C1 domain explained

C1 domain (also known as phorbol esters/diacylglycerol binding domain) binds an important secondary messenger diacylglycerol (DAG), as well as the analogous phorbol esters.^[1] Phorbol esters can directly stimulate protein kinase C, PKC.

Phorbol esters (such as PMA) are analogues of DAG and potent tumor promoters that cause a variety of physiological changes when administered to both cells and tissues. DAG activates a family of serine/threonine protein kinases, collectively known as protein kinase C (PKC). Phorbol esters can directly stimulate PKC.

The N-terminal region of PKC, known as C1, binds PMA and DAG in a phospholipid and zinc-dependent fashion.^[2] The C1 region contains one or two copies of a cysteine-rich domain, which is about 50 amino-acid residues long, and which is essential for DAG/PMA-binding.

The DAG/PMA-binding domain binds two zinc ions; the ligands of these metal ions are probably the six cysteines and two histidines that are conserved in this domain.

Human proteins containing this domain

AKAP13

ARAF; ARHGAP29; ARHGEF2; BRAF; CDC42BPA; CDC42BPB; CDC42BPG;CHN1

CHN2; CIT; CIC; DGKA; DGKB; DGKD; DGKE; DGKG;DGKH

DGKI; DGKK; DGKQ; DGKZ; GMIP; HMHA1; KSR1;KSR2

MYO9A; MYO9B; PDZD8; PRKCA; PRKCB1; PRKCD; PRKCE;PRKCG

PRKCH; PRKCI; PRKCN; PRKCQ; PRKCZ; PRKD1; PRKD2;PRKD3

RACGAP1; RAF1; RASGRP; RASGRP1; RASGRP2; RASGRP3; RASGRP4;RASSF1

RASSF5; ROCK1; ROCK2; STAC; STAC2; STAC3; TENC1;UNC13A

UNC13B; UNC13C; VAV1; VAV2; VAV3;

External links

• - Orientations of C1 domains in membranes (OPM)

Notes and References

1. Azzi A, Boscoboinik D, Hensey C . The protein kinase C family . Eur. J. Biochem. . 208 . 3 . 547–557 . 1992 . 1396661 . 10.1111/j.1432-1033.1992.tb17219.x. free .
2. Kikkawa U, Nishizuka Y, Igarashi K, Fujii T, Ono Y, Kuno T, Tanaka C . Phorbol ester binding to protein kinase C requires a cysteine-rich zinc-finger-like sequence . Proc. Natl. Acad. Sci. U.S.A. . 86 . 13 . 4868–4871 . 1989 . 2500657 . 10.1073/pnas.86.13.4868 . 297516. free .