CYTF_HUMAN
ID CYTF_HUMAN Reviewed; 145 AA.
AC O76096; Q6FH95; Q7Z4J8; Q9UED4;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Cystatin-F;
DE AltName: Full=Cystatin-7;
DE AltName: Full=Cystatin-like metastasis-associated protein;
DE Short=CMAP;
DE AltName: Full=Leukocystatin;
DE Flags: Precursor;
GN Name=CST7;
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].
RX PubMed=9632704; DOI=10.1074/jbc.273.26.16400;
RA Halfon S., Ford J., Foster J., Dowling L., Lucian L., Sterling M., Xu Y.,
RA Weiss M., Ikeda M., Liggett D., Helms A., Caux C., Lebecque S., Hannum C.,
RA Menon S., McClanahan T., Gorman D., Zurawski G.;
RT "Leukocystatin, a new class II cystatin expressed selectively by
RT hematopoietic cells.";
RL J. Biol. Chem. 273:16400-16408(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9733783; DOI=10.1074/jbc.273.38.24797;
RA Ni J., Fernandez M.A., Danielsson L., Chillakuru R.A., Zhang J., Grubb A.,
RA Su J., Gentz R., Abrahamson M.;
RT "Cystatin F is a glycosylated human low molecular weight cysteine
RT proteinase inhibitor.";
RL J. Biol. Chem. 273:24797-24804(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10945474; DOI=10.1006/geno.2000.6237;
RA Morita M., Hara Y., Tamai Y., Arakawa H., Nishimura S.;
RT "Genomic construct and mapping of the gene for CMAP (leukocystatin/cystatin
RT F, CST7) and identification of a proximal novel gene, BSCv (C20orf3).";
RL Genomics 67:87-91(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND SUBCELLULAR LOCATION.
RC TISSUE=Blood;
RX PubMed=12423348; DOI=10.1046/j.1432-1033.2002.03252.x;
RA Nathanson C.M., Wasselius J., Wallin H., Abrahamson M.;
RT "Regulated expression and intracellular localization of cystatin F in human
RT U937 cells.";
RL Eur. J. Biochem. 269:5502-5511(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Morita M., Arakawa H., Yoshiuchi N.;
RT "Human homologue of murine CMAP.";
RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
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 (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
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 MRNA].
RC TISSUE=Lung;
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 [10]
RP CLEAVAGE OF SIGNAL PEPTIDE [LARGE SCALE ANALYSIS] AFTER GLY-19, AND
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 [11]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 20-145, SUBUNIT, GLYCOSYLATION AT
RP ASN-62 AND ASN-115, AND DISULFIDE BONDS.
RX PubMed=16601115; DOI=10.1074/jbc.m601033200;
RA Schuettelkopf A.W., Hamilton G., Watts C., van Aalten D.M.F.;
RT "Structural basis of reduction-dependent activation of human cystatin F.";
RL J. Biol. Chem. 281:16570-16575(2006).
CC -!- FUNCTION: Inhibits papain and cathepsin L but with affinities lower
CC than other cystatins. May play a role in immune regulation through
CC inhibition of a unique target in the hematopoietic system.
CC -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000269|PubMed:16601115}.
CC -!- INTERACTION:
CC O76096; P53634: CTSC; NbExp=2; IntAct=EBI-2807448, EBI-1047323;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12423348}. Cytoplasm
CC {ECO:0000269|PubMed:12423348}.
CC -!- TISSUE SPECIFICITY: Primarily expressed in peripheral blood cells and
CC spleen.
CC -!- SIMILARITY: Belongs to the cystatin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH15507.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAP88827.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA34941.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB11886.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF031824; AAC39788.1; -; mRNA.
DR EMBL; AF036342; AAC35747.1; -; mRNA.
DR EMBL; AB029636; BAB11886.1; ALT_INIT; Genomic_DNA.
DR EMBL; AJ510167; CAD52872.1; -; Genomic_DNA.
DR EMBL; AJ510168; CAD52872.1; JOINED; Genomic_DNA.
DR EMBL; AJ510169; CAD52872.1; JOINED; Genomic_DNA.
DR EMBL; AJ510170; CAD52872.1; JOINED; Genomic_DNA.
DR EMBL; AB015225; BAA34941.1; ALT_INIT; mRNA.
DR EMBL; BT009825; AAP88827.1; ALT_INIT; mRNA.
DR EMBL; CR541860; CAG46658.1; -; mRNA.
DR EMBL; CR541878; CAG46676.1; -; mRNA.
DR EMBL; AL035661; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC015507; AAH15507.1; ALT_INIT; mRNA.
DR CCDS; CCDS13165.2; -.
DR RefSeq; NP_003641.3; NM_003650.3.
DR PDB; 2CH9; X-ray; 2.10 A; A=20-145.
DR PDBsum; 2CH9; -.
DR AlphaFoldDB; O76096; -.
DR SMR; O76096; -.
DR BioGRID; 114100; 13.
DR IntAct; O76096; 10.
DR MINT; O76096; -.
DR STRING; 9606.ENSP00000420384; -.
DR MEROPS; I25.007; -.
DR GlyGen; O76096; 3 sites, 1 O-linked glycan (1 site).
DR iPTMnet; O76096; -.
DR PhosphoSitePlus; O76096; -.
DR BioMuta; CST7; -.
DR EPD; O76096; -.
DR jPOST; O76096; -.
DR MassIVE; O76096; -.
DR PaxDb; O76096; -.
DR PeptideAtlas; O76096; -.
DR PRIDE; O76096; -.
DR ProteomicsDB; 50415; -.
DR Antibodypedia; 24951; 182 antibodies from 34 providers.
DR DNASU; 8530; -.
DR Ensembl; ENST00000480798.2; ENSP00000420384.1; ENSG00000077984.6.
DR GeneID; 8530; -.
DR KEGG; hsa:8530; -.
DR MANE-Select; ENST00000480798.2; ENSP00000420384.1; NM_003650.4; NP_003641.3.
DR UCSC; uc002wtx.2; human.
DR CTD; 8530; -.
DR DisGeNET; 8530; -.
DR GeneCards; CST7; -.
DR HGNC; HGNC:2479; CST7.
DR HPA; ENSG00000077984; Tissue enriched (bone).
DR MIM; 603253; gene.
DR neXtProt; NX_O76096; -.
DR OpenTargets; ENSG00000077984; -.
DR PharmGKB; PA26980; -.
DR VEuPathDB; HostDB:ENSG00000077984; -.
DR eggNOG; ENOG502S5CP; Eukaryota.
DR GeneTree; ENSGT00940000160277; -.
DR HOGENOM; CLU_118168_1_0_1; -.
DR InParanoid; O76096; -.
DR OMA; VVPWLQH; -.
DR OrthoDB; 1565344at2759; -.
DR PhylomeDB; O76096; -.
DR PathwayCommons; O76096; -.
DR SignaLink; O76096; -.
DR BioGRID-ORCS; 8530; 11 hits in 1064 CRISPR screens.
DR ChiTaRS; CST7; human.
DR EvolutionaryTrace; O76096; -.
DR GeneWiki; CST7_(gene); -.
DR GenomeRNAi; 8530; -.
DR Pharos; O76096; Tbio.
DR PRO; PR:O76096; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; O76096; protein.
DR Bgee; ENSG00000077984; Expressed in granulocyte and 110 other tissues.
DR Genevisible; O76096; HS.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:ARUK-UCL.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:ARUK-UCL.
DR GO; GO:0005768; C:endosome; IDA:ARUK-UCL.
DR GO; GO:0005615; C:extracellular space; IDA:ARUK-UCL.
DR GO; GO:0005794; C:Golgi apparatus; IDA:ARUK-UCL.
DR GO; GO:0005770; C:late endosome; IBA:GO_Central.
DR GO; GO:0005764; C:lysosome; IDA:ARUK-UCL.
DR GO; GO:0005771; C:multivesicular body; IDA:ARUK-UCL.
DR GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IBA:GO_Central.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; TAS:ProtInc.
DR GO; GO:0030414; F:peptidase inhibitor activity; IDA:ARUK-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:ARUK-UCL.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
DR GO; GO:0097340; P:inhibition of cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:1903979; P:negative regulation of microglial cell activation; IBA:GO_Central.
DR GO; GO:0010466; P:negative regulation of peptidase activity; IDA:ARUK-UCL.
DR GO; GO:0031643; P:positive regulation of myelination; IBA:GO_Central.
DR CDD; cd00042; CY; 1.
DR InterPro; IPR042886; Cystatin-F.
DR InterPro; IPR000010; Cystatin_dom.
DR InterPro; IPR046350; Cystatin_sf.
DR PANTHER; PTHR47141; PTHR47141; 1.
DR Pfam; PF00031; Cystatin; 1.
DR SMART; SM00043; CY; 1.
DR SUPFAM; SSF54403; SSF54403; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Disulfide bond; Glycoprotein; Protease inhibitor;
KW Reference proteome; Secreted; Signal; Thiol protease inhibitor.
FT SIGNAL 1..19
FT /evidence="ECO:0000255, ECO:0007744|PubMed:25944712"
FT CHAIN 20..145
FT /note="Cystatin-F"
FT /id="PRO_0000006646"
FT MOTIF 81..85
FT /note="Secondary area of contact"
FT SITE 37
FT /note="Reactive site"
FT CARBOHYD 62
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16601115"
FT CARBOHYD 115
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16601115"
FT DISULFID 26
FT /note="Interchain (with C-63)"
FT /evidence="ECO:0000269|PubMed:16601115"
FT DISULFID 63
FT /note="Interchain (with C-26)"
FT /evidence="ECO:0000269|PubMed:16601115"
FT DISULFID 99..110
FT /evidence="ECO:0000269|PubMed:16601115"
FT DISULFID 124..144
FT /evidence="ECO:0000269|PubMed:16601115"
FT HELIX 47..63
FT /evidence="ECO:0007829|PDB:2CH9"
FT STRAND 67..100
FT /evidence="ECO:0007829|PDB:2CH9"
FT HELIX 107..109
FT /evidence="ECO:0007829|PDB:2CH9"
FT TURN 116..118
FT /evidence="ECO:0007829|PDB:2CH9"
FT STRAND 121..131
FT /evidence="ECO:0007829|PDB:2CH9"
FT HELIX 132..134
FT /evidence="ECO:0007829|PDB:2CH9"
FT STRAND 136..145
FT /evidence="ECO:0007829|PDB:2CH9"
SQ SEQUENCE 145 AA; 16454 MW; B2BCC4F76857CB0F CRC64;
MRAAGTLLAF CCLVLSTTGG PSPDTCSQDL NSRVKPGFPK TIKTNDPGVL QAARYSVEKF
NNCTNDMFLF KESRITRALV QIVKGLKYML EVEIGRTTCK KNQHLRLDDC DFQTNHTLKQ
TLSCYSEVWV VPWLQHFEVP VLRCH
