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PR00005

Identifier
APPLEDOMAIN  [View Relations]  [View Alignment]  
Accession
PR00005
No. of Motifs
3
Creation Date
21-OCT-1994  (UPDATE 10-JUN-1999)
Title
Apple domain signature
Database References

PROSITE; PS00495 APPLE
BLOCKS; BL00495
PFAM; PF00024 apple
INTERPRO; IPR000177
Literature References
1. BEAUBIEN, G., ROSINSKI-CHUPIN, I., MATTEI, M.G., MBIKAY, M., 
CHRETIEN, M. AND SEIDAH, N.G.
Gene structure and chromosomal localization of plasma kallikrein.
BIOCHEMISTRY 30 1628-1635 (1991).
 
2. CHUNG, D.W., FUJIKAWA, K., MCMULLEN, B.A. AND DAVIE, E.W.
Human plasma prekallikrein, a zymogen to a serine protease that contains
four tandem repeats.
BIOCHEMISTRY 25 2410-2417 (1986).
 
3. MCMULLEN, B.A., FUJIKAWA, K. AND DAVIE, E.W.
Location of the disulphide bonds in human plasma prekallikrein: the presence
of four novel apple domains in the amino-terminal portion of the molecule.
BIOCHEMISTRY 30 2050-2056 (1991).

Documentation
Kallikrein and coagulation factor XI are both plasma proteins that 
participate in the early phase of the intrinsic blood coagulation pathway
[1]. These proteins share a high degree of sequence similarity, and there
is evidence to show that a gene duplication event from a common ancestor
resulted in the existence of both kallikrein and factor XI [1]. The
proteins have the same domain topology: an N-terminal region, which contains
four 90-amino acid tandem repeats; and a C-terminal region, which is similar
to the trypsin family of serine proteases [2]. The proteins are activated
by factor XIIa, which cleaves an internal Arg-Ile bond separating the 
repeat region and the serine protease domain [2].
 
Each of the N-terminal repeats contains 6 cysteine residues, which form
three disulphide bonds linking the first and the sixth, the second and the
fifth, and the third and fourth cysteines [3]. Schematically, this can be
drawn in the form of an apple, hence the term "apple domain". The fourth
repeat contains an additional 2 Cys residues between the third and fourth
cysteines, and these form an extra loop in the domain [3].
 
APPLEDOMAIN is a 3-element fingerprint that provides a signature for the
apple domain. The fingerprint was derived from an initial alignment of 4
sequences: the motifs span the full domain length, motif 1 including the
second, third and fourth cysteines, motif 2 containing the fifth, and
motif 3 the sixth cysteine - cf. PROSITE pattern APPLE (PS00495). A single
iteration on OWL24.0 was required to reach convergence, no further
sequences being identified beyond the starting set. 
 
An update on SPTR37_9f identified a true set of 4 sequences.
Summary Information
4 codes involving  3 elements
0 codes involving 2 elements
Composite Feature Index
3444
2000
123
True Positives
FA11_HUMAN    KAL_HUMAN     KAL_MOUSE     KAL_RAT       
Sequence Titles
FA11_HUMAN  COAGULATION FACTOR XI PRECURSOR (EC 3.4.21.27) (PLASMA THROMBOPLASTIN ANTECEDENT) (PTA) - HOMO SAPIENS (HUMAN). 
KAL_HUMAN PLASMA KALLIKREIN PRECURSOR (EC 3.4.21.34) (PLASMA PREKALLIKREIN) (KININOGENIN) (FLETCHER FACTOR) - HOMO SAPIENS (HUMAN).
KAL_MOUSE PLASMA KALLIKREIN PRECURSOR (EC 3.4.21.34) (PLASMA PREKALLIKREIN) (KININOGENIN) (FLETCHER FACTOR) - MUS MUSCULUS (MOUSE).
KAL_RAT PLASMA KALLIKREIN PRECURSOR (EC 3.4.21.34) (PLASMA PREKALLIKREIN) (KININOGENIN) (FLETCHER FACTOR) - RATTUS NORVEGICUS (RAT).
Scan History
OWL24_0    1  100  NSINGLE    
OWL28_0 1 100 NSINGLE
SPTR37_9f 2 9 NSINGLE
Initial Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
AFVCRTICTYHPNCLFFTFY KAL_HUMAN 224 224 -
AFVCRTVCTFHPNCLFFTFY KAL_RAT 224 224 -
AKYCQVVCTYHPRCLLFTFT FA11_HUMAN 43 43 -
AFVCRTICTFHPNCLFFTFY KAL_MOUSE 224 224 -

Motif 2 width=17
Element Seqn Id St Int Rpt
RNVCFLKTSKSGRPSPP KAL_MOUSE 253 9 -
WFTCVLKDSVTETLPRV FA11_HUMAN 73 10 -
RNVCLLKTSESGTPSSS KAL_HUMAN 253 9 -
RNVCFLKTSKSGRPSPP KAL_RAT 253 9 -

Motif 3 width=16
Element Seqn Id St Int Rpt
IQENAVSGYSLFTCRK KAL_RAT 271 1 -
PQENAISGYSLLTCRK KAL_MOUSE 271 1 -
NRTAAISGYSFKQCSH FA11_HUMAN 90 1 -
PQENTISGYSLLTCKR KAL_HUMAN 271 1 -
Final Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
AFVCRTICTFHPNCLFFTFY KAL_MOUSE 224 224 -
AFVCRTICTYHPNCLFFTFY KAL_HUMAN 224 224 -
AFVCRTVCTFHPNCLFFTFY KAL_RAT 224 224 -
AFVCGRICTHHPGCLFFTFF FA11_HUMAN 223 223 R2
AQECQERCTDDVHCHFFTYA FA11_HUMAN 133 133 R1

Motif 2 width=17
Element Seqn Id St Int Rpt
RNVCFLKTSKSGRPSPP KAL_MOUSE 253 9 -
RNVCLLKTSESGTPSSS KAL_HUMAN 253 9 -
RNVCFLKTSKSGRPSPP KAL_RAT 253 9 -
RNLCLLKTSESGLPSTR FA11_HUMAN 252 9 R2
RNICLLKHTQTGTPTRI FA11_HUMAN 162 9 R1

Motif 3 width=16
Element Seqn Id St Int Rpt
PQENAISGYSLLTCRK KAL_MOUSE 271 1 -
PQENTISGYSLLTCKR KAL_HUMAN 271 1 -
IQENAVSGYSLFTCRK KAL_RAT 271 1 -
KKSKALSGFSLQSCRH FA11_HUMAN 270 1 R2
KLDKVVSGFSLKSCAL FA11_HUMAN 180 1 R1