Reviewed, UniProtKB/Swiss-Prot P50570 (DYN2_HUMAN)

Names and origin

Protein names

Recommended name:
    Dynamin-2
    EC=3.6.5.5

Gene names

Name:	DNM2
Synonyms:	DYN2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	870 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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. Cytoplasm › cytoskeleton. Cell junction › synapse › postsynaptic cell membrane › postsynaptic density. Cell junction › synapse. 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 process	Endocytosis
Cellular component	Cell junction Cell membrane Cytoplasm Cytoskeleton Membrane Microtubule Postsynaptic cell membrane Synapse
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Charcot-Marie-Tooth disease Disease mutation
Ligand	GTP-binding Nucleotide-binding
Molecular function	Hydrolase Motor protein
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	G2/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 component	cell 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 function	GTP 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...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ABL1	P00519	1	EBI-346547,EBI-375543
CRK	P46108	1	EBI-346547,EBI-886
FNBP1	Q96RU3	1	EBI-346547,EBI-1111248
HCK	P08631	1	EBI-346547,EBI-346340
MPHOSPH6	Q99547	1	EBI-346547,EBI-373187

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 870	870	Dynamin-2		PRO_0000206570
Regions
	Domain	519 – 625	107	PH
	Domain	653 – 744	92	GED
	Nucleotide binding	38 – 45	8	GTP By similarity
	Nucleotide binding	136 – 140	5	GTP By similarity
	Nucleotide binding	205 – 208	4	GTP By similarity
	Compositional bias	747 – 866	120	Pro-rich
Amino acid modifications
	Modified residue	298	1	Phosphoserine By similarity
	Modified residue	302	1	Phosphoserine By similarity
	Modified residue	597	1	Phosphotyrosine By similarity
	Modified residue	766	1	Phosphothreonine
Natural variations
	Alternative sequence	516 – 519	4	Missing in isoform 2.		VSP_001325
	Natural variant	263	1	P → L: dbSNP rs3745674.		VAR_031961
	Natural variant	368	1	E → K in ADCNM.		VAR_031962
	Natural variant	369	1	R → Q in ADCNM.		VAR_031963
	Natural variant	369	1	R → W in ADCNM; reduced association with the centrosome.		VAR_031964
	Natural variant	465	1	R → W in ADCNM; reduced association with the centrosome.		VAR_031965
	Natural variant	555 – 557	3	Missing in CMTDIB; may affect binding to vesicles and membranes in favor of binding to microtubules; may affect receptor-mediated endocytosis.		VAR_031966
	Natural variant	562	1	K → E in CMTDIB; with neutropenia.		VAR_031967
	Natural variant	618	1	A → T in ADCNM; severe.		VAR_039041
	Natural variant	619	1	S → L in ADCNM; severe.		VAR_039042
	Natural variant	619	1	S → W in ADCNM; severe.		VAR_039043
	Natural variant	625	1	Missing in ADCNM; severe.		VAR_039044
Experimental info
	Sequence conflict	155 – 156	2	QI → RV in AAA88025. Ref.1
	Sequence conflict	316	1	N → I in AAA88025. Ref.1
	Sequence conflict	324	1	R → P in AAA88025. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 10, 2004. Version 2. Checksum: 2F4567B75980935D	FASTA	870	98,064
	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
	Isoform 2 [UniParc]. Checksum: C76BA1762A012127		866	97,652
	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 AIPNQVIRRG WLTINNISLM KGGSKEYWFV 550 560 570 580 590 600 LTAESLSWYK DEEEKEKKYM LPLDNLKIRD VEKGFMSNKH VFAIFNTEQR NVYKDLRQIE 610 620 630 640 650 660 LACDSQEDVD SWKASFLRAG VYPEKDQAEN EDGAQENTFS MDPQLERQVE TIRNLVDSYV 670 680 690 700 710 720 AIINKSIRDL MPKTIMHLMI NNTKAFIHHE LLAYLYSSAD QSSLMEESAD QAQRRDDMLR 730 740 750 760 770 780 MYHALKEALN IIGDISTSTV STPVPPPVDD TWLQSASSHS PTPQRRPVSS IHPPGRPPAV 790 800 810 820 830 840 RGPTPGPPLI PVPVGAAASF SAPPIPSRPG PQSVFANSDL FPAPPQIPSR PVRIPPGIPP 850 860 GVPSRRPPAA PSRPTIIRPA EPSLLD

References

	« Hide 'large scale' referencesShow '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. , 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

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

PIR

JC4305.

RefSeq

NP_001005360.1.
NP_001005361.1.
NP_001005362.1.
NP_004936.2.

UniGene

Hs.211463

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2YS1	NMR	-	A	514-625	[»]

SMR

P50570. Positions 6-304, 518-629.

ModBase

Search...

Protein-protein interaction databases

IntAct

P50570.

PTM databases

PhosphoSite

P50570.

Genome annotation databases

Ensembl

ENSG00000079805. Homo sapiens. [Contig view]

GeneID

1785.

KEGG

hsa:1785.

Organism-specific databases

H-InvDB

HIX0014755.

HGNC

HGNC:2974. DNM2.

MIM

160150. phenotype.
602378. gene.
606482. phenotype.

Orphanet

595. Centronuclear myopathy.
90114. Charcot-Marie-Tooth disease, dominant-intermediate type.
100044. Charcot-Marie-Tooth disease, dominant-intermediate type B.
596. Myotubular myopathy.

PharmGKB

PA27442.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOVERGEN

P50570.

Enzyme and pathway databases

Reactome

REACT_9480. Gap junction trafficking and regulation.

Gene expression databases

ArrayExpress

P50570.

CleanEx

HS_DNM2.

GermOnline

ENSG00000079805. Homo sapiens.

Family and domain databases

InterPro

IPR000375. Dynamin_central.
IPR001401. Dynamin_GTPase.
IPR003130. GED.
IPR001849. PH.
IPR011993. PH_type.
[Graphical view]

Gene3D

G3DSA:2.30.29.30. PH_type. 1 hit.

Pfam

PF01031. Dynamin_M. 1 hit.
PF00350. Dynamin_N. 1 hit.
PF02212. GED. 1 hit.
PF00169. PH. 1 hit.
[Graphical view]

PRINTS

PR00195. DYNAMIN.

SMART

SM00053. DYNc. 1 hit.
SM00302. GED. 1 hit.
SM00233. PH. 1 hit.
[Graphical view]

PROSITE

PS00410. DYNAMIN. 1 hit.
PS51388. GED. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

7257.

SOURCE

Search...

Entry information

Entry name

DYN2_HUMAN

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)