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Reviewed, UniProtKB/Swiss-Prot P06396 (GELS_HUMAN)

Last modified June 16, 2009. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Gelsolin
Alternative name(s):
    Actin-depolymerizing factor
      Short name=ADF
    Brevin
    AGEL
Gene names
Name: GSN
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length782 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Calcium-regulated, actin-modulating protein that binds to the plus (or barbed) ends of actin monomers or filaments, preventing monomer exchange (end-blocking or capping). It can promote the assembly of monomers into filaments (nucleation) as well as sever filaments already formed.

Subunit structure

Binds to actin and to fibronectin. Ref.4

Subcellular location

Isoform 2: Cytoplasmcytoskeleton.

Isoform 1: Secreted.

Tissue specificity

Phagocytic cells, platelets, fibroblasts, nonmuscle cells, smooth and skeletal muscle cells.

Post-translational modification

Phosphorylation on Tyr-86, Tyr-409, Tyr-465, Tyr-603 and Tyr-651 in vitro is induced in presence of phospholipids.

Involvement in disease

Defects in GSN are the cause of amyloidosis type 5 (AMYL5) [MIM:105120]; also known as familial amyloidosis Finnish type. AMYL5 is a hereditary generalized amyloidosis due to gelsolin amyloid deposition. It is typically characterized by cranial neuropathy and lattice corneal dystrophy. Most patients have modest involvement of internal organs, but severe systemic disease can develop in some individuals causing peripheral polyneuropathy, amyloid cardiomyopathy, and nephrotic syndrome leading to renal failure. Ref.5 Ref.6 Ref.13 Ref.14

Sequence similarities

Belongs to the villin/gelsolin family.

Contains 6 gelsolin-like repeats.

Alternative products

This entry describes 2 isoforms produced by alternative initiation. [Align] [Select]
Isoform 1 (identifier: P06396-1)

Also known as: Secreted; Plasma;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P06396-2)

Also known as: Cytoplasmic;

The sequence of this isoform differs from the canonical sequence as follows:
     1-51: Missing.
Note: Initiator Met-1 may be either removed, or N-acetylated.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2727
Chain28 – 782755Gelsolin
PRO_0000036385

Regions

Repeat76 – 12651Gelsolin-like 1
Repeat198 – 23841Gelsolin-like 2
Repeat314 – 35643Gelsolin-like 3
Repeat453 – 50452Gelsolin-like 4
Repeat576 – 61641Gelsolin-like 5
Repeat679 – 72143Gelsolin-like 6
Region53 – 176124Actin-severing Potential
Region123 – 1264Actin-actin interfilament contact point
Region162 – 1698Polyphosphoinositide binding By similarity
Region188 – 1969Polyphosphoinositide binding By similarity
Region434 – 782349Actin-binding, Ca-sensitive Potential

Amino acid modifications

Modified residue861Phosphotyrosine; by SRC; in vitro Ref.9
Modified residue4091Phosphotyrosine; by SRC; in vitro Ref.9
Modified residue4651Phosphotyrosine; by SRC Ref.9
Modified residue6031Phosphotyrosine; by SRC; in vitro Ref.9
Modified residue6511Phosphotyrosine; by SRC; in vitro Ref.9
Disulfide bond215 ↔ 228In isoform 1 Ref.7 Ref.8

Natural variations

Alternative sequence1 – 5151Missing in isoform 2.
VSP_018959
Natural variant221S → L in a breast cancer sample; somatic mutation. Ref.15
VAR_036337
Natural variant1291A → T: dbSNP rs2230287.
VAR_024690
Natural variant2011T → I in a breast cancer sample; somatic mutation. Ref.15
VAR_036338
Natural variant2141D → N in AMYL5. Ref.13 Ref.14
VAR_007718
Natural variant2141D → Y in AMYL5. Ref.13 Ref.14
VAR_007719
Natural variant6111S → N in a breast cancer sample; somatic mutation. Ref.15
VAR_036339
Natural variant6681R → L: dbSNP rs9696578.
VAR_033958

Secondary structure

................................................................................................ 782
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Secreted) (Plasma) [UniParc].

Last modified January 1, 1988. Version 1.
Checksum: 8CEBC52257A160F7

FASTA78285,698
        10         20         30         40         50         60 
MAPHRPAPAL LCALSLALCA LSLPVRAATA SRGASQAGAP QGRVPEARPN SMVVEHPEFL 

        70         80         90        100        110        120 
KAGKEPGLQI WRVEKFDLVP VPTNLYGDFF TGDAYVILKT VQLRNGNLQY DLHYWLGNEC 

       130        140        150        160        170        180 
SQDESGAAAI FTVQLDDYLN GRAVQHREVQ GFESATFLGY FKSGLKYKKG GVASGFKHVV 

       190        200        210        220        230        240 
PNEVVVQRLF QVKGRRVVRA TEVPVSWESF NNGDCFILDL GNNIHQWCGS NSNRYERLKA 

       250        260        270        280        290        300 
TQVSKGIRDN ERSGRARVHV SEEGTEPEAM LQVLGPKPAL PAGTEDTAKE DAANRKLAKL 

       310        320        330        340        350        360 
YKVSNGAGTM SVSLVADENP FAQGALKSED CFILDHGKDG KIFVWKGKQA NTEERKAALK 

       370        380        390        400        410        420 
TASDFITKMD YPKQTQVSVL PEGGETPLFK QFFKNWRDPD QTDGLGLSYL SSHIANVERV 

       430        440        450        460        470        480 
PFDAATLHTS TAMAAQHGMD DDGTGQKQIW RIEGSNKVPV DPATYGQFYG GDSYIILYNY 

       490        500        510        520        530        540 
RHGGRQGQII YNWQGAQSTQ DEVAASAILT AQLDEELGGT PVQSRVVQGK EPAHLMSLFG 

       550        560        570        580        590        600 
GKPMIIYKGG TSREGGQTAP ASTRLFQVRA NSAGATRAVE VLPKAGALNS NDAFVLKTPS 

       610        620        630        640        650        660 
AAYLWVGTGA SEAEKTGAQE LLRVLRAQPV QVAEGSEPDG FWEALGGKAA YRTSPRLKDK 

       670        680        690        700        710        720 
KMDAHPPRLF ACSNKIGRFV IEEVPGELMQ EDLATDDVML LDTWDQVFVW VGKDSQEEEK 

       730        740        750        760        770        780 
TEALTSAKRY IETDPANRDR RTPITVVKQG FEPPSFVGWF LGWDDDYWSV DPLDRAMAEL 


AA 

« Hide

Isoform 2 (Cytoplasmic).

Checksum: 0C5C30CE497A0684
Show »

FASTA73180,641

References

« Hide 'large scale' references
[1]"Plasma and cytoplasmic gelsolins are encoded by a single gene and contain a duplicated actin-binding domain."
Kwiatkowski D.J., Stossel T.P., Orkin S.H., Mole J.E., Colten H.R., Yin H.L.
Nature 323:455-458(1986) [PubMed: 3020431] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE INITIATION.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Colon and Pancreas.
[3]"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides."
Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J.
Nat. Biotechnol. 21:566-569(2003) [PubMed: 12665801] [Abstract]
Cited for: PROTEIN SEQUENCE OF 53-72 (ISOFORM 2).
Tissue: Platelet.
[4]"Human plasma gelsolin binds to fibronectin."
Lind S.E., Janmey P.A.
J. Biol. Chem. 259:13262-13266(1984) [PubMed: 6092370] [Abstract]
Cited for: INTERACTION WITH FIBRONECTIN.
[5]"Amyloid protein in familial amyloidosis (Finnish type) is homologous to gelsolin, an actin-binding protein."
Haltia M., Prelli F., Ghiso J., Kiuru S., Sommer H., Palo J., Frangione B.
Biochem. Biophys. Res. Commun. 167:927-932(1990) [PubMed: 2157434] [Abstract]
Cited for: IDENTITY OF AMYL5 AMYLOID PROTEIN WITH GELSOLIN.
[6]"Finnish hereditary amyloidosis. Amino acid sequence homology between the amyloid fibril protein and human plasma gelsoline."
Maury C.P.J., Alli K., Baumann M.
FEBS Lett. 260:85-87(1990) [PubMed: 2153578] [Abstract]
Cited for: IDENTITY OF AMYL5 AMYLOID PROTEIN WITH GELSOLIN.
[7]"The plasma and cytoplasmic forms of human gelsolin differ in disulfide structure."
Wen D., Corina K., Chow E.P., Miller S., Janmey P.A., Pepinsky R.B.
Biochemistry 35:9700-9709(1996) [PubMed: 8703941] [Abstract]
Cited for: DISULFIDE BOND.
[8]"Functional consequences of disulfide bond formation in gelsolin."
Allen P.G.
FEBS Lett. 401:89-94(1997) [PubMed: 9003812] [Abstract]
Cited for: DISULFIDE BOND.
[9]"Identification of Tyr438 as the major in vitro c-Src phosphorylation site in human gelsolin: a mass spectrometric approach."
De Corte V., Demol H., Goethals M., Van Damme J., Gettemans J., Vandekerckhove J.
Protein Sci. 8:234-241(1999) [PubMed: 10210201] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-86; TYR-409; TYR-465; TYR-603 AND TYR-651.
[10]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[11]"Structure of gelsolin segment 1-actin complex and the mechanism of filament severing."
McLaughlin P.J., Gooch J.T., Mannherz H.-G., Weeds A.G.
Nature 364:685-692(1993) [PubMed: 8395021] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 28-503.
[12]"Spectroscopic studies of a phosphoinositide-binding peptide from gelsolin: behavior in solutions of mixed solvent and anionic micelles."
Xian W., Vegners R., Janmey P.A., Braunlin W.H.
Biophys. J. 69:2695-2702(1995) [PubMed: 8599675] [Abstract]
Cited for: STRUCTURE BY NMR OF 177-196.
[13]"Gelsolin variant (Asn-187) in familial amyloidosis, Finnish type."
Ghiso J., Haltia M., Prelli F., Novello J., Frangione B.
Biochem. J. 272:827-830(1990) [PubMed: 2176481] [Abstract]
Cited for: VARIANT AMYL5 ASN-214.
[14]"Gelsolin-derived familial amyloidosis caused by asparagine or tyrosine substitution for aspartic acid at residue 187."
de la Chapelle A., Tolvanen R., Boysen G., Santavy J., Bleeker-Wagemakers L., Maury C.P.J., Kere J.
Nat. Genet. 2:157-160(1992) [PubMed: 1338910] [Abstract]
Cited for: VARIANTS AMYL5 ASN-214 AND TYR-214.
[15]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed: 16959974] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-22; ILE-201 AND ASN-611.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

X04412 mRNA. Translation: CAA28000.1.
BC017491 mRNA. Translation: AAH17491.1.
BC026033 mRNA. Translation: AAH26033.1.
IPIIPI00026314.
IPI00646773.
PIRFAHUP. A03011.
RefSeqNP_000168.1.
UniGeneHs.522373

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1C0FX-ray2.40S53-176[»]
1C0GX-ray2.00S53-176[»]
1D4XX-ray1.75G52-177[»]
1DEJX-ray2.40S53-176[»]
1EQYX-ray2.30S52-176[»]
1ESVX-ray2.00S52-176[»]
1H1VX-ray2.99G439-769[»]
1KCQX-ray1.65A185-288[»]
1MDUX-ray2.20A/D52-176[»]
1NLVX-ray1.80G52-176[»]
1NM1X-ray1.80G52-176[»]
1NMDX-ray1.90G52-176[»]
1P8XX-ray2.00A/B/C439-782[»]
1P8ZX-ray2.60G52-187[»]
1SOLNMR-A177-196[»]
1T44X-ray2.00G55-179[»]
1YAGX-ray1.90G52-176[»]
1YVNX-ray2.10G52-176[»]
2FF3X-ray2.00A52-179[»]
2FF6X-ray2.05G51-179[»]
2FH1X-ray1.55A/B/C439-782[»]
2FH2X-ray2.50A/B/C439-782[»]
2FH3X-ray2.87A/B/C439-782[»]
2FH4X-ray3.00A/B/C439-782[»]
3CI5X-ray1.70G52-176[»]
3CIPX-ray1.60G52-176[»]
3CJBX-ray3.21G52-176[»]
3CJCX-ray3.90G52-176[»]
SMRP06396. Positions 54-782.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP:2196N.
IntActP06396. 9 interactions.

PTM databases

PhosphoSiteP06396.

2-D gel databases

OGPP06396.

Proteomic databases

PeptideAtlasP06396.
PRIDEP06396.

Genome annotation databases

EnsemblENSG00000148180. Homo sapiens. [Contig view]
GeneID2934.
KEGGhsa:2934.

Organism-specific databases

GeneCardsGC09P123070.
H-InvDBHIX0008346.
HGNCHGNC:4620. GSN.
HPACAB010823.
CAB016728.
MIM105120. phenotype.
137350. gene.
Orphanet69. Amyloidosis.
85448. Familial amyloidosis, Finnish type.
PharmGKBPA29011.
GenAtlasSearch...

Phylogenomic databases

HOGENOMP06396.
HOVERGENP06396.
OMAP06396. WQGAQST.

Enzyme and pathway databases

Pathway_Interaction_DBcaspase_pathway. Caspase cascade in apoptosis.
ar_pathway. Coregulation of Androgen receptor activity.
faspathway. FAS signaling pathway (CD95).
avb3_opn_pathway. Osteopontin-mediated events.
ReactomeREACT_578. Apoptosis.

Gene expression databases

ArrayExpressP06396.
BgeeP06396.
CleanExHS_GSN.
GermOnlineENSG00000148180. Homo sapiens.

Family and domain databases

InterProIPR007122. Gelsolin.
IPR007123. Gelsoln.
[Graphical view]
PANTHERPTHR11977. Gelsolin. 1 hit.
PfamPF00626. Gelsolin. 6 hits.
[Graphical view]
PRINTSPR00597. GELSOLIN.
SMARTSM00262. GEL. 6 hits.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio11625.
PMAP-CutDBP06396.
SOURCESearch...

Entry information

Entry nameGELS_HUMAN
AccessionPrimary (citable) accession number: P06396
Secondary accession number(s): Q8WVV7
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 1, 1988
Last modified: June 16, 2009
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents