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Q9UBF9 (MYOTI_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Myotilin
Alternative name(s):
57 kDa cytoskeletal protein
Myofibrillar titin-like Ig domains protein
Titin immunoglobulin domain protein
Gene names
Name:MYOT
Synonyms:TTID
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length498 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Component of a complex of multiple actin cross-linking proteins. Involved in the control of myofibril assembly and stability at the Z lines in muscle cells. Ref.7

Subunit structure

Homodimer. Interacts with ACTA1, ACTN1, FLNA, FLNB, FLNC and MYOZ2. Interacts with the C-terminal region of MYOZ1. Ref.2 Ref.6 Ref.7 Ref.8 Ref.11

Subcellular location

Cell membranesarcolemma. Cytoplasmcytoskeleton. CytoplasmmyofibrilsarcomereZ line. Note: Sarcomeric, also localized to the sarcolemma. Colocalizes with MYOZ1 at the Z-lines in skeletal muscle. Ref.2 Ref.8

Tissue specificity

Expressed in skeletal muscle (at protein level). Expressed in skeletal muscle, heart, bone marrow and thyroid gland. Ref.1 Ref.2

Involvement in disease

Limb-girdle muscular dystrophy 1A (LGMD1A) [MIM:159000]: An autosomal dominant degenerative myopathy with onset within a mean age of 28 years. 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.12

Myopathy, myofibrillar, 3 (MFM3) [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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13

Spheroid body myopathy (SBM) [MIM:182920]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.15

Sequence similarities

Belongs to the myotilin/palladin family.

Contains 2 Ig-like C2-type (immunoglobulin-like) domains.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

FLNCQ143156EBI-296701,EBI-489954

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9UBF9-1)

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: Q9UBF9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-184: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 498498Myotilin
PRO_0000072687

Regions

Domain250 – 33586Ig-like C2-type 1
Domain349 – 44193Ig-like C2-type 2
Region79 – 15072Necessary for interaction with ACTN1
Region215 – 498284Necessary for interaction with ACTA1
Region215 – 493279Necessary for interaction with FLNC

Natural variations

Alternative sequence1 – 184184Missing in isoform 2.
VSP_041450
Natural variant331S → I in a colorectal cancer sample; somatic mutation. Ref.16
VAR_035520
Natural variant391S → F in SBM. Ref.15
VAR_029532
Natural variant501Q → R.
Corresponds to variant rs34717730 [ dbSNP | Ensembl ].
VAR_049914
Natural variant551S → F in LGMD1A and MFM3. Ref.12 Ref.13
VAR_021569
Natural variant571T → I in LGMD1A; does not abolish interaction with ACTN1. Ref.11
Corresponds to variant rs28937597 [ dbSNP | Ensembl ].
VAR_021570
Natural variant601S → C in MFM3. Ref.13
VAR_021571
Natural variant601S → F in MFM3. Ref.13
VAR_021572
Natural variant741K → Q. Ref.1 Ref.2 Ref.5
Corresponds to variant rs41431944 [ dbSNP | Ensembl ].
VAR_029533
Natural variant951S → I in MFM3. Ref.13
VAR_021573

Secondary structure

........................................... 498
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 2, 2010. Version 2.
Checksum: 7F226DD43A0C611B

FASTA49855,395
        10         20         30         40         50         60 
MFNYERPKHF IQSQNPCGSR LQPPGPETSS FSSQTKQSSI IIQPRQCTEQ RFSASSTLSS 

        70         80         90        100        110        120 
HITMSSSAFP ASPKQHAGSN 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 

« Hide

Isoform 2 [UniParc].

Checksum: F4B4033F166A94D2
Show »

FASTA31435,147

References

« Hide '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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANT GLN-74.
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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBUNIT, INTERACTION WITH ACTN1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANT GLN-74.
Tissue: Skeletal muscle.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Pericardium.
[4]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT GLN-74.
Tissue: Liver.
[6]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FLNC.
[7]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MYOFIBRIL ASSEMBLY AND STABILITY, SUBUNIT, INTERACTION WITH ACTA1.
[8]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FLNA; FLNB; FLNC; MYOZ1 AND MYOZ2, SUBCELLULAR LOCATION.
[9]"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] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 249-344.
[10]"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.
[11]"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] [Europe PMC] [Abstract]
Cited for: VARIANT LGMD1A ILE-57, INTERACTION WITH ACTN1.
[12]"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] [Europe PMC] [Abstract]
Cited for: VARIANT LGMD1A PHE-55.
[13]"Mutations in myotilin cause myofibrillar myopathy."
Selcen D., Engel A.G.
Neurology 62:1363-1371(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MFM3 PHE-55; CYS-60; PHE-60 AND ILE-95.
[14]Erratum
Selcen D., Engel A.G.
Neurology 63:405-405(2004)
[15]"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] [Europe PMC] [Abstract]
Cited for: VARIANT SBM PHE-39.
[16]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] ILE-33.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF133820 mRNA. Translation: AAD29051.2.
AF144477 mRNA. Translation: AAD44754.1.
AK300088 mRNA. Translation: BAG61891.1.
AC106791 Genomic DNA. No translation available.
BC005376 mRNA. Translation: AAH05376.1.
CCDSCCDS4194.1. [Q9UBF9-1]
CCDS47268.1. [Q9UBF9-2]
RefSeqNP_001129412.1. NM_001135940.1. [Q9UBF9-2]
NP_006781.1. NM_006790.2.
UniGeneHs.84665.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2KDGNMR-A249-344[»]
2KKQNMR-A344-449[»]
ProteinModelPortalQ9UBF9.
SMRQ9UBF9. Positions 249-449.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114878. 10 interactions.
IntActQ9UBF9. 7 interactions.
STRING9606.ENSP00000239926.

PTM databases

PhosphoSiteQ9UBF9.

Polymorphism databases

DMDM311033402.

Proteomic databases

PaxDbQ9UBF9.
PRIDEQ9UBF9.

Protocols and materials databases

DNASU9499.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000239926; ENSP00000239926; ENSG00000120729. [Q9UBF9-1]
ENST00000421631; ENSP00000391185; ENSG00000120729. [Q9UBF9-2]
GeneID9499.
KEGGhsa:9499.
UCSCuc003lbv.3. human. [Q9UBF9-1]

Organism-specific databases

CTD9499.
GeneCardsGC05P137203.
GeneReviewsMYOT.
HGNCHGNC:12399. MYOT.
HPAHPA037733.
MIM159000. phenotype.
182920. phenotype.
604103. gene.
609200. phenotype.
neXtProtNX_Q9UBF9.
Orphanet266. Autosomal dominant limb-girdle muscular dystrophy type 1A.
98911. Distal myotilinopathy.
268129. Spheroid body myopathy.
PharmGKBPA37064.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG147321.
HOGENOMHOG000028074.
HOVERGENHBG066530.
InParanoidQ9UBF9.
OMADSVKLEC.
PhylomeDBQ9UBF9.

Gene expression databases

ArrayExpressQ9UBF9.
BgeeQ9UBF9.
CleanExHS_MYOT.
GenevestigatorQ9UBF9.

Family and domain databases

Gene3D2.60.40.10. 2 hits.
InterProIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
[Graphical view]
PfamPF07679. I-set. 2 hits.
[Graphical view]
SMARTSM00409. IG. 1 hit.
SM00408. IGc2. 1 hit.
[Graphical view]
PROSITEPS50835. IG_LIKE. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMYOT. human.
EvolutionaryTraceQ9UBF9.
GeneWikiMyotilin.
GenomeRNAi9499.
NextBio35590.
PROQ9UBF9.
SOURCESearch...

Entry information

Entry nameMYOTI_HUMAN
AccessionPrimary (citable) accession number: Q9UBF9
Secondary accession number(s): A0A4R6, B4DT79
Entry history
Integrated into UniProtKB/Swiss-Prot: March 29, 2005
Last sequence update: November 2, 2010
Last modified: July 9, 2014
This is version 125 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM