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 13-FEB-2019, entry version 212. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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 RT precursor 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., RA Isemura S., Sanada K.; RT "The human cystatin C gene (CST3) is a member of the cystatin gene RT family 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 RT related to a mutation in the cystatin C gene, an inhibitor of cysteine RT 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 RT 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., RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., RA Korn B., Zuo D., Hu Y., 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., RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., RA 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., RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., RA 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., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA 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 RT project: 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 RT presence 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; 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 RT of 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 RT verified 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., RA Scherl A., Burgess J., Corthals G.L., Burkhard P.R., RA Hochstrasser D.F.; RT "Cystatin C as a potential cerebrospinal fluid marker for the RT diagnosis of 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., RA White M.R., Grierson I.; RT "A dual Golgi- and mitochondria-localised Ala25Ser precursor cystatin RT C: an additional tool for characterising intracellular mis- RT localisation leading 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., RA Brinkmalm G., 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 RT using top-down Fourier-transform ion cyclotron resonance mass RT 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., RA Buerckstuemmer T., 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., RA Fischer-Posovszky P., Mariman E.C., Renes J.; RT "Resveratrol-induced changes of the human adipocyte secretion RT 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 RT 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., RA Ayoub D., 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., RA Abrahamson M., 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 RT beta-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 RT disease-causing mutation and specific diagnosis by polymerase chain RT reaction based 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 CC regulator of this enzyme activity. CC -!- SUBUNIT: Homodimer. CC -!- INTERACTION: CC Self; NbExp=8; IntAct=EBI-948622, EBI-948622; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:20189825}. CC -!- TISSUE SPECIFICITY: Expressed in submandibular and sublingual CC saliva but not in parotid saliva (at protein level). Expressed in CC various body fluids, such as the cerebrospinal fluid and plasma. CC Expressed in highest levels in the epididymis, vas deferens, CC brain, thymus, and ovary and the lowest in the submandibular CC gland. {ECO:0000269|PubMed:15274116, ECO:0000269|PubMed:20189825}. CC -!- PTM: The Thr-25 variant is O-glycosylated with a core 1 or CC possibly core 8 glycan. The signal peptide of the O-glycosylated CC Thr-25 variant is cleaved between Ala-20 and Val-21. CC {ECO:0000269|PubMed:19838169}. CC -!- MASS SPECTROMETRY: Mass=13334.5829; Mass_error=0.0140; CC Method=Electrospray; Range=27-146; CC Evidence={ECO:0000269|PubMed:20189825}; CC -!- DISEASE: Amyloidosis 6 (AMYL6) [MIM:105150]: A hereditary CC generalized amyloidosis due to cystatin C amyloid deposition. CC Cystatin C amyloid accumulates in the walls of arteries, CC arterioles, and sometimes capillaries and veins of the brain, and CC in various organs including lymphoid tissue, spleen, salivary CC glands, and seminal vesicles. Amyloid deposition in the cerebral CC vessels results in cerebral amyloid angiopathy, cerebral CC hemorrhage and premature stroke. Cystatin C levels in the CC cerebrospinal fluid are abnormally low. CC {ECO:0000269|PubMed:1352269, ECO:0000269|PubMed:2541223}. Note=The CC disease is caused by mutations affecting the gene represented in CC this entry. CC -!- DISEASE: Macular degeneration, age-related, 11 (ARMD11) CC [MIM:611953]: A form of age-related macular degeneration, a CC multifactorial eye disease and the most common cause of CC irreversible vision loss in the developed world. In most patients, CC the disease is manifest as ophthalmoscopically visible yellowish CC accumulations of protein and lipid that lie beneath the retinal CC pigment epithelium and within an elastin-containing structure CC known as Bruch membrane. {ECO:0000269|PubMed:11815350, CC ECO:0000269|PubMed:19838169, ECO:0000269|PubMed:2764935}. CC Note=Disease susceptibility is associated with variations CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Potential cerebrospinal fluid marker for the CC diagnosis of Creutzfeldt-Jakob disease. CC -!- SIMILARITY: Belongs to the cystatin family. {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- 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 UniGene; Hs.304682; -. 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 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 ProteinModelPortal; P01034; -. DR SMR; P01034; -. DR BioGrid; 107853; 7. DR IntAct; P01034; 5. DR MINT; P01034; -. DR STRING; 9606.ENSP00000366124; -. DR MEROPS; I25.004; -. DR iPTMnet; P01034; -. DR PhosphoSitePlus; P01034; -. DR BioMuta; CST3; -. DR DMDM; 118183; -. DR DOSAC-COBS-2DPAGE; P01034; -. DR UCD-2DPAGE; P01034; -. DR EPD; P01034; -. DR jPOST; P01034; -. DR MaxQB; P01034; -. DR PaxDb; P01034; -. DR PeptideAtlas; P01034; -. DR PRIDE; P01034; -. DR ProteomicsDB; 51311; -. DR DNASU; 1471; -. DR Ensembl; ENST00000376925; ENSP00000366124; ENSG00000101439. DR Ensembl; ENST00000398409; ENSP00000381446; ENSG00000101439. DR Ensembl; ENST00000398411; ENSP00000381448; ENSG00000101439. DR GeneID; 1471; -. DR KEGG; hsa:1471; -. DR UCSC; uc002wtm.5; human. DR CTD; 1471; -. DR DisGeNET; 1471; -. DR EuPathDB; HostDB:ENSG00000101439.8; -. DR GeneCards; CST3; -. DR HGNC; HGNC:2475; CST3. DR HPA; CAB000118; -. DR HPA; HPA013143; -. 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 eggNOG; ENOG410IZZH; Eukaryota. DR eggNOG; ENOG4112CFJ; LUCA. DR GeneTree; ENSGT00940000154755; -. DR HOGENOM; HOG000231754; -. DR HOVERGEN; HBG009556; -. DR InParanoid; P01034; -. DR KO; K13899; -. DR OMA; HDQPHLM; -. DR OrthoDB; 1565344at2759; -. DR PhylomeDB; 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 ChiTaRS; CST3; human. DR EvolutionaryTrace; P01034; -. DR GeneWiki; Cystatin_C; -. DR GenomeRNAi; 1471; -. DR PMAP-CutDB; P01034; -. DR PRO; PR:P01034; -. DR Proteomes; UP000005640; Chromosome 20. DR Bgee; ENSG00000101439; Expressed in 222 organ(s), highest expression level in pigmented layer of retina. DR ExpressionAtlas; P01034; baseline and differential. DR Genevisible; P01034; HS. 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:1904724; C:tertiary granule lumen; TAS:Reactome. 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:0002020; F:protease binding; IPI:BHF-UCL. DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome. 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: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:BHF-UCL. DR GO; GO:0045861; P:negative regulation of proteolysis; IDA:UniProtKB. DR GO; GO:0043312; P:neutrophil degranulation; TAS:Reactome. DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome. 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; IPR027214; Cystatin. DR InterPro; IPR000010; Cystatin_dom. DR InterPro; IPR018073; Prot_inh_cystat_CS. DR PANTHER; PTHR11413; PTHR11413; 1. DR Pfam; PF00031; Cystatin; 1. DR SMART; SM00043; CY; 1. DR PROSITE; PS00287; CYSTATIN; 1. PE 1: Evidence at protein level; KW 3D-structure; Age-related macular degeneration; Amyloid; Amyloidosis; KW Complete proteome; Direct protein sequencing; Disease mutation; KW Disulfide bond; Glycoprotein; Phosphoprotein; Polymorphism; KW Protease inhibitor; Reference proteome; Secreted; Signal; KW Thiol protease inhibitor. FT SIGNAL 1 26 {ECO:0000269|PubMed:15340161, FT ECO:0000269|PubMed:6283552, FT ECO:0000269|PubMed:6365094, FT ECO:0000269|PubMed:6662498}. FT CHAIN 27 146 Cystatin-C. {ECO:0000269|PubMed:2541223, FT ECO:0000269|PubMed:3495457}. FT /FTId=PRO_0000006639. FT MOTIF 81 85 Secondary area of contact. FT SITE 37 37 Reactive site. FT MOD_RES 43 43 Phosphoserine; by FAM20C. FT {ECO:0000269|PubMed:26091039}. FT DISULFID 99 109 FT DISULFID 123 143 FT VARIANT 25 25 A -> T (in ARMD11; alters processing and FT glycosylation; dbSNP:rs1064039). FT {ECO:0000269|PubMed:19838169, FT ECO:0000269|PubMed:2764935}. FT /FTId=VAR_011893. FT VARIANT 94 94 L -> Q (in AMYL6; dbSNP:rs28939068). FT {ECO:0000269|PubMed:1352269, FT ECO:0000269|PubMed:2541223}. FT /FTId=VAR_002207. FT MUTAGEN 25 25 A->S: Shows a dual distribution to the FT Golgi apparatus and to the mitochondria. FT {ECO:0000269|PubMed:16635487}. FT STRAND 40 42 {ECO:0000244|PDB:3GAX}. FT HELIX 47 63 {ECO:0000244|PDB:3GAX}. FT STRAND 67 101 {ECO:0000244|PDB:3GAX}. FT HELIX 106 108 {ECO:0000244|PDB:1R4C}. FT HELIX 115 118 {ECO:0000244|PDB:3GAX}. FT STRAND 121 130 {ECO:0000244|PDB:3GAX}. FT TURN 131 134 {ECO:0000244|PDB:3GAX}. FT STRAND 135 145 {ECO:0000244|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 //