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P63167 (DYL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 111. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length89 AA.
Sequence statusComplete.
Protein existenceEvidence 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 1and 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 MYZAP. Part of an astrin (SPAG5)-kinastrin (SKAP) complex containing KNSTRN, SPAG5, PLK1, DYNLL1 and SGOL2. Interacts with ATMIN; this interaction inhibits ATMIN transcriptional activity and hence may play a role in a feedback loop whereby DYNLL1 inhibits transactivation of its own promoter by ATMIN. Interacts with NEK9 (not phosphorylated at 'Ser-944'). Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.9 Ref.10 Ref.11 Ref.13 Ref.15 Ref.16 Ref.18

Subcellular location

Cytoplasmcytoskeleton. 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 ATMIN, PAK1 and estrogen. Ref.7 Ref.16

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

Sequence similarities

Belongs to the dynein light chain family.

Ontologies

Keywords
   Biological processApoptosis
Host-virus interaction
Transcription
Transcription regulation
Transport
   Cellular componentCytoplasm
Cytoskeleton
Dynein
Microtubule
Mitochondrion
Nucleus
   Molecular functionActivator
Motor protein
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG2/M transition of mitotic cell cycle

Traceable author statement. Source: Reactome

actin cytoskeleton organization

Traceable author statement Ref.1. Source: ProtInc

anatomical structure morphogenesis

Traceable author statement Ref.1. Source: ProtInc

antigen processing and presentation of exogenous peptide antigen via MHC class II

Traceable author statement. Source: Reactome

apoptotic process

Traceable author statement. Source: Reactome

female gamete generation

Traceable author statement Ref.1. Source: ProtInc

intrinsic apoptotic signaling pathway

Traceable author statement. Source: Reactome

microtubule-based process

Inferred from electronic annotation. Source: InterPro

mitotic cell cycle

Traceable author statement. Source: Reactome

negative regulation of phosphorylation

Inferred from direct assay PubMed 18579519. Source: UniProtKB

positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway

Traceable author statement. Source: Reactome

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

substantia nigra development

Inferred from expression pattern PubMed 22926577. Source: UniProt

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

transport

Inferred from electronic annotation. Source: UniProtKB-KW

viral process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcentrosome

Inferred from direct assay PubMed 21399614. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.7Ref.1. Source: UniProtKB

cytoplasmic dynein complex

Inferred from sequence or structural similarity. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

kinetochore

Inferred from direct assay PubMed 20133940. Source: UniProtKB

microtubule

Inferred from electronic annotation. Source: UniProtKB-KW

mitochondrion

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitotic spindle

Inferred from direct assay PubMed 20133940. Source: UniProtKB

nucleus

Inferred from direct assay Ref.7. Source: UniProtKB

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionmotor activity

Traceable author statement Ref.1. Source: ProtInc

nitric-oxide synthase regulator activity

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction PubMed 14607844Ref.7Ref.9PubMed 18579519PubMed 20133940Ref.16. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

GNB2L1P632446EBI-349105,EBI-296739
MYZAPP0CAP16EBI-349105,EBI-7929343

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 8989Dynein light chain 1, cytoplasmic
PRO_0000195125

Regions

Region67 – 8923Interaction with ESR1

Amino acid modifications

Modified residue361N6-acetyllysine Ref.12
Modified residue881Phosphoserine Ref.5

Experimental info

Mutagenesis671T → A: Abolishes interaction with PAK1. Ref.11
Mutagenesis881S → A: Abolishes growth factor-mediated phosphorylation. Increases BCL2L11 protein level and promotes apoptosis. Ref.5 Ref.10
Mutagenesis881S → E: Abolishes homodimerization. Abolishes interaction with BCL2L11 isoform 1 and isoform 2. Ref.5 Ref.10

Secondary structure

............. 89
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P63167 [UniParc].

Last modified September 27, 2004. Version 1.
Checksum: F5E7647D092BEB3A

FASTA8910,366
        10         20         30         40         50         60 
MCDRKAVIKN ADMSEEMQQD SVECATQALE KYNIEKDIAA HIKKEFDKKY NPTWHCIVGR 

        70         80 
NFGSYVTHET KHFIYFYLGQ VAILLFKSG 

« Hide

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: SUBUNIT, INTERACTION WITH PAK1, MUTAGENESIS OF THR-67.
[12]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-36, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MYZAP.
[14]"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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"The astrin-kinastrin/SKAP complex localizes to microtubule plus ends and facilitates chromosome alignment."
Dunsch A.K., Linnane E., Barr F.A., Gruneberg U.
J. Cell Biol. 192:959-968(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH KNSTRN; SPAG5; PLK1 AND SGOL2.
[16]"ATM substrate Chk2-interacting Zn2+ finger (ASCIZ) Is a bi-functional transcriptional activator and feedback sensor in the regulation of dynein light chain (DYNLL1) expression."
Jurado S., Conlan L.A., Baker E.K., Ng J.L., Tenis N., Hoch N.C., Gleeson K., Smeets M., Izon D., Heierhorst J.
J. Biol. Chem. 287:3156-3164(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ATMIN, INDUCTION.
[17]"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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 5-89.
[18]"Structural analysis of the regulation of the DYNLL/LC8 binding to Nek9 by phosphorylation."
Gallego P., Velazquez-Campoy A., Regue L., Roig J., Reverter D.
J. Biol. Chem. 288:12283-12294(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH NEK9, INTERACTION WITH NEK9.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U32944 mRNA. Translation: AAB04149.1.
CR407672 mRNA. Translation: CAG28600.1.
CCDSCCDS9200.1.
RefSeqNP_001032583.1. NM_001037494.1.
NP_001032584.1. NM_001037495.1.
NP_003737.1. NM_003746.2.
UniGeneHs.5120.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1CMIX-ray2.50A/B5-89[»]
3ZKEX-ray2.20A/C/E/G/I/K1-89[»]
3ZKFX-ray2.60A/C/E/G/I/K1-89[»]
ProteinModelPortalP63167.
SMRP63167. Positions 5-89.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114206. 124 interactions.
IntActP63167. 52 interactions.
MINTMINT-156345.
STRING9606.ENSP00000242577.

PTM databases

PhosphoSiteP63167.

Polymorphism databases

DMDM52783578.

Proteomic databases

MaxQBP63167.
PaxDbP63167.
PeptideAtlasP63167.
PRIDEP63167.

Protocols and materials databases

DNASU8655.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000242577; ENSP00000242577; ENSG00000088986.
ENST00000392508; ENSP00000376296; ENSG00000088986.
ENST00000392509; ENSP00000376297; ENSG00000088986.
ENST00000548342; ENSP00000447907; ENSG00000088986.
ENST00000549989; ENSP00000446614; ENSG00000088986.
GeneID8655.
KEGGhsa:8655.
UCSCuc001tyj.3. human.

Organism-specific databases

CTD8655.
GeneCardsGC12P120908.
HGNCHGNC:15476. DYNLL1.
MIM601562. gene.
neXtProtNX_P63167.
PharmGKBPA134972261.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG312371.
HOVERGENHBG002133.
InParanoidP63167.
KOK10418.
OMAECATQAM.
OrthoDBEOG7BZVVQ.
PhylomeDBP63167.
TreeFamTF300264.

Enzyme and pathway databases

ReactomeREACT_115566. Cell Cycle.
REACT_578. Apoptosis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpressP63167.
BgeeP63167.
CleanExHS_DLC1.
HS_DYNLL1.
GenevestigatorP63167.

Family and domain databases

Gene3D3.30.740.10. 1 hit.
InterProIPR019763. Dynein_light_1/2_CS.
IPR001372. Dynein_light_chain_typ-1/2.
[Graphical view]
PANTHERPTHR11886. PTHR11886. 1 hit.
PfamPF01221. Dynein_light. 1 hit.
[Graphical view]
PROSITEPS01239. DYNEIN_LIGHT_1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP63167.
GeneWikiDYNLL1.
GenomeRNAi8655.
NextBio32461.
PROP63167.
SOURCESearch...

Entry information

Entry nameDYL1_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 111 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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 documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM