Reviewed, UniProtKB/Swiss-Prot P06396 (GELS_HUMAN)

Names and origin

Protein names

Recommended name:
    Gelsolin
Alternative name(s):
    Actin-depolymerizing factor
      Short name=ADF
    Brevin
    AGEL

Gene names

Name:

GSN

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	782 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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: Cytoplasm › cytoskeleton. 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.

Ontologies

Keywords
Cellular component	Amyloid Cytoplasm Cytoskeleton Secreted
Coding sequence diversity	Alternative initiation Polymorphism
Disease	Amyloidosis Disease mutation
Domain	Repeat Signal
Ligand	Actin-binding Calcium
Molecular function	Actin capping
PTM	Disulfide bond Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	actin filament polymerization Ref.1 Inferred from direct assay. Source: UniProtKB actin filament severing Ref.1 Inferred from direct assay. Source: UniProtKB barbed-end actin filament capping Traceable author statement. Source: ProtInc
Cellular component	actin cytoskeleton Traceable author statement. Source: ProtInc cytosol Ref.1 Inferred from direct assay. Source: UniProtKB extracellular region Ref.1 Inferred from direct assay. Source: UniProtKB
Molecular function	actin binding Inferred from electronic annotation. Source: UniProtKB-KW calcium ion binding Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
act-1	P10983	1	EBI-351506,EBI-312653	From a different organism.
ARRB1	P49407	1	EBI-351506,EBI-743313
ARRB2	P32121	1	EBI-351506,EBI-714559
CASP4	P49662	1	EBI-351506,EBI-1057327
MDM2	Q00987	1	EBI-1018556,EBI-389668
PPM1B	O75688	1	EBI-351506,EBI-1047039

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 27

27

Chain

28 – 782

755

Gelsolin

PRO_0000036385

Regions

Repeat

76 – 126

51

Gelsolin-like 1

Repeat

198 – 238

41

Gelsolin-like 2

Repeat

314 – 356

43

Gelsolin-like 3

Repeat

453 – 504

52

Gelsolin-like 4

Repeat

576 – 616

41

Gelsolin-like 5

Repeat

679 – 721

43

Gelsolin-like 6

Region

53 – 176

124

Actin-severing Potential

Region

123 – 126

4

Actin-actin interfilament contact point

Region

162 – 169

8

Polyphosphoinositide binding By similarity

Region

188 – 196

9

Polyphosphoinositide binding By similarity

Region

434 – 782

349

Actin-binding, Ca-sensitive Potential

Amino acid modifications

Modified residue

86

1

Phosphotyrosine; by SRC; in vitro Ref.9

Modified residue

409

1

Phosphotyrosine; by SRC; in vitro Ref.9

Modified residue

465

1

Phosphotyrosine; by SRC Ref.9

Modified residue

603

1

Phosphotyrosine; by SRC; in vitro Ref.9

Modified residue

651

1

Phosphotyrosine; by SRC; in vitro Ref.9

Disulfide bond

215 ↔ 228

In isoform 1 Ref.7 Ref.8

Natural variations

Alternative sequence

1 – 51

51

Missing in isoform 2.

VSP_018959

Natural variant

22

1

S → L in a breast cancer sample; somatic mutation. Ref.15

VAR_036337

Natural variant

129

1

A → T: dbSNP rs2230287.

VAR_024690

Natural variant

201

1

T → I in a breast cancer sample; somatic mutation. Ref.15

VAR_036338

Natural variant

214

1

D → N in AMYL5. Ref.13 Ref.14

VAR_007718

Natural variant

214

1

D → Y in AMYL5. Ref.13 Ref.14

VAR_007719

Natural variant

611

1

S → N in a breast cancer sample; somatic mutation. Ref.15

VAR_036339

Natural variant

668

1

R → L: dbSNP rs9696578.

VAR_033958

Secondary structure

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782

Helix Strand Turn

Details...

Helix

57 – 61

5

Beta strand

64 – 74

11

Beta strand

77 – 80

4

Helix

83 – 85

3

Beta strand

88 – 90

3

Beta strand

94 – 102

9

Beta strand

108 – 116

9

Helix

122 – 138

17

Turn

139 – 141

3

Beta strand

143 – 149

7

Helix

155 – 158

4

Beta strand

166 – 169

4

Beta strand

188 – 203

16

Helix

207 – 209

3

Beta strand

214 – 219

6

Beta strand

221 – 228

8

Helix

234 – 250

17

Beta strand

256 – 262

7

Helix

268 – 274

7

Beta strand

447 – 453

7

Beta strand

456 – 459

4

Helix

462 – 464

3

Beta strand

467 – 469

3

Beta strand

472 – 482

11

Beta strand

485 – 494

10

Helix

500 – 516

17

Turn

517 – 519

3

Beta strand

521 – 527

7

Helix

533 – 537

5

Turn

538 – 541

4

Beta strand

544 – 548

5

Turn

553 – 555

3

Beta strand

562 – 570

9

Beta strand

576 – 581

6

Helix

585 – 587

3

Beta strand

592 – 597

6

Beta strand

602 – 606

5

Helix

612 – 624

13

Beta strand

630 – 633

4

Helix

639 – 644

6

Helix

655 – 658

4

Beta strand

668 – 671

4

Helix

690 – 692

3

Beta strand

697 – 702

6

Beta strand

707 – 711

5

Helix

717 – 733

17

Beta strand

744 – 748

5

Helix

754 – 757

4

Beta strand

760 – 762

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Secreted) (Plasma) [UniParc]. Last modified January 1, 1988. Version 1. Checksum: 8CEBC52257A160F7	FASTA	782	85,698
	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
	Isoform 2 (Cytoplasmic). Checksum: 0C5C30CE497A0684	FASTA	731	80,641
	10 20 30 40 50 60 MVVEHPEFLK AGKEPGLQIW RVEKFDLVPV PTNLYGDFFT GDAYVILKTV QLRNGNLQYD 70 80 90 100 110 120 LHYWLGNECS QDESGAAAIF TVQLDDYLNG RAVQHREVQG FESATFLGYF KSGLKYKKGG 130 140 150 160 170 180 VASGFKHVVP NEVVVQRLFQ VKGRRVVRAT EVPVSWESFN NGDCFILDLG NNIHQWCGSN 190 200 210 220 230 240 SNRYERLKAT QVSKGIRDNE RSGRARVHVS EEGTEPEAML QVLGPKPALP AGTEDTAKED 250 260 270 280 290 300 AANRKLAKLY KVSNGAGTMS VSLVADENPF AQGALKSEDC FILDHGKDGK IFVWKGKQAN 310 320 330 340 350 360 TEERKAALKT ASDFITKMDY PKQTQVSVLP EGGETPLFKQ FFKNWRDPDQ TDGLGLSYLS 370 380 390 400 410 420 SHIANVERVP FDAATLHTST AMAAQHGMDD DGTGQKQIWR IEGSNKVPVD PATYGQFYGG 430 440 450 460 470 480 DSYIILYNYR HGGRQGQIIY NWQGAQSTQD EVAASAILTA QLDEELGGTP VQSRVVQGKE 490 500 510 520 530 540 PAHLMSLFGG KPMIIYKGGT SREGGQTAPA STRLFQVRAN SAGATRAVEV LPKAGALNSN 550 560 570 580 590 600 DAFVLKTPSA AYLWVGTGAS EAEKTGAQEL LRVLRAQPVQ VAEGSEPDGF WEALGGKAAY 610 620 630 640 650 660 RTSPRLKDKK MDAHPPRLFA CSNKIGRFVI EEVPGELMQE DLATDDVMLL DTWDQVFVWV 670 680 690 700 710 720 GKDSQEEEKT EALTSAKRYI ETDPANRDRR TPITVVKQGF EPPSFVGWFL GWDDDYWSVD 730 PLDRAMAELA A

References

	« Hide 'large scale' referencesShow '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. , 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

GeneReviews

Wikipedia

Gelsolin entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

X04412 mRNA. Translation: CAA28000.1.
BC017491 mRNA. Translation: AAH17491.1.
BC026033 mRNA. Translation: AAH26033.1.

IPI

IPI00026314.
IPI00646773.

PIR

FAHUP. A03011.

RefSeq

NP_000168.1.

UniGene

Hs.522373

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1C0F	X-ray	2.40	S	53-176	[»]
1C0G	X-ray	2.00	S	53-176	[»]
1D4X	X-ray	1.75	G	52-177	[»]
1DEJ	X-ray	2.40	S	53-176	[»]
1EQY	X-ray	2.30	S	52-176	[»]
1ESV	X-ray	2.00	S	52-176	[»]
1H1V	X-ray	2.99	G	439-769	[»]
1KCQ	X-ray	1.65	A	185-288	[»]
1MDU	X-ray	2.20	A/D	52-176	[»]
1NLV	X-ray	1.80	G	52-176	[»]
1NM1	X-ray	1.80	G	52-176	[»]
1NMD	X-ray	1.90	G	52-176	[»]
1P8X	X-ray	2.00	A/B/C	439-782	[»]
1P8Z	X-ray	2.60	G	52-187	[»]
1SOL	NMR	-	A	177-196	[»]
1T44	X-ray	2.00	G	55-179	[»]
1YAG	X-ray	1.90	G	52-176	[»]
1YVN	X-ray	2.10	G	52-176	[»]
2FF3	X-ray	2.00	A	52-179	[»]
2FF6	X-ray	2.05	G	51-179	[»]
2FH1	X-ray	1.55	A/B/C	439-782	[»]
2FH2	X-ray	2.50	A/B/C	439-782	[»]
2FH3	X-ray	2.87	A/B/C	439-782	[»]
2FH4	X-ray	3.00	A/B/C	439-782	[»]
3CI5	X-ray	1.70	G	52-176	[»]
3CIP	X-ray	1.60	G	52-176	[»]
3CJB	X-ray	3.21	G	52-176	[»]
3CJC	X-ray	3.90	G	52-176	[»]

SMR

P06396. Positions 54-782.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:2196N.

IntAct

P06396. 9 interactions.

PTM databases

PhosphoSite

P06396.

2-D gel databases

OGP

P06396.

Proteomic databases

PeptideAtlas

P06396.

PRIDE

P06396.

Genome annotation databases

Ensembl

ENSG00000148180. Homo sapiens. [Contig view]

GeneID

2934.

KEGG

hsa:2934.

Organism-specific databases

GeneCards

GC09P123070.

H-InvDB

HIX0008346.

HGNC

HGNC:4620. GSN.

HPA

CAB010823.
CAB016728.

MIM

105120. phenotype.
137350. gene.

Orphanet

69. Amyloidosis.
85448. Familial amyloidosis, Finnish type.

PharmGKB

PA29011.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P06396.

HOVERGEN

P06396.

OMA

P06396. WQGAQST.

Enzyme and pathway databases

Pathway_Interaction_DB

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

Reactome

REACT_578. Apoptosis.

Gene expression databases

ArrayExpress

P06396.

Bgee

P06396.

CleanEx

HS_GSN.

GermOnline

ENSG00000148180. Homo sapiens.

Family and domain databases

InterPro

IPR007122. Gelsolin.
IPR007123. Gelsoln.
[Graphical view]

PANTHER

PTHR11977. Gelsolin. 1 hit.

Pfam

PF00626. Gelsolin. 6 hits.
[Graphical view]

PRINTS

PR00597. GELSOLIN.

SMART

SM00262. GEL. 6 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

11625.

PMAP-CutDB

P06396.

SOURCE

Search...

Entry information

Entry name

GELS_HUMAN

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)