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Protein

Cystatin-M

Gene

CST6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Shows moderate inhibition of cathepsin B but is not active against cathepsin C.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei36 – 361Reactive site

GO - Molecular functioni

  • cysteine-type endopeptidase inhibitor activity Source: ProtInc

GO - Biological processi

  • anatomical structure morphogenesis Source: ProtInc
  • epidermis development Source: Ensembl
  • negative regulation of endopeptidase activity Source: GOC
Complete GO annotation...

Keywords - Molecular functioni

Protease inhibitor, Thiol protease inhibitor

Protein family/group databases

MEROPSiI25.006.

Names & Taxonomyi

Protein namesi
Recommended name:
Cystatin-M
Alternative name(s):
Cystatin-6
Cystatin-E
Gene namesi
Name:CST6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:2478. CST6.

Subcellular locationi

GO - Cellular componenti

  • cornified envelope Source: Ensembl
  • extracellular exosome Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA26979.

Polymorphism and mutation databases

BioMutaiCST6.
DMDMi2494024.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2828CuratedAdd
BLAST
Chaini29 – 149121Cystatin-MPRO_0000006648Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi98 ↔ 113By similarity
Disulfide bondi126 ↔ 146By similarity
Glycosylationi137 – 1371N-linked (GlcNAc...)Sequence analysis

Post-translational modificationi

Substrate for transglutaminases. Acts as an acyl acceptor but not as an acyl donor.

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ15828.
PaxDbiQ15828.
PeptideAtlasiQ15828.
PRIDEiQ15828.

PTM databases

iPTMnetiQ15828.
PhosphoSiteiQ15828.

Expressioni

Tissue specificityi

Restricted to the stratum granulosum of normal skin, the stratum granulosum/spinosum of psoriatic skin, and the secretory coils of eccrine sweat glands. Low expression levels are found in the nasal cavity.1 Publication

Gene expression databases

BgeeiQ15828.
CleanExiHS_CST6.
GenevisibleiQ15828. HS.

Organism-specific databases

HPAiCAB019316.
HPA044963.

Interactioni

Protein-protein interaction databases

BioGridi107856. 37 interactions.
IntActiQ15828. 6 interactions.
MINTiMINT-8247486.

Structurei

Secondary structure

1
149
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi38 – 414Combined sources
Helixi46 – 6217Combined sources
Beta strandi65 – 9935Combined sources
Turni102 – 1065Combined sources
Helixi110 – 1123Combined sources
Helixi118 – 1203Combined sources
Beta strandi123 – 13311Combined sources
Helixi134 – 1363Combined sources
Beta strandi138 – 14811Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4N6LX-ray1.95A29-149[»]
4N6MX-ray2.90A/B29-149[»]
4N6NX-ray1.87B29-149[»]
4N6OX-ray1.80B29-149[»]
ProteinModelPortaliQ15828.
SMRiQ15828. Positions 36-149.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi80 – 845Secondary area of contact

Sequence similaritiesi

Belongs to the cystatin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410J4P1. Eukaryota.
ENOG410Y20I. LUCA.
GeneTreeiENSGT00840000129890.
HOGENOMiHOG000231754.
HOVERGENiHBG009556.
InParanoidiQ15828.
KOiK13902.
OMAiSLYYFRD.
OrthoDBiEOG7M98J9.
PhylomeDBiQ15828.

Family and domain databases

InterProiIPR027214. Cystatin.
IPR000010. Cystatin_dom.
IPR018073. Prot_inh_cystat_CS.
[Graphical view]
PANTHERiPTHR11413. PTHR11413. 1 hit.
PfamiPF00031. Cystatin. 1 hit.
[Graphical view]
SMARTiSM00043. CY. 1 hit.
[Graphical view]
PROSITEiPS00287. CYSTATIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q15828-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MARSNLPLAL GLALVAFCLL ALPRDARARP QERMVGELRD LSPDDPQVQK
60 70 80 90 100
AAQAAVASYN MGSNSIYYFR DTHIIKAQSQ LVAGIKYFLT MEMGSTDCRK
110 120 130 140
TRVTGDHVDL TTCPLAAGAQ QEKLRCDFEV LVVPWQNSSQ LLKHNCVQM
Length:149
Mass (Da):16,511
Last modified:November 1, 1997 - v1
Checksum:i2076A78BFC9FAC8C
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U62800 mRNA. Translation: AAB06566.1.
U81233 mRNA. Translation: AAB61305.1.
AY145051 Genomic DNA. Translation: AAN52757.1.
BC031334 mRNA. Translation: AAH31334.1.
CCDSiCCDS8126.1.
RefSeqiNP_001314.1. NM_001323.3.
UniGeneiHs.139389.

Genome annotation databases

EnsembliENST00000312134; ENSP00000311313; ENSG00000175315.
GeneIDi1474.
KEGGihsa:1474.
UCSCiuc001ogr.4. human.

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U62800 mRNA. Translation: AAB06566.1.
U81233 mRNA. Translation: AAB61305.1.
AY145051 Genomic DNA. Translation: AAN52757.1.
BC031334 mRNA. Translation: AAH31334.1.
CCDSiCCDS8126.1.
RefSeqiNP_001314.1. NM_001323.3.
UniGeneiHs.139389.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4N6LX-ray1.95A29-149[»]
4N6MX-ray2.90A/B29-149[»]
4N6NX-ray1.87B29-149[»]
4N6OX-ray1.80B29-149[»]
ProteinModelPortaliQ15828.
SMRiQ15828. Positions 36-149.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107856. 37 interactions.
IntActiQ15828. 6 interactions.
MINTiMINT-8247486.

Protein family/group databases

MEROPSiI25.006.

PTM databases

iPTMnetiQ15828.
PhosphoSiteiQ15828.

Polymorphism and mutation databases

BioMutaiCST6.
DMDMi2494024.

Proteomic databases

MaxQBiQ15828.
PaxDbiQ15828.
PeptideAtlasiQ15828.
PRIDEiQ15828.

Protocols and materials databases

DNASUi1474.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000312134; ENSP00000311313; ENSG00000175315.
GeneIDi1474.
KEGGihsa:1474.
UCSCiuc001ogr.4. human.

Organism-specific databases

CTDi1474.
GeneCardsiCST6.
HGNCiHGNC:2478. CST6.
HPAiCAB019316.
HPA044963.
MIMi601891. gene.
neXtProtiNX_Q15828.
PharmGKBiPA26979.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J4P1. Eukaryota.
ENOG410Y20I. LUCA.
GeneTreeiENSGT00840000129890.
HOGENOMiHOG000231754.
HOVERGENiHBG009556.
InParanoidiQ15828.
KOiK13902.
OMAiSLYYFRD.
OrthoDBiEOG7M98J9.
PhylomeDBiQ15828.

Miscellaneous databases

GeneWikiiCST6_(gene).
GenomeRNAii1474.
PROiQ15828.
SOURCEiSearch...

Gene expression databases

BgeeiQ15828.
CleanExiHS_CST6.
GenevisibleiQ15828. HS.

Family and domain databases

InterProiIPR027214. Cystatin.
IPR000010. Cystatin_dom.
IPR018073. Prot_inh_cystat_CS.
[Graphical view]
PANTHERiPTHR11413. PTHR11413. 1 hit.
PfamiPF00031. Cystatin. 1 hit.
[Graphical view]
SMARTiSM00043. CY. 1 hit.
[Graphical view]
PROSITEiPS00287. CYSTATIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Identification, cloning, and characterization of cystatin M, a novel cysteine proteinase inhibitor, down-regulated in breast cancer."
    Sotiropoulou G., Anisowicz A., Sager R.
    J. Biol. Chem. 272:903-910(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Cystatin E is a novel human cysteine proteinase inhibitor with structural resemblance to family 2 cystatins."
    Ni J., Abrahamson M., Zhang M., Fernandez M.A., Grubb A., Su J., Yu G.L., Li Y., Parmelee D., Xing L., Coleman T.A., Gentz S., Thotakura R., Nguyen N., Hesselberg M., Gentz R.
    J. Biol. Chem. 272:10853-10858(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "The human cystatin M/E gene (CST6): exclusion candidate gene for harlequin ichthyosis."
    Zeeuwen P.L., Dale B.A., de Jongh G.J., van Vlijmen-Willems I.M., Fleckman P., Kimball J.R., Stephens K., Schalkwijk J.
    J. Invest. Dermatol. 121:65-68(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Tissue: Blood.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Prostate.
  5. "Cystatin M/E expression is restricted to differentiated epidermal keratinocytes and sweat glands: a new skin-specific proteinase inhibitor that is a target for cross-linking by transglutaminase."
    Zeeuwen P.L., Van Vlijmen-Willems I.M., Jansen B.J., Sotiropoulou G., Curfs J.H., Meis J.F., Janssen J.J., Van Ruissen F., Schalkwijk J.
    J. Invest. Dermatol. 116:693-701(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION, TISSUE SPECIFICITY.

Entry informationi

Entry nameiCYTM_HUMAN
AccessioniPrimary (citable) accession number: Q15828
Secondary accession number(s): Q540N7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: June 8, 2016
This is version 136 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.