A-kinase anchor protein 13 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the ''AKAP13''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. This protein is also called AKAP-Lbc because it encodes the lymphocyte blast crisis (Lbc)

oncogene An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

, and ARHGEF13/RhoGEF13 because it contains a guanine nucleotide exchange factor (GEF)

domain Domain may refer to: Mathematics *Domain of a function, the set of input values for which the (total) function is defined **Domain of definition of a partial function **Natural domain of a partial function **Domain of holomorphy of a function * Do ...

for the

RhoA Transforming protein RhoA, also known as Ras homolog family member A (RhoA), is a small GTPase protein in the Rho family of GTPases that in humans is encoded by the ''RHOA'' gene. While the effects of RhoA activity are not all well known, it is ...

small GTP-binding protein.

Function

A-kinase anchor protein 13/Rho guanine nucleotide exchange factor 13 is

guanine nucleotide exchange factor Guanine nucleotide exchange factors (GEFs) are proteins or protein domains that activate monomeric GTPases by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP). A variety of unrelated structu ...

(GEF) for the

small GTPase Small GTPases (), also known as small G-proteins, are a family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate (GTP). They are a type of G-protein found in the cytosol that are homologous to the alpha subunit of heterotri ...

protein. Rho is a

protein that is inactive when bound to the

guanine Guanine () ( symbol G or Gua) is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine (uracil in RNA). In DNA, guanine is paired with cytosine. The guanine nucleoside is called ...

nucleotide Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules wi ...

GDP Gross domestic product (GDP) is a monetary measure of the market value of all the final goods and services produced and sold (not resold) in a specific time period by countries. Due to its complex and subjective nature this measure is ofte ...

. But when acted on by Rho GEF proteins such as AKAP13, this GDP is released and replaced by GTP, leading to the active state of Rho. In this active, GTP-bound conformation, Rho can bind to and activate specific

effector Effector may refer to: *Effector (biology), a molecule that binds to a protein and thereby alters the activity of that protein * ''Effector'' (album), a music album by the Experimental Techno group Download * ''EFFector'', a publication of the El ...

proteins and

enzymes Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...

to regulate cellular functions. In particular, active Rho is a major regulator of the cell

actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over ...

cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...

. AKAP13 is a member of a group of four RhoGEF proteins known to be activated by

G protein coupled receptors G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...

coupled to the G₁₂ and G₁₃

heterotrimeric G proteins Heterotrimeric G protein, also sometimes referred to as the ''"large" G proteins'' (as opposed to the subclass of smaller, monomeric small GTPases) are membrane-associated G proteins that form a heterotrimeric complex. The biggest non-structura ...

. The others are

ARHGEF1 Rho guanine nucleotide exchange factor 1 is a protein that in humans is encoded by the ''ARHGEF1'' gene. This protein is also called RhoGEF1 or p115-RhoGEF. Function Rho guanine nucleotide exchange factor 1 is guanine nucleotide exchange fac ...

(also known as p115-RhoGEF), ARHGEF11 (also known as PDZ-RhoGEF), and

ARHGEF12 Rho guanine nucleotide exchange factor 12 is a protein that in humans is encoded by the ''ARHGEF12'' gene. This protein is also called RhoGEF12 or Leukemia-associated Rho guanine nucleotide exchange factor (LARG). Function Rho guanine nucleotid ...

(also known as LARG). GPCR-regulated AKAP13 (and these related GEF proteins) acts as an effector for G₁₂ and G₁₃ G proteins. Unlike the other three members, AKAP13 does not function as RGS family GTPase-activating proteins (GAPs) to increase the rate of GTP hydrolysis of G₁₂/G₁₃ alpha proteins. The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins that have the common function of binding to the regulatory subunit of protein kinase A (PKA), thus confining the holoenzyme to discrete locations within the cell. The AKAP13 gene encodes a member of the AKAP family since the protein binds tightly to PKA, especially in the heart. Alternative splicing of this gene results in at least 3 transcript variants encoding different isoforms. All three contain the Dbl oncogene homology (DH) domain plus Pleckstrin homology (PH) domain (DH/PH domain) characteristic of Rho family GEFs, while only the longer two isoforms also contain the AKAP domain. Therefore, these isoforms may function as scaffolding proteins to coordinate Rho signaling and protein kinase A signaling.

Interactions

AKAP13 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with: * CTNNAL1 *

Estrogen receptor alpha Estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor (mainly found as a chromatin-binding protein) that is activated by the sex ...

GNA12 Guanine nucleotide-binding protein subunit alpha-12 is a protein that in humans is encoded by the ''GNA12'' gene. Interactions and functions The GNA12 gene encodes the G12 G protein alpha subunit. Together with GNA13, these two proteins compri ...

GNA13 Guanine nucleotide-binding protein subunit alpha-13 is a protein that in humans is encoded by the ''GNA13'' gene. Interactions and functions The GNA13 gene encodes the G13 G protein alpha subunit. Together with GNA12, these two proteins comp ...

PRKAR2A cAMP-dependent protein kinase type II-alpha regulatory subunit is an enzyme that in humans is encoded by the ''PRKAR2A'' gene. Function cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activ ...

References

External links

* *

Function

Interactions

See also

References

External links

Further reading