EF hand

Pfam_box
Symbol = efhand
Name = EF hand


width =
caption = Calmodulin with four EF-Hand-motifs.
Pfam= PF00036
PROSITE=PDOC00018
InterPro= IPR002048
SMART=
SCOP = 1osa
TCDB =
OPM family=
OPM protein= 1djx
PDB=PDB3|1s6jA:375-402 PDB3|1s6iA:375-403 PDB3|1m39A:141-169PDB3|2a4jA:141-169 PDB3|1oqpA:138-166 PDB3|2bbnA:121-148PDB3|2bkhB:121-148 PDB3|1mxeA:121-148 PDB3|4cln :121-148PDB3|2bbmA:121-148 PDB3|1cdmA:121-146 PDB3|1lin :121-148PDB3|2bkiB:121-148 PDB3|1oojA:121-148 PDB3|1osa :121-148PDB3|1clm :121-147 PDB3|1n0yB:121-148 PDB3|1exrA:121-148PDB3|1rfjA:121-149 PDB3|1ggzA:121-148 PDB3|1ak8 :48-75PDB3|1sw8A:48-76 PDB3|1j7oA:48-76 PDB3|1f70A:48-76PDB3|1r2uA:56-84 PDB3|1r6pA:56-84 PDB3|1j1eA:56-84The EF hand is a helix-turn-helix structural domain found in a large family of calcium-binding proteins. It consists of two alpha helices positioned roughly perpendicular to one another and linked by a short loop region (usually about 12 amino acids) that usually binds calcium ions. The motif takes its name from traditional nomenclature used in describing the protein parvalbumin, which contains three such motifs and is probably involved in muscle relaxation via its calcium-binding activity. EF hands also appear in each structural domain of the signaling protein calmodulin and in the muscle protein troponin-C.

Binding site

The calcium ion is bound by both protein backbone atoms and by amino acid side chains, specifically those of the acidic amino acid residues, aspartate and glutamate. These residues are negatively charged and will make a charge-interaction with the positively charged calcium ion. The EF hand motif was among the first structural motifs whose sequence requirements were analyzed in detail. Five of the loop residues bind calcium and thus have a strong preference for oxygen-containing side chains, especially aspartate and glutamate. The sixth residue in the loop is necessarily glycine due to the conformational requirements of the backbone. The remaining residues are typically hydrophobic and form a hydrophobic core that binds the stabilizes the two helices.

In an EF-hand loop the calcium ion is coordinated in a pentagonal bipyramidal configuration. The six residues involved in the binding are in positions 1, 3, 5, 7, 9 and 12; these residues are denoted by X, Y, Z, -Y, -X and -Z. The invariant Glu or Asp at position 12 provides two oxygens for liganding Ca (bidentate ligand).

Classification

The EF-hands can be divided into two classes: signaling proteinsand buffering/transport proteins. The first group is the largestand includes the most well-known members of the family such ascalmodulin, troponin C and S100B. These proteins typically undergoa calcium-dependent conformational change which opens a target bindingsite. The latter group is represented by calbindin D9k and do notundergo calcium dependent conformational changes.

ubfamilies

*EPS15 homology (EH) domain InterPro|IPR000261

Human proteins containing this domain

ACTN1; ACTN2; ACTN3; ACTN4; APBA2BP; AYTL1; AYTL2; C14orf143;
CABP1; CABP2; CABP3; CABP4; CABP5; CABP7; CALB1; CALB2;
CALM2; CALM3; CALML3; CALML4; CALML5; CALML6; CALN1; CALU;
CAPN1; CAPN11; CAPN2; CAPN3; CAPN9; CAPNS1; CAPNS2; CAPS;
CAPS2; CAPSL; CBARA1; CETN1; CETN2; CETN3; CHP; CHP2;
CIB1; CIB2; CIB3; CIB4; CRNN; DGKA; DGKB; DGKG;
DST; DUOX1; DUOX2; EFCAB1; EFCAB2; EFCAB4A; EFCAB4B; EFCAB6;
EFCBP1; EFCBP2; EFHA1; EFHA2; EFHB; EFHC1; EFHD1; EFHD2;
EPS15; EPS15L1; FKBP10; FKBP14; FKBP7; FKBP9; FKBP9L; FREQ;
FSTL1; FSTL5; GCA; GPD2; GUCA1A; GUCA1B; GUCA1C; hippocalcin;
HPCAL1; HPCAL4; HZGJ; IFPS; ITSN1; ITSN2; KCNIP1; KCNIP2;
KCNIP3; KCNIP4; KIAA1799; LCP1; MACF1; MRLC2; MRLC3; MST133;
MYL1; MYL2; MYL5; MYL6B; MYL7; MYL9; MYLC2PL; MYLPF;
NCALD; NIN; NKD1; NKD2; NLP; NOX5; NUCB1; NUCB2; OCM; PDCD6;
PEF1; PKD2; PLCD1; PLCD4; PLCH1; PLCH2; PLS1; PLS3;
PP1187; PPEF1; PPEF2; PPP3R1; PPP3R2; PRKCSH; PVALB; RAB11FIP3;
RASEF; RASGRP; RASGRP1; RASGRP2; RASGRP3; RCN1; RCN2; RCN3;
RCV1; RCVRN; REPS1; RHBDL3; RHOT1; RHOT2; RPTN; RYR2;
RYR3; S100A1; S100A11; S100A12; S100A6; S100A8; S100A9; S100B;
S100G; S100Z; SCAMC-2; SCGN; SDF4; SLC25A12; SLC25A13; SLC25A23;
SLC25A24; SLC25A25; SPATA21; SPTA1; SPTAN1; SRI; TBC1D9; TBC1D9B;
TCHH; TESC; TNNC1; TNNC2; USP32; VSNL1; ZZEF1;

ee also

Another distinct calcium-binding motif composed of alpha helices is the dockerin domain.

External links

* [http://scop.mrc-lmb.cam.ac.uk/scop/data/scop.b.b.ei.html SCOP EF-hand fold]

Further reading

* Branden C, Tooze J. (1999). "Introduction to Protein Structure" 2nd ed. Garland Publishing: New York, NY.
*Evolution of EF-hand calcium-modulated proteins. II. Domains of several subfamilies have diverse evolutionary histories. Nakayama S, Moncrief ND, Kretsinger RH; J Mol Evol 1992;34:416-448. PMID|1602495
*Comparison of terbium (III) luminescence enhancement in mutants of EF hand calcium binding proteins. Hogue CW, MacManus JP, Banville D, Szabo AG; J Biol Chem 1992;267:13340-13347. PMID|1618836
*EF-hand motifs in inositol phospholipid-specific phospholipase C. Bairoch A, Cox JA; FEBS Lett 1990;269:454-456.PMID|2401372
*The evolving model of calmodulin structure, function and activation. Finn BE, Forsen S; Structure 1995;3:7-11. PMID|7743133