Reviewed, UniProtKB/Swiss-Prot Q9UBF9 (MYOTI_HUMAN)

Names and originHide

Protein names

Recommended name:
Myotilin

Alternative name(s):
Titin immunoglobulin domain protein
Myofibrillar titin-like Ig domains protein
57 kDa cytoskeletal protein

Gene names

Name:	MYOT
Synonyms:	TTID

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributesHide

Sequence length	498 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)Hide

Function	Component of a complex of multiple actin cross-linking proteins. Involved in the control of myofibril assembly and stability at the Z-disks in muscle cells. Ref.5
Subunit structure	Homodimer. Interacts with ACTA1, ACTN1, FLNA, FLNB, FLNC and MYOZ2. Interacts with the C-terminal region of MYOZ1. Ref.5 Ref.2 Ref.4 Ref.6 Ref.9
Subcellular location	Cell membrane › sarcolemma. Cytoplasm › cytoskeleton. Cytoplasm › myofibril › sarcomere › Z-disk. Note: Sarcomeric, also localized to the sarcolemma. Colocalizes with MYOZ1 at the Z-lines in skeletal muscle. Ref.2 Ref.6
Tissue specificity	Expressed in skeletal muscle (at protein level). Expressed in skeletal muscle, heart, bone marrow and thyroid gland. Ref.2 Ref.1
Involvement in disease	Defects in MYOT are the cause of limb-girdle muscular dystrophy type 1A (LGMD1A) [MIM:159000]. LGMD1A is an autosomal dominant degenerative myopathy with onset within a mean age of 28 years. LGMD1A is characterized by progressive skeletal muscle weakness of the hip and shoulder girdles, later progressing to include distal weakness, as well as a distinctive dysarthric pattern of speech. Affected muscle exhibits disorganization and streaming of the Z-line. Ref.9 Ref.10 Defects in MYOT are the cause of myopathy myofibrillar myotylin-related (MFM-MYOT) [MIM:609200]. A neuromuscular disorder characterized by progressive skeletal muscle weakness greater distally than proximally, tight heel cords, hyporeflexia, cardiomyopathy and peripheral neuropathy in some patients. Affected muscle exhibits disorganization and streaming of the Z-line, presence of large hyaline structures, excessive accumulation of myotilin and other ectopically expressed proteins and prominent congophilic deposits. Ref.11 Defects in MYOT are the cause of spheroid body myopathy (SBM) [MIM:182920]. SBM is an autosomal dominant form of myofibrillar myopathy (MFM), characterized by slowly progressing proximal muscle weakness and dysarthric nasal speech. There is no evidence of cardiomyopathy. Muscle biopsy shows spheroid bodies within the type I muscle fibers. Ref.13
Sequence similarities	Belongs to the myotilin/palladin family. Contains 2 Ig-like C2-type (immunoglobulin-like) domains.

OntologiesHide

Keywords
Cellular component	Cell membrane Cytoplasm Cytoskeleton Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Limb-girdle muscular dystrophy Myofibrillar myopathy
Domain	Immunoglobulin domain Repeat
Ligand	Actin-binding
Molecular function	Muscle protein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	muscle contraction Traceable author statement. Source: ProtInc
Cellular component	Z disc Inferred from electronic annotation. Source: UniProtKB-SubCell actin cytoskeleton Traceable author statement. Source: ProtInc sarcolemma Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	actin binding Inferred from electronic annotation. Source: UniProtKB-KW structural constituent of muscle Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactionsHide

With	Entry	#Exp.	IntAct	Notes
FLNC	Q14315	5	EBI-296701,EBI-489954

Sequence annotation (Features)Hide

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 498

498

Myotilin

PRO_0000072687

Regions

Domain

250 – 335

86

Ig-like C2-type 1

Domain

349 – 441

93

Ig-like C2-type 2

Region

79 – 150

72

Necessary for interaction with ACTN1

Region

215 – 498

284

Necessary for interaction with ACTA1

Region

215 – 493

279

Necessary for interaction with FLNC

Natural variations

Natural variant

33

1

S → I in a colorectal cancer sample; somatic mutation. Ref.14

VAR_035520

Natural variant

39

1

S → F in SBM. Ref.13

VAR_029532

Natural variant

50

1

Q → R. [dbSNP:rs34717730]

VAR_049914

Natural variant

55

1

S → F in LGMD1A and MFM-MYOT. Ref.10 Ref.11

VAR_021569

Natural variant

57

1

T → I in LGMD1A; does not abolish interaction with ACTN1. [dbSNP:rs28937597] Ref.9

VAR_021570

Natural variant

60

1

S → C in MFM-MYOT. Ref.11

VAR_021571

Natural variant

60

1

S → F in MFM-MYOT. Ref.11

VAR_021572

Natural variant

74

1

Q → K. [dbSNP:rs41431944]

VAR_029533

Natural variant

95

1

S → I in MFM-MYOT. Ref.11

VAR_021573

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

498

Helix Strand Turn

Details...

Beta strand

259 – 262

4

Beta strand

267 – 271

5

Beta strand

280 – 285

6

Beta strand

294 – 296

3

Beta strand

298 – 300

3

Beta strand

306 – 312

7

Helix

315 – 317

3

Beta strand

321 – 326

6

Beta strand

332 – 336

5

Beta strand

338 – 341

4

SequencesHide

	Sequence		Length	Mass (Da)
	Q9UBF9-1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: C9C8467F9A64F91F	FASTA	498	55,395
	10 20 30 40 50 60 MFNYERPKHF IQSQNPCGSR LQPPGPETSS FSSQTKQSSI IIQPRQCTEQ RFSASSTLSS 70 80 90 100 110 120 HITMSSSAFP ASPQQHAGSN PGQRVTTTYN QSPASFLSSI LPSQPDYNSS KIPSAMDSNY 130 140 150 160 170 180 QQSSAGQPIN AKPSQTANAK PIPRTPDHEI QGSKEALIQD LERKLKCKDT LLHNGNQRLT 190 200 210 220 230 240 YEEKMARRLL GPQNAAAVFQ AQDDSGAQDS QQHNSEHARL QVPTSQVRSR STSRGDVNDQ 250 260 270 280 290 300 DAIQEKFYPP RFIQVPENMS IDEGRFCRMD FKVSGLPAPD VSWYLNGRTV QSDDLHKMIV 310 320 330 340 350 360 SEKGLHSLIF EVVRASDAGA YACVAKNRAG EATFTVQLDV LAKEHKRAPM FIYKPQSKKV 370 380 390 400 410 420 LEGDSVKLEC QISAIPPPKL FWKRNNEMVQ FNTDRISLYQ DNTGRVTLLI KDVNKKDAGW 430 440 450 460 470 480 YTVSAVNEAG VTTCNTRLDV TARPNQTLPA PKQLRVRPTF SKYLALNGKG LNVKQAFNPE 490 GEFQRLAAQS GLYESEEL

ReferencesHide

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"TTID: a novel gene at 5q31 encoding a protein with titin-like features." Godley L.A., Lai F., Liu J., Zhao N., Le Beau M.M. Genomics 60:226-233(1999) [PubMed: 10486214] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Bone marrow.
[2]	"Myotilin, a novel sarcomeric protein with two Ig-like domains, is encoded by a candidate gene for limb-girdle muscular dystrophy." Salmikangas P., Mykkaenen O.M., Groenholm M., Heiska L., Kere J., Carpen O. Hum. Mol. Genet. 8:1329-1336(1999) [PubMed: 10369880] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBUNIT, INTERACTION WITH ACTN1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Skeletal muscle.
[3]	"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]. Tissue: Liver.
[4]	"Indications for a novel muscular dystrophy pathway: gamma-filamin, the muscle-specific filamin isoform, interacts with myotilin." van der Ven P.F.M., Wiesner S., Salmikangas P., Auerbach D., Himmel M., Kempa S., Hayess K., Pacholsky D., Taivainen A., Schroeder R., Carpen O., Fuerst D.O. J. Cell Biol. 151:235-248(2000) [PubMed: 11038172] [Abstract] Cited for: INTERACTION WITH FLNC.
[5]	"Myotilin, the limb-girdle muscular dystrophy 1A (LGMD1A) protein, cross-links actin filaments and controls sarcomere assembly." Salmikangas P., van der Ven P.F.M., Lalowski M., Taivainen A., Zhao F., Suila H., Schroeder R., Lappalainen P., Fuerst D.O., Carpen O. Hum. Mol. Genet. 12:189-203(2003) [PubMed: 12499399] [Abstract] Cited for: FUNCTION IN MYOFIBRIL ASSEMBLY AND STABILITY, SUBUNIT, INTERACTION WITH ACTA1.
[6]	"The Z-disc proteins myotilin and FATZ-1 interact with each other and are connected to the sarcolemma via muscle-specific filamins." Gontier Y., Taivainen A., Fontao L., Sonnenberg A., van der Flier A., Carpen O., Faulkner G., Borradori L. J. Cell Sci. 118:3739-3749(2005) [PubMed: 16076904] [Abstract] Cited for: INTERACTION WITH FLNA; FLNB; FLNC; MYOZ1 AND MYOZ2, SUBCELLULAR LOCATION.
[7]	"Solution structure of the first immunoglobulin domain of human myotilin." Heikkinen O., Permi P., Koskela H., Carpen O., Ylaenne J., Kilpelaeinen I. J. Biomol. NMR 44:107-112(2009) [PubMed: 19418025] [Abstract] Cited for: STRUCTURE BY NMR OF 249-344.
[8]	"Solution NMR structure of the Ig-like C2-type 2 domain of human myotilin. Northeast structural genomics target HR3158." Northeast structural genomics consortium (NESG) Submitted (JUL-2009) to the PDB data bank Cited for: STRUCTURE BY NMR OF 344-449.
[9]	"Myotilin is mutated in limb girdle muscular dystrophy 1A." Hauser M.A., Horrigan S.K., Salmikangas P., Torian U.M., Viles K.D., Dancel R., Tim R.W., Taivainen A., Bartoloni L., Gilchrist J.M., Stajich J.M., Gaskell P.C., Gilbert J.R., Vance J.M., Pericak-Vance M.A., Carpen O., Westbrook C.A., Speer M.C. Hum. Mol. Genet. 9:2141-2147(2000) [PubMed: 10958653] [Abstract] Cited for: VARIANT LGMD1A ILE-57, INTERACTION WITH ACTN1.
[10]	"Myotilin mutation found in second pedigree with LGMD1A." Hauser M.A., Conde C.B., Kowaljow V., Zeppa G., Taratuto A.L., Torian U.M., Vance J.M., Pericak-Vance M.A., Speer M.C., Rosa A.L. Am. J. Hum. Genet. 71:1428-1432(2002) [PubMed: 12428213] [Abstract] Cited for: VARIANT LGMD1A PHE-55.
[11]	"Mutations in myotilin cause myofibrillar myopathy." Selcen D., Engel A.G. Neurology 62:1363-1371(2004) [PubMed: 15111675] [Abstract] Cited for: VARIANTS MFM-MYOT PHE-55; CYS-60; PHE-60 AND ILE-95.
[12]	Erratum Selcen D., Engel A.G. Neurology 63:405-405(2004)
[13]	"A mutation in myotilin causes spheroid body myopathy." Foroud T., Pankratz N., Batchman A.P., Pauciulo M.W., Vidal R., Miravalle L., Goebel H.H., Cushman L.J., Azzarelli B., Horak H., Farlow M., Nichols W.C. Neurology 65:1936-1940(2005) [PubMed: 16380616] [Abstract] Cited for: VARIANT SBM PHE-39.
[14]	"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: VARIANT [LARGE SCALE ANALYSIS] ILE-33.
+	Additional computationally mapped references.

Web resourcesHide

GeneReviews

Cross-referencesHide

Sequence databases

EMBL
GenBank
DDBJ

AF133820 mRNA. Translation: AAD29051.2.
AF144477 mRNA. Translation: AAD44754.1.
BC005376 mRNA. Translation: AAH05376.1.

IPI

IPI00009551.

RefSeq

NP_001129412.1.
NP_006781.1.

UniGene

Hs.84665

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2KDG	NMR	-	A	249-344	[»]
2KKQ	NMR	-	A	344-449	[»]

SMR

Q9UBF9. Positions 248-441.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UBF9. 2 interactions.

STRING

Q9UBF9.

PTM databases

PhosphoSite

Q9UBF9.

Proteomic databases

PRIDE

Q9UBF9.

Genome annotation databases

Ensembl

ENST00000239926; ENSP00000239926; ENSG00000120729; Homo sapiens. [Genome view]

GeneID

9499.

KEGG

hsa:9499.

UCSC

uc003lbv.1. human.

Organism-specific databases

CTD

9499.

GeneCards

GC05P137233.

H-InvDB

HIX0005203.

HGNC

HGNC:12399. MYOT.

MIM

159000. phenotype.
182920. phenotype.
604103. gene.
609200. phenotype.

Orphanet

266. Autosomal dominant limb-girdle muscular dystrophy type 1A.
98911. Myotilinopathy.

PharmGKB

PA37064.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG09505.

HOGENOM

HBG444120.

HOVERGEN

HBG066530.

InParanoid

Q9UBF9.

Gene expression databases

ArrayExpress

Q9UBF9.

Bgee

Q9UBF9.

CleanEx

HS_MYOT.

Genevestigator

Q9UBF9.

GermOnline

ENSG00000120729. Homo sapiens.

Family and domain databases

InterPro

IPR007110. Ig-like.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
[Graphical view]

Gene3D

G3DSA:2.60.40.10. Ig-like_fold. 2 hits.

Pfam

PF07679. I-set. 2 hits.
[Graphical view]

SMART

SM00409. IG. 1 hit.
SM00408. IGc2. 1 hit.
[Graphical view]

PROSITE

PS50835. IG_LIKE. 2 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

35590.

SOURCE

Search...

Entry informationHide

Entry name

MYOTI_HUMAN

Accession

Primary (citable) accession number: Q9UBF9
Secondary accession number(s): A0A4R6

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 29, 2005
Last sequence update:	May 1, 2000
Last modified:	July 13, 2010
This is version 87 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.