C1 domain

Pfam_box
Symbol = C1_1
Name = Phorbol esters/diacylglycerol binding domain (C1 domain)


width =200
caption = C1 domain of PKC-delta (1ptr) Middle plane of the lipid bilayer - black dots. Boundary of the hydrocarbon core region - blue dots (cytoplasmic side). Layer of lipid phosphates - yellow dots.
Pfam= PF00130
InterPro= IPR002219
SMART= C1
PROSITE= PDOC00379
SCOP = 2cpk
TCDB =
OPM family= 63
OPM protein= 1ptr
PDB=PDB3|1ptr :231-280 PDB3|1ptq :231-280 PDB3|1xa6A:215-267PDB3|1y8fA:567-616 PDB3|1far :139-187 PDB3|1faq :139-187PDB3|1kbfA:334-378 PDB3|1kbeA:334-378 PDB3|1r79A:236-286

C1 domain (also known as phorbol esters/diacylglycerol binding domain) binds an important secondary messenger diacylglycerol (DAG), as well as the analogous phorbol esterscite journal |author=Azzi A, Boscoboinik D, Hensey C |title=The protein kinase C family |journal=Eur. J. Biochem. |volume=208 |issue=3 |pages=547–557 |year=1992 |pmid=1396661 |doi=10.1111/j.1432-1033.1992.tb17219.x] . Phorbol esters can directly stimulate protein kinase C, PKC. The N-terminal region of PKC, known as C1, has been showncite journal |author=Kikkawa U, Nishizuka Y, Igarashi K, Fujii T, Ono Y, Kuno T, Tanaka C |title=Phorbol ester binding to protein kinase C requires a cysteine-rich zinc-finger-like sequence |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=86 |issue=13 |pages=4868–4871 |year=1989 |pmid=2500657 |doi=10.1073/pnas.86.13.4868]

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. 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; 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;

References

External links

* [http://smart.embl-heidelberg.de/smart/do_annotation.pl?&DOMAIN=c1 C1 domains in SMART]
* [http://www.sanger.ac.uk//cgi-bin/Pfam/getacc?PF00130 C1 domains in Pfam]
* - Orientations of C1 domains in membranes (OPM)