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PR00295

Identifier
STEFINA  [View Relations]  [View Alignment]  
Accession
PR00295
No. of Motifs
4
Creation Date
07-MAR-1995  (UPDATE 07-JUN-1999)
Title
Stefin A signature
Database References

PROSITE; PS00287 CYSTATIN
BLOCKS; BL00287
INTERPRO; IPR001713
PDB; 1STF
SCOP; 1STF
CATH; 1STF
Literature References
1. MARTIN, J.R., CRAVEN, C.J., JERALA, R., KROON-ZITKO, L., ZEROVNIK, E.
TURK, V. AND WALTHO, J.P.
The 3-dimensional solution structure of human stefin A.
J.MOL.BIOL. 246  331-343 (1995). 
 
2. TURK, V. AND BODE, W. 
The cystatins: protein inhibitors of cysteine proteinases.
FEBS LETT. 285 213-219 (1991).

Documentation
Stefin A is a member of the cystatin superfamily, which are tight,
reversibly-binding inhibitors of the papain-like cysteine proteases [1].
The inhibitors are involved in the control mechanism responsible for
protein breakdown, and are thought to help protect cells from inappropriate
endogenous or external proteolysis [2]. 
 
The cystatin superfamily comprises 3 families: the stefins, cystatins 
and kininogens. The stefin family includes proteins that lack disulphide 
bonds and carbohydrates. The most abundant source of stefin A is poly-
morphonuclear leucocytes from the liver, but it is also found in extracts
of squamous epithelia from the mouth and oesophagus, and has been localised
to the cytoplasm of the strata corneum and granulosum of the epidermis. The
selective distribution of the inhibitor correlates with tissues that
constitute a "first line of defence" against pathogenic organisms. Stefin A
may thus provide a protective function as an inhibitor of cysteine
proteases utilised as invasive tools by many infectious agents [1].
 
The structure of stefin A contains a 5-stranded anti-parallel beta-sheet,
wrapped around a central helix. The loops formed between the strands are
involved in inhibitor binding, one of these containing a QVVAG sequence,
which is highly conserved in most members of the cystatin superfamily [2].
 
STEFINA is a 4-element fingerprint that provides a signature for stefins.
The fingerprint was derived from an initial alignment of 6 sequences: the
motifs were drawn from conserved regions spanning the full alignment
length, motifs 2 and 3 encompassing the region encoded by PROSITE pattern
CYSTATIN (PS00287), which contains the conserved QVVAG motif implicated in
protease binding. Two iterations on OWL25.2 were required to reach
convergence, at which point a true set comprising 11 sequences was
identified.
 
An update on SPTR37_9f identified a true set of 18 sequences, and 1
partial match.
Summary Information
  18 codes involving  4 elements
1 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
418181818
31110
20000
1234
True Positives
CPI1_PIG      CYT1_MOUSE    CYT1_PIG      CYT2_MOUSE    
CYT3_MOUSE CYT4_MOUSE CYT5_PIG CYT8_PIG
CYTA_BOVIN CYTA_HUMAN CYTA_RAT CYTB_BOVIN
CYTB_HUMAN CYTB_MOUSE CYTB_PIG CYTB_RAT
CYTB_SHEEP P01035
True Positive Partials
Codes involving 3 elements
Q90517
Sequence Titles
CPI1_PIG    LEUKOCYTE CYSTEINE PROTEINASE INHIBITOR 1 (PLCPI) (STEFIN D1) - SUS SCROFA (PIG). 
CYT1_MOUSE STEFIN 1 - MUS MUSCULUS (MOUSE).
CYT1_PIG CYSTATIN A1 (STEFIN A1) - SUS SCROFA (PIG).
CYT2_MOUSE STEFIN 2 - MUS MUSCULUS (MOUSE).
CYT3_MOUSE STEFIN 3 - MUS MUSCULUS (MOUSE).
CYT4_MOUSE STEFIN HOMOLOG - MUS MUSCULUS (MOUSE).
CYT5_PIG CYSTATIN A5 (STEFIN A5) - SUS SCROFA (PIG).
CYT8_PIG CYSTATIN A8 (STEFIN A8) - SUS SCROFA (PIG).
CYTA_BOVIN CYSTATIN A (STEFIN A) (CYSTATIN AS) - BOS TAURUS (BOVINE).
CYTA_HUMAN CYSTATIN A (STEFIN A) (CYSTATIN AS) - HOMO SAPIENS (HUMAN).
CYTA_RAT CYSTATIN ALPHA (EPIDERMAL THIOL PROTEINASE INHIBITOR) (STEFIN, EPIDERMAL) (CYSTATIN A) - RATTUS NORVEGICUS (RAT).
CYTB_BOVIN CYSTATIN B (STEFIN B) - BOS TAURUS (BOVINE).
CYTB_HUMAN CYSTATIN B (LIVER THIOL PROTEINASE INHIBITOR) (CPI-B) (STEFIN B) - HOMO SAPIENS (HUMAN).
CYTB_MOUSE CYSTATIN B (STEFIN B) - MUS MUSCULUS (MOUSE).
CYTB_PIG CYSTATIN B (STEFIN B) - SUS SCROFA (PIG).
CYTB_RAT CYSTATIN B (LIVER THIOL PROTEINASE INHIBITOR) (STEFIN B) (CYSTATIN BETA) - RATTUS NORVEGICUS (RAT).
CYTB_SHEEP CYSTATIN B (STEFIN B) - OVIS ARIES (SHEEP).
P01035

Q90517 DOPAMINE RECEPTOR - FUGU RUBRIPES (JAPANESE PUFFERFISH) (TAKIFUGU RUBRIPES).
Scan History
OWL25_2    2  100  NSINGLE    
SPTR37_9f 2 19 NSINGLE
Initial Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
GGLSEARPATPEIQMIADKV CYT1_MOUSE 10 10 -
GGVSEAKPATPEIQEVADKV CYTA_RAT 10 10 -
GAPSATMPATTETQEIADKV CYTB_RAT 4 4 -
GGLSEARPATSEIQEIADKV CYT2_MOUSE 10 10 -
GGFSDTQDATAEIQAIADQV P01035 7 7 -
GGVSEASRATPEIQMIANKV CYT3_MOUSE 4 4 -

Motif 2 width=20
Element Seqn Id St Int Rpt
LEEQTNEKYEKFEAVEYKSQ CYT1_MOUSE 33 3 -
LEEKTNEKYEKFKVVEYKSQ CYTA_RAT 33 3 -
LEEKANQKFDVFKAISFRRQ CYTB_RAT 27 3 -
LEEKTNEKYEKFKAIEYKVQ CYT2_MOUSE 33 3 -
LEEKENKKFPVFKAVKFRSQ P01035 30 3 -
LEAKTNKKYEKFEAVEYKTQ CYT3_MOUSE 27 3 -

Motif 3 width=20
Element Seqn Id St Int Rpt
VVAGQNLFIKIDVGNGCFLH CYT1_MOUSE 53 0 -
VVAGQILFMKVDVGNGRFLH CYTA_RAT 53 0 -
VVAGTNFFIKVDVGEEKCVH CYTB_RAT 47 0 -
VVQGLNYFIKMNVGRGCYLH CYT2_MOUSE 53 0 -
VVAGMNYLIKVQVDEDDFVH P01035 50 0 -
VVAGENIFIKMDVGHGCFIH CYT3_MOUSE 47 0 -

Motif 4 width=18
Element Seqn Id St Int Rpt
LKLKGYQTNKTKTDELTS CYT1_MOUSE 85 12 -
LKLLDYQTNKTKNDELTD CYTA_RAT 85 12 -
LTLSSYQTDKEKHDELTY CYTB_RAT 80 13 -
LELTGYKAKQTNNDELTY CYT2_MOUSE 85 12 -
VALTSYQTNKVRHDELTY P01035 83 13 -
YELHGYQTDKTMDEELTY CYT3_MOUSE 79 12 -
Final Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
GGLTEARPATPEIQEIATTV CYT1_PIG 9 9 -
GGLTEPRPATPEIQEIANKV CPI1_PIG 9 9 -
GGLTEPRPATPEIQEIANKV CYT8_PIG 9 9 -
GGLTEPRPATPEIQEIANKV CYT5_PIG 9 9 -
GGLSEARPATPEIQMIADKV CYT1_MOUSE 10 10 -
GGLTEARPATAEVQEIADRV CYT4_MOUSE 4 4 -
GAPSATQPATAETQHIADQV CYTB_HUMAN 4 4 -
GAPSATQPATAEIQAIADKV CYTB_PIG 4 4 -
GGTSATQPATAETQAIADKV CYTB_BOVIN 4 4 -
GAPSATQPATAETQAIADKV CYTB_SHEEP 4 4 -
GGVSEAKPATPEIQEVADKV CYTA_RAT 10 10 -
GGLSEAKPATPEIQEIVDKV CYTA_HUMAN 4 4 -
GAPSATMPATTETQEIADKV CYTB_RAT 4 4 -
GGLTEAKPATIEIQEIANMV CYTA_BOVIN 4 4 -
GGLSEARPATSEIQEIADKV CYT2_MOUSE 10 10 -
GGFSDTQDATAEIQAIADQV P01035 7 7 -
GGVSEASRATPEIQMIANKV CYT3_MOUSE 4 4 -
GAPSATMPATAETQEVADQV CYTB_MOUSE 4 4 -

Motif 2 width=20
Element Seqn Id St Int Rpt
LEEKTNKTYEKFEAVEYKSQ CYT1_PIG 32 3 -
LEEKTNKTYEKFEAIIYRSQ CPI1_PIG 32 3 -
LEEKTKKTYEKFEAIIYRSQ CYT8_PIG 32 3 -
LEEKTKKTYEKFEAIIYRSQ CYT5_PIG 32 3 -
LEEQTNEKYEKFEAVEYKSQ CYT1_MOUSE 33 3 -
LEEETNEKYEIFKAVEYKTQ CYT4_MOUSE 27 3 -
LEEKENKKFPVFKAVSFKSQ CYTB_HUMAN 27 3 -
LEEKENKTFPVFKAVEFKSQ CYTB_PIG 27 3 -
LEEKENKKFPVFKALEFKSQ CYTB_BOVIN 27 3 -
LEEKENKKFPVFKALEFKSQ CYTB_SHEEP 27 3 -
LEEKTNEKYEKFKVVEYKSQ CYTA_RAT 33 3 -
LEEKTNETYGKLEAVQYKTQ CYTA_HUMAN 27 3 -
LEEKANQKFDVFKAISFRRQ CYTB_RAT 27 3 -
LEEKTNETYEEFTAIEYKSQ CYTA_BOVIN 27 3 -
LEEKTNEKYEKFKAIEYKVQ CYT2_MOUSE 33 3 -
LEEKENKKFPVFKAVKFRSQ P01035 30 3 -
LEAKTNKKYEKFEAVEYKTQ CYT3_MOUSE 27 3 -
LESKENQKFDVFKAISFKRQ CYTB_MOUSE 27 3 -

Motif 3 width=20
Element Seqn Id St Int Rpt
VVAGINYYIKVHVGGNSYVH CYT1_PIG 52 0 -
VVAGTNYYIKVHVGGNNYVH CPI1_PIG 52 0 -
VVAGTNYYIKVHVGGNSYVH CYT8_PIG 52 0 -
VVAGTNYYIKVHVGGNSYVH CYT5_PIG 52 0 -
VVAGQNLFIKIDVGNGCFLH CYT1_MOUSE 53 0 -
VVAGVNYFIKMDVGGGCFTH CYT4_MOUSE 47 0 -
VVAGTNYFIKVHVGDEDFVH CYTB_HUMAN 47 0 -
VVAGRNLFIKVQVDDDDFVH CYTB_PIG 47 0 -
LVAGKNYFIKVQVDEDDFVH CYTB_BOVIN 47 0 -
LVAGKNYFIKVQVDEDDFVH CYTB_SHEEP 47 0 -
VVAGQILFMKVDVGNGRFLH CYTA_RAT 53 0 -
VVAGTNYYIKVRAGDNKYMH CYTA_HUMAN 47 0 -
VVAGTNFFIKVDVGEEKCVH CYTB_RAT 47 0 -
VVAGINYYIKIQTGDNRYIH CYTA_BOVIN 47 0 -
VVQGLNYFIKMNVGRGCYLH CYT2_MOUSE 53 0 -
VVAGMNYLIKVQVDEDDFVH P01035 50 0 -
VVAGENIFIKMDVGHGCFIH CYT3_MOUSE 47 0 -
IVAGTNLFIKVDVGGDKCVH CYTB_MOUSE 47 0 -

Motif 4 width=18
Element Seqn Id St Int Rpt
LELSGYQVDKTKDDELTG CYT1_PIG 85 13 -
LKLIGYQVDKTKDDELTG CPI1_PIG 85 13 -
LKLIGYQVDKTKDDELTG CYT8_PIG 85 13 -
LKLIGYQVDKTKDDELTS CYT5_PIG 85 13 -
LKLKGYQTNKTKTDELTS CYT1_MOUSE 85 12 -
LELTGYQTNKTEDDELTY CYT4_MOUSE 79 12 -
LTLSNYQTNKAKHDELTY CYTB_HUMAN 80 13 -
LTLSSYQTNKSRHDELTY CYTB_PIG 80 13 -
VALTSYQTNKGRHDELTY CYTB_BOVIN 80 13 -
VALTSYQTNKGRHDELTY CYTB_SHEEP 80 13 -
LKLLDYQTNKTKNDELTD CYTA_RAT 85 12 -
LVLTGYQVDKNKDDELTG CYTA_HUMAN 80 13 -
LTLSSYQTDKEKHDELTY CYTB_RAT 80 13 -
LILTGYQVDKTKDDELAG CYTA_BOVIN 80 13 -
LELTGYKAKQTNNDELTY CYT2_MOUSE 85 12 -
VALTSYQTNKVRHDELTY P01035 83 13 -
YELHGYQTDKTMDEELTY CYT3_MOUSE 79 12 -
LTLSSYQTNKERHDELSY CYTB_MOUSE 80 13 -