CaMPDB :: Substrate

SB0061 : [alpha]-II-Spectrin, [alpha]-fodrin, non-erythrocytic

* Basic Information

Organism	Homo sapiens (human)
Protein Names	spectrin, alpha, non-erythrocytic 1 (alpha-fodrin) [Homo sapiens]; spectrin, alpha, non-erythrocytic 1 (alpha-fodrin); non-erythrocytic spectrin alpha; Spectrin alpha chain, non-erythrocytic 1; Alpha-II spectrin; Fodrin alpha chain; Spectrin, non-erythroid alpha subunit
Gene Names	SPTAN1; NEAS, SPTA2; NEAS; SPTA2; spectrin, alpha, non-erythrocytic 1
Gene Locus	9q33-q34; chromosome 9
GO Function	GO:0003779 - actin binding [Evidence TAS] [PMID 2307671]; GO:0005516 - calmodulin binding [Evidence IEA]; GO:0005509 - calcium ion binding [Evidence IEA]; GO:0005200 - structural constituent of cytoskeleton [Evidence TAS] [PMID 2307671]

Entrez Protein	Entrez Nucleotide	Entrez Gene	UniProt	OMIM	HGNC	HPRD	KEGG
NP_003118	NM_003127	6709	Q13813	182810	HGNC:11273	01684	hsa:6709

* Information From OMIM

Description: The spectrins, including nonerythrocytic alpha-spectrin-1 (SPTAN1), are a family of widely-distributed filamentous cytoskeletal proteins with have a highly conserved 106-amino acid repeat structure. Spectrins are heterodimers of a constant alpha-chain and variable, tissue-specific beta-chains. Functions of these proteins include regulation of receptor binding and actin crosslinking (Leto et al., 1988).

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* Structure Information

1. Primary Information

Length: 2472 aa

Average Mass: 284.279 kDa

Monoisotopic Mass: 284.107 kDa

2. Domain Information

Annotated Domains: interpro / pfam / smart / prosite

Computationally Assigned Domains (Pfam+HMMER):

domain name	begin	end	score	e-value
Spectrin repeat 1.	11	42	74.0	1.0
Gas vesicle protein G 1.	59	84	14.0	0.4
Vegetative insecticide protein 3A N terminal 1.	96	194	75.0	0.1
Response gene to complement 32 protein family 1.	350	370	109.0	0.0
Spectrin repeat 2.	468	570	2.0	6.0
Gas vesicle protein G 2.	587	611	13.0	0.1
Peroxidase, family 2 1.	700	760	102.0	0.0
Tetrabrachion 1.	765	776	20.0	0.0
Gas vesicle protein G 3.	849	873	21.0	0.1
Ca2+ insensitive EF hand 1.	949	979	32.0	0.1
Bacterial SH3 domain 1.	982	1022	13.0	0.0
Spectrin repeat 3.	1056	1088	72.0	0.9
Spectrin repeat 4.	1096	1166	6.0	7.7
--- cleavage 1176 ---
Spectrin repeat 5.	1207	1229	81.0	0.2
Response gene to complement 32 protein family 2.	1301	1348	85.0	0.1
Response gene to complement 32 protein family 3.	1539	1562	108.0	0.0
Gas vesicle protein G 4.	1565	1588	13.0	0.1
Response gene to complement 32 protein family 4.	1714	1774	73.0	0.5
EF-hand domain 1.	1832	1843	13.0	0.0
Ca2+ insensitive EF hand 2.	1855	1877	43.0	0.0
Peroxidase, family 2 2.	1892	1958	102.0	0.2
Spectrin repeat 6.	1978	2081	3.0	4.5
Spectrin repeat 7.	2092	2194	2.0	2.4
Spectrin repeat 8.	2206	2310	2.0	9.0
EF-hand domain pair 1.	2326	2344	26.0	0.0
EF-hand domain pair 2.	2370	2395	27.0	0.0
EF-hand domain pair 3.	2420	2430	39.0	0.0

3. Sequence Information

Fasta Sequence: SB0061.fasta

Amino Acid Sequence and Secondary Structures (PsiPred):

4. 3D Information

Known Structures in PDB: 2FOT (X-ray; 245 A; C=1172-1211), 3F31 (X-ray; 230 A; A/B=1-147), 3FB2 (X-ray; 230 A; A/B=1337-1544)

* Cleavage Information

1 [sites] cleaved by Calpain 1

Source Reference: [PubMed ID: 2844821] Harris AS, Croall DE, Morrow JS, The calmodulin-binding site in alpha-fodrin is near the calcium-dependent protease-I cleavage site. J Biol Chem. 1988 Oct 25;263(30):15754-61.

Cleavage sites (±10aa)

[Site 1] VQAVQQQEVY¹¹⁷⁶-GMMPRDETDS

Tyr¹¹⁷⁶ Gly

P10	P9	P8	P7	P6	P5	P4	P3	P2	P1

Val¹¹⁶⁷	Gln¹¹⁶⁸	Ala¹¹⁶⁹	Val¹¹⁷⁰	Gln¹¹⁷¹	Gln¹¹⁷²	Gln¹¹⁷³	Glu¹¹⁷⁴	Val¹¹⁷⁵	Tyr¹¹⁷⁶

P1'	P2'	P3'	P4'	P5'	P6'	P7'	P8'	P9'	P10'
Gly¹¹⁷⁷	Met¹¹⁷⁸	Met¹¹⁷⁹	Pro¹¹⁸⁰	Arg¹¹⁸¹	Asp¹¹⁸²	Glu¹¹⁸³	Thr¹¹⁸⁴	Asp¹¹⁸⁵	Ser¹¹⁸⁶

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

Reference peptide (cleaved bond±30 residues)
LKDINKVAEDLESEGLMAEEVQAVQQQEVYGMMPRDETDSKTASPWKSARLMVHTVATFN

Summary

#	organism	max score	hits	top seq
1	Homo sapiens	127.00	6	alpha II spectrin
2	N/A	127.00	2	nonerythroid alpha-spectrin
3	Rattus norvegicus	125.00	2	alpha-spectrin 2
4	Canis familiaris	125.00	1	PREDICTED: similar to Spectrin alpha chain, brain
5	Mus musculus	122.00	6	SPTA2_MOUSE Spectrin alpha chain, brain (Spectrin
6	Gallus gallus	119.00	3	spectrin, alpha, non-erythrocytic 1 (alpha-fodrin
7	Tetraodon nigroviridis	82.40	1	unnamed protein product

Top-ranked sequences

organism	matching
Homo sapiens	Query 1147 LKDINKVAEDLESEGLMAEEVQAVQQQEVY#GMMPRDETDSKTASPWKSARLMVHTVATFN 1206 \|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|#\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\| Query 1147 LKDINKVAEDLESEGLMAEEVQAVQQQEVY#GMMPRDETDSKTASPWKSARLMVHTVATFN 1206
N/A	Query 1147 LKDINKVAEDLESEGLMAEEVQAVQQQEVY#GMMPRDETDSKTASPWKSARLMVHTVATFN 1206 \|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|#\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\| Query 1147 LKDINKVAEDLESEGLMAEEVQAVQQQEVY#GMMPRDETDSKTASPWKSARLMVHTVATFN 1206
Rattus norvegicus	Query 1147 LKDINKVAEDLESEGLMAEEVQAVQQQEVY#GMMPRDETDSKTASPWKSARLMVHTVATFN 1206 \|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|#\|\|\|\|\|\|\| \|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\| Sbjct 1147 LKDINKVAEDLESEGLMAEEVQAVQQQEVY#GMMPRDEADSKTASPWKSARLMVHTVATFN 1206
Canis familiaris	Query 1147 LKDINKVAEDLESEGLMAEEVQAVQQQEVY#GMMPRDETDSKTASPWKSARLMVHTVATFN 1206 \|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|#\|\|\|\|\|\|+\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\| Sbjct 1243 LKDINKVAEDLESEGLMAEEVQAVQQQEVY#GMMPRDDTDSKTASPWKSARLMVHTVATFN 1302
Mus musculus	Query 1147 LKDINKVAEDLESEGLMAEEVQAVQQQEVY#GMMPRDETDSKTASPWKSARLMVHTVATFN 1206 \|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|#\| \|\|\|\|\| \|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\| Sbjct 1147 LKDINKVAEDLESEGLMAEEVQAVQQQEVY#GAMPRDEADSKTASPWKSARLMVHTVATFN 1206
Gallus gallus	Query 1147 LKDINKVAEDLESEGLMAEEVQAVQQQEVY#GMMPRDETDSKTASPWKSARLMVHTVATFN 1206 \|\|\|\|\|\|\|\| \|\|\|\|\|\|\|\|\|\|\|\|\|\|\|+ \|\|\|\|#\|\|\|\|\|\|\|\|\|\|\|\| \|\|\|\|\|\|\|+\|\|\|\|\|\|\|\|\| Sbjct 1147 LKDINKVANDLESEGLMAEEVQAVEHQEVY#GMMPRDETDSKTVSPWKSARMMVHTVATFN 1206
Tetraodon nigroviridis	Query 1147 LKDINKVAEDLESEGLMAEE---VQAVQQQEVY#GMMP-RDETDSKTASPWKSARLMVHTV 1202 \|+\|\|\|\|\|\| +\|\|\|\|\|\|\|\|\|\| \|\|\| \|\|\|\|+ #\| \| +\|\| \|\|\|\|\|\|\|\|\|+ \|\| \| \| Sbjct 1267 LRDINKVAAELESEGLMAEETPMVQAQQQQELL#GAAPGKDEADSKTASPWKNVRLAVQTT 1326 Query 1203 ATFN 1206 \| \|\| Sbjct 1327 ANFN 1330

* References

[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.

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[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: 16889989] ... Sridharan DM, McMahon LW, Lambert MW, alphaII-Spectrin interacts with five groups of functionally important proteins in the nucleus. Cell Biol Int. 2006 Nov;30(11):866-78. Epub 2006 Jun 30.

[PubMed ID: 16192640] ... Miyazaki K, Takeda N, Ishimaru N, Omotehara F, Arakaki R, Hayashi Y, Analysis of in vivo role of alpha-fodrin autoantigen in primary Sjogren's syndrome. Am J Pathol. 2005 Oct;167(4):1051-9.

[PubMed ID: 15948206] ... Takamure M, Murata KY, Tamada Y, Azuma M, Ueno S, Calpain-dependent alpha-fodrin cleavage at the sarcolemma in muscle diseases. Muscle Nerve. 2005 Sep;32(3):303-9.

[PubMed ID: 15673434] ... Suzuki T, Li W, Zhang JP, Tian QB, Sakagami H, Usuda N, Kondo H, Fujii T, Endo S, A novel scaffold protein, TANC, possibly a rat homolog of Drosophila rolling pebbles (rols), forms a multiprotein complex with various postsynaptic density proteins. Eur J Neurosci. 2005 Jan;21(2):339-50.

[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: 12446661] ... Nedrelow JH, Cianci CD, Morrow JS, c-Src binds alpha II spectrin's Src homology 3 (SH3) domain and blocks calpain susceptibility by phosphorylating Tyr1176. J Biol Chem. 2003 Feb 28;278(9):7735-41. Epub 2002 Nov 20.

[PubMed ID: 11971983] ... Nicolas G, Fournier CM, Galand C, Malbert-Colas L, Bournier O, Kroviarski Y, Bourgeois M, Camonis JH, Dhermy D, Grandchamp B, Lecomte MC, Tyrosine phosphorylation regulates alpha II spectrin cleavage by calpain. Mol Cell Biol. 2002 May;22(10):3527-36.

[PubMed ID: 8993318] ... Stabach PR, Cianci CD, Glantz SB, Zhang Z, Morrow JS, Site-directed mutagenesis of alpha II spectrin at codon 1175 modulates its mu-calpain susceptibility. Biochemistry. 1997 Jan 7;36(1):57-65.

[PubMed ID: 1905928] ... Bennett AF, Hayes NV, Baines AJ, Site specificity in the interactions of synapsin 1 with tubulin. Biochem J. 1991 Jun 15;276 ( Pt 3):793-9.

[PubMed ID: 1902666] ... Frappier T, Stetzkowski-Marden F, Pradel LA, Interaction domains of neurofilament light chain and brain spectrin. Biochem J. 1991 Apr 15;275 ( Pt 2):521-7.

[PubMed ID: 2141335] ... Davis LH, Bennett V, Mapping the binding sites of human erythrocyte ankyrin for the anion exchanger and spectrin. J Biol Chem. 1990 Jun 25;265(18):10589-96.

[PubMed ID: 2307671] ... Moon RT, McMahon AP, Generation of diversity in nonerythroid spectrins. Multiple polypeptides are predicted by sequence analysis of cDNAs encompassing the coding region of human nonerythroid alpha-spectrin. J Biol Chem. 1990 Mar 15;265(8):4427-33.

[PubMed ID: 492324] ... Bennett V, Immunoreactive forms of human erythrocyte ankyrin are present in diverse cells and tissues. Nature. 1979 Oct 18;281(5732):597-9.