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PR00001

Identifier
GLABLOOD  [View Relations]  [View Alignment]  
Accession
PR00001
No. of Motifs
3
Creation Date
12-JUL-1991  (UPDATE 27-JUN-1999)
Title
Coagulation factor GLA domain signature
Database References

PROSITE; PS00011 GLU_CARBOXYLATION
BLOCKS; BL00011
PFAM; PF00594 gla
INTERPRO; IPR002383
PDB; 1APO; 2PF2
SCOP; 1APO; 2PF2
CATH; 1APO; 2PF2
Literature References
1. SORIANO-GARCIA, M., CHANG, H.P., TULINSKY, A., RAVICHANDRAN, K.G.
AND SKRZYPCZAK-JANKUN, E.
Structure of calcium prothrombin fragment 1 including the conformation
of the Gla domain.
BIOCHEMISTRY 28 6805-6810 (1989).
 
2. CHURCH, W.R., MESSIER, T., HOWARD, P.R., AMIRAL, J., MEYER, D. 
AND MANN, K.G.
A conserved epitope on several human vitamin K-dependent proteins.
J.BIOL.CHEM. 263 6259-6267 (1988).
 
3. FRIEZNER DEGEN, S.J. AND DAVIE, E.W.
Nucleotide sequence of the gene for human prothrombin.
BIOCHEMISTRY 26 6165-6177 (1987).

Documentation
Coagulation proteins, such as factors VII, IX and X, proteins C and S, and 
prothrombin, contain gamma-carboxyglutamic acid residues: these vary in 
number between 9 and 12, and are produced by post-translational 
modification of Glu residues by a vitamin K-dependent carboxylase. Calcium 
ions bind to the gamma-carboxyglutamic acid residues of the Gla domain and 
support the binding of these vitamin K-dependent proteins to acidic 
phospholipid vesicles, resulting in the production of a soluble fibrin clot.
 
The Gla domain is an N-terminal module of about 48 residues that contains
carboxylated Glu residues responsible for high-affinity calcium binding.
It terminates with a conserved aromatic residue, and at its centre has a
conserved Gla-x(3)-Gla-x-Cys motif, which seems to be important for the
substrate recognition by the carboxylase. The domain is dominated by
secondary structure comprising 3 turns of alpha-helix and 5 short beta-
strands arranged into 2 beta-structural units. Cys residues 18 and 23 of
the Gla domain participate in a disulphide bridge to form a small conserved
loop close to a cluster of conserved aromatic residues.
 
GLABLOOD is a 3-element fingerprint that provides a signature for the N-
terminal `Gla domain' of coagulation proteins. The fingerprint was derived
from an initial alignment of 6 sequences (after Soriano-Garcia [1]): the
motifs span the region encoded by PROSITE pattern GLU_CARBOXYLATION
(PS00011), 1 and 2 encoding the Gla-x(3)-Gla-x-Cys motif. Four iterations
on OWL11.0 were required to reach convergence, at which point a true set
comprising 29 sequences was identified. A single partial match was also
found, a coagulation factor fragment, which lacks part of motif 3. 
 
An update on SPTR37_9f identified a true set of 38 sequences, and 1
partial match.
Summary Information
38 codes involving  3 elements
0 codes involving 2 elements
Composite Feature Index
3383838
2000
123
True Positives
FA10_BOVIN    FA10_CHICK    FA10_HUMAN    FA10_RABIT    
FA7_BOVIN FA7_HUMAN FA7_MOUSE FA7_RABIT
FA9_BOVIN FA9_CANFA FA9_HUMAN O14668
O14669 O54740 O88947 PRTC_HUMAN
PRTC_MOUSE PRTC_RAT PRTS_BOVIN PRTS_HUMAN
PRTS_MOUSE PRTS_RAT PRTZ_BOVIN PRTZ_HUMAN
Q14339 Q14393 Q15213 Q16519
Q17343 Q61109 Q61592 Q63207
Q63772 Q91001 THRB_BOVIN THRB_HUMAN
THRB_MOUSE THRB_RAT
Sequence Titles
FA10_BOVIN  COAGULATION FACTOR X PRECURSOR (EC 3.4.21.6) (STUART FACTOR) - BOS TAURUS (BOVINE). 
FA10_CHICK COAGULATION FACTOR X PRECURSOR (EC 3.4.21.6) (STUART FACTOR) (VIRUS ACTIVATING PROTEASE) (VAP) - GALLUS GALLUS (CHICKEN).
FA10_HUMAN COAGULATION FACTOR X PRECURSOR (EC 3.4.21.6) (STUART FACTOR) - HOMO SAPIENS (HUMAN).
FA10_RABIT COAGULATION FACTOR X PRECURSOR (EC 3.4.21.6) (STUART FACTOR) - ORYCTOLAGUS CUNICULUS (RABBIT).
FA7_BOVIN COAGULATION FACTOR VII (EC 3.4.21.21) - BOS TAURUS (BOVINE).
FA7_HUMAN COAGULATION FACTOR VII PRECURSOR (EC 3.4.21.21) (EPTACOG ALFA) - HOMO SAPIENS (HUMAN).
FA7_MOUSE COAGULATION FACTOR VII PRECURSOR (EC 3.4.21.21) - MUS MUSCULUS (MOUSE).
FA7_RABIT COAGULATION FACTOR VII PRECURSOR (EC 3.4.21.21) - ORYCTOLAGUS CUNICULUS (RABBIT).
FA9_BOVIN COAGULATION FACTOR IX (EC 3.4.21.22) (CHRISTMAS FACTOR) - BOS TAURUS (BOVINE).
FA9_CANFA COAGULATION FACTOR IX PRECURSOR (EC 3.4.21.22) (CHRISTMAS FACTOR) - CANIS FAMILIARIS (DOG).
FA9_HUMAN COAGULATION FACTOR IX PRECURSOR (EC 3.4.21.22) (CHRISTMAS FACTOR) - HOMO SAPIENS (HUMAN).
O14668 PROLINE-RICH GLA PROTEIN 1 - HOMO SAPIENS (HUMAN).
O14669 PROLINE-RICH GLA PROTEIN 2 - HOMO SAPIENS (HUMAN).
O54740 COAGULATION FACTOR X PRECURSOR (EC 3.4.21.6) - MUS MUSCULUS (MOUSE).
O88947 COAGULATION FACTOR X PRECURSOR - MUS MUSCULUS (MOUSE).
PRTC_HUMAN VITAMIN-K DEPENDENT PROTEIN C PRECURSOR (EC 3.4.21.69) (AUTOPROTHROMBIN IIA) (ANTICOAGULANT PROTEIN C) (BLOOD COAGULATION FACTOR XIV) - HOMO SAPIENS (HUMAN).
PRTC_MOUSE VITAMIN-K DEPENDENT PROTEIN C PRECURSOR (EC 3.4.21.69) (AUTOPROTHROMBIN IIA) (ANTICOAGULANT PROTEIN C) (BLOOD COAGULATION FACTOR XIV) - MUS MUSCULUS (MOUSE).
PRTC_RAT VITAMIN-K DEPENDENT PROTEIN C PRECURSOR (EC 3.4.21.69) (AUTOPROTHROMBIN IIA) (ANTICOAGULANT PROTEIN C) (BLOOD COAGULATION FACTOR XIV) - RATTUS NORVEGICUS (RAT).
PRTS_BOVIN VITAMIN K-DEPENDENT PROTEIN S PRECURSOR - BOS TAURUS (BOVINE).
PRTS_HUMAN VITAMIN K-DEPENDENT PROTEIN S PRECURSOR - HOMO SAPIENS (HUMAN).
PRTS_MOUSE VITAMIN K-DEPENDENT PROTEIN S PRECURSOR - MUS MUSCULUS (MOUSE).
PRTS_RAT VITAMIN K-DEPENDENT PROTEIN S PRECURSOR - RATTUS NORVEGICUS (RAT).
PRTZ_BOVIN VITAMIN K-DEPENDENT PROTEIN Z - BOS TAURUS (BOVINE).
PRTZ_HUMAN VITAMIN K-DEPENDENT PROTEIN Z PRECURSOR - HOMO SAPIENS (HUMAN).
Q14339 PREPROFACTOR VIIB PRECURSOR - HOMO SAPIENS (HUMAN).
Q14393 GROWTH-ARREST-SPECIFIC PROTEIN - HOMO SAPIENS (HUMAN).
Q15213 PROTEIN Z PRECURSOR - HOMO SAPIENS (HUMAN).
Q16519 PROTEIN S PRECURSOR - HOMO SAPIENS (HUMAN).
Q17343 UNC-44 ANKYRINS - Caenorhabditis elegans.
Q61109 COAGULATION FACTOR VII - MUS MUSCULUS (MOUSE).
Q61592 GAS 6 MRNA ASSOCIATED WITH GROWTH-ARREST - MUS MUSCULUS (MOUSE).
Q63207 FACTOR X - RATTUS NORVEGICUS (RAT).
Q63772 GROWTH POTENTIATING FACTOR PRECURSOR - RATTUS NORVEGICUS (RAT).
Q91001 THROMBIN - GALLUS GALLUS (CHICKEN).
THRB_BOVIN PROTHROMBIN PRECURSOR (EC 3.4.21.5) - BOS TAURUS (BOVINE).
THRB_HUMAN PROTHROMBIN PRECURSOR (EC 3.4.21.5) (COAGULATION FACTOR II) - HOMO SAPIENS (HUMA
THRB_MOUSE PROTHROMBIN PRECURSOR (EC 3.4.21.5) - MUS MUSCULUS (MOUSE).
THRB_RAT PROTHROMBIN PRECURSOR (EC 3.4.21.5) - RATTUS NORVEGICUS (RAT).
Scan History
OWL11_0    4  50   NSINGLE    
OWL17_1 1 70 NSINGLE
OWL18_0 1 50 NSINGLE
OWL19_1 1 50 NSINGLE
OWL26_0 1 100 NSINGLE
SPTR37_9f 2 100 NSINGLE
Initial Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
KLEEFVQGNLEREC KFHU 51 51 -
FLEEVRKGNLEREC TBHU 40 40 -
FLEEMKKGHLEREC EXHU 32 32 -
FLEEVRKGNLEREC EZEC545 5 5 -
FLEELRPGSLEREC FA7_HUMAN 64 64 -
FLEEVRKGNLEREC EZEC546 4 4 -

Motif 2 width=14
Element Seqn Id St Int Rpt
MEETCSYEEAREVF EXHU 46 0 -
LEEPCSREEAFEAL EZEC545 19 0 -
VEETCSYEEAFEAL EZEC546 18 0 -
MEEKCSFEEAREVF KFHU 65 0 -
VEETCSYEEAFEAL TBHU 54 0 -
KEEQCSFEEAREIF FA7_HUMAN 78 0 -

Motif 3 width=15
Element Seqn Id St Int Rpt
ENTERTTEFWKQYVD KFHU 79 0 -
ESSTATDVFWAKYTA TBHU 68 0 -
EDSDKTNEFWNKYKD EXHU 60 0 -
ESLSATDAFWAKYTA EZEC545 33 0 -
KDAERTKLFWISYSD FA7_HUMAN 92 0 -
ESSTATDVFWAKYTA EZEC546 32 0 -
Final Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
FFEEIKKGNLEREC Q63207 44 44 -
FLEEVKQGNLEREC FA10_BOVIN 44 44 -
FLEELKKGNLEREC FA10_RABIT 44 44 -
KLEEFVQGNLEREC FA9_HUMAN 51 51 -
KLEEFVRGNLEREC FA9_CANFA 44 44 -
FLEEMKKGHLEREC FA10_HUMAN 44 44 -
KLEEFVRGNLEREC FA9_BOVIN 5 5 -
LLEETKKGNLEREC PRTS_RAT 45 45 -
LLEETKQGNLEREC PRTS_HUMAN 45 45 -
LLEETKQGNLEREC Q16519 19 19 -
FLEELRPGSLEREC FA7_RABIT 43 43 -
FLEEMKQGNIEREC FA10_CHICK 44 44 -
FLEELRPGSLEREC FA7_HUMAN 64 64 -
FLEELRPGSLEREC Q14339 42 42 -
LLEETKKGNLEREC PRTS_BOVIN 45 45 -
FFEEFKKGNLEREC O54740 44 44 -
FFEEFKKGNLEREC O88947 44 44 -
LFEETMKGNLEREC PRTS_MOUSE 45 45 -
VFEEAKQGHLEREC Q14393 52 52 -
FLEELRKGNLEREC THRB_MOUSE 48 48 -
FLEELRKGNLEREC THRB_RAT 48 48 -
LLEELWPGSLEREC FA7_MOUSE 45 45 -
LLEELWPGSLEREC Q61109 45 45 -
FLEEMRPGSLEREC PRTC_MOUSE 45 45 -
FLEEVRAGSLEREC PRTC_RAT 45 45 -
LLEELFEGNLEKEC Q15213 67 67 -
LLEELFEGNLEKEC PRTZ_HUMAN 45 45 -
FLEEVRKGNLEREC THRB_HUMAN 47 47 -
LLEELFEGHLEKEC PRTZ_BOVIN 5 5 -
VFEEAKQGHLEREC Q63772 49 49 -
FLEELLPGSLEREC FA7_BOVIN 4 4 -
FFEEIRQGNIEREC O14668 24 24 -
FLEEVRKGNLEREC THRB_BOVIN 48 48 -
FLEEMIKGNLEREC Q91001 48 48 -
VFEEAKQGHLEREC Q61592 49 49 -
DLELLTPGNLEREC O14669 54 54 -
FLEELRHSSLEREC PRTC_HUMAN 46 46 -
FLRAARAGDLEKVL Q17343 37 37 -

Motif 2 width=14
Element Seqn Id St Int Rpt
VEEICSFEEAREVF Q63207 58 0 -
LEEACSLEEAREVF FA10_BOVIN 58 0 -
MEENCSYEEALEVF FA10_RABIT 58 0 -
MEEKCSFEEAREVF FA9_HUMAN 65 0 -
IEEKCSFEEAREVF FA9_CANFA 58 0 -
MEETCSYEEAREVF FA10_HUMAN 58 0 -
KEEKCSFEEAREVF FA9_BOVIN 19 0 -
IEELCNKEEAREVF PRTS_RAT 59 0 -
IEELCNKEEAREVF PRTS_HUMAN 59 0 -
IEELCNKEEAREVF Q16519 33 0 -
KEELCSFEEAREVF FA7_RABIT 57 0 -
NEERCSKEEAREAF FA10_CHICK 58 0 -
KEEQCSFEEAREIF FA7_HUMAN 78 0 -
KEEQCSFEEAREIF Q14339 56 0 -
IEELCNKEEAREIF PRTS_BOVIN 59 0 -
MEEICSYEEVREIF O54740 58 0 -
MEEICSYEEVREIF O88947 58 0 -
IEELCNKEEAREVF PRTS_MOUSE 59 0 -
VEELCSREEAREVF Q14393 66 0 -
VEEQCSYEEAFEAL THRB_MOUSE 62 0 -
VEEQCSYEEAFEAL THRB_RAT 62 0 -
NEEQCSFEEAREIF FA7_MOUSE 59 0 -
NEEQCSFEEAREIF Q61109 59 0 -
MEEICDFEEAQEIF PRTC_MOUSE 59 0 -
MEEICDFEEAQEIF PRTC_RAT 59 0 -
YEEICVYEEAREVF Q15213 81 0 -
YEEICVYEEAREVF PRTZ_HUMAN 59 0 -
VEETCSYEEAFEAL THRB_HUMAN 61 0 -
WEEICVYEEAREVF PRTZ_BOVIN 19 0 -
VEEVCSKEEAREVF Q63772 63 0 -
REELCSFEEAHEIF FA7_BOVIN 18 0 -
KEEFCTFEEAREAF O14668 38 0 -
LEEPCSREEAFEAL THRB_BOVIN 62 0 -
LEETCNYEEAFEAL Q91001 62 0 -
VEEVCSKEEAREVF Q61592 63 0 -
LEERCSWEEAREYF O14669 68 0 -
IEEICDFEEAKEIF PRTC_HUMAN 60 0 -
DEEKLEGHEEKEVL Q17343 2260 2209 -

Motif 3 width=15
Element Seqn Id St Int Rpt
EDNEKTTEFWNKYED Q63207 72 0 -
EDAEQTDEFWSKYKD FA10_BOVIN 72 0 -
EDREKTNEFWNKYVD FA10_RABIT 72 0 -
ENTERTTEFWKQYVD FA9_HUMAN 79 0 -
ENTEKTTEFWKQYVD FA9_CANFA 72 0 -
EDSDKTNEFWNKYKD FA10_HUMAN 72 0 -
ENTEKTTEFWKQYVD FA9_BOVIN 33 0 -
ENNPETDYFYPKYLG PRTS_RAT 73 0 -
ENDPETDYFYPKYLV PRTS_HUMAN 73 0 -
ENDPETDYFYPKYLV Q16519 47 0 -
QSTERTKQFWITYND FA7_RABIT 71 0 -
EDNEKTEEFWNIYVD FA10_CHICK 72 0 -
KDAERTKLFWISYSD FA7_HUMAN 92 0 -
KDAERTKLFWISYSD Q14339 70 0 -
ENNPETEYFYPKYLG PRTS_BOVIN 73 0 -
EDDEKTKEYWTKYKD O54740 72 0 -
EDDEKTKEYWTKYKD O88947 72 0 -
ENNPETDYFYPKYLG PRTS_MOUSE 73 0 -
ENDPETDYFYPRYLD Q14393 80 0 -
ESPQDTDVFWAKYTV THRB_MOUSE 76 0 -
ESPQDTDVFWAKYTV THRB_RAT 76 0 -
KSPERTKQFWIVYSD FA7_MOUSE 73 0 -
KSPERTKQFWIVYSD Q61109 73 0 -
QNVEDTLAFWIKYFD PRTC_MOUSE 73 0 -
QNVEDTLAFWIKYFD PRTC_RAT 73 0 -
ENEVVTDEFWRRYKG Q15213 95 0 -
ENEVVTDEFWRRYKG PRTZ_HUMAN 73 0 -
ESSTATDVFWAKYTA THRB_HUMAN 75 0 -
EDDETTDEFWRTYMG PRTZ_BOVIN 33 0 -
ENDPETDYFYPRYQE Q63772 77 0 -
RNEERTRQFWVSYND FA7_BOVIN 32 0 -
ENNEKTKEFWSTYTK O14668 52 0 -
ESLSATDAFWAKYTA THRB_BOVIN 76 0 -
ESTVDTDAFWAKYQV Q91001 76 0 -
ENDPETEYFYPRYQE Q61592 77 0 -
EDNTLTERFWESYIY O14669 82 0 -
QNVDDTLAFWSKHVD PRTC_HUMAN 74 0 -
TSTTETREFDRPELD Q17343 3040 766 -