Reviewed,
UniProtKB/Swiss-Prot Q9UBF9 (MYOTI_HUMAN)
Last modified
July 13, 2010.
Version 87.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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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 |
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| 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 cytoskeletonTraceable author statement. Source: ProtInc sarcolemmaInferred from electronic annotation. Source: UniProtKB-SubCell |
| Molecular function | actin binding Inferred from electronic annotation. Source: UniProtKB-KW structural constituent of muscleTraceable author statement. Source: ProtInc |
| Complete GO annotation... | |
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 | |||||||||||||||||||||||||||||
Helix Strand Turn | |||||||||||||||||||||||||||||
| 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
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ReferencesHide
| « 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: 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. Velculescu V.E.Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ILE-33. |
| + | Additional computationally mapped references. |
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 |
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| 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 |
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| 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. | ||||||||
Relevant documentsHide
| Human chromosome 5 Human chromosome 5: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with


