Reviewed, UniProtKB/Swiss-Prot Q14203 (DCTN1_HUMAN)

Names and origin

Protein names

Recommended name:
    Dynactin subunit 1
Alternative name(s):
    150 kDa dynein-associated polypeptide
    DAP-150
      Short name=DP-150
    p150-glued
    p135

Gene names

Name:

DCTN1

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 attributes

Sequence length	1278 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Required for the cytoplasmic dynein-driven retrograde movement of vesicles and organelles along microtubules. Dynein-dynactin interaction is a key component of the mechanism of axonal transport of vesicles and organelles.
Subunit structure	Large macromolecular complex of at least 10 components; p150(glued) binds directly to microtubules and to cytoplasmic dynein. Interacts with the C-terminus of MAPRE1, MAPRE2 and MAPRE3. Ref.6
Subcellular location	Cytoplasm. Cytoplasm › cytoskeleton.
Tissue specificity	Brain.
Post-translational modification	Phosphorylated.
Involvement in disease	Defects in DCTN1 are the cause of distal hereditary motor neuronopathy type 7B (HMN7B) [MIM:607641] also known as progressive lower motor neuron disease (PLMND). HMN7B is a neuromuscular disorder. Distal hereditary motor neuronopathies constitute a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. Ref.10
Sequence similarities	Belongs to the dynactin 150 kDa subunit family. Contains 1 CAP-Gly domain.

Ontologies

Keywords
Cellular component	Cytoplasm Cytoskeleton Dynein Microtubule
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Neurodegeneration
Domain	Coiled coil
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	cell death Inferred from electronic annotation. Source: UniProtKB-KW mitosis Non-traceable author statement. Source: ProtInc nervous system development Non-traceable author statement. Source: UniProtKB
Cellular component	cytosol Inferred from Experiment. Source: Reactome dynein complex Inferred from electronic annotation. Source: UniProtKB-KW kinetochore Inferred from direct assay. Source: UniProtKB microtubule Inferred from electronic annotation. Source: UniProtKB-KW spindle pole Inferred from direct assay. Source: UniProtKB
Molecular function	motor activity Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ACTR1B	P42025	1	EBI-724352,EBI-367493
AKTIP	Q9H8T0	1	EBI-724352,EBI-711399
BBS4	Q96RK4	3	EBI-724352,EBI-1805814
BZW1	Q7L1Q6	1	EBI-724352,EBI-1046727
GSTK1	Q9Y2Q3	1	EBI-724352,EBI-1053767
RFXANK	O14593	1	EBI-724352,EBI-1057665

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform p150 (identifier: Q14203-1)

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 p135 (identifier: Q14203-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-138: MAQSKRHVYS...SKLRGLKPKK → MMRQ

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1278

1278

Dynactin subunit 1

PRO_0000083518

Regions

Domain

48 – 90

43

CAP-Gly

Coiled coil

213 – 547

335

Potential

Coiled coil

943 – 1049

107

Potential

Coiled coil

1182 – 1211

30

Potential

Compositional bias

164 – 191

28

Ser-rich

Amino acid modifications

Modified residue

230

1

N6-acetyllysine Ref.8

Modified residue

541

1

Phosphoserine By similarity

Natural variations

Alternative sequence

1 – 138

138

MAQSK…LKPKK → MMRQ in isoform p135.

VSP_000760

Natural variant

59

1

G → S in HMN7B. Ref.10

VAR_015850

Natural variant

163

1

A → P

VAR_001373

Natural variant

287

1

L → M: dbSNP rs13420401.

VAR_048677

Natural variant

495

1

R → Q: dbSNP rs17721059.

VAR_048678

Experimental info

Sequence conflict

10

1

S → N Ref.2

Sequence conflict

10

1

S → N in CAA67333. Ref.3

Sequence conflict

132 – 138

7

Missing Ref.2

Sequence conflict

132 – 138

7

Missing in CAA67333. Ref.3

Sequence conflict

712

1

D → V Ref.2

Sequence conflict

712

1

D → V in CAA67333. Ref.3

Sequence conflict

1081

1

V → M in AAP35404. Ref.5

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

1278

Helix Strand Turn

Details...

Beta strand

32 – 35

4

Turn

36 – 38

3

Beta strand

41 – 48

8

Beta strand

51 – 55

5

Beta strand

57 – 65

9

Beta strand

67 – 73

7

Beta strand

76 – 78

3

Beta strand

86 – 89

4

Helix

91 – 93

3

Beta strand

94 – 96

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform p150 [UniParc]. Last modified October 18, 2001. Version 3. Checksum: 6DCEA5E67856E4BC	FASTA	1,278	141,695
	10 20 30 40 50 60 MAQSKRHVYS RTPSGSRMSA EASARPLRVG SRVEVIGKGH RGTVAYVGAT LFATGKWVGV 70 80 90 100 110 120 ILDEAKGKND GTVQGRKYFT CDEGHGIFVR QSQIQVFEDG ADTTSPETPD SSASKVLKRE 130 140 150 160 170 180 GTDTTAKTSK LRGLKPKKAP TARKTTTRRP KPTRPASTGV AGASSSLGPS GSASAGELSS 190 200 210 220 230 240 SEPSTPAQTP LAAPIIPTPV LTSPGAVPPL PSPSKEEEGL RAQVRDLEEK LETLRLKRAE 250 260 270 280 290 300 DKAKLKELEK HKIQLEQVQE WKSKMQEQQA DLQRRLKEAR KEAKEALEAK ERYMEEMADT 310 320 330 340 350 360 ADAIEMATLD KEMAEERAES LQQEVEALKE RVDELTTDLE ILKAEIEEKG SDGAASSYQL 370 380 390 400 410 420 KQLEEQNARL KDALVRMRDL SSSEKQEHVK LQKLMEKKNQ ELEVVRQQRE RLQEELSQAE 430 440 450 460 470 480 STIDELKEQV DAALGAEEMV EMLTDRNLNL EEKVRELRET VGDLEAMNEM NDELQENARE 490 500 510 520 530 540 TELELREQLD MAGARVREAQ KRVEAAQETV ADYQQTIKKY RQLTAHLQDV NRELTNQQEA 550 560 570 580 590 600 SVERQQQPPP ETFDFKIKFA ETKAHAKAIE MELRQMEVAQ ANRHMSLLTA FMPDSFLRPG 610 620 630 640 650 660 GDHDCVLVLL LMPRLICKAE LIRKQAQEKF ELSENCSERP GLRGAAGEQL SFAAGLVYSL 670 680 690 700 710 720 SLLQATLHRY EHALSQCSVD VYKKVGSLYP EMSAHERSLD FLIELLHKDQ LDETVNVEPL 730 740 750 760 770 780 TKAIKYYQHL YSIHLAEQPE DCTMQLADHI KFTQSALDCM SVEVGRLRAF LQGGQEATDI 790 800 810 820 830 840 ALLLRDLETS CSDIRQFCKK IRRRMPGTDA PGIPAALAFG PQVSDTLLDC RKHLTWVVAV 850 860 870 880 890 900 LQEVAAAAAQ LIAPLAENEG LLVAALEELA FKASEQIYGT PSSSPYECLR QSCNILISTM 910 920 930 940 950 960 NKLATAMQEG EYDAERPPSK PPPVELRAAA LRAEITDAEG LGLKLEDRET VIKELKKSLK 970 980 990 1000 1010 1020 IKGEELSEAN VRLSLLEKKL DSAAKDADER IEKVQTRLEE TQALLRKKEK EFEETMDALQ 1030 1040 1050 1060 1070 1080 ADIDQLEAEK AELKQRLNSQ SKRTIEGLRG PPPSGIATLV SGIAGEEQQR GAIPGQAPGS 1090 1100 1110 1120 1130 1140 VPGPGLVKDS PLLLQQISAM RLHISQLQHE NSILKGAQMK ASLASLPPLH VAKLSHEGPG 1150 1160 1170 1180 1190 1200 SELPAGALYR KTSQLLETLN QLSTHTHVVD ITRTSPAAKS PSAQLMEQVA QLKSLSDTVE 1210 1220 1230 1240 1250 1260 KLKDEVLKET VSQRPGATVP TDFATFPSSA FLRAKEEQQD DTVYMGKVTF SCAAGFGQRH 1270 RLVLTQEQLH QLHSRLIS
	Isoform p135. Checksum: D4011CF3E4BF06F6	FASTA	1,144	127,404
	10 20 30 40 50 60 MMRQAPTARK TTTRRPKPTR PASTGVAGAS SSLGPSGSAS AGELSSSEPS TPAQTPLAAP 70 80 90 100 110 120 IIPTPVLTSP GAVPPLPSPS KEEEGLRAQV RDLEEKLETL RLKRAEDKAK LKELEKHKIQ 130 140 150 160 170 180 LEQVQEWKSK MQEQQADLQR RLKEARKEAK EALEAKERYM EEMADTADAI EMATLDKEMA 190 200 210 220 230 240 EERAESLQQE VEALKERVDE LTTDLEILKA EIEEKGSDGA ASSYQLKQLE EQNARLKDAL 250 260 270 280 290 300 VRMRDLSSSE KQEHVKLQKL MEKKNQELEV VRQQRERLQE ELSQAESTID ELKEQVDAAL 310 320 330 340 350 360 GAEEMVEMLT DRNLNLEEKV RELRETVGDL EAMNEMNDEL QENARETELE LREQLDMAGA 370 380 390 400 410 420 RVREAQKRVE AAQETVADYQ QTIKKYRQLT AHLQDVNREL TNQQEASVER QQQPPPETFD 430 440 450 460 470 480 FKIKFAETKA HAKAIEMELR QMEVAQANRH MSLLTAFMPD SFLRPGGDHD CVLVLLLMPR 490 500 510 520 530 540 LICKAELIRK QAQEKFELSE NCSERPGLRG AAGEQLSFAA GLVYSLSLLQ ATLHRYEHAL 550 560 570 580 590 600 SQCSVDVYKK VGSLYPEMSA HERSLDFLIE LLHKDQLDET VNVEPLTKAI KYYQHLYSIH 610 620 630 640 650 660 LAEQPEDCTM QLADHIKFTQ SALDCMSVEV GRLRAFLQGG QEATDIALLL RDLETSCSDI 670 680 690 700 710 720 RQFCKKIRRR MPGTDAPGIP AALAFGPQVS DTLLDCRKHL TWVVAVLQEV AAAAAQLIAP 730 740 750 760 770 780 LAENEGLLVA ALEELAFKAS EQIYGTPSSS PYECLRQSCN ILISTMNKLA TAMQEGEYDA 790 800 810 820 830 840 ERPPSKPPPV ELRAAALRAE ITDAEGLGLK LEDRETVIKE LKKSLKIKGE ELSEANVRLS 850 860 870 880 890 900 LLEKKLDSAA KDADERIEKV QTRLEETQAL LRKKEKEFEE TMDALQADID QLEAEKAELK 910 920 930 940 950 960 QRLNSQSKRT IEGLRGPPPS GIATLVSGIA GEEQQRGAIP GQAPGSVPGP GLVKDSPLLL 970 980 990 1000 1010 1020 QQISAMRLHI SQLQHENSIL KGAQMKASLA SLPPLHVAKL SHEGPGSELP AGALYRKTSQ 1030 1040 1050 1060 1070 1080 LLETLNQLST HTHVVDITRT SPAAKSPSAQ LMEQVAQLKS LSDTVEKLKD EVLKETVSQR 1090 1100 1110 1120 1130 1140 PGATVPTDFA TFPSSAFLRA KEEQQDDTVY MGKVTFSCAA GFGQRHRLVL TQEQLHQLHS RLIS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human DCTN1: genomic structure and evaluation as a candidate for Alstrom syndrome." Collin G.B., Nishina P.M., Marshall J.D., Naggert J.K. Genomics 53:359-364(1998) [PubMed: 9799602] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING.
[2]	"Localization of the DCTN1 gene encoding p150Glued to human chromosome 2p13 by fluorescence in situ hybridization." Holzbaur E.L.F., Tokito M.K. Genomics 31:398-399(1996) [PubMed: 8838327] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 9-1278. Tissue: Brain.
[3]	"Functionally distinct isoforms of dynactin are expressed in human neurons." Tokito M.K., Howland D.S., Lee V.M.-Y., Holzbaur E.L.F. Mol. Biol. Cell 7:1167-1180(1996) [PubMed: 8856662] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 9-1278, ALTERNATIVE SPLICING. Tissue: Brain.
[4]	"The genomic structure of DCTN1, a candidate gene for limb-girdle muscular dystrophy." Tokito M.K., Holzbaur E.L.F. Biochim. Biophys. Acta 1442:432-436(1998) [PubMed: 9805007] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 18-1278.
[5]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1081-1278.
[6]	"Characterization of functional domains of human EB1 family proteins." Bu W., Su L.-K. J. Biol. Chem. 278:49721-49731(2003) [PubMed: 14514668] [Abstract] Cited for: INTERACTION WITH MAPRE1; MAPRE2 AND MAPRE3.
[7]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[8]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-230, MASS SPECTROMETRY.
[9]	"Solution structure of the CAP-GLY domain in human dynactin 1." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 1-99.
[10]	"Mutant dynactin in motor neuron disease." Puls I., Jonnakuty C., LaMonte B.H., Holzbaur E.L., Tokito M., Mann E., Floeter M.K., Bidus K., Drayna D., Oh S.J., Brown R.H. Jr., Ludlow C.L., Fischbeck K.H. Nat. Genet. 33:455-456(2003) [PubMed: 12627231] [Abstract] Cited for: VARIANT HMN7B SER-59.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF064205, AF064203, AF064204 Genomic DNA. Translation: AAD55811.1.
AF064205, AF064204 Genomic DNA. Translation: AAD55812.1.
X98801 mRNA. Translation: CAA67333.1.
AF086947 , AF086927, AF086928, AF086929, AF086930, AF086931, AF086932, AF086933, AF086934, AF086935, AF086936, AF086937, AF086938, AF086939, AF086940, AF086941, AF086942, AF086943, AF086944, AF086945, AF086946 Genomic DNA. Translation: AAD03694.1.
BT006758 mRNA. Translation: AAP35404.1.

IPI

IPI00029485.
IPI00219114.

RefSeq

NP_004073.2.
NP_075408.1.

UniGene

Hs.516111

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1TXQ	X-ray	1.80	A	15-107	[»]
2COY	NMR	-	A	1-99	[»]
2HKN	X-ray	1.87	A/B	18-111	[»]
2HKQ	X-ray	1.86	B	18-111	[»]
2HL3	X-ray	2.03	A/B	18-111	[»]
2HL5	X-ray	1.93	C/D	18-111	[»]
2HQH	X-ray	1.80	A/B/C/D	15-107	[»]
3E2U	X-ray	2.60	A/B/C/D	15-111	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q14203. 15 interactions.

STRING

Q14203.

PTM databases

PhosphoSite

Q14203.

2-D gel databases

OGP

Q14203.

Proteomic databases

PRIDE

Q14203.

Genome annotation databases

Ensembl

ENST00000361874; ENSP00000354791; ENSG00000204843; Homo sapiens. [Genome view]
ENST00000362071; ENSP00000354516; ENSG00000204843; Homo sapiens. [Genome view]
ENST00000393999; ENSP00000377568; ENSG00000204843; Homo sapiens. [Genome view]
ENST00000394003; ENSP00000377571; ENSG00000204843; Homo sapiens. [Genome view]
ENST00000407639; ENSP00000384844; ENSG00000204843; Homo sapiens. [Genome view]
ENST00000409240; ENSP00000386406; ENSG00000204843; Homo sapiens. [Genome view]
ENST00000409348; ENSP00000386269; ENSG00000204843; Homo sapiens. [Genome view]
ENST00000409438; ENSP00000387270; ENSG00000204843; Homo sapiens. [Genome view]
ENST00000409567; ENSP00000386843; ENSG00000204843; Homo sapiens. [Genome view]
ENST00000409868; ENSP00000387327; ENSG00000204843; Homo sapiens. [Genome view]
ENST00000413111; ENSP00000413268; ENSG00000204843; Homo sapiens. [Genome view]
ENST00000417090; ENSP00000402509; ENSG00000204843; Homo sapiens. [Genome view]
ENST00000421392; ENSP00000409363; ENSG00000204843; Homo sapiens. [Genome view]
ENST00000428589; ENSP00000396724; ENSG00000204843; Homo sapiens. [Genome view]
ENST00000434055; ENSP00000416711; ENSG00000204843; Homo sapiens. [Genome view]
ENST00000437375; ENSP00000395312; ENSG00000204843; Homo sapiens. [Genome view]
ENST00000440727; ENSP00000400059; ENSG00000204843; Homo sapiens. [Genome view]
ENST00000449655; ENSP00000407484; ENSG00000204843; Homo sapiens. [Genome view]
ENST00000454119; ENSP00000404038; ENSG00000204843; Homo sapiens. [Genome view]
ENST00000458655; ENSP00000414315; ENSG00000204843; Homo sapiens. [Genome view]

GeneID

1639.

UCSC

uc002skv.1. human.
uc002skx.1. human.

Organism-specific databases

CTD

1639.

GeneCards

GC02M074441.

H-InvDB

HIX0002180.

HGNC

HGNC:2711. DCTN1.

HPA

CAB009108.

MIM

601143. gene.
607641. phenotype.

Orphanet

139589. Distal hereditary motor neuropathy, type 7.
178509. Perry syndrome.

PharmGKB

PA27180.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q14203.

HOVERGEN

Q14203.

Enzyme and pathway databases

Reactome

REACT_152. Cell Cycle, Mitotic.

Gene expression databases

ArrayExpress

Q14203.

Bgee

Q14203.

CleanEx

HS_DCTN1.

Genevestigator

Q14203.

GermOnline

ENSG00000204843. Homo sapiens.

Family and domain databases

InterPro

IPR000938. Cytoskel-assoc-prot_CAP-Gly.
[Graphical view]

Pfam

PF01302. CAP_GLY. 1 hit.
[Graphical view]

PROSITE

PS00845. CAP_GLY_1. 1 hit.
PS50245. CAP_GLY_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

6734.

PMAP-CutDB

Q14203.

SOURCE

Search...

Entry information

Entry name

DCTN1_HUMAN

Accession

Primary (citable) accession number: Q14203
Secondary accession number(s): O95296 , Q9BRM9, Q9UIU1, Q9UIU2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	October 18, 2001
Last modified:	November 3, 2009
This is version 92 of the entry and version 3 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.