Summary: Profilin
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Profilin Edit Wikipedia article
| Profilin | |||||||||||
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| Identifiers | |||||||||||
| Symbol | Profilin | ||||||||||
| Pfam | PF00235 | ||||||||||
| InterPro | IPR002097 | ||||||||||
| SMART | PROF | ||||||||||
| PROSITE | PS00414 | ||||||||||
| SCOPe | 2btf / SUPFAM | ||||||||||
| CDD | cd00148 | ||||||||||
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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]
Contents
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
References
- ^ 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)
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
External links
- Profilins at the US National Library of Medicine Medical Subject Headings (MeSH)
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External database links
| HOMSTRAD: | profilin |
| PROSITE: | PDOC00372 |
| SCOP: | 2acg |
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.
| Molecular function | actin binding (GO:0003779) |
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_N Profilin Robl_LC7 Sedlin_N SLM4 SRP-alpha_N SRX Sybindin uDENNAlignments
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 (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...
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| Seed (233) |
Full (3549) |
Representative proteomes | UniProt (6407) |
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| RP15 (710) |
RP35 (1774) |
RP55 (2914) |
RP75 (3807) |
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| PP/heatmap | 1 | ||||||
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| Seed (233) |
Full (3549) |
Representative proteomes | UniProt (6407) |
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| RP15 (710) |
RP35 (1774) |
RP55 (2914) |
RP75 (3807) |
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full 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.
Curation
| Seed source: | Prosite |
| Previous IDs: | profilin; |
| Type: | Domain |
| Sequence Ontology: | SO:0000417 |
| Author: |
Finn RD 
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| Number in seed: | 233 |
| Number in full: | 3549 |
| Average length of the domain: | 124.60 aa |
| Average identity of full alignment: | 29 % |
| Average coverage of the sequence by the domain: | 86.47 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 127 | ||||||||||||
| Family (HMM) version: | 21 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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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 110 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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