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PR00003

Identifier
4DISULPHCORE  [View Relations]  [View Alignment]  
Accession
PR00003
No. of Motifs
4
Creation Date
31-OCT-1994  (UPDATE 22-JUN-1999)
Title
4-disulphide core signature
Database References

PROSITE; PS00317 4_DISULPHIDE_CORE
BLOCKS; BL00317
PFAM; PF00095 wap
INTERPRO; IPR002221
Literature References
1. HENNIGHAUSEN, L.G. AND SIPPEL, A.E.
Mouse whey acidic protein is a novel member of the family of 4-disulfide
core proteins.
NUCLEIC ACIDS RES. 10 2677-2684 (1982).
 
2. WIEDOW, O., SCHROEDER, J.-M., GREGORY, H., YOUNG, J.A. AND
CHRISTOPHERS, E.
Elafin - An elastase-specific inhibitor of human skin - Purification,
characterisation, and complete amino acid sequence.
J.BIOL.CHEM. 265 14791-14795 (1990).
 
3. DEAR, T.N., RAMSHAW, I.A. AND KEFFORD, R.F.
Differential expression of a novel gene, WDNM1, in non-metastatic rat
mammary adenocarcinoma cells.
CANCER RES. 48 5203-5209 (1988).
 
4. LEGOUIS, R., HARDELIN, J.-P., LEVILLIERS, J., CLAVERIE, J.-M., 
COMPAIN, S., WUNDERLE, V., MILLASSEAU, P., LE PASLIER, D., COHEN, D., 
CATERINA, D., BOUGUELERET, L., DELEMARRE-VAN DE WAAL, H., LUTFALLA, G.,
WEISSENBACH, J. AND PETIT, C.
The candidate gene for the X-linked Kallmann syndrome encodes a protein
related to adhesion molecules.
CELL 67 423-435 (1991).

Documentation
A group of proteins containing 8 characteristically-spaced cysteine
residues, which are involved in disulphide bond formation, have been
termed `4-disulphide core' proteins [1]. While the pattern of conserved 
cysteines suggests that the sequences may adopt a similar fold, the
overall degree of sequence similarity is low (e.g. a few Pro and Gly
residues are reasonably well conserved, as is the polar/acidic nature of
residues between the third and fourth Cys, but otherwise there is little 
sequence conservation). The group of sequences that share this pattern
include whey acidic protein (WAP) [1], elafin (an elastase-specific 
inhibitor from human skin) [2], WDNM1 protein (which is involved in the
metastatic potential of adenocarcinomas in rats) [3], Kallmann syndrome
protein [4], and so on.
 
4DISULPHCORE is a 4-element fingerprint that provides a signature for the
4-disulphide core proteins. The fingerprint was derived from an initial
alignment of 7 sequences: the motifs encode 7 of the 8 well-conserved
Cys residues. Two iterations on OWL24.0 were required to reach convergence,
at which point a true set comprising 17 sequences was identified. Four
partial matches were also found, all of which fail to make significant 
matches with one or two motifs - in this fingerprint, the power of 
discrimination is compromised by the fact that the motifs are necessarily
short, because the sequence conservation is so poor.
 
An update on SPTR37_9f identified a true set of 24 sequences, and 9
partial matches.
Summary Information
  24 codes involving  4 elements
0 codes involving 3 elements
5 codes involving 2 elements
Composite Feature Index
424242424
30000
21241
1234
True Positives
ALK1_HUMAN    ALK1_PIG      CALU_CAVPO    ELAF_HUMAN    
ELAF_PIG EP4_CANFA IBP_CARCR KALM_CHICK
KALM_HUMAN O44131 O44341 O44397
O62299 P79389 Q29127 Q90369
Q91450 Q98988 SPAI_PIG WAP3_PIG
WAP_CAMDR WAP_PIG WAP_RAT WDNM_MOUSE
True Positive Partials
Codes involving 2 elements
ALK1_MOUSE EP4_HUMAN Q61023 WAP_MOUSE
WAP_RABIT
Sequence Titles
ALK1_HUMAN  ANTILEUKOPROTEINASE 1 PRECURSOR (ALP) (HUSI-1) (SEMINAL PROTEINASE INHIBITOR) (SECRETORY LEUKOCYTE PROTEASE INHIBITOR) (BLPI) (MUCUS PROTEINASE INHIBITOR) (MPI) - HOMO SAPIENS (HUMAN). 
ALK1_PIG ANTILEUKOPROTEINASE - SUS SCROFA (PIG).
CALU_CAVPO CALTRIN-LIKE PROTEIN II - CAVIA PORCELLUS (GUINEA PIG).
ELAF_HUMAN ELAFIN PRECURSOR (ELASTASE-SPECIFIC INHIBITOR) (ESI) (SKIN-DERIVED ANTILEUKOPROTEINASE) (SKALP) - HOMO SAPIENS (HUMAN).
ELAF_PIG ELAFIN PRECURSOR (WAP-1 PROTEIN) - SUS SCROFA (PIG).
EP4_CANFA MAJOR EPIDIDYMIS-SPECIFIC PROTEIN E4 PRECURSOR (CE4) (EPIDIDYMAL SECRETORY PROTEIN E4) - CANIS FAMILIARIS (DOG).
IBP_CARCR CHELONIANIN (BASIC PROTEASE INHIBITOR) (RTPI) - CARETTA CARETTA (LOGGERHEAD).
KALM_CHICK KALLMANN SYNDROME PROTEIN HOMOLOG PRECURSOR - GALLUS GALLUS (CHICKEN).
KALM_HUMAN KALLMANN SYNDROME PROTEIN PRECURSOR (ADHESION MOLECULE-LIKE X-LINKED) - HOMO SAPIENS (HUMAN).
O44131 C08G9.2 PROTEIN - CAENORHABDITIS ELEGANS.
O44341 LUSTRIN A - HALIOTIS RUFESCENS (CALIFORNIA RED ABALONE).
O44397 PUTATIVE PORIN PRECURSOR - TRICHURIS TRICHIURA.
O62299 K03D10.1 PROTEIN - CAENORHABDITIS ELEGANS.
P79389 ELAFIN FAMILY MEMBER PROTEIN PRECURSOR - SUS SCROFA (PIG).
Q29127 ELAFIN HOMOLOG - SUS SCROFA (PIG).
Q90369 KALLMANN SYNDROME PROTEIN HOMOLOG KAL - COTURNIX COTURNIX JAPONICA (JAPANESE QUAIL).
Q91450 ANTILEUKOPROTEINASE PRECURSOR - SALVELINUS FONTINALIS (BROOK TROUT).
Q98988 OVULATORY PROTEIN-2 PRECURSOR - SALVELINUS FONTINALIS (BROOK TROUT).
SPAI_PIG SODIUM/POTASSIUM ATPASE INHIBITOR SPAI-2 PRECURSOR (WAP-2 PROTEIN) - SUS SCROFA (PIG).
WAP3_PIG WAP-3 PROTEIN PRECURSOR - SUS SCROFA (PIG).
WAP_CAMDR WHEY ACIDIC PROTEIN (WAP) - CAMELUS DROMEDARIUS (DROMEDARY) (ARABIAN CAMEL).
WAP_PIG WHEY ACIDIC PROTEIN PRECURSOR (WAP) - SUS SCROFA (PIG).
WAP_RAT WHEY ACIDIC PROTEIN PRECURSOR (WHEY PHOSPHOPROTEIN) (WAP) - RATTUS NORVEGICUS (RAT).
WDNM_MOUSE WDNM1 PROTEIN PRECURSOR - MUS MUSCULUS (MOUSE).

ALK1_MOUSE ANTILEUKOPROTEINASE 1 PRECURSOR (ALP) (SECRETORY LEUKOCYTE PROTEASE INHIBITOR) - MUS MUSCULUS (MOUSE).
EP4_HUMAN MAJOR EPIDIDYMIS-SPECIFIC PROTEIN E4 PRECURSOR (HE4) (EPIDIDYMAL SECRETORY PROTEIN E4) - HOMO SAPIENS (HUMAN).
Q61023 WHEY ACIDIC PROTEIN - MUS MUSCULUS (MOUSE).
WAP_MOUSE WHEY ACIDIC PROTEIN PRECURSOR (WAP) - MUS MUSCULUS (MOUSE).
WAP_RABIT WHEY ACIDIC PROTEIN PRECURSOR (WAP) - ORYCTOLAGUS CUNICULUS (RABBIT).
Scan History
OWL24_0    2  375  NSINGLE    
SPTR37_9f 4 170 NSINGLE
Initial Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
FNSVQSMCSD WAP_RAT 27 27 -
KSFKAGVCPP ALK1_HUMAN 28 28 -
PPERPGVCPK IBP_TURRS 60 60 -
AINRPGSCPR CALU_CAVPO 7 7 -
LSVKQGDCPA KALM_CHICK 122 122 -
LLSKRGHCPR SPAI_PIG 13 13 -
VSTKPGSCPI ELAF_HUMAN 69 69 -

Motif 2 width=8
Element Seqn Id St Int Rpt
ECQSDWQC ALK1_HUMAN 50 12 -
GCDSDSDC IBP_TURRS 79 9 -
SCEADSEC KALM_CHICK 145 13 -
KCWRDYDC SPAI_PIG 35 12 -
RCLKDTDC ELAF_HUMAN 91 12 -
NCQTNEEC WAP_RAT 47 10 -
KCTSDYDC CALU_CAVPO 29 12 -

Motif 3 width=10
Element Seqn Id St Int Rpt
CKEGQKCCFD IBP_TURRS 86 -1 -
CSGVKKCCSN KALM_CHICK 152 -1 -
CPGVKKCCEG SPAI_PIG 42 -1 -
CPGIKKCCEG ELAF_HUMAN 98 -1 -
CAQNDMCCPS WAP_RAT 54 -1 -
CPGKKRCCPD ALK1_HUMAN 57 -1 -
CPKPQKCCPG CALU_CAVPO 36 -1 -

Motif 4 width=9
Element Seqn Id St Int Rpt
TCGIKCLDP ALK1_HUMAN 67 0 -
YCGKQCYQP CALU_CAVPO 46 0 -
GCGHTCQVP KALM_CHICK 162 0 -
GCGYICLTV IBP_TURRS 96 0 -
FCGKDCLYP SPAI_PIG 52 0 -
SCGMACFVP ELAF_HUMAN 108 0 -
SCGRSCKTP WAP_RAT 64 0 -
Final Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
LLTKPGSCPR Q29127 95 95 -
LLTKPGSCPR ELAF_PIG 119 119 -
LSVKQGDCPA KALM_CHICK 122 122 -
LSVKQGDCPA Q90369 121 121 -
LLSKRGHCPR SPAI_PIG 13 13 -
STAKPGVCPR Q91450 31 31 -
LLVKQGDCPA KALM_HUMAN 127 127 -
LFPKPGVCPK WAP3_PIG 97 97 -
STAKPGVCPR Q98988 31 31 -
VSTKPGSCPI ELAF_HUMAN 69 69 -
RLQKPGSCPA O44341 1379 1379 -
LHYKPGLCPW P79389 133 133 -
PKEKPGACPK WDNM_MOUSE 26 26 -
VKVKPGKCPV ALK1_PIG 65 65 -
PVPKAGRCPW WAP_PIG 76 76 -
PVLKDGRCPW WAP_CAMDR 61 61 -
FNSVQSMCSD WAP_RAT 27 27 -
PTTKVGQCPS O44131 122 122 -
SRTKPGSCPP O44397 149 149 -
KSFKAGVCPP ALK1_HUMAN 28 28 -
AINRPGSCPR CALU_CAVPO 7 7 -
YQEKPGACPS O62299 62 62 -
PPERPGVCPK IBP_CARCR 60 60 -
EVEKTGVCPQ EP4_CANFA 29 29 -

Motif 2 width=8
Element Seqn Id St Int Rpt
RCLSDAQC Q29127 117 12 -
RCLSDAQC ELAF_PIG 141 12 -
SCEADSEC KALM_CHICK 145 13 -
SCEADSEC Q90369 144 13 -
KCWRDYDC SPAI_PIG 35 12 -
LCSSDSDC Q91450 51 10 -
SCEVDNEC KALM_HUMAN 150 13 -
KCWRDSHC WAP3_PIG 118 11 -
LCSKDSDC Q98988 51 10 -
RCLKDTDC ELAF_HUMAN 91 12 -
RCFCDNDC O44341 1400 11 -
KCWRDSHC P79389 155 12 -
RCTGDGSC WDNM_MOUSE 47 11 -
HCKTDSQC ALK1_PIG 87 12 -
ECSRDDQC WAP_PIG 100 14 -
DCSRDDQC WAP_CAMDR 85 14 -
NCQTNEEC WAP_RAT 47 10 -
SCKVDDDC O44131 681 549 -
FCQSDYDC O44397 270 111 -
ECQSDWQC ALK1_HUMAN 50 12 -
KCTSDYDC CALU_CAVPO 29 12 -
LCQMDGEC O62299 83 11 -
GCDSDSDC IBP_CARCR 79 9 -
ECVSDAQC EP4_CANFA 48 9 -

Motif 3 width=10
Element Seqn Id St Int Rpt
CPGVKKCCEG Q29127 124 -1 -
CPGLKKCCEG ELAF_PIG 148 -1 -
CSGVKKCCSN KALM_CHICK 152 -1 -
CSGVKKCCSN Q90369 151 -1 -
CPGVKKCCEG SPAI_PIG 42 -1 -
CPNDEKCCHN Q91450 58 -1 -
CSGVKKCCSN KALM_HUMAN 157 -1 -
CPGVKKCCPS WAP3_PIG 125 -1 -
CPNDEKCCHN Q98988 58 -1 -
CPGIKKCCEG ELAF_HUMAN 98 -1 -
CRGNLKCCSN O44341 1407 -1 -
CPGVMKCCEG P79389 162 -1 -
CSGNMKCCSN WDNM_MOUSE 54 -1 -
CLGDLKCCKS ALK1_PIG 94 -1 -
CRGNKKCCFS WAP_PIG 107 -1 -
CEGNKKCCFS WAP_CAMDR 92 -1 -
CAQNDMCCPS WAP_RAT 54 -1 -
CAGVAKCCDD O44131 746 57 -
CDGSKKCCLT O44397 378 100 -
CPGKKRCCPD ALK1_HUMAN 57 -1 -
CPKPQKCCPG CALU_CAVPO 36 -1 -
CPETQKCCSS O62299 90 -1 -
CKEGQKCCFD IBP_CARCR 86 -1 -
CADNLKCCQA EP4_CANFA 55 -1 -

Motif 4 width=9
Element Seqn Id St Int Rpt
FCGKDCMDP Q29127 134 0 -
FCGKACMDP ELAF_PIG 158 0 -
GCGHTCQVP KALM_CHICK 162 0 -
GCGHTCQVP Q90369 161 0 -
FCGKDCLYP SPAI_PIG 52 0 -
GCGHVCIAP Q91450 68 0 -
GCGHTCQVP KALM_HUMAN 167 0 -
LCGKGCVTP WAP3_PIG 135 0 -
GCGHDCIAP Q98988 209 141 -
SCGMACFVP ELAF_HUMAN 108 0 -
GCGRTCQKP O44341 1417 0 -
FCGNECSYP P79389 172 0 -
GCGHACKPP WDNM_MOUSE 64 0 -
MCGKVCLTP ALK1_PIG 104 0 -
SCAMRCLDP WAP_PIG 117 0 -
SCAMRCLDP WAP_CAMDR 102 0 -
SCGRSCKTP WAP_RAT 64 0 -
SCGTMCSAP O44131 1387 631 -
SIGYDCKAP O44397 388 0 -
TCGIKCLDP ALK1_HUMAN 67 0 -
YCGKQCYQP CALU_CAVPO 46 0 -
GCSRQCLKP O62299 100 0 -
GCGYICLTV IBP_CARCR 96 0 -
GCATICHLP EP4_CANFA 65 0 -