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49  structures 440  species 2  interactions 1081  sequences 8  architectures

Family: Profilin (PF00235)

Summary: Profilin

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Profilin Edit Wikipedia article

Profilin
Profilin actin complex.png
Profilin (blue) in complex with actin (green). (PDB code: 2BTF)
Identifiers
Symbol Profilin
Pfam PF00235
InterPro IPR002097
SMART PROF
PROSITE PS00414
SCOP 2btf
SUPERFAMILY 2btf

Profilin is an actin-binding protein involved in the dynamic turnover and restructuring of the actin cytoskeleton. It is found in all eukaryotic organisms in most cells. Profilin is important for spatially and temporally controlled growth of actin microfilaments, which is an essential process in cellular locomotion and cell shape changes. This restructuring of the actin cytoskeleton is essential for processes such as organ development, wound healing, and the hunting down of infectious intruders by cells of the immune system.

Profilin also binds sequences rich in the amino acid proline in diverse proteins. While most profilin in the cell is bound to actin, profilins have over 50 different binding partners. Many of those are related to actin regulation, but profilin also seems to be involved in activities in the nucleus such as mRNA splicing.[1]

Profilin binds some variants of membrane phospholipids (Phosphatidylinositol (4,5)-bisphosphate and Inositol triphosphate). The function of this interaction is the sequestration of profilin in an "inactive" form, from where it can be released by action of the enzyme phospholipase C.

Profilin is the major allergen present in birch, grass, and other pollen.

Profilin sources and distribution[edit]

Profilins are proteins of molecular weights of roughly 14–16 kDa. They are present as single genes in yeast, insects, and worms, and as multiple genes in many other organisms including plants. In mammalian cells, four profilin isoforms have been discovered; profilin-I is expressed in most tissues while profilin-II is predominant in brain and kidney.[2]

Profilin in the regulation of actin dynamics[edit]

Profilin enhances actin growth in two ways:

  • Profilin binds to monomeric actin thereby occupying an actin-actin contact site; in effect, profilin sequesters actin from the pool of polymerizable actin monomers. However, profilin also catalyzes the exchange of actin-bound ADP to ATP thereby converting poorly polymerizing ADP-actin monomers into readily polymerizing ATP-actin monomers. On top of that, profilin has a higher affinity for ATP- than for ADP-actin monomers. Thus in a mixture of actin, profilin, and nucleotides (ADP and ATP), actin will polymerize to a certain extent, which may be estimated by the law of mass action.
  • Profilin-actin complexes are fed into growing actin polymers by proteins such as formin, WASP and VASP (that contain proline-rich FH2-domains). This mode of stimulated actin polymerization is much faster than unaided polymerization. Profilin is essential for this mode of polymerization because it recruits the actin monomers to the proline-rich proteins.

Profilin also negatively regulates PI(3,4)P2 limiting recruitment of lamellipodin to the leading edge of the cell

Profilin is one of the most abundant actin monomer binders, but proteins such as CAP and (in mammals) thymosin β4 have some functional overlaps with profilin. In contrast, ADF/cofilin has some properties that antagonize profilin action.

History of profilin discovery[edit]

Profilin was first described by Uno Lindberg and co-workers in the early 1970s as the first actin monomer binding protein.[3] It followed the realization that not only muscle, but also non-muscle cells, contained high concentrations of actin, albeit in part in an unpolymerized form. Profilin was then believed to sequester actin monomers (keep them in a pro-filamentous form), and release them upon a signal to make them accessible for fast actin polymer growth.

Genes[edit]

References[edit]

  1. ^ Di Nardo A, Gareus R, Kwiatkowski D, Witke W (November 2000). "Alternative splicing of the mouse profilin II gene generates functionally different profilin isoforms". J. Cell. Sci. 113 (Pt 21): 3795–803. PMID 11034907. 
  2. ^ Witke W, Podtelejnikov AV, Di Nardo A, et al. (February 1998). "In mouse brain profilin I and profilin II associate with regulators of the endocytic pathway and actin assembly". EMBO J. 17 (4): 967–76. doi:10.1093/emboj/17.4.967. PMC 1170446. PMID 9463375. 
  3. ^ Carlsson L, Nyström LE, Sundkvist I, Markey F, Lindberg U (September 1977). "Actin polymerizability is influenced by profilin, a low molecular weight protein in non-muscle cells". J. Mol. Biol. 115 (3): 465–83. doi:10.1016/0022-2836(77)90166-8. PMID 563468. 

Bae YH, Ding Z, Das T, Wells A, Gertler F, Roy P (November 2010). "Profilin1 regulates PI(3,4)P2 and lamellipodin accumulation at the leading edge thus influencing motility of MDA-MB-231 cells". Proc. Natl. Acad. Sci. U.S.A. 107 (50): 21547–21552. doi:10.1073/pnas.1002309107. PMC 3003040. PMID 21115820. 

External links[edit]

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR002097

Profilin is a small eukaryotic protein that binds to monomeric actin (G-actin) in a 1:1 ratio thus preventing the polymerisation of actin into filaments (F-actin). It can also in certain circumstance promote actin polymerisation. Profilin also binds to polyphosphoinositides such as PIP2. Overall sequence similarity among profilin from organisms which belong to different phyla (ranging from fungi to mammals) is low, but the N-terminal region is relatively well conserved. That region is thought to be involved in the binding to actin.

A protein structurally similar to profilin is present in the genome of Variola virus and Vaccinia virus (gene A42R).

Some of the proteins in this family are allergens. Allergies are hypersensitivity reactions of the immune system to specific substances called allergens (such as pollen, stings, drugs, or food) that, in most people, result in no symptoms. A nomenclature system has been established for antigens (allergens) that cause IgE-mediated atopic allergies in humans [WHO/IUIS Allergen Nomenclature Subcommittee King T.P., Hoffmann D., Loewenstein H., Marsh D.G., Platts-Mills T.A.E., Thomas W. Bull. World Health Organ. 72:797-806(1994)]. This nomenclature system is defined by a designation that is composed of the first three letters of the genus; a space; the first letter of the species name; a space and an arabic number. In the event that two species names have identical designations, they are discriminated from one another by adding one or more letters (as necessary) to each species designation.

The allergens in this family include allergens with the following designations: Ara t 8, Bet v 2, Cyn d 12, Hel a 2, Mer a 1 and Phl p 11.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan PF (CL0431), which has the following description:

The families here all show the Profilin-like fold, and represent both the Profilin (actin-binding protein) (55770) and the Roadblock/LC7 domain-type (103196) superfamilies.

The clan contains the following 3 members:

MAPKK1_Int Profilin Robl_LC7

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

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(72)
Full
(1081)
Representative proteomes NCBI
(984)
Meta
(4)
RP15
(172)
RP35
(257)
RP55
(346)
RP75
(440)
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  Seed
(72)
Full
(1081)
Representative proteomes NCBI
(984)
Meta
(4)
RP15
(172)
RP35
(257)
RP55
(346)
RP75
(440)
Alignment:
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  Seed
(72)
Full
(1081)
Representative proteomes NCBI
(984)
Meta
(4)
RP15
(172)
RP35
(257)
RP55
(346)
RP75
(440)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

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Seed source: Prosite
Previous IDs: profilin;
Type: Domain
Author: Finn RD
Number in seed: 72
Number in full: 1081
Average length of the domain: 121.20 aa
Average identity of full alignment: 33 %
Average coverage of the sequence by the domain: 90.65 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.9 20.9
Trusted cut-off 20.9 20.9
Noise cut-off 20.8 20.8
Model length: 121
Family (HMM) version: 14
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 2 interactions for this family. More...

Actin Profilin

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Profilin domain has been found. There are 49 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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