Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2012) Nucleic Acids Res , doi:10.1093/nar/gkr931

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GEL Gelsolin homology domain

SMART accession number:	SM00262
Description:	Gelsolin/severin/villin homology domain. Calcium-binding and actin-binding. Both intra- and extracellular domains.
Interpro abstract (IPR007122):	Gelsolin is a cytoplasmic, calcium-regulated, actin-modulating protein that binds to the barbed ends of actin filaments, preventing monomer exchange (end-blocking or capping) [(PUBMED:3023087)]. It can promote nucleation (the assembly of monomers into filaments), as well as sever existing filaments. In addition, this protein binds with high affinity to fibronectin. Plasma gelsolin and cytoplasmic gelsolin are derived from a single gene by alternate initiation sites and differential splicing. Sequence comparisons indicate an evolutionary relationship between gelsolin, villin, fragmin and severin [(PUBMED:2850369)]. Six large repeating segments occur in gelsolin and villin, and 3 similar segments in severin and fragmin. While the multiple repeats have yet to be related to any known function of the actin-severing proteins, the superfamily appears to have evolved from an ancestral sequence of 120 to 130 amino acid residues [(PUBMED:2850369)].
GO function:	actin binding (GO:0003779)
Family alignment:	View or CHROMA formatCLUSTALW formatMSF formatFASTA formatPIR format

There are 2846 GEL domains in 696 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a GEL domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with GEL domain is also avaliable.

  Useful shortcuts: Expand all nodes or Collapse tree
  Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Takifugu rubripes

• Cellular role (predicted cellular role)

• Binding / catalysis: Calcium, actin

• Disease (disease genes where sequence variants are found in this domain)

• SwissProt sequences and OMIM curated human diseases associated with missense mutations within the GEL domain.

  Protein	Disease
  Gelsolin (P06396) (SMART)	OMIM:137350: Amyloidosis, Finnish type OMIM:105120:

• Metabolism (metabolic pathways involving proteins which contain this domain)

• % proteins involved KEGG pathway ID Description 100.00 map04810 Regulation of actin cytoskeleton This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with GEL domain which could be assigned to a KEGG orthologous group, and not all proteins containing GEL domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

• Structure (3D structures containing this domain)

• 3D Structures of GEL domains in PDB

  PDB code	Main view	Title
  1c0f		Crystal structure of dictyostelium caatp-actin in complex with gelsolin segment 1
  1c0g		Crystal structure of 1:1 complex between gelsolin segment 1 and a dictyostelium/tetrahymena chimera actin (mutant 228: q228k/t229a/a230y/e360h)
  1d0n		The crystal structure of calcium-free equine plasma gelsolin.
  1d4x		Crystal structure of caenorhabditis elegans mg-atp actin complexed with human gelsolin segment 1 at 1.75 a resolution.
  1dej		Crystal structure of a dictyostelium/tetrahymena chimera actin (mutant 646: q228k/t229a/a230y/a231k/s232e/e360h) in complex with human gelsolin segment 1
  1eqy		Complex between rabbit muscle alpha-actin: human gelsolin domain 1
  1esv		Complex between latrunculin a:rabbit muscle alpha actin:human gelsolin domain 1
  1h1v		Gelsolin g4-g6/actin complex
  1j72		Crystal structure of mutant macrophage capping protein (cap g) with actin-severing activity in the ca2+-free form
  1jhw		Ca2+-binding mimicry in the crystal structure of the eu3+- bound mutant human macrophage capping protein cap g
  1kcq		Human gelsolin domain 2 with a cd2+ bound
  1mdu		Crystal structure of the chicken actin trimer complexed with human gelsolin segment 1 (gs-1)
  1nlv		Crystal structure of dictyostelium discoideum actin complexed with ca atp and human gelsolin segment 1
  1nm1		Crystal structure of d. dicsoideum actin complexed with gelsolin segment 1 and mg atp at 1.8 a resolution
  1nmd		Crystal structure of d. discoideum actin-gelsolin segment 1 complex crystallized in presence of lithium atp
  1nph		Gelsolin domains 4-6 in active, actin free conformation identifies sites of regulatory calcium ions
  1p8x		The calcium-activated c-terminal half of gelsolin
  1p8z		Complex between rabbit muscle alpha-actin: human gelsolin residues val26-glu156
  1rgi		Crystal structure of gelsolin domains g1-g3 bound to actin
  1svq		Structure of severin domain 2 in solution
  1svr		Structure of severin domain 2 in solution
  1svy		Severin domain 2, 1.75 angstrom crystal structure
  1t44		Structural basis of actin sequestration by thymosin-b4: implications for arp2/3 activation
  1yag		Structure of the yeast actin-human gelsolin segment 1 complex
  1yvn		The yeast actin val 159 asn mutant complex with human gelsolin segment 1.
  2ff3		Crystal structure of gelsolin domain 1:n-wasp v2 motif hybrid in complex with actin
  2ff6		Crystal structure of gelsolin domain 1:ciboulot domain 2 hybrid in complex with actin
  2fgh		Atp bound gelsolin
  2fh1		C-terminal half of gelsolin soaked in low calcium at ph 4.5
  2fh2		C-terminal half of gelsolin soaked in egta at ph 4.5
  2fh3		C-terminal half of gelsolin soaked in low calcium at ph 8
  2fh4		C-terminal half of gelsolin soaked in egta at ph 8
  2vik		Refined structure of the actin-severing domain villin 14t, determined by solution nmr, minimized average structure
  2vil		Refined structure of the actin-severing domain villin 14t, determined by solution nmr, 11 structures
  3ci5		Complex of phosphorylated dictyostelium discoideum actin with gelsolin
  3cip		Complex of dictyostelium discoideum actin with gelsolin
  3cjb		Actin dimer cross-linked by v. cholerae martx toxin and complexed with gelsolin-segment 1
  3cjc		Actin dimer cross-linked by v. cholerae martx toxin and complexed with dnase i and gelsolin-segment 1
  3ffk		Crystal structure of human gelsolin domains g1-g3 bound to actin
  3ffn		Crystal structure of calcium-free human gelsolin
  3fg6		Structure of the c-terminus of adseverin
  3fg7		The crystal structure of villin domain 6

• Links (links to other resources describing this domain)

• PFAM	Gelsolin
  INTERPRO	IPR007122

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