CaMPDB :: Substrate

SB0090 : Filamin A

* Basic Information

Organism	Homo sapiens (human)
Protein Names	filamin-A isoform 1 [Homo sapiens]; filamin-A isoform 1; actin binding protein 280; filamin-A; endothelial actin-binding protein; non-muscle filamin; filamin-1; alpha-filamin; Filamin-A; FLN-A; Actin-binding protein 280; ABP-280; Alpha-filamin; Endothelial actin-binding protein; Filamin-1; Non-muscle filamin
Gene Names	FLNA; FLN, FLN1; FLN; FLN1; filamin A, alpha
Gene Locus	Xq28; chromosome X
GO Function	Not available

Entrez Protein	Entrez Nucleotide	Entrez Gene	UniProt	OMIM	HGNC	HPRD	KEGG
NP_001447	NM_001456	2316	Q5HY53	300017	HGNC:3754	N/A	hsa:2316

* Information From OMIM

Description: The FLNA gene encodes filamin A, a widely expressed 280-kD actin-binding protein that regulates reorganization of the actin cytoskeleton by interacting with integrins, transmembrane receptor complexes, and second messengers. Filamins crosslink actin filaments into orthogonal networks in the cytoplasm and participate in the anchoring of membrane proteins to the actin cytoskeleton. Remodeling of the cytoskeleton is central to the modulation of cell shape and migration (Maestrini et al., 1993; Fox et al., 1998).

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* Structure Information

1. Primary Information

Length: 2639 aa

Average Mass: 280.015 kDa

Monoisotopic Mass: 279.843 kDa

2. Domain Information

Annotated Domains: interpro / pfam / smart / prosite

Computationally Assigned Domains (Pfam+HMMER):

domain name	begin	end	score	e-value
CAMSAP CH domain 1.	61	117	10.0	0.1
CAMSAP CH domain 2.	184	208	12.0	0.0
Rib/alpha-like repeat 1.	305	333	32.0	0.1
Domain of unknown function (DUF5060) 1.	334	360	52.0	0.1
Domain of unknown function (DUF5060) 2.	436	460	54.0	0.0
YtkA-like 1.	523	554	54.0	0.2
Domain of unknown function (DUF5060) 3.	633	647	62.0	0.0
Bacterial Ig-like domain (group 3) 1.	695	751	14.0	0.0
Domain of unknown function (DUF5060) 4.	829	847	55.0	0.0
Domain of unknown function (DUF5060) 5.	930	943	57.0	0.0
Domain of unknown function (DUF5060) 6.	1031	1046	62.0	0.0
YtkA-like 2.	1117	1137	64.0	0.0
Y_Y_Y domain 1.	1214	1235	27.0	0.0
Domain of unknown function (DUF5060) 7.	1315	1333	58.0	0.0
YtkA-like 3.	1397	1426	56.0	0.0
Calponin homology (CH) domain 1.	1491	1512	75.0	0.0
Domain of unknown function (DUF5060) 8.	1600	1617	56.0	0.0
YtkA-like 4.	1675	1714	39.0	0.0
--- cleavage 1761 ---
Domain of unknown function (DUF5060) 9.	1821	1830	61.0	0.0
PapC N-terminal domain 1.	1919	1941	26.0	0.0
Filamin/ABP280 repeat 1.	1980	2027	49.0	0.0
Domain of unknown function (DUF5060) 10.	2095	2107	61.0	0.0
Domain of unknown function (DUF5060) 11.	2185	2207	55.0	0.0
YtkA-like 5.	2292	2305	64.0	0.0
Domain of unknown function (DUF5060) 12.	2377	2399	57.0	0.0
Domain of unknown function (DUF5060) 13.	2474	2487	59.0	0.0
Y_Y_Y domain 2.	2607	2624	30.0	0.0

3. Sequence Information

Fasta Sequence: SB0090.fasta

Amino Acid Sequence and Secondary Structures (PsiPred):

4. 3D Information

Known Structures in PDB: 2AAV (NMR; -; A=1863-1956), 2BP3 (X-ray; 232 A; A/B=1863-1956), 2BRQ (X-ray; 210 A; A/B=2236-2329), 2J3S (X-ray; 250 A; A/B=2045-2329), 2JF1 (X-ray; 220 A; A=2236-2329), 2K3T (NMR; -; A=2427-2522), 2K7P (NMR; -; A=1772-1956), 2K7Q (NMR; -; A=1954-2141), 2MTP (NMR; -; A=2236-2330), 2W0P (X-ray; 190 A; A/B=2236-2329), 2WFN (X-ray; 320 A; A/B=1-278), 3CNK (X-ray; 165 A; A/B=2559-2647), 3HOC (X-ray; 230 A; A/B=2-269), 3HOP (X-ray; 230 A; A/B=2-269), 3HOR (X-ray; 270 A; A/B=2-269), 3ISW (X-ray; 280 A; A/B=2236-2329), 3RGH (X-ray; 244 A; A/B=1158-1252), 4M9P (X-ray; 172 A; A=478-766)

* Cleavage Information

1 [sites] cleaved by Calpain 1 or 2

Source Reference: [PubMed ID: 2391361] Gorlin JB, Yamin R, Egan S, Stewart M, Stossel TP, Kwiatkowski DJ, Hartwig JH, Human endothelial actin-binding protein (ABP-280, nonmuscle filamin): a molecular leaf spring. J Cell Biol. 1990 Sep;111(3):1089-105.

Cleavage sites (±10aa)

[Site 1] QYTYAQGGQQ¹⁷⁶¹-TWAPERPLVG

Gln¹⁷⁶¹ Thr

P10	P9	P8	P7	P6	P5	P4	P3	P2	P1

Gln¹⁷⁵²	Tyr¹⁷⁵³	Thr¹⁷⁵⁴	Tyr¹⁷⁵⁵	Ala¹⁷⁵⁶	Gln¹⁷⁵⁷	Gly¹⁷⁵⁸	Gly¹⁷⁵⁹	Gln¹⁷⁶⁰	Gln¹⁷⁶¹

P1'	P2'	P3'	P4'	P5'	P6'	P7'	P8'	P9'	P10'
Thr¹⁷⁶²	Trp¹⁷⁶³	Ala¹⁷⁶⁴	Pro¹⁷⁶⁵	Glu¹⁷⁶⁶	Arg¹⁷⁶⁷	Pro¹⁷⁶⁸	Leu¹⁷⁶⁹	Val¹⁷⁷⁰	Gly¹⁷⁷¹

Sequence conservation (by blast) Sequence conservation (by blast)

Reference peptide (cleaved bond±30 residues)
ALAGDQPSVQPPLRSQQLAPQYTYAQGGQQTWAPERPLVGVNGLDVTSLRPFDLVIPFTI

Summary

#	organism	max score	hits	top seq
1	Homo sapiens	125.00	8	unnamed protein product
2	Homo sapiens	125.00	2	filamin A, alpha isoform 1
3	N/A	112.00	2	FLNA_MOUSE Filamin-A (Alpha-filamin) (Filamin-1)
4	Mus musculus	109.00	5	AF353668_1 filamin A
5	Gallus gallus	48.10	2	filamin
6	Tetraodon nigroviridis	42.00	2	unnamed protein product
7	Rattus norvegicus	35.40	1	PREDICTED: similar to Filamin-C (Gamma-filamin) (
8	Canis familiaris	34.70	2	PREDICTED: similar to Filamin C (Gamma-filamin) (
9	Dictyostelium discoideum AX4	31.60	1	hypothetical protein DDBDRAFT_0218111

Top-ranked sequences

organism	matching
Homo sapiens	Query 1732 ALAGDQPSVQPPLRSQQLAPQYTYAQGGQQ#TWAPERPLVGVNGLDVTSLRPFDLVIPFTI 1791 \|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|#\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\| Query 1732 ALAGDQPSVQPPLRSQQLAPQYTYAQGGQQ#TWAPERPLVGVNGLDVTSLRPFDLVIPFTI 1791
Homo sapiens	Query 1732 ALAGDQPSVQPPLRSQQLAPQYTYAQGGQQ#TWAPERPLVGVNGLDVTSLRPFDLVIPFTI 1791 \|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|#\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\| Query 1732 ALAGDQPSVQPPLRSQQLAPQYTYAQGGQQ#TWAPERPLVGVNGLDVTSLRPFDLVIPFTI 1791
N/A	Query 1732 ALAGDQPSVQPPLRSQQLAPQYTYAQGGQQ#TWAPERPLVGVNGLDVTSLRPFDLVIPFTI 1791 \|\|\|\|\|\|\|+\|\| \|\|\|\|\|\|\|\|\|\|\| \| \|\| \|\|#\|\| \|\|\|\|+\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\| Sbjct 1740 ALAGDQPTVQTPLRSQQLAPQYNYPQGSQQ#TWIPERPMVGVNGLDVTSLRPFDLVIPFTI 1799
Mus musculus	Query 1732 ALAGDQPSVQPPLRSQQLAPQYTYAQGGQQ#TWAPERPLVGVNGLDVTSLRPFDLVIPFTI 1791 \|\|\|\|\|\|\|+\|\| \|\|\|\|\|\|\|\|\|\|\| \| \|\| \|\|#\|\| \|\|\|\|+\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\| Sbjct 50 ALAGDQPTVQTPLRSQQLAPQYNYPQGSQQ#TWIPERPMVGVNGLDVTSLRPFDLVIPFTI 109
Gallus gallus	Query 1761 Q#TWAPERPLVGVNGLDVTSLRPFDLVIPFTI 1791 \|# \| \|\|\|\|+\|\|\|\|\|\|\| \|\|\|\|\|\|\|\|\| \|\| Sbjct 62 Q#VMATERPLLGVNGLDV-GLRPFDLVIPLTI 91
Tetraodon nigroviridis	Query 1764 APERPLVGVNGLDVTSLRPFDLVIPFTI 1791 \| +\|\|+ \|+\|\|\|\|\| \|\|\|\|\|\|\|\|\|\|\|\| Sbjct 1718 ATDRPM-GMNGLDVAGLRPFDLVIPFTI 1744
Rattus norvegicus	Query 1738 PSVQPPLRSQQLAPQYTYAQGGQ--Q#TWAPERPLVGVNGLDVTSLRPFDLVIPFTI 1791 \| \|+ \| \|\| \| + \| # \|\| \| \|+\| \| \|+ + \|\|\|\|+\|\|\|\|\|\|+ Sbjct 1740 PHVEEPAEVLQLHQPYAPLRPGTCPT#HWATEEPVVPVEPLE-SMLRPFNLVIPFTV 1794
Canis familiaris	Query 1738 PSVQPPLRSQQLAPQYTYAQGGQQ#TWAPERPLVGVNGLDVTSLRPFDLVIPFTI 1791 \| \|+ \| \|\| \|\| # \|\| \| \|+\| ++ + \|\|\|\|+\|\|\|\|\|\|+ Sbjct 1732 PHVEEPADVLQLPRPSTYPT----#HWATEEPVVPAEPME-SMLRPFNLVIPFTV 1780
Dictyostelium discoideum AX4	Query 1736 DQPSVQPPLRSQQLAPQYTYAQGGQQ#TWAPERPLVGVNG 1774 ++ \|\| \|++ \| \|\| + \| \|\| # \| \| \| \|+\|\| Sbjct 1418 NKKQVQSPMKPNQPPPQSS-VQSGQT#PMKPRRSLGGING 1455

* References

[PubMed ID: 24403084] Noam Y, Ehrengruber MU, Koh A, Feyen P, Manders EM, Abbott GW, Wadman WJ, Baram TZ, Filamin A promotes dynamin-dependent internalization of hyperpolarization-activated cyclic nucleotide-gated type 1 (HCN1) channels and restricts Ih in hippocampal neurons. J Biol Chem. 2014 Feb 28;289(9):5889-903. doi: 10.1074/jbc.M113.522060. Epub 2014

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[PubMed ID: 24200678] ... Duval D, Lardeux A, Le Tourneau T, Norris RA, Markwald RR, Sauzeau V, Probst V, Le Marec H, Levine R, Schott JJ, Merot J, Valvular dystrophy associated filamin A mutations reveal a new role of its first repeats in small-GTPase regulation. Biochim Biophys Acta. 2014 Feb;1843(2):234-44. doi: 10.1016/j.bbamcr.2013.10.022.

[PubMed ID: 18083107] ... Rikova K, Guo A, Zeng Q, Possemato A, Yu J, Haack H, Nardone J, Lee K, Reeves C, Li Y, Hu Y, Tan Z, Stokes M, Sullivan L, Mitchell J, Wetzel R, Macneill J, Ren JM, Yuan J, Bakalarski CE, Villen J, Kornhauser JM, Smith B, Li D, Zhou X, Gygi SP, Gu TL, Polakiewicz RD, Rush J, Comb MJ, Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell. 2007 Dec 14;131(6):1190-203.

[PubMed ID: 17322306] ... Sugiyama N, Masuda T, Shinoda K, Nakamura A, Tomita M, Ishihama Y, Phosphopeptide enrichment by aliphatic hydroxy acid-modified metal oxide chromatography for nano-LC-MS/MS in proteomics applications. Mol Cell Proteomics. 2007 Jun;6(6):1103-9. Epub 2007 Feb 23.

[PubMed ID: 17408621] ... Cukier IH, Li Y, Lee JM, Cyclin B1/Cdk1 binds and phosphorylates Filamin A and regulates its ability to cross-link actin. FEBS Lett. 2007 Apr 17;581(8):1661-72. Epub 2007 Mar 28.

[PubMed ID: 17081983] ... Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M, Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48.

[PubMed ID: 16565220] ... Nousiainen M, Sillje HH, Sauer G, Nigg EA, Korner R, Phosphoproteome analysis of the human mitotic spindle. Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5391-6. Epub 2006 Mar 24.

[PubMed ID: 15592455] ... Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ, Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat Biotechnol. 2005 Jan;23(1):94-101. Epub 2004 Dec 12.

[PubMed ID: 15302935] ... Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villen J, Li J, Cohn MA, Cantley LC, Gygi SP, Large-scale characterization of HeLa cell nuclear phosphoproteins. Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12130-5. Epub 2004 Aug 9.

[PubMed ID: 15225631] ... Travis MA, van der Flier A, Kammerer RA, Mould AP, Sonnenberg A, Humphries MJ, Interaction of filamin A with the integrin beta 7 cytoplasmic domain: role of alternative splicing and phosphorylation. FEBS Lett. 2004 Jul 2;569(1-3):185-90.

[PubMed ID: 11290523] ... Borbiev T, Verin AD, Shi S, Liu F, Garcia JG, Regulation of endothelial cell barrier function by calcium/calmodulin-dependent protein kinase II. Am J Physiol Lung Cell Mol Physiol. 2001 May;280(5):L983-90.

[PubMed ID: 11336782] ... van der Flier A, Sonnenberg A, Structural and functional aspects of filamins. Biochim Biophys Acta. 2001 Apr 23;1538(2-3):99-117.

[PubMed ID: 11153914] ... Chakarova C, Wehnert MS, Uhl K, Sakthivel S, Vosberg HP, van der Ven PF, Furst DO, Genomic structure and fine mapping of the two human filamin gene paralogues FLNB and FLNC and comparative analysis of the filamin gene family. Hum Genet. 2000 Dec;107(6):597-611.

[PubMed ID: 8088819] ... Patrosso MC, Repetto M, Villa A, Milanesi L, Frattini A, Faranda S, Mancini M, Maestrini E, Toniolo D, Vezzoni P, The exon-intron organization of the human X-linked gene (FLN1) encoding actin-binding protein 280. Genomics. 1994 May 1;21(1):71-6.

[PubMed ID: 7689010] ... Maestrini E, Patrosso C, Mancini M, Rivella S, Rocchi M, Repetto M, Villa A, Frattini A, Zoppe M, Vezzoni P, et al., Mapping of two genes encoding isoforms of the actin binding protein ABP-280, a dystrophin like protein, to Xq28 and to chromosome 7. Hum Mol Genet. 1993 Jun;2(6):761-6.

[PubMed ID: 20301567] ... Robertson S, Otopalatodigital Spectrum Disorders

[PubMed ID: 20301392] ... Sheen VL, Bodell A, Walsh CA, X-Linked Periventricular Heterotopia

[PubMed ID: 1733165] ... Hoar DI, Field LL, Beards F, Hoganson G, Rollnick B, Hoo JJ, Tentative assignment of gene for oto-palato-digital syndrome to distal Xq (Xq26-q28). Am J Med Genet. 1992 Jan 15;42(2):170-2.

[PubMed ID: 2248958] ... Hock RS, Davis G, Speicher DW, Purification of human smooth muscle filamin and characterization of structural domains and functional sites. Biochemistry. 1990 Oct 9;29(40):9441-51.