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Distantly related calcium binding domains


The EF-hand calcium binding proteins comprise a very large, well-characterized family of soluble proteins that uses a distinctive helix-loop-helix structural motif to bind Ca++. Frequently multiple EF-hand domains are found in Ca-regulated proteins together with a larger structural or functional domain. Recently it was reported that the BM40/SPARC/osteonectin family of extracellular calcium binding proteins contain an EF-hand-like domain that can be readily superimposed on the traditional calmodulin-type EF-hand domain.

In this case, a "bridge" protein is:

HSU06863_1 follistatin-related protein precursor [Homo sapiens]

However, when the full-length version of this protein is used to search the database, only the SPARC/osteonectin/follistatin proteins are detected:

The best scores are:                              s-w Z-score E(43470)
SPRC_CAEEL SPARC PRECURSOR (SECRETED PROTEIN ACIDI  257 280.5 3.5e-09
FSA_SHEEP FOLLISTATIN PRECURSOR (FS) (ACTIVIN-BIND  249 270.0 1.4e-08
FSA_HUMAN FOLLISTATIN 1 AND 2 PRECURSOR (FS) (ACTI  249 269.9 1.4e-08
FSA_RAT FOLLISTATIN PRECURSOR (FS) (ACTIVIN-BINDIN  249 269.8 1.4e-08
FSA_PIG FOLLISTATIN A AND A' PRECURSOR (FS) (ACTIV  249 269.8 1.4e-08
SPRC_XENLA SPARC PRECURSOR (SECRETED PROTEIN ACIDI  206 223.7 5.1e-06
QR1_COTJA QR1 PROTEIN PRECURSOR.                    207 218.9 9.5e-06
SPRC_CHICK SPARC PRECURSOR (SECRETED PROTEIN ACIDI  194 210.6 2.7e-05
SC1_RAT MATRIX GLYCOPROTEIN SC1 PRECURSOR.          197 208.4 3.6e-05
AGRI_CHICK AGRIN PRECURSOR.                         204 207.9 3.9e-05
FSA_XENLA FOLLISTATIN (FS) (ACTIVIN-BINDING PROTEI  180 197.1 0.00016
SPRC_MOUSE SPARC PRECURSOR (SECRETED PROTEIN ACIDI  180 195.2 0.00020
AGRI_RAT AGRIN PRECURSOR.                           192 194.8 0.00021
SPRC_HUMAN SPARC PRECURSOR (SECRETED PROTEIN ACIDI  175 189.7 0.0004
SPRC_BOVIN SPARC PRECURSOR (SECRETED PROTEIN ACIDI  168 182.0 0.0011

IAC2_BOVIN ACROSIN INHIBITORS IIA AND IIB (BUSI-II  144 167.9 0.0066
CFAI_HUMAN COMPLEMENT FACTOR I PRECURSOR (EC 3.4.2  148 155.4  0.033
MUC2_HUMAN MUCIN 2 (INTESTINAL MUCIN 2) (FRAGMENTS  154 152.1  0.050
IACA_PIG SEMINAL PLASMA ACROSIN INHIBITOR A1.       130 151.6  0.053
IOVO_CHICK OVOMUCOID PRECURSOR.                     135 148.5  0.079
IACS_PIG SPERM-ASSOCIATED ACROSIN INHIBITOR.        126 146.6   0.10
IELA_ANESU ELASTASE INHIBITOR.                      123 146.1   0.11
THBI_RHOPR THROMBIN INHIBITOR.                      124 141.7   0.19
IOV7_CHICK OVOINHIBITOR PRECURSOR.                  132 139.4   0.25
NCS1_RAT NEURONAL CALCIUM SENSOR 1 (NCS-1).         124 137.3   0.34
SP2C_STRPU SPEC 2C PROTEIN.                         116 130.1   0.84
IPS2_RAT PANCREATIC SECRETORY TRYPSIN INHIBITOR II  111 129.4   0.92
IBP_TURRS CHELONIANIN (BASIC PROTEASE INHIBITOR) (  112 128.0   1.1
IAC2_HUMAN ACROSIN-TRYPSIN INHIBITOR II PRECURSOR   110 127.8   1.1
PE60_PIG PEPTIDE PEC-60 PRECURSOR.                  109 126.5   1.3
YNX3_CAEEL HYPOTHETICAL 337.6 KD PROTEIN T20G5.3 I  131 124.7   1.7
IPST_ANGAN PROBABLE PANCREATIC PROTEINASE INHIBITO  105 124.7   1.7
IPST_PIG PANCREATIC SECRETORY TRYPSIN INHIBITOR.    103 123.1   2.1
IPSG_VULVU DOUBLE-HEADED PROTEASE INHIBITOR, SUBMA  105 120.1   3.0
IAC1_BOVIN ACROSIN INHIBITOR I (BUSI-I).            100 119.0   3.5
DP87_DICDI DP87 PROTEIN.                            112 116.3   4.9
SP60_DICDI SPORE COAT PROTEIN SP60 PRECURSOR.       110 116.1   5.1
LDTI_HIRME LEECH-DERIVED TRYPTASE INHIBITOR (LDTI)   95 115.8   5.3
IPST_SHEEP PANCREATIC SECRETORY TRYPSIN INHIBITOR.   95 114.3   6.3
VA34_VARV PROTEIN A34.                              102 114.0   6.6
MT1_CANGA METALLOTHIONEIN-I.                         95 113.6   7.0
IPST_BOVIN PANCREATIC SECRETORY TRYPSIN INHIBITOR.   94 113.2   7.3
LDLR_CRIGR LOW-DENSITY LIPOPROTEIN RECEPTOR PRECUR  112 113.2   7.4
BDR1_HUMAN CALCIUM-BINDING PROTEIN BDR-1.           102 113.1   7.5
IPST_HUMAN PANCREATIC SECRETORY TRYPSIN INHIBITOR    95 111.8   8.7
PU92_SCICO PUFF II/9-2 PROTEIN PRECURSOR.           103 111.3   9.4

Note that here, again, it appears that possibly unrelated sequences are obtaining "significant" similarity scores.

The result is quite different if the search is performed with the calcium-binding domain only.


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