P63167 (DYL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Dynein light chain 1, cytoplasmic

Alternative name(s):
8 kDa dynein light chain
Short name=DLC8
Dynein light chain LC8-type 1
Protein inhibitor of neuronal nitric oxide synthase
Short name=PIN

Gene names

Name:	DYNLL1
Synonyms:	DLC1, DNCL1, DNCLC1, HDLC1

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	89 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in changing or maintaining the spatial distribution of cytoskeletal structures. Ref.3 Ref.5 Ref.7 Ref.9 Binds and inhibits the catalytic activity of neuronal nitric oxide synthase. Ref.3 Ref.5 Ref.7 Ref.9 Promotes transactivation functions of ESR1 and plays a role in the nuclear localization of ESR1. Ref.3 Ref.5 Ref.7 Ref.9 Regulates apoptotic activities of BCL2L11 by sequestering it to microtubules. Upon apoptotic stimuli the BCL2L11-DYNLL1 complex dissociates from cytoplasmic dynein and translocates to mitochondria and sequesters BCL2 thus neutralizing its antiapoptotic activity. Ref.3 Ref.5 Ref.7 Ref.9
Subunit structure	Homodimer. Monomer; the monomeric form is incapable of binding to target proteins. The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs); the composition seems to vary in respect to the IC, LIC and LC composition. The heavy chain homodimer serves as a scaffold for the probable homodimeric assembly of the respective non-catalytic subunits. The ICs and LICs bind directly to the HC dimer and the LCs assemble on the IC dimer. Interacts with rabies P protein By similarity. Interacts with TXNDC17. Interacts with WWC1 and ESR1. The WWC1-DYNLL1 interaction is mandatory for the recruitment and transactivation functions of ESR1 or DYNLL1 to the target chromatin. Interacts with BCL2L11 isoform 1 and isoform 2. Interacts with BCL2; the interaction is greatly enhanced in the nucleus and in mitochondria upon induction of apoptosis. Interacts with PAK1; the interaction requires dimeric DYNLL1. Interacts with human spumaretrovirus Gag protein; this interaction is critical for intracellular microtubule-dependent viral genome transport toward the centrosome. Interacts with GCOM1. Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.9 Ref.10 Ref.11 Ref.14
Subcellular location	Cytoplasm › cytoskeleton. Nucleus. Mitochondrion. Note: Upon induction of apoptosis translocates together with BCL2L11 to mitochondria. Ref.1 Ref.7
Tissue specificity	Ubiquitous. Ref.1
Induction	Up-regulated by PAK1 and estrogen. Ref.3 Ref.5 Ref.7
Post-translational modification	Phosphorylation at Ser-88 appears to control the dimer-monomer transition. According to Ref.5, it is phosphorylated at Ser-88 by PAK1, however, according to Ref.11, the DYNLL1 dimer is not accessible for PAK1 and the phosphorylation could not be demonstrated in vitro. Ref.5 Ref.12
Sequence similarities	Belongs to the dynein light chain family.

Ontologies

Keywords
Biological process	Apoptosis Host-virus interaction Transcription Transcription regulation Transport
Cellular component	Cytoplasm Cytoskeleton Dynein Microtubule Mitochondrion Nucleus
Molecular function	Activator Motor protein
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	G2/M transition of mitotic cell cycle Traceable author statement. Source: Reactome actin cytoskeleton organization Traceable author statement. Source: ProtInc activation of pro-apoptotic gene products Traceable author statement. Source: Reactome anatomical structure morphogenesis Traceable author statement. Source: ProtInc female gamete generation Traceable author statement. Source: ProtInc induction of apoptosis by intracellular signals Traceable author statement. Source: Reactome interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW microtubule-based process Inferred from electronic annotation. Source: InterPro negative regulation of phosphorylation Inferred from direct assay. Source: UniProtKB regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	centrosome Inferred from direct assay. Source: UniProtKB cytoplasmic dynein complex Inferred from sequence or structural similarity. Source: UniProtKB cytosol Traceable author statement. Source: Reactome microtubule Inferred from electronic annotation. Source: UniProtKB-KW mitochondrion Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay Ref.7. Source: UniProtKB plasma membrane Traceable author statement. Source: Reactome
Molecular function	motor activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GNB2L1	P63244	6	EBI-349105,EBI-296739

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 89

89

Dynein light chain 1, cytoplasmic

PRO_0000195125

Regions

Region

67 – 89

23

Interaction with ESR1

Amino acid modifications

Modified residue

36

1

N6-acetyllysine Ref.13

Modified residue

65

1

Phosphotyrosine Ref.12

Modified residue

88

1

Phosphoserine Ref.5

Experimental info

Mutagenesis

67

1

T → A: Abolishes interaction with PAK1. Ref.11

Mutagenesis

88

1

S → A: Abolishes growth factor-mediated phosphorylation. Increases BCL2L11 protein level and promotes apoptosis. Ref.5 Ref.10

Mutagenesis

88

1

S → E: Abolishes homodimerization. Abolishes interaction with BCL2L11 isoform 1 and isoform 2. Ref.5 Ref.10

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

89

Helix Strand Turn

Details...

Beta strand

7 – 11

5

Helix

15 – 31

17

Helix

35 – 50

16

Beta strand

54 – 69

16

Beta strand

73 – 78

6

Beta strand

81 – 87

7

Sequences

	Sequence		Length	Mass (Da)
	P63167 [UniParc]. Last modified September 27, 2004. Version 1. Checksum: F5E7647D092BEB3A	FASTA	89	10,366
	10 20 30 40 50 60 MCDRKAVIKN ADMSEEMQQD SVECATQALE KYNIEKDIAA HIKKEFDKKY NPTWHCIVGR 70 80 NFGSYVTHET KHFIYFYLGQ VAILLFKSG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cytoplasmic dynein (ddlc1) mutations cause morphogenetic defects and apoptotic cell death in Drosophila melanogaster." Dick T., Ray K., Salz H.K., Chia W. Mol. Cell. Biol. 16:1966-1977(1996) [PubMed: 8628263] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex." Puthalakath H., Huang D.C., O'Reilly L.A., King S.M., Strasser A. Mol. Cell 3:287-296(1999) [PubMed: 10198631] [Abstract] Cited for: FUNCTION IN REGULATION OF APOPTOSIS, INTERACTION WITH BCL2L11 AND BCL2.
[4]	"Targeting of incoming retroviral Gag to the centrosome involves a direct interaction with the dynein light chain 8." Petit C., Giron M.L., Tobaly-Tapiero J., Bittoun P., Real E., Jacob Y., Tordo N., De The H., Saib A. J. Cell Sci. 116:3433-3442(2003) [PubMed: 12857789] [Abstract] Cited for: INTERACTION WITH HUMAN SPUMARETROVIRUS GAG.
[5]	"Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes." Vadlamudi R.K., Bagheri-Yarmand R., Yang Z., Balasenthil S., Nguyen D., Sahin A.A., den Hollander P., Kumar R. Cancer Cell 5:575-585(2004) [PubMed: 15193260] [Abstract] Cited for: FUNCTION IN REGULATION OF BCL2L11, INTERACTION WITH PAK1 AND BCL2L11, PHOSPHORYLATION AT SER-88, MUTAGENESIS OF SER-88.
[6]	"Roles of TRP14, a thioredoxin-related protein in tumor necrosis factor-alpha signaling pathways." Jeong W., Chang T.-S., Boja E.S., Fales H.M., Rhee S.G. J. Biol. Chem. 279:3151-3159(2004) [PubMed: 14607843] [Abstract] Cited for: INTERACTION WITH TXNDC17.
[7]	"Functional regulation of oestrogen receptor pathway by the dynein light chain 1." Rayala S.K., den Hollander P., Balasenthil S., Yang Z., Broaddus R.R., Kumar R. EMBO Rep. 6:538-544(2005) [PubMed: 15891768] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INDUCTION, INTERACTION WITH ESR1.
[8]	Erratum Rayala S.K., den Hollander P., Balasenthil S., Yang Z., Broaddus R.R., Kumar R. EMBO Rep. 6:1101-1101(2005)
[9]	"Essential role of KIBRA in co-activator function of dynein light chain 1 in mammalian cells." Rayala S.K., den Hollander P., Manavathi B., Talukder A.H., Song C., Peng S., Barnekow A., Kremerskothen J., Kumar R. J. Biol. Chem. 281:19092-19099(2006) [PubMed: 16684779] [Abstract] Cited for: FUNCTION, INTERACTION WITH WWC1.
[10]	"Serine 88 phosphorylation of the 8-kDa dynein light chain 1 is a molecular switch for its dimerization status and functions." Song C., Wen W., Rayala S.K., Chen M., Ma J., Zhang M., Kumar R. J. Biol. Chem. 283:4004-4013(2008) [PubMed: 18084006] [Abstract] Cited for: SUBUNIT, INTERACTION WITH BCL2L11, MUTAGENESIS OF SER-88.
[11]	"Biochemical and structural characterization of the Pak1-LC8 interaction." Lightcap C.M., Sun S., Lear J.D., Rodeck U., Polenova T., Williams J.C. J. Biol. Chem. 283:27314-27324(2008) [PubMed: 18650427] [Abstract] Cited for: SUBUNIT, INTERACTION WITH PAK1, MUTAGENESIS OF THR-67.
[12]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-65, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[13]	"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-36, MASS SPECTROMETRY.
[14]	"Structural basis for the interaction between dynein light chain 1 and the glutamate channel homolog GRINL1A." Garcia-Mayoral M.F., Martinez-Moreno M., Albar J.P., Rodriguez-Crespo I., Bruix M. FEBS J. 277:2340-2350(2010) [PubMed: 20412299] [Abstract] Cited for: INTERACTION WITH GCOM1.
[15]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]	"Structure of the PIN/LC8 dimer with a bound peptide." Liang J., Jaffrey S.R., Guo W., Snyder S.H., Clardy J. Nat. Struct. Biol. 6:735-740(1999) [PubMed: 10426949] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 5-89.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U32944 mRNA. Translation: AAB04149.1.
CR407672 mRNA. Translation: CAG28600.1.

IPI

IPI00019329.

RefSeq

NP_001032583.1. NM_001037494.1.
NP_001032584.1. NM_001037495.1.
NP_003737.1. NM_003746.2.

UniGene

Hs.5120.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CMI	X-ray	2.50	A/B	5-89	[»]

ProteinModelPortal

P63167.

SMR

P63167. Positions 5-89.

ModBase

Search...

Protein-protein interaction databases

IntAct

P63167. 32 interactions.

MINT

MINT-156345.

STRING

P63167.

PTM databases

PhosphoSite

P63167.

Polymorphism databases

DMDM

52783578.

Proteomic databases

PeptideAtlas

P63167.

PRIDE

P63167.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000242577; ENSP00000242577; ENSG00000088986.
ENST00000392508; ENSP00000376296; ENSG00000088986.
ENST00000392509; ENSP00000376297; ENSG00000088986.

GeneID

8655.

KEGG

hsa:8655.

UCSC

uc001tyj.1. human.

Organism-specific databases

CTD

8655.

GeneCards

GC12P120908.

H-InvDB

HIX0036835.
HIX0202123.

HGNC

HGNC:15476. DYNLL1.

MIM

601562. gene.

neXtProt

NX_P63167.

PharmGKB

PA134972261.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG20803.

HOGENOM

HBG627578.

HOVERGEN

HBG002133.

InParanoid

P63167.

OrthoDB

EOG473PSW.

PhylomeDB

P63167.

Enzyme and pathway databases

Reactome

REACT_152. Cell Cycle, Mitotic.
REACT_578. Apoptosis.

Gene expression databases

ArrayExpress

P63167.

Bgee

P63167.

CleanEx

HS_DLC1.
HS_DYNLL1.

Genevestigator

P63167.

GermOnline

ENSG00000088986. Homo sapiens.

Family and domain databases

InterPro

IPR019763. Dynein_light_1/2_CS.
IPR001372. Dynein_light_chain_typ-1/2.
[Graphical view]

Gene3D

G3DSA:3.30.740.10. Dynein_light1. 1 hit.

KO

K10418.

PANTHER

PTHR11886. Dynein_light1. 1 hit.

Pfam

PF01221. Dynein_light. 1 hit.
[Graphical view]

SUPFAM

SSF54648. Dynein_light_chain_typ-1/2. 1 hit.

PROSITE

PS01239. DYNEIN_LIGHT_1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

32461.

SOURCE

Search...

Entry information

Entry name

DYL1_HUMAN

Accession

Primary (citable) accession number: P63167
Secondary accession number(s): Q15701

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 27, 2004
Last sequence update:	September 27, 2004
Last modified:	January 25, 2012
This is version 83 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.