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Reviewed, UniProtKB/Swiss-Prot P50570 (DYN2_HUMAN)

Last modified November 25, 2008. Version 84. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Dynamin-2
    EC=3.6.5.5
Gene names
Name: DNM2
Synonyms: DYN2
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length870 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Microtubule-associated force-producing protein involved in producing microtubule bundles and able to bind and hydrolyze GTP. Most probably involved in vesicular trafficking processes, in particular endocytosis.

Catalytic activity

GTP + H(2)O = GDP + phosphate.

Subunit structure

Interacts with SHANK1, SHANK2, SH3BP4 and NOSTRIN.

Subcellular location

Cytoplasm. Cytoplasmcytoskeleton. Cell junctionsynapsepostsynaptic cell membranepostsynaptic density. Cell junctionsynapse. Note= Microtubule-associated. Also found in the postsynaptic density of neuronal cells.

Tissue specificity

Ubiquitously expressed.

Involvement in disease

Defects in DNM2 are a cause of centronuclear myopathy autosomal dominant (ADCNM) [MIM:160150]; also known as autosomal dominant myotubular myopathy. Centronuclear myopathies (CNMs) are congenital muscle disorders characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. CNMs comprise a wide spectrum of phenotypes, ranging from severe neonatal to mild late-onset familial forms. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers.

Defects in DNM2 are the cause of dominant intermediate Charcot-Marie-Tooth disease B (CMTDIB) [MIM:606482]. Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. CMT neuropathy is subdivided into CMT1 and CMT2 types on the basis of electrophysiologic and neuropathologic criteria. CMT1 is a demyelinating neuropathy, whereas CMT2 is an axonal neuropathy. Most patients with CMT are classified as having CMT1 or CMT2 by use of a cut-off value of 38 m/s for the motor median nerve conduction velocity (NCV). However, in some families with CMT, patients have motor median NCVs ranging from 25 to 45 m/s. This form is designated intermediate CMT. Intermediate CMT is genetically heterogeneous.

Sequence similarities

Belongs to the dynamin family.

Contains 1 GED domain.

Contains 1 PH domain.

Ontologies

Keywords

   Biological processEndocytosis
   Cellular componentCell junction
Cell membrane
Cytoplasm
Cytoskeleton
Membrane
Microtubule
Postsynaptic cell membrane
Synapse
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseCharcot-Marie-Tooth disease
Disease mutation
   LigandGTP-binding
Nucleotide-binding
   Molecular functionHydrolase
Motor protein
   PTMPhosphoprotein
   Technical term3D-structure

Gene Ontology (GO)

   Biological processG2/M transition of mitotic cell cycle Ref.1

Non-traceable author statement. Source: UniProtKB

endocytosis Ref.4

Non-traceable author statement. Source: UniProtKB

positive regulation of apoptosis

Non-traceable author statement. Source: UniProtKB

regulation of transcription

Non-traceable author statement. Source: UniProtKB

signal transduction

Non-traceable author statement. Source: UniProtKB

synaptic vesicle transport Ref.4

Non-traceable author statement. Source: UniProtKB

   Cellular componentcell junction

Inferred from electronic annotation. Source: UniProtKB-KW

cytoplasm

Non-traceable author statement. Source: UniProtKB

microtubule

Inferred from electronic annotation. Source: UniProtKB-KW

postsynaptic membrane Ref.4

Inferred from direct assay. Source: UniProtKB

   Molecular functionGTP binding Ref.1

Non-traceable author statement. Source: UniProtKB

GTPase activity Ref.4

Non-traceable author statement. Source: UniProtKB

enzyme binding Ref.4

Non-traceable author statement. Source: UniProtKB

microtubule binding Ref.1

Non-traceable author statement. Source: UniProtKB

motor activity

Inferred from electronic annotation. Source: UniProtKB-KW

transcription activator activity

Non-traceable author statement. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P50570-1)

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: P50570-2)

The sequence of this isoform differs from the canonical sequence as follows:
     516-519: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 870870Dynamin-2
PRO_0000206570

Regions

Domain519 – 625107PH
Domain653 – 74492GED
Nucleotide binding38 – 458GTP By similarity
Nucleotide binding136 – 1405GTP By similarity
Nucleotide binding205 – 2084GTP By similarity
Compositional bias747 – 866120Pro-rich

Amino acid modifications

Modified residue2981Phosphoserine By similarity
Modified residue3021Phosphoserine By similarity
Modified residue5971Phosphotyrosine By similarity
Modified residue7661Phosphothreonine

Natural variations

Alternative sequence516 – 5194Missing in isoform 2.
VSP_001325
Natural variant2631P → L: dbSNP rs3745674.
VAR_031961
Natural variant3681E → K in ADCNM.
VAR_031962
Natural variant3691R → Q in ADCNM.
VAR_031963
Natural variant3691R → W in ADCNM; reduced association with the centrosome.
VAR_031964
Natural variant4651R → W in ADCNM; reduced association with the centrosome.
VAR_031965
Natural variant555 – 5573Missing in CMTDIB; may affect binding to vesicles and membranes in favor of binding to microtubules; may affect receptor-mediated endocytosis.
VAR_031966
Natural variant5621K → E in CMTDIB; with neutropenia.
VAR_031967
Natural variant6181A → T in ADCNM; severe.
VAR_039041
Natural variant6191S → L in ADCNM; severe.
VAR_039042
Natural variant6191S → W in ADCNM; severe.
VAR_039043
Natural variant6251Missing in ADCNM; severe.
VAR_039044

Experimental info

Sequence conflict155 – 1562QI → RV in AAA88025. Ref.1
Sequence conflict3161N → I in AAA88025. Ref.1
Sequence conflict3241R → P in AAA88025. Ref.1

Sequences

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

Last modified May 10, 2004. Version 2.
Checksum: 2F4567B75980935D

FASTA87098,064
        10         20         30         40         50         60 
MGNRGMEELI PLVNKLQDAF SSIGQSCHLD LPQIAVVGGQ SAGKSSVLEN FVGRDFLPRG 

        70         80         90        100        110        120 
SGIVTRRPLI LQLIFSKTEH AEFLHCKSKK FTDFDEVRQE IEAETDRVTG TNKGISPVPI 

       130        140        150        160        170        180 
NLRVYSPHVL NLTLIDLPGI TKVPVGDQPP DIEYQIKDMI LQFISRESSL ILAVTPANMD 

       190        200        210        220        230        240 
LANSDALKLA KEVDPQGLRT IGVITKLDLM DEGTDARDVL ENKLLPLRRG YIGVVNRSQK 

       250        260        270        280        290        300 
DIEGKKDIRA ALAAERKFFL SHPAYRHMAD RMGTPHLQKT LNQQLTNHIR ESLPALRSKL 

       310        320        330        340        350        360 
QSQLLSLEKE VEEYKNFRPD DPTRKTKALL QMVQQFGVDF EKRIEGSGDQ VDTLELSGGA 

       370        380        390        400        410        420 
RINRIFHERF PFELVKMEFD EKDLRREISY AIKNIHGVRT GLFTPDLAFE AIVKKQVVKL 

       430        440        450        460        470        480 
KEPCLKCVDL VIQELINTVR QCTSKLSSYP RLREETERIV TTYIREREGR TKDQILLLID 

       490        500        510        520        530        540 
IEQSYINTNH EDFIGFANAQ QRSTQLNKKR AIPNQGEILV IRRGWLTINN ISLMKGGSKE 

       550        560        570        580        590        600 
YWFVLTAESL SWYKDEEEKE KKYMLPLDNL KIRDVEKGFM SNKHVFAIFN TEQRNVYKDL 

       610        620        630        640        650        660 
RQIELACDSQ EDVDSWKASF LRAGVYPEKD QAENEDGAQE NTFSMDPQLE RQVETIRNLV 

       670        680        690        700        710        720 
DSYVAIINKS IRDLMPKTIM HLMINNTKAF IHHELLAYLY SSADQSSLME ESADQAQRRD 

       730        740        750        760        770        780 
DMLRMYHALK EALNIIGDIS TSTVSTPVPP PVDDTWLQSA SSHSPTPQRR PVSSIHPPGR 

       790        800        810        820        830        840 
PPAVRGPTPG PPLIPVPVGA AASFSAPPIP SRPGPQSVFA NSDLFPAPPQ IPSRPVRIPP 

       850        860        870 
GIPPGVPSRR PPAAPSRPTI IRPAEPSLLD 

« Hide

Isoform 2 [UniParc].

Checksum: C76BA1762A012127
Show »

86697,652

References

« Hide 'large scale' references
[1]"Isolation of an ubiquitously expressed cDNA encoding human dynamin II, a member of the large GTP-binding protein family."
Diatloff-Zito C., Gordon A.J.E., Duchaud E., Merlin G.
Gene 163:301-306(1995) [PubMed: 7590285] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
[2]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed: 15057824] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] (ISOFORMS 1 AND 2).
Tissue: Ovary and Uterus.
[4]"Dynamin isoform-specific interaction with the shank/ProSAP scaffolding proteins of the postsynaptic density and actin cytoskeleton."
Okamoto P.M., Gamby C., Wells D., Fallon J., Vallee R.B.
J. Biol. Chem. 276:48458-48465(2001) [PubMed: 11583995] [Abstract]
Cited for: INTERACTION WITH SHANK PROTEINS.
[5]"Large-scale characterization of HeLa cell nuclear phosphoproteins."
Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-766, MASS SPECTROMETRY.
Tissue: Epithelium.
[6]"TTP specifically regulates the internalization of the transferrin receptor."
Tosoni D., Puri C., Confalonieri S., Salcini A.E., De Camilli P., Tacchetti C., Di Fiore P.P.
Cell 123:875-888(2005) [PubMed: 16325581] [Abstract]
Cited for: INTERACTION WITH SH3BP4.
[7]"NOSTRIN functions as a homotrimeric adaptor protein facilitating internalization of eNOS."
Icking A., Matt S., Opitz N., Wiesenthal A., Mueller-Esterl W., Schilling K.
J. Cell Sci. 118:5059-5069(2005) [PubMed: 16234328] [Abstract]
Cited for: INTERACTION WITH NOSTRIN.
[8]"Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease."
Zuechner S., Noureddine M., Kennerson M., Verhoeven K., Claeys K., De Jonghe P., Merory J., Oliveira S.A., Speer M.C., Stenger J.E., Walizada G., Zhu D., Pericak-Vance M.A., Nicholson G., Timmerman V., Vance J.M.
Nat. Genet. 37:289-294(2005) [PubMed: 15731758] [Abstract]
Cited for: VARIANTS CMTDIB 555-ASP--GLU-557 DEL AND GLU-562, CHARACTERIZATION OF VARIANT CMTDIB 555-ASP--GLU-557 DEL.
[9]"Mutations in dynamin 2 cause dominant centronuclear myopathy."
Bitoun M., Maugenre S., Jeannet P.-Y., Lacene E., Ferrer X., Laforet P., Martin J.-J., Laporte J., Lochmueller H., Beggs A.H., Fardeau M., Eymard B., Romero N.B., Guicheney P.
Nat. Genet. 37:1207-1209(2005) [PubMed: 16227997] [Abstract]
Cited for: VARIANTS ADCNM LYS-368; TRP-369; GLN-369 AND TRP-465, CHARACTERIZATION OF VARIANTS ADCNM TRP-369 AND TRP-465.
[10]"Dynamin 2 mutations cause sporadic centronuclear myopathy with neonatal onset."
Bitoun M., Bevilacqua J.A., Prudhon B., Maugenre S., Taratuto A.L., Monges S., Lubieniecki F., Cances C., Uro-Coste E., Mayer M., Fardeau M., Romero N.B., Guicheney P.
Ann. Neurol. 62:666-670(2007) [PubMed: 17932957] [Abstract]
Cited for: VARIANTS ADCNM THR-618; LEU-619; TRP-619 AND VAL-625 DEL.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

L36983 mRNA. Translation: AAA88025.1.
AC007229 Genomic DNA. Translation: AAD23604.1.
AC011475 Genomic DNA. No translation available.
AC011552 Genomic DNA. No translation available.
AC011554 Genomic DNA. No translation available.
AC112707 Genomic DNA. No translation available.
BC039596 mRNA. Translation: AAH39596.1.
BC054501 mRNA. Translation: AAH54501.1.
PIRJC4305.
RefSeqNP_001005360.1.
NP_001005361.1.
NP_001005362.1.
NP_004936.2.
UniGeneHs.211463

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
2YS1NMR-A514-625[»]
SMRP50570. Positions 6-304, 518-629.
ModBaseSearch...

Protein-protein interaction databases

IntActP50570.

PTM databases

PhosphoSiteP50570.

Genome annotation databases

EnsemblENSG00000079805. Homo sapiens. [Contig view]
GeneID1785.
KEGGhsa:1785.

Organism-specific databases

H-InvDBHIX0014755.
HGNCHGNC:2974. DNM2.
MIM160150. phenotype.
602378. gene.
606482. phenotype.
Orphanet595. Centronuclear myopathy.
90114. Charcot-Marie-Tooth disease, dominant-intermediate type.
100044. Charcot-Marie-Tooth disease, dominant-intermediate type B.
596. Myotubular myopathy.
PharmGKBPA27442.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOVERGENP50570.

Enzyme and pathway databases

ReactomeREACT_9480. Gap junction trafficking and regulation.

Gene expression databases

ArrayExpressP50570.
CleanExHS_DNM2.
GermOnlineENSG00000079805. Homo sapiens.

Family and domain databases

InterProIPR000375. Dynamin_central.
IPR001401. Dynamin_GTPase.
IPR003130. GED.
IPR001849. PH.
IPR011993. PH_type.
[Graphical view]
Gene3DG3DSA:2.30.29.30. PH_type. 1 hit.
PfamPF01031. Dynamin_M. 1 hit.
PF00350. Dynamin_N. 1 hit.
PF02212. GED. 1 hit.
PF00169. PH. 1 hit.
[Graphical view]
PRINTSPR00195. DYNAMIN.
SMARTSM00053. DYNc. 1 hit.
SM00302. GED. 1 hit.
SM00233. PH. 1 hit.
[Graphical view]
PROSITEPS00410. DYNAMIN. 1 hit.
PS51388. GED. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio7257.
SOURCESearch...

Entry information

Entry nameDYN2_HUMAN
AccessionPrimary (citable) accession number: P50570
Secondary accession number(s): Q5I0Y0, Q7Z5S3, Q9UPH4
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 10, 2004
Last modified: November 25, 2008
This is version 84 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 19

Human chromosome 19: 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

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references ·