CST9_HUMAN
ID CST9_HUMAN Reviewed; 159 AA.
AC Q5W186; B2RP76; Q8TD53;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 07-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Cystatin-9;
DE AltName: Full=Cystatin-like molecule;
DE Flags: Precursor;
GN Name=CST9;
GN Synonyms=CLM {ECO:0000303|PubMed:12535658},
GN CTES7A {ECO:0000303|PubMed:20565543};
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], FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR
RP LOCATION, INDUCTION BY LPS, AND VARIANT PHE-48.
RC TISSUE=Bone marrow stroma;
RX PubMed=12535658; DOI=10.1016/s0006-291x(02)02985-6;
RA Sun H., Li N., Wang X., Liu S., Chen T., Zhang L., Wan T., Cao X.;
RT "Molecular cloning and characterization of a novel cystatin-like molecule,
RT CLM, from human bone marrow stromal cells.";
RL Biochem. Biophys. Res. Commun. 301:176-182(2003).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP TISSUE SPECIFICITY.
RX PubMed=20565543; DOI=10.1111/j.1525-142x.2010.00418.x;
RA Frygelius J., Arvestad L., Wedell A., Toehoenen V.;
RT "Evolution and human tissue expression of the Cres/Testatin subgroup genes,
RT a reproductive tissue specific subgroup of the type 2 cystatins.";
RL Evol. Dev. 12:329-342(2010).
RN [5]
RP FUNCTION.
RX PubMed=23922243; DOI=10.2119/molmed.2013.00081;
RA Eaves-Pyles T., Patel J., Arigi E., Cong Y., Cao A., Garg N., Dhiman M.,
RA Pyles R.B., Arulanandam B., Miller A.L., Popov V.L., Soong L.,
RA Carlsen E.D., Coletta C., Szabo C., Almeida I.C.;
RT "Immunomodulatory and antibacterial effects of cystatin 9 against
RT Francisella tularensis.";
RL Mol. Med. 19:263-275(2013).
CC -!- FUNCTION: May be involved in testis development (By similarity). May
CC play a role in hematopoietic differentiation or inflammation
CC (PubMed:12535658). Has immunomodulatory and antimicrobial functions
CC against Francisella tularensis, a Gram-negative bacteria
CC (PubMed:23922243). {ECO:0000250|UniProtKB:Q9Z0H6,
CC ECO:0000269|PubMed:12535658, ECO:0000269|PubMed:23922243}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12535658}. Note=May
CC be targeted through the Golgi via the secretory pathway.
CC {ECO:0000269|PubMed:12535658}.
CC -!- TISSUE SPECIFICITY: Expressed in heart, placenta, lung, liver, skeletal
CC muscle and pancreas (PubMed:12535658). Not expressed in brain
CC (PubMed:12535658). Expressed in epididymis, kidney, testis, spinal
CC cord, and thymus with a strong expression in epididymis and kidney and
CC a weak expression in the spinal cord and thymus (PubMed:20565543).
CC {ECO:0000269|PubMed:12535658, ECO:0000269|PubMed:20565543}.
CC -!- INDUCTION: Up-regulated by bacterial lipopolysaccharides (LPS), in some
CC cancer cells such as promyelocytic leukemia cells (HL-60) or
CC myelomonocytic leukemia cells (U-937). {ECO:0000269|PubMed:12535658}.
CC -!- SIMILARITY: Belongs to the cystatin family. {ECO:0000305}.
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DR EMBL; AF494536; AAM18055.1; -; mRNA.
DR EMBL; AL121894; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC137302; AAI37303.1; -; mRNA.
DR EMBL; BC137303; AAI37304.1; -; mRNA.
DR CCDS; CCDS33450.1; -.
DR RefSeq; NP_001008693.2; NM_001008693.2.
DR AlphaFoldDB; Q5W186; -.
DR SMR; Q5W186; -.
DR BioGRID; 126160; 89.
DR IntAct; Q5W186; 4.
DR STRING; 9606.ENSP00000366170; -.
DR MEROPS; I25.065; -.
DR BioMuta; CST9; -.
DR DMDM; 74748036; -.
DR PaxDb; Q5W186; -.
DR PRIDE; Q5W186; -.
DR Antibodypedia; 24910; 141 antibodies from 20 providers.
DR DNASU; 128822; -.
DR Ensembl; ENST00000376971.4; ENSP00000366170.4; ENSG00000173335.5.
DR GeneID; 128822; -.
DR KEGG; hsa:128822; -.
DR MANE-Select; ENST00000376971.4; ENSP00000366170.4; NM_001008693.3; NP_001008693.2.
DR UCSC; uc002wtl.4; human.
DR CTD; 128822; -.
DR DisGeNET; 128822; -.
DR GeneCards; CST9; -.
DR HGNC; HGNC:13261; CST9.
DR HPA; ENSG00000173335; Tissue enriched (breast).
DR MIM; 616543; gene.
DR neXtProt; NX_Q5W186; -.
DR OpenTargets; ENSG00000173335; -.
DR PharmGKB; PA134898267; -.
DR VEuPathDB; HostDB:ENSG00000173335; -.
DR eggNOG; ENOG502TAJ0; Eukaryota.
DR GeneTree; ENSGT00940000164098; -.
DR HOGENOM; CLU_118168_3_0_1; -.
DR InParanoid; Q5W186; -.
DR OMA; HIFNLQN; -.
DR OrthoDB; 1577727at2759; -.
DR PhylomeDB; Q5W186; -.
DR PathwayCommons; Q5W186; -.
DR SignaLink; Q5W186; -.
DR BioGRID-ORCS; 128822; 9 hits in 1060 CRISPR screens.
DR ChiTaRS; CST9; human.
DR GenomeRNAi; 128822; -.
DR Pharos; Q5W186; Tbio.
DR PRO; PR:Q5W186; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q5W186; protein.
DR Bgee; ENSG00000173335; Expressed in caput epididymis and 17 other tissues.
DR Genevisible; Q5W186; HS.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0019730; P:antimicrobial humoral response; IDA:UniProtKB.
DR InterPro; IPR043250; CST9-like.
DR InterPro; IPR046350; Cystatin_sf.
DR PANTHER; PTHR46945; PTHR46945; 1.
DR SUPFAM; SSF54403; SSF54403; 1.
PE 2: Evidence at transcript level;
KW Antimicrobial; Protease inhibitor; Reference proteome; Secreted; Signal;
KW Thiol protease inhibitor.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..159
FT /note="Cystatin-9"
FT /id="PRO_0000314693"
FT VARIANT 48
FT /note="L -> F (in dbSNP:rs2983640)"
FT /evidence="ECO:0000269|PubMed:12535658"
FT /id="VAR_038045"
SQ SEQUENCE 159 AA; 18135 MW; 89280B27DB7A3C0A CRC64;
MSSPQRRKAM PWALSLLLMG FQLLVTYAWC SEEEMGGNNK IVQDPMFLAT VEFALNTFNV
QSKEEHAYRL LRVLSSWRED SMDRKWRGKM VFSMNLQLRQ TVCRKFEDDI DNCPFQESLE
LNNVRQGISF PQVHSCGCCM GCGVGTGAAD KAIPRDKGK