CaMPDB :: Substrate

SB0073 : Dystrophin

* Basic Information

Organism	Homo sapiens (human)
Protein Names	dystrophin Dp427m isoform [Homo sapiens]; dystrophin Dp427m isoform; Dystrophin
Gene Names	DMD; dystrophin
Gene Locus	Xp21.2; chromosome X
GO Function	Not available

Entrez Protein	Entrez Nucleotide	Entrez Gene	UniProt	OMIM	HGNC	HPRD	KEGG
NP_003997	NM_004006	1756	P11532	300377	HGNC:2928	02303	hsa:1756

* Information From OMIM

Description: The DMD gene encodes dystrophin, a large muscle protein that is mutant in Duchenne (OMIM:310200) and Becker (OMIM:300376) muscular dystrophy, defined as progressive deterioration of muscle tissue and resultant weakness.

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* Structure Information

1. Primary Information

Length: 3685 aa

Average Mass: 426.686 kDa

Monoisotopic Mass: 426.426 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.	36	55	12.0	0.0
CAMSAP CH domain 2.	153	195	10.0	0.0
Latarcin precursor 1.	322	359	14.0	0.0
Spc7 kinetochore protein 1.	440	510	160.0	9.4
Spc7 kinetochore protein 2.	579	663	198.0	7.2
--- cleavage 690 ---
Spc7 kinetochore protein 3.	757	854	159.0	4.2
Spc7 kinetochore protein 4.	970	1071	153.0	10.4
Apolipoprotein A1/A4/E domain 1.	1100	1243	52.0	12.5
Spc7 kinetochore protein 5.	1298	1394	154.0	6.4
Spc7 kinetochore protein 6.	1451	1595	114.0	16.9
Spc7 kinetochore protein 7.	1675	1766	142.0	7.8
Spectrin repeat 1.	1798	1871	33.0	9.6
Spectrin repeat 2.	1877	1977	1.0	5.7
--- cleavage 1992 ---
Spc7 kinetochore protein 8.	2024	2157	151.0	2.4
Spc7 kinetochore protein 9.	2168	2235	191.0	7.8
Spc7 kinetochore protein 10.	2287	2339	189.0	8.4
Spc7 kinetochore protein 11.	2498	2600	157.0	18.7
EF hand 1.	2612	2650	86.0	0.1
Spc7 kinetochore protein 12.	2669	2766	164.0	5.7
Spc7 kinetochore protein 13.	2897	2979	197.0	4.9
WW domain 1.	3059	3086	3.0	2.1
ASCH domain 1.	3137	3167	39.0	0.0
EF-hand 1.	3211	3302	1.0	0.0
Zinc finger, ZZ type 1.	3308	3352	2.0	4.2
Latarcin precursor 2.	3367	3386	57.0	0.1
Spc7 kinetochore protein 14.	3504	3599	163.0	9.0

3. Sequence Information

Fasta Sequence: SB0073.fasta

Amino Acid Sequence and Secondary Structures (PsiPred):

4. 3D Information

Known Structures in PDB: 1DXX (X-ray; 260 A; A/B/C/D=1-246), 1EG3 (X-ray; 200 A; A=3046-3306), 1EG4 (X-ray; 200 A; A=3046-3306), 3UUN (X-ray; 230 A; A/B=338-456)

* Cleavage Information

2 [sites] cleaved by Calpain 2

Source Reference: [PubMed ID: 1490998] Yoshida M, Suzuki A, Shimizu T, Ozawa E, Proteinase-sensitive sites on isolated rabbit dystrophin. J Biochem. 1992 Oct;112(4):433-9.

Cleavage sites (±10aa)

[Site 1] VMETVTTVTT⁶⁹⁰-REQILVKHAQ

Thr⁶⁹⁰ Arg

P10	P9	P8	P7	P6	P5	P4	P3	P2	P1

Val⁶⁸¹	Met⁶⁸²	Glu⁶⁸³	Thr⁶⁸⁴	Val⁶⁸⁵	Thr⁶⁸⁶	Thr⁶⁸⁷	Val⁶⁸⁸	Thr⁶⁸⁹	Thr⁶⁹⁰

P1'	P2'	P3'	P4'	P5'	P6'	P7'	P8'	P9'	P10'
Arg⁶⁹¹	Glu⁶⁹²	Gln⁶⁹³	Ile⁶⁹⁴	Leu⁶⁹⁵	Val⁶⁹⁶	Lys⁶⁹⁷	His⁶⁹⁸	Ala⁶⁹⁹	Gln⁷⁰⁰

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

Reference peptide (cleaved bond±30 residues)
STAQISQAVTTTQPSLTQTTVMETVTTVTTREQILVKHAQEELPPPPPQKKRQITVDSEI

Summary

#	organism	max score	hits	top seq
1	Homo sapiens	117.00	5	dystrophin
2	N/A	117.00	3	DMD_HUMAN Dystrophin
3	Mus musculus	98.20	1	dystrophin, muscular dystrophy
4	Canis lupus familiaris	96.30	2	dystrophin
5	Gallus gallus	82.80	1	dystrophin
6	Takifugu rubripes	45.40	1	putative dystrophin

Top-ranked sequences

organism	matching
Homo sapiens	Query 661 STAQISQAVTTTQPSLTQTTVMETVTTVTT#REQILVKHAQEELPPPPPQKKRQITVDSEI 720 \|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|#\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\| Query 661 STAQISQAVTTTQPSLTQTTVMETVTTVTT#REQILVKHAQEELPPPPPQKKRQITVDSEI 720
N/A	Query 661 STAQISQAVTTTQPSLTQTTVMETVTTVTT#REQILVKHAQEELPPPPPQKKRQITVDSEI 720 \|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|#\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\| Query 661 STAQISQAVTTTQPSLTQTTVMETVTTVTT#REQILVKHAQEELPPPPPQKKRQITVDSEI 720
Mus musculus	Query 661 STAQISQAVTTTQPSLTQTTVMETVTTVTT#REQILVKHAQEELPPPPPQKKRQITVDSEI 720 \|+\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\| \|\|\|#\|\|\|\|+\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|+ Sbjct 663 SSAQISQAVTTTQPSLTQTTVMETVTMVTT#REQIMVKHAQEELPPPPPQKKRQITVDSEL 722
Canis lupus familiaris	Query 661 STAQISQAVTTTQPSLTQTTVMETVTTVTT#REQILVKHAQEELPPPPPQKKRQITVDSEI 720 \|+\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\| \|\|\|#\|\| \|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\| \|\|\|\|\| Sbjct 662 SSAQISQAVTTTQPSLTQTTVMETVTMVTT#REHILVKHAQEELPPPPPQKKRQIIVDSEI 721
Gallus gallus	Query 661 STAQISQAVTTTQPSLTQTTVMETVTTVTT#REQILVKHAQEELPPPPPQKKRQITVDSEI 720 + \|+\|\|\|\|\|\|\|\| \|\|\|\|\|\|\|\|\|\|\|\| \|\|\|#\|\|\|\|\|\|\|\|\|+\|\|\|\|\|\|\|\| \|\|\|\|+ \|\|\|\|\| Sbjct 663 DSKQVSQAVTTTQTSLTQTTVMETVTMVTT#REQILVKHAKEELPPPPPHKKRQLLVDSEI 722
Takifugu rubripes	Query 661 STAQISQAVTTTQPSLTQTTVMETVTTVTT#REQI-LVKHAQEELPPPPPQKKRQITVDSE 719 \| +\|+\| \|\| \| \| +\| \|\|\| \| \|#\|\|++ \|+ +\| \|\|\|\|\|\|\|\|+ \|\|\|\| Sbjct 686 SISQLSSAVNAPQESELTHSVTATVTKVIT#REKVSAVRQTRE---SPPPQKKRQVAVDSE 742 Query 720 I 720 + Sbjct 743 L 743

[Site 2] MVMTEDMPLE¹⁹⁹²-ISYVPSTYLT

Glu¹⁹⁹² Ile

P10	P9	P8	P7	P6	P5	P4	P3	P2	P1

Met¹⁹⁸³	Val¹⁹⁸⁴	Met¹⁹⁸⁵	Thr¹⁹⁸⁶	Glu¹⁹⁸⁷	Asp¹⁹⁸⁸	Met¹⁹⁸⁹	Pro¹⁹⁹⁰	Leu¹⁹⁹¹	Glu¹⁹⁹²

P1'	P2'	P3'	P4'	P5'	P6'	P7'	P8'	P9'	P10'
Ile¹⁹⁹³	Ser¹⁹⁹⁴	Tyr¹⁹⁹⁵	Val¹⁹⁹⁶	Pro¹⁹⁹⁷	Ser¹⁹⁹⁸	Thr¹⁹⁹⁹	Tyr²⁰⁰⁰	Leu²⁰⁰¹	Thr²⁰⁰²

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

Reference peptide (cleaved bond±30 residues)
FAQFRRLNFAQIHTVREETMMVMTEDMPLEISYVPSTYLTEITHVSQALLEVEQLLNAPD

Summary

#	organism	max score	hits	top seq
1	Homo sapiens	127.00	4	unnamed protein product
2	N/A	127.00	2	DMD_HUMAN Dystrophin
3	Canis lupus familiaris	113.00	1	dystrophin
4	Mus musculus	101.00	1	dystrophin, muscular dystrophy
5	Gallus gallus	79.70	1	dystrophin
6	Mus musculus	32.00	5	mitochondrial trifunctional protein, beta subunit
7	Rattus norvegicus	32.00	1	mitochondrial trifunctional protein, beta subunit

Top-ranked sequences

organism	matching
Homo sapiens	Query 1963 FAQFRRLNFAQIHTVREETMMVMTEDMPLE#ISYVPSTYLTEITHVSQALLEVEQLLNAPD 2022 \|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|#\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\| Query 1963 FAQFRRLNFAQIHTVREETMMVMTEDMPLE#ISYVPSTYLTEITHVSQALLEVEQLLNAPD 2022
N/A	Query 1963 FAQFRRLNFAQIHTVREETMMVMTEDMPLE#ISYVPSTYLTEITHVSQALLEVEQLLNAPD 2022 \|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|#\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\| Query 1963 FAQFRRLNFAQIHTVREETMMVMTEDMPLE#ISYVPSTYLTEITHVSQALLEVEQLLNAPD 2022
Canis lupus familiaris	Query 1963 FAQFRRLNFAQIHTVREETMMVMTEDMPLE#ISYVPSTYLTEITHVSQALLEVEQLLNAPD 2022 \|\|\|\|\|\|\|\|\|\|\|\|\|\|\| \|\|+++ \|\|\|\|\|\|\|\|#\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\| \|\|\|+\|\|\|\|\|\| Sbjct 1965 FAQFRRLNFAQIHTVHEESVVAMTEDMPLE#ISYVPSTYLTEITHVSQALSEVEELLNAPD 2024
Mus musculus	Query 1963 FAQFRRLNFAQIHTVREETMMVMTEDMPLE#ISYVPSTYLTEITHVSQALLEVEQLLNAPD 2022 \|\|\|\|\|\|\|\|\|\|\|\|\|\|+ \|\|\|\|+\| \|\|\|\|\|\|+#+\|\|\|\|\|\|\|\|\|\|\|+\|+ \|\|\| \|\|+ \|\|\| \|+ Sbjct 1965 FAQFRRLNFAQIHTLHEETMVVTTEDMPLD#VSYVPSTYLTEISHILQALSEVDHLLNTPE 2024
Gallus gallus	Query 1963 FAQFRRLNFAQIHTVREETMMVMTEDMPLE#ISYVPSTYLTEITHVSQALLEVEQLLNAP 2021 \|\|\|\|\|\|\|\|+\|\|\| \|\| \|+\| \|\|\|\| \| +\|# +\|\|\|\|\|\|\| \|\| + \|\|\| \|\|\|+ \|\|+\| Sbjct 1965 FAQFRRLNYAQIQTVLEDTTFVMTESMTVE#TTYVPSTYLAEILQLLQALSEVEERLNSP 2023
Mus musculus	Query 1982 MMVMTEDMPLE#ISYVPSTYLTEITHVSQALLEVEQLLNAP 2021 \|++\|+\|\| \| #+ \| \| \|\| + +\|\|\| +\|\|\| \| Sbjct 319 MLIMSEDRALA#MGYKPKAYLRDFIYVSQD--PKDQLLLGP 356
Rattus norvegicus	Query 1982 MMVMTEDMPLE#ISYVPSTYLTEITHVSQALLEVEQLLNAP 2021 \|++\|+\|\| \| #+ \| \| \|\| + +\|\|\| +\|\|\| \| Sbjct 319 MLIMSEDRALA#MGYKPKAYLRDFIYVSQD--PKDQLLLGP 356

* References

[PubMed ID: 24770780] Wang Y, Yang Y, Liu J, Chen XC, Liu X, Wang CZ, He XY, Whole dystrophin gene analysis by next-generation sequencing: a comprehensive genetic diagnosis of Duchenne and Becker muscular dystrophy. Mol Genet Genomics. 2014 Oct;289(5):1013-21. doi: 10.1007/s00438-014-0847-z. Epub

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[PubMed ID: 25108525] ... Wein N, Vulin A, Falzarano MS, Szigyarto CA, Maiti B, Findlay A, Heller KN, Uhlen M, Bakthavachalu B, Messina S, Vita G, Passarelli C, Brioschi S, Bovolenta M, Neri M, Gualandi F, Wilton SD, Rodino-Klapac LR, Yang L, Dunn DM, Schoenberg DR, Weiss RB, Howard MT, Ferlini A, Flanigan KM, Translation from a DMD exon 5 IRES results in a functional dystrophin isoform that attenuates dystrophinopathy in humans and mice. Nat Med. 2014 Sep;20(9):992-1000. doi: 10.1038/nm.3628. Epub 2014 Aug 10.

[PubMed ID: 24996370] ... Guo X, Dai Y, Cui L, Fang Q, A novel dystrophin deletion mutation in a becker muscular dystrophy patient with early-onset dilated cardiomyopathy. Can J Cardiol. 2014 Aug;30(8):956.e1-3. doi: 10.1016/j.cjca.2014.05.002. Epub

[PubMed ID: 24793134] ... Wang Y, Marino-Enriquez A, Bennett RR, Zhu M, Shen Y, Eilers G, Lee JC, Henze J, Fletcher BS, Gu Z, Fox EA, Antonescu CR, Fletcher CD, Guo X, Raut CP, Demetri GD, van de Rijn M, Ordog T, Kunkel LM, Fletcher JA, Dystrophin is a tumor suppressor in human cancers with myogenic programs. Nat Genet. 2014 Jun;46(6):601-6. doi: 10.1038/ng.2974. Epub 2014 May 4.

[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: 20301486] ... Hershberger RE, Morales A, Dilated Cardiomyopathy Overview

[PubMed ID: 20301298] ... Darras BT, Miller DT, Urion DK, Dystrophinopathies

[PubMed ID: 1307253] ... Nigro V, Politano L, Nigro G, Romano SC, Molinari AM, Puca GA, Detection of a nonsense mutation in the dystrophin gene by multiple SSCP. Hum Mol Genet. 1992 Oct;1(7):517-20.

[PubMed ID: 1307251] ... Gorecki DC, Monaco AP, Derry JM, Walker AP, Barnard EA, Barnard PJ, Expression of four alternative dystrophin transcripts in brain regions regulated by different promoters. Hum Mol Genet. 1992 Oct;1(7):505-10.

[PubMed ID: 1319059] ... Lederfein D, Levy Z, Augier N, Mornet D, Morris G, Fuchs O, Yaffe D, Nudel U, A 71-kilodalton protein is a major product of the Duchenne muscular dystrophy gene in brain and other nonmuscle tissues. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5346-50.

[PubMed ID: 3282674] ... Koenig M, Monaco AP, Kunkel LM, The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell. 1988 Apr 22;53(2):219-28.