-
RT dimensional domain swapping.";
RL Nat. Struct. Biol. 8:316-320(2001).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (3.03 ANGSTROMS) OF 27-146.
RX PubMed=16170782; DOI=10.1002/prot.20633;
RA Janowski R., Kozak M., Abrahamson M., Grubb A., Jaskolski M.;
RT "3D domain-swapped human cystatin C with amyloid-like intermolecular beta-
RT sheets.";
RL Proteins 61:570-578(2005).
RN [26]
RP VARIANT AMYL6 GLN-94.
RX PubMed=1352269; DOI=10.1007/bf00194306;
RA Abrahamson M., Jonsdottir S., Olafsson I., Jensson O., Grubb A.;
RT "Hereditary cystatin C amyloid angiopathy: identification of the disease-
RT causing mutation and specific diagnosis by polymerase chain reaction based
RT analysis.";
RL Hum. Genet. 89:377-380(1992).
RN [27]
RP VARIANT ARMD11 THR-25.
RX PubMed=11815350; DOI=10.1136/bjo.86.2.214;
RA Zurdel J., Finckh U., Menzer G., Nitsch R.M., Richard G.;
RT "CST3 genotype associated with exudative age related macular
RT degeneration.";
RL Br. J. Ophthalmol. 86:214-219(2002).
CC -!- FUNCTION: As an inhibitor of cysteine proteinases, this protein is
CC thought to serve an important physiological role as a local regulator
CC of this enzyme activity.
CC -!- SUBUNIT: Homodimer.
CC -!- INTERACTION:
CC P01034; P05067: APP; NbExp=3; IntAct=EBI-948622, EBI-77613;
CC P01034; P01034: CST3; NbExp=8; IntAct=EBI-948622, EBI-948622;
CC PRO_0000006639; PRO_0000026502 [Q99538]: LGMN; NbExp=4; IntAct=EBI-29036734, EBI-29020361;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:20189825}.
CC -!- TISSUE SPECIFICITY: Expressed in submandibular and sublingual saliva
CC but not in parotid saliva (at protein level). Expressed in various body
CC fluids, such as the cerebrospinal fluid and plasma. Expressed in
CC highest levels in the epididymis, vas deferens, brain, thymus, and
CC ovary and the lowest in the submandibular gland.
CC {ECO:0000269|PubMed:15274116, ECO:0000269|PubMed:20189825}.
CC -!- PTM: The Thr-25 variant is O-glycosylated with a core 1 or possibly
CC core 8 glycan. The signal peptide of the O-glycosylated Thr-25 variant
CC is cleaved between Ala-20 and Val-21. {ECO:0000269|PubMed:19838169}.
CC -!- MASS SPECTROMETRY: Mass=13334.5829; Mass_error=0.0140;
CC Method=Electrospray; Evidence={ECO:0000269|PubMed:20189825};
CC -!- DISEASE: Amyloidosis 6 (AMYL6) [MIM:105150]: A hereditary generalized
CC amyloidosis due to cystatin C amyloid deposition. Cystatin C amyloid
CC accumulates in the walls of arteries, arterioles, and sometimes
CC capillaries and veins of the brain, and in various organs including
CC lymphoid tissue, spleen, salivary glands, and seminal vesicles. Amyloid
CC deposition in the cerebral vessels results in cerebral amyloid
CC angiopathy, cerebral hemorrhage and premature stroke. Cystatin C levels
CC in the cerebrospinal fluid are abnormally low.
CC {ECO:0000269|PubMed:1352269, ECO:0000269|PubMed:2541223}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Macular degeneration, age-related, 11 (ARMD11) [MIM:611953]: A
CC form of age-related macular degeneration, a multifactorial eye disease
CC and the most common cause of irreversible vision loss in the developed
CC world. In most patients, the disease is manifest as ophthalmoscopically
CC visible yellowish accumulations of protein and lipid that lie beneath
CC the retinal pigment epithelium and within an elastin-containing
CC structure known as Bruch membrane. {ECO:0000269|PubMed:11815350,
CC ECO:0000269|PubMed:19838169, ECO:0000269|PubMed:2764935}. Note=Disease
CC susceptibility is associated with variants affecting the gene
CC represented in this entry.
CC -!- MISCELLANEOUS: Potential cerebrospinal fluid marker for the diagnosis
CC of Creutzfeldt-Jakob disease.
CC -!- SIMILARITY: Belongs to the cystatin family. {ECO:0000305}.
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DR EMBL; X05607; CAA29096.1; -; mRNA.
DR EMBL; M27891; AAA52164.1; -; Genomic_DNA.
DR EMBL; M27889; AAA52164.1; JOINED; Genomic_DNA.
DR EMBL; M27890; AAA52164.1; JOINED; Genomic_DNA.
DR EMBL; X61681; CAA43856.2; -; Genomic_DNA.
DR EMBL; X61682; CAA43856.2; JOINED; Genomic_DNA.
DR EMBL; X61683; CAA43856.2; JOINED; Genomic_DNA.
DR EMBL; X52255; CAA36497.1; -; Genomic_DNA.
DR EMBL; AK312213; BAG35146.1; -; mRNA.
DR EMBL; BT006839; AAP35485.1; -; mRNA.
DR EMBL; CR541988; CAG46785.1; -; mRNA.
DR EMBL; CR542018; CAG46815.1; -; mRNA.
DR EMBL; AL121894; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471133; EAX10137.1; -; Genomic_DNA.
DR EMBL; CH471133; EAX10138.1; -; Genomic_DNA.
DR EMBL; BC013083; AAH13083.1; -; mRNA.
DR EMBL; BC110305; AAI10306.1; -; mRNA.
DR CCDS; CCDS13158.1; -.
DR PIR; S10216; UDHU.
DR RefSeq; NP_000090.1; NM_000099.3.
DR RefSeq; NP_001275543.1; NM_001288614.1.
DR PDB; 1G96; X-ray; 2.50 A; A=27-146.
DR PDB; 1R4C; X-ray; 2.18 A; A/B/C/D/E/F/G/H=37-146.
DR PDB; 1TIJ; X-ray; 3.03 A; A/B=27-146.
DR PDB; 3GAX; X-ray; 1.70 A; A/B=27-146.
DR PDB; 3NX0; X-ray; 2.04 A; A/B=27-146.
DR PDB; 3PS8; X-ray; 2.55 A; A=27-146.
DR PDB; 3QRD; X-ray; 2.19 A; A/B/C/D=27-146.
DR PDB; 3S67; X-ray; 2.26 A; A=27-146.
DR PDB; 3SVA; X-ray; 3.02 A; A=27-146.
DR PDB; 6ROA; X-ray; 2.65 A; A/B=27-146.
DR PDB; 6RPV; Other; -; A=27-146.
DR PDBsum; 1G96; -.
DR PDBsum; 1R4C; -.
DR PDBsum; 1TIJ; -.
DR PDBsum; 3GAX; -.
DR PDBsum; 3NX0; -.
DR PDBsum; 3PS8; -.
DR PDBsum; 3QRD; -.
DR PDBsum; 3S67; -.
DR PDBsum; 3SVA; -.
DR PDBsum; 6ROA; -.
DR PDBsum; 6RPV; -.
DR AlphaFoldDB; P01034; -.
DR SMR; P01034; -.
DR BioGRID; 107853; 27.
DR IntAct; P01034; 9.
DR MINT; P01034; -.
DR STRING; 9606.ENSP00000381448; -.
DR MEROPS; I25.004; -.
DR iPTMnet; P01034; -.
DR MetOSite; P01034; -.
DR PhosphoSitePlus; P01034; -.
DR BioMuta; CST3; -.
DR DMDM; 118183; -.
DR DOSAC-COBS-2DPAGE; P01034; -.
DR UCD-2DPAGE; P01034; -.
DR CPTAC; non-CPTAC-1114; -.
DR EPD; P01034; -.
DR jPOST; P01034; -.
DR MassIVE; P01034; -.
DR MaxQB; P01034; -.
DR PaxDb; P01034; -.
DR PeptideAtlas; P01034; -.
DR PRIDE; P01034; -.
DR ProteomicsDB; 51311; -.
DR Antibodypedia; 2285; 1499 antibodies from 46 providers.
DR DNASU; 1471; -.
DR Ensembl; ENST00000376925.8; ENSP00000366124.3; ENSG00000101439.9.
DR Ensembl; ENST00000398409.1; ENSP00000381446.1; ENSG00000101439.9.
DR Ensembl; ENST00000398411.5; ENSP00000381448.1; ENSG00000101439.9.
DR GeneID; 1471; -.
DR KEGG; hsa:1471; -.
DR MANE-Select; ENST00000376925.8; ENSP00000366124.3; NM_000099.4; NP_000090.1.
DR UCSC; uc002wtm.5; human.
DR CTD; 1471; -.
DR DisGeNET; 1471; -.
DR GeneCards; CST3; -.
DR HGNC; HGNC:2475; CST3.
DR HPA; ENSG00000101439; Tissue enhanced (brain).
DR MalaCards; CST3; -.
DR MIM; 105150; phenotype.
DR MIM; 604312; gene.
DR MIM; 611953; phenotype.
DR neXtProt; NX_P01034; -.
DR OpenTargets; ENSG00000101439; -.
DR Orphanet; 100008; ACys amyloidosis.
DR PharmGKB; PA26976; -.
DR VEuPathDB; HostDB:ENSG00000101439; -.
DR eggNOG; ENOG502SC50; Eukaryota.
DR GeneTree; ENSGT00940000154755; -.
DR HOGENOM; CLU_118168_0_1_1; -.
DR InParanoid; P01034; -.
DR OMA; YTVPWLG; -.
DR OrthoDB; 1565344at2759; -.
DR PhylomeDB; P01034; -.
DR PathwayCommons; P01034; -.
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-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR Reactome; R-HSA-977225; Amyloid fiber formation.
DR SignaLink; P01034; -.
DR BioGRID-ORCS; 1471; 15 hits in 1083 CRISPR screens.
DR ChiTaRS; CST3; human.
DR EvolutionaryTrace; P01034; -.
DR GeneWiki; Cystatin_C; -.
DR GenomeRNAi; 1471; -.
DR Pharos; P01034; Tbio.
DR PRO; PR:P01034; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; P01034; protein.
DR Bgee; ENSG00000101439; Expressed in right frontal lobe and 196 other tissues.
DR ExpressionAtlas; P01034; baseline and differential.
DR Genevisible; P01034; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; TAS:ARUK-UCL.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IMP:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IDA:ARUK-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
DR GO; GO:1904724; C:tertiary granule lumen; TAS:Reactome.
DR GO; GO:0031982; C:vesicle; IBA:GO_Central.
DR GO; GO:0001540; F:amyloid-beta binding; IPI:BHF-UCL.
DR GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0030414; F:peptidase inhibitor activity; IDA:ARUK-UCL.
DR GO; GO:0002020; F:protease binding; IPI:BHF-UCL.
DR GO; GO:0006952; P:defense response; IDA:BHF-UCL.
DR GO; GO:0060313; P:negative regulation of blood vessel remodeling; IEP:BHF-UCL.
DR GO; GO:0010711; P:negative regulation of collagen catabolic process; IEP:BHF-UCL.
DR GO; GO:2000117; P:negative regulation of cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0060311; P:negative regulation of elastin catabolic process; IMP:BHF-UCL.
DR GO; GO:0010716; P:negative regulation of extracellular matrix disassembly; IEP:BHF-UCL.
DR GO; GO:0010466; P:negative regulation of peptidase activity; IDA:ARUK-UCL.
DR GO; GO:0045861; P:negative regulation of proteolysis; IDA:UniProtKB.
DR GO; GO:0034103; P:regulation of tissue remodeling; IEP:BHF-UCL.
DR GO; GO:0097435; P:supramolecular fiber organization; IGI:BHF-UCL.
DR CDD; cd00042; CY; 1.
DR InterPro; IPR000010; Cystatin_dom.
DR InterPro; IPR046350; Cystatin_sf.
DR InterPro; IPR018073; Prot_inh_cystat_CS.
DR Pfam; PF00031; Cystatin; 1.
DR SMART; SM00043; CY; 1.
DR SUPFAM; SSF54403; SSF54403; 1.
DR PROSITE; PS00287; CYSTATIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Age-related macular degeneration; Amyloid; Amyloidosis;
KW Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein;
KW Phosphoprotein; Protease inhibitor; Reference proteome; Secreted; Signal;
KW Thiol protease inhibitor.
FT SIGNAL 1..26
FT /evidence="ECO:0000269|PubMed:15340161,
FT ECO:0000269|PubMed:6283552, ECO:0000269|PubMed:6365094,
FT ECO:0000269|PubMed:6662498"
FT CHAIN 27..146
FT /note="Cystatin-C"
FT /evidence="ECO:0000269|PubMed:2541223,
FT ECO:0000269|PubMed:3495457"
FT /id="PRO_0000006639"
FT MOTIF 81..85
FT /note="Secondary area of contact"
FT SITE 37
FT /note="Reactive site"
FT MOD_RES 43
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT DISULFID 99..109
FT DISULFID 123..143
FT VARIANT 25
FT /note="A -> T (in ARMD11; alters processing and
FT glycosylation; dbSNP:rs1064039)"
FT /evidence="ECO:0000269|PubMed:19838169,
FT ECO:0000269|PubMed:2764935"
FT /id="VAR_011893"
FT VARIANT 94
FT /note="L -> Q (in AMYL6; dbSNP:rs28939068)"
FT /evidence="ECO:0000269|PubMed:1352269,
FT ECO:0000269|PubMed:2541223"
FT /id="VAR_002207"
FT MUTAGEN 25
FT /note="A->S: Shows a dual distribution to the Golgi
FT apparatus and to the mitochondria."
FT /evidence="ECO:0000269|PubMed:16635487"
FT STRAND 40..42
FT /evidence="ECO:0007829|PDB:3GAX"
FT HELIX 47..63
FT /evidence="ECO:0007829|PDB:3GAX"
FT STRAND 67..101
FT /evidence="ECO:0007829|PDB:3GAX"
FT HELIX 106..108
FT /evidence="ECO:0007829|PDB:1R4C"
FT HELIX 115..118
FT /evidence="ECO:0007829|PDB:3GAX"
FT STRAND 121..130
FT /evidence="ECO:0007829|PDB:3GAX"
FT TURN 131..134
FT /evidence="ECO:0007829|PDB:3GAX"
FT STRAND 135..145
FT /evidence="ECO:0007829|PDB:3GAX"
SQ SEQUENCE 146 AA; 15799 MW; 75EF049CAE2E8B2B CRC64;
MAGPLRAPLL LLAILAVALA VSPAAGSSPG KPPRLVGGPM DASVEEEGVR RALDFAVGEY
NKASNDMYHS RALQVVRARK QIVAGVNYFL DVELGRTTCT KTQPNLDNCP FHDQPHLKRK
AFCSFQIYAV PWQGTMTLSK STCQDA
