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CST5 Gene

protein-coding   GIFtS: 55
GCID: GC20M023851

Cystatin D

  Search for CST5
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Cystatin D1 2
Cystatin 52
cystatin-52
cystatin-D2
Cysteine-Proteinase Inhibitor2
Cystatin-53

External Ids:    HGNC: 24771   Entrez Gene: 14732   Ensembl: ENSG000001703677   OMIM: 1238585   UniProtKB: P283253   

Export aliases for CST5 gene to outside databases

Previous GC identifers: GC20M023844 GC20M023804


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for CST5 Gene:
The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members
are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory
activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type
2 cystatins and the kininogens. The type 2 cystatin proteins are a class of cysteine proteinase inhibitors found
in a variety of human fluids and secretions. The cystatin locus on chromosome 20 contains the majority of the
type 2 cystatin genes and pseudogenes. This gene is located in the cystatin locus and encodes a protein found in
saliva and tears. The encoded protein may play a protective role against proteinases present in the oral cavity.
(provided by RefSeq, Jul 2008)

GeneCards Summary for CST5 Gene:
CST5 (cystatin D) is a protein-coding gene. GO annotations related to this gene include cysteine-type endopeptidase inhibitor activity. An important paralog of this gene is CST4.

UniProtKB/Swiss-Prot: CYTD_HUMAN, P28325
Function: Cysteine proteinase inhibitor that possibly plays a protective role against proteinases present in the
oral cavity. The order of preference for inhibition is cathepsin S > cathepsin H > cathepsin L > cathepsin B

Gene Wiki entry for CST5 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000020.11  NC_018931.2  NT_011387.9  
Regulatory elements:
   Regulatory transcription factor binding sites in the CST5 gene promoter:
         SREBP-1a   Zic1   SREBP-1c   MyoD   Nkx2-5   Nkx5-1   TGIF   SREBP-1b   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidCST5 promoter sequence
   Search Chromatin IP Primers for CST5

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat CST5


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 20p11.21   Ensembl cytogenetic band:  20p11.21   HGNC cytogenetic band: 20p11.21

CST5 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
CST5 gene location

GeneLoc information about chromosome 20         GeneLoc Exon Structure

GeneLoc location for GC20M023851:  view genomic region     (about GC identifiers)

Start:
23,856,572 bp from pter      End:
23,860,387 bp from pter
Size:
3,816 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: CYTD_HUMAN, P28325 (See protein sequence)
Recommended Name: Cystatin-D precursor  
Size: 142 amino acids; 16080 Da
Subunit: Monomer
Mass spectrometry: Mass=13154.4675; Mass_error=0.0101; Method=Electrospray; Range=29-142; Note=Variant Arg-46;
Source=PubMed:20189825;
Mass spectrometry: Mass=13596.7015; Mass_error=0.0049; Method=Electrospray; Range=25-142; Note=Variant Arg-46;
Source=PubMed:20189825;
Caution: The truncated forms found may result from N-terminal proteolysis (PubMed:20189825)
2 PDB 3D structures from and Proteopedia for CST5:
1RN7 (3D)        1ROA (3D)    
Secondary accessions: Q5JRF5 Q9UCA0

Explore the universe of human proteins at neXtProt for CST5: NX_P28325

Explore proteomics data for CST5 at MOPED


See CST5 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins: NP_001891.2  
ENSEMBL proteins: 
 ENSP00000307132  

CST5 Human Recombinant Protein Products:

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(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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3 InterPro protein domains:
 IPR018073 Prot_inh_cystat_CS
 IPR000010 Prot_inh_cystat
 IPR027214 Cystatin

Graphical View of Domain Structure for InterPro Entry P28325

ProtoNet protein and cluster: P28325

2 Blocks protein domains:
IPB000010 Cysteine protease inhibitor
IPB003243 Proteinase inhibitor I25A and I25B


UniProtKB/Swiss-Prot: CYTD_HUMAN, P28325
Similarity: Belongs to the cystatin family


Find genes that share domains with CST5           About GenesLikeMe


(According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

     UniProtKB/Swiss-Prot Summary: CYTD_HUMAN, P28325
Function: Cysteine proteinase inhibitor that possibly plays a protective role against proteinases present in the
oral cavity. The order of preference for inhibition is cathepsin S > cathepsin H > cathepsin L > cathepsin B
Biophysicochemical properties: Temperature dependence: Thermostable;

     Genatlas biochemistry entry for CST5:
cystatin D,cysteine proteinase inhibitor,found at high levels in salviva,tears,seminal plasma,type 2 family

     Gene Ontology (GO): 2 molecular function terms:    About this table

GO IDQualified GO termEvidencePubMed IDs
GO:0004869cysteine-type endopeptidase inhibitor activity IDA8083219
GO:0005515protein binding IPI8083219
     
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Phenotypes:
     1 GenomeRNAi human phenotype for CST5:
 Decreased cilium length after  

     3 MGI mutant phenotypes (inferred from 1 allele(MGI details for Cst10):
 homeostasis/metabolism  limbs/digits/tail  skeleton 

Find genes that share phenotypes with CST5           About GenesLikeMe

Animal Models:
     MGI mouse knock-out Cst10tm1Hkaw for CST5

   inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for CST5
   inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for CST5

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miRNA
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hsa-mir-181a-5p (MIRT025131)

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(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot
CYTD_HUMAN, P28325: Secreted
Subcellular locations from COMPARTMENTS: 

CompartmentConfidence
extracellular5

Gene Ontology (GO): 2 cellular component terms:    About this table

GO IDQualified GO termEvidencePubMed IDs
GO:0005576extracellular region IDA8083219
GO:0070062extracellular vesicular exosome IDA19199708

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(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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SuperPaths for CST5 About    
See pathways by source

SuperPathContained pathways About
1Salivary secretion
Salivary secretion0.34
2Endochondral Ossification
Endochondral Ossification


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Pathways by source                                                                                                                                                                 See SuperPaths
Show all pathways


1 BioSystems Pathway for CST5
    Endochondral Ossification



1 Kegg Pathway  (Kegg details for CST5):
    Salivary secretion

    Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for CST5
Interactions:

    Search GeneGlobe Interaction Network for CST5

STRING Interaction Network Preview (showing 1 interactants - click image to see more details)

1 Interacting protein for CST5 (P283253 ENSP000003071324) via UniProtKB, MINT, STRING, and/or I2D
InteractantInteraction Details
GeneCardExternal ID(s)
CTSSP257743, ENSP000003579814I2D: score=2 STRING: ENSP00000357981
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Gene Ontology (GO): 1 biological process term:    About this table

GO IDQualified GO termEvidencePubMed IDs
GO:0010951negative regulation of endopeptidase activity TAS1939105

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(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore
   Browse drugs & compounds from Enzo Life Sciences
  Browse compounds at ApexBio 

Browse Tocris compounds for CST5 (CYTD)

1 Novoseek inferred chemical compound relationship for CST5 gene    About this table
Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
cysteine 65.7 16 8083219 (4), 9573825 (2), 1939105 (2), 8340398 (1) (see all 8)



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(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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REFSEQ mRNAs for CST5 gene: 
NM_001900.4  

Unigene Cluster for CST5:

Cystatin D
Hs.121489  [show with all ESTs]
Unigene Representative Sequence: CB987021
1 Ensembl transcript including schematic representation, and UCSC links where relevant:
ENST00000304710(uc002wtr.1)
miRNA
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Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat CST5
Primer
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OriGene qPCR primer pairs and template standards for CST5
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Pre-validated RT2 qPCR Primer Assay in human, mouse, rat CST5
  QuantiTect SYBR Green Assays in human, mouse, rat CST5
  QuantiFast Probe-based Assays in human, mouse, rat CST5

Additional mRNA sequence: 

BC062678.1 BC069514.1 X70377.1 

1 DOTS entry:

DT.204835 

13 AceView cDNA sequences:

BC062678 NM_001900 BC069514 X70377 CB957678 BP334744 BP334786 BP333996 
BP334002 BP334304 CB987021 BP333854 CB985957 

GeneLoc Exon Structure


(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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CST5 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>2/3
CGAP TAG: CGCCTGCACC
CST5 Expression
About this image

CST5 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

CST5 Protein Expression

SOURCE GeneReport for Unigene cluster: Hs.121489

UniProtKB/Swiss-Prot: CYTD_HUMAN, P28325
Tissue specificity: Expressed in submandibular and sublingual saliva but not in parotid saliva (at protein level).
Expressed in parotid gland but not in seminal vesicle, prostate, epididymis, testis, ovary, placenta, thyroid,
gastric corpus, small intestine, liver, or gall bladder tissue

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In Situ
Assay Products:
 

 
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(Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of chordates.

Orthologs for CST5 gene from Selected species (see all 9)    About this table
Organism Taxonomic
classification
Gene Description Human
Similarity
Orthology
Type
Details
mouse
(Mus musculus)
Mammalia Cst101 , 5 cystatin 10 (chondrocytes)1, 5 57.62(n)1
42.64(a)1
  2 (73.80 cM)5
582141  NM_021405.21  NP_067380.11 
 1494050575 
chicken
(Gallus gallus)
Aves gga-mir-35266
Gallus gallus cystatin C (CST3), mRNA.
32(a)
1 → many
3(14928612-14932913)
lizard
(Anolis carolinensis)
Reptilia --
Uncharacterized protein
35(a)
1 → many
4(82204275-82217421)
zebrafish
(Danio rerio)
Actinopterygii cst36
cystatin C (amyloid angiopathy and cerebral hemorr...
28(a)
many ↔ many
13(33900031-33908388) ENSDARG00000007795


ENSEMBL Gene Tree for CST5 (if available)
TreeFam Gene Tree for CST5 (if available)

(Paralogs according to 1HomoloGene,
2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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Paralogs for CST5 gene
CST42  CST22  CSTL12  CST82  CST12  CST32  CST112  
10 SIMAP similar genes for CST5 using alignment to 1 protein entry:     CYTD_HUMAN:
CST2    CST4    CST1    CST3    CST9LP1    CST11
CST8    CST6    CSTL1    CST7

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1 Pseudogenes.org Pseudogene for CST5
PGOHUM00000247471


(SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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Selected SNPs for CST5 (see all 224)    About this table                                 

Genomic DataTranscription Related DataAllele Frequencies
SNP IDValidClinical
significance
Chr 20 posSequence#AA
Chg
TypeMore#Allele
freq
PopTotal
sample
More
----------
rs1453784121,2
--23856120(+) CCCTGA/GGGCAC 1 -- int10--------
rs1139121471,2
F--23856176(+) TCTTGC/TCCATC 1 -- int12Minor allele frequency- T:0.04CSA WA 119
rs1926231441,2
--23856226(+) CACATA/TCACAC 1 -- int10--------
rs750186251,2
C--23856272(+) CTTGTG/TGAAAG 1 -- int10--------
rs780018991,2
C--23856273(+) TTGTGA/GAAAGA 1 -- int10--------
rs769681581,2
C--23856274(+) TGTGGA/TAAGAA 1 -- int10--------
rs1491889321,2
C--23856292(+) TCGATC/TGCTAT 1 -- int10--------
rs60492011,2
C,F,H--23856378(+) ATCCAC/TGGCCT 1 -- int16Minor allele frequency- T:0.07NS EA CSA WA 540
rs2019504451,2
--23856508(+) GCTTC-/ATAAAGG 1 -- int10--------
rs1174404851,2
C,F--23856551(+) CCAAAC/TAGCCA 1 -- int11Minor allele frequency- T:0.03EA 120

HapMap Linkage Disequilibrium report for CST5 (23856572 - 23860387 bp)

Structural Variations
     Database of Genomic Variants (DGV) 2 variations for CST5:    About this table    
Variant IDTypeSubtypePubMed ID
dgv698e201CNV Deletion23290073
nsv833944CNV Gain17160897

Site Specific Mutation Identification with PCR Assays
SeqTarget long-range PCR primers for resequencing CST5
DNA2.0 Custom Variant and Variant Library Synthesis for CST5

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 123858    OMIM disorders: --


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Genetic Association Database (GAD): CST5
Human Genome Epidemiology (HuGE) Navigator: CST5 (1 document)

Export disorders for CST5 gene to outside databases

(in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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PubMed articles for CST5 gene, integrated from 10 sources (see all 30):
(articles sorted by number of sources associating them with CST5)
    Utopia: connect your pdf to the dynamic
world of online information

  1. Structure and expression of the gene encoding cystatin D, a novel human cysteine proteinase inhibitor. (PubMed id 1939105)1, 2, 3, 9 Freije J.P....Lopez-Otin C. (J. Biol. Chem. 1991)
  2. Structural and functional characterization of two allelic variants of human cystatin D sharing a characteristic inhibition spectrum against mammalian cysteine proteinases. (PubMed id 8083219)1, 2, 9 Balbin M....Abrahamson M. (J. Biol. Chem. 1994)
  3. Crystal structure of human cystatin D, a cysteine peptidase inhibitor with restricted inhibition profile. (PubMed id 15728581)1, 2, 9 Alvarez-Fernandez M.... Su X.D. (J. Biol. Chem. 2005)
  4. Human cystatin D. cDNA cloning, characterization of the Escherichia coli expressed inhibitor, and identification of the native protein in saliva. (PubMed id 8340398)1, 2, 9 Freije J.P.... Lopez-Otin C. (J. Biol. Chem. 1993)
  5. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PubMed id 20379614)1, 4 Rose J.E....Uhl G.R. (Mol. Med. 2010)
  6. Genome-wide association scan identifies candidate polymorphisms associated with differential response to anti-TNF treatment in rheumatoid arthritis. (PubMed id 18615156)1, 4 Liu C....Gregersen P.K. (Mol. Med. 2008)
  7. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1, 2 Gerhard D.S.... Malek J. (Genome Res. 2004)
  8. The DNA sequence and comparative analysis of human chromosome 20. (PubMed id 11780052)1, 2 Deloukas P....Rogers J. (Nature 2001)
  9. A sequence variation in the human cystatin D gene resulting in an amino acid (Cys/Arg) polymorphism at the protein level. (PubMed id 8444475)1, 2 Balbin M.... Lopez-Otin C. (Hum. Genet. 1993)
  10. Cystatin D is a candidate tumor suppressor gene induced by vitamin D in human colon cancer cells. (PubMed id 19662683)1, 9 Alvarez-DA-az S....MuA+oz A. (J. Clin. Invest. 2009)

(in PubMed, OMIM, and NCBI Bookshelf)
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 ANDOR
Aliases
Free Text  

  Query String
PubMed
OMIM
NCBI Bookshelf
  (Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 1473 HGNC: 2477 AceView: CST5 Ensembl:ENSG00000170367 euGenes: HUgn1473
ECgene: CST5 Kegg: 1473 H-InvDB: CST5

(According to HUGE)
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  --

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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NameDescription
PharmGKB entry for CST5 Pharmacogenomics, SNPs, Pathways

(Patent information from GeneIP,
Licensable technologies from WIS Yeda, Salk, Tufts,
IP news from LifeMap Sciences, Inc.)
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Patent Information for CST5 gene:
Search GeneIP for patents involving CST5

GeneCards and IP:
Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, eBioscience, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory, genOway)
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