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107  structures 1462  species 0  interactions 3901  sequences 47  architectures

Family: Profilin (PF00235)

Summary: Profilin

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This is the Wikipedia entry entitled "Profilin". More...

Profilin Edit Wikipedia article

Profilin actin complex.png
Profilin (blue) in complex with actin (green). (PDB code: 2BTF)

Profilin is an actin-binding protein involved in the dynamic turnover and restructuring of the actin cytoskeleton. [1] 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.[2]

Profilin binds some variants of membrane phospholipids (phosphatidylinositol (4,5)-bisphosphate and inositol trisphosphate). 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 (via IgE) present in birch, grass, and other pollen. It is essential to host cell invasion by Toxoplasma gondii. Toxoplasma profilin is the specific pathogen-associated molecular pattern (PAMP) of TLRs 5, 11, and 12.[3]

Profilin sources and distribution

Profilins are proteins of molecular weights of roughly 14–19 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.[4]

Profilin in the regulation of actin dynamics

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 FH1-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 lamellipodia to the leading edge of the cell.[citation needed]

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

Profilin was first described by Lars Carlsson in the lab of Uno Lindberg and co-workers in the early 1970s as the first actin monomer binding protein.[5] 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.

Human genes


  1. ^ Gunning PW, Ghoshdastider U, Whitaker S, Popp D, Robinson RC (2015). "The evolution of compositionally and functionally distinct actin filaments". Journal of Cell Science. 128 (11): 2009–19. doi:10.1242/jcs.165563. PMID 25788699.CS1 maint: uses authors parameter (link)
  2. ^ Di Nardo A, Gareus R, Kwiatkowski D, Witke W (November 2000). "Alternative splicing of the mouse profilin II gene generates functionally different profilin isoforms" (PDF). Journal of Cell Science. 113 (Pt 21): 3795–803. PMID 11034907.
  3. ^ Salazar Gonzalez RM, Shehata H, O'Connell MJ, Yang Y, Moreno-Fernandez ME, Chougnet CA, Aliberti J (August 2014). "Toxoplasma gondii- derived profilin triggers human toll-like receptor 5-dependent cytokine production". Journal of Innate Immunity. 6 (5): 685–694. doi:10.1159/000362367. PMC 4141014. PMID 24861338.
  4. ^ 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 Journal. 17 (4): 967–76. doi:10.1093/emboj/17.4.967. PMC 1170446. PMID 9463375.
  5. ^ 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". Journal of Molecular Biology. 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". Proceedings of the National Academy of Sciences of the United States of America. 107 (50): 21547–21552. Bibcode:2010PNAS..10721547B. doi:10.1073/pnas.1002309107. PMC 3003040. PMID 21115820.

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

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Profilin Provide feedback

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External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR005455

This entry represents the Profilin family, which are small eukaryotic proteins that have different functions. In plants, they are major allergens present in pollens [ PUBMED:21458043 ].

The majority of the Profilin family members binds to monomeric actin (G-actin) in a 1:1 ratio thus preventing the polymerisation of actin into filaments (F-actin). They can also in certain circumstance promote actin polymerisation [ PUBMED:16542844 ]. However, some Profilin family members, such as Profilin4 from mammals, does not binds to actin and may have functions distinct from regulating actin dynamics [ PUBMED:19419568 ]. It plays a role in the assembly of branched actin filament networks, by activating WASP via binding to WASP's proline rich domain [ PUBMED:11137023 ]. Profilin may link the cytoskeleton with major signalling pathways by interacting with components of the phosphatidylinositol cycle and Ras pathway [ PUBMED:7945274 , PUBMED:1651167 ].

This entry also includes Asgard archaea profilins (Thor profilin, Loki profilin-1 and Loki profilin-2), which bind to actin and regulate the structure of the cytoskeleton. This indicates that Asgard archaea have a functional eukaryotic-like actin machinery [ PUBMED:30283132 ].

Some Profilins can also bind to polyphosphoinositides such as PIP2 [ PUBMED:11034907 ]. 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. The N-terminal region is thought to be involved in actin binding.

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 21 members:

Clat_adaptor_s FNIP_N Fuz_longin_1 Fuz_longin_2 Fuz_longin_3 Intu_longin_1 Intu_longin_2 Intu_longin_3 LAMTOR5 Longin Longin_2 MAPKK1_Int Nyv1_longin Profilin Robl_LC7 Sedlin_N SLM4 SRP-alpha_N SRX Sybindin uDENN


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Curation and family details

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Seed source: Prosite
Previous IDs: profilin;
Type: Domain
Sequence Ontology: SO:0000417
Author: Finn RD
Number in seed: 233
Number in full: 3901
Average length of the domain: 125.50 aa
Average identity of full alignment: 29 %
Average coverage of the sequence by the domain: 87.18 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.0 25.0
Trusted cut-off 25.3 25.0
Noise cut-off 24.9 24.9
Model length: 127
Family (HMM) version: 22
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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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 107 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 sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0P0UZ97 View 3D Structure Click here
A0A0R4IPL1 View 3D Structure Click here
A0A1B0GT24 View 3D Structure Click here
A0A1D6M0H9 View 3D Structure Click here
A0A1D6NCZ8 View 3D Structure Click here
A0A1D6QR53 View 3D Structure Click here
A4I7N0 View 3D Structure Click here
A4KA55 View 3D Structure Click here
A4KA56 View 3D Structure Click here
A4KA57 View 3D Structure Click here
A4KA58 View 3D Structure Click here
A4KA59 View 3D Structure Click here
A4KA60 View 3D Structure Click here
A4KA61 View 3D Structure Click here
A5WWI6 View 3D Structure Click here
A7XZJ7 View 3D Structure Click here
B4FCP0 View 3D Structure Click here
B6T6Y5 View 3D Structure Click here
C0PNL3 View 3D Structure Click here
C6SVT2 View 3D Structure Click here
C6TLM1 View 3D Structure Click here
E7F0A1 View 3D Structure Click here
I1J4G4 View 3D Structure Click here
I1K601 View 3D Structure Click here
I1K602 View 3D Structure Click here
I1KJR5 View 3D Structure Click here
I1KPV7 View 3D Structure Click here
I1MCV8 View 3D Structure Click here
I1NCB8 View 3D Structure Click here
M0RCP6 View 3D Structure Click here
O22655 View 3D Structure Click here
O65809 View 3D Structure Click here
O65810 View 3D Structure Click here
P02584 View 3D Structure Click here
P07274 View 3D Structure Click here
P07737 View 3D Structure Click here
P25843 View 3D Structure Click here
P26199 View 3D Structure Click here
P26200 View 3D Structure Click here
P32006 View 3D Structure Click here