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Q61644 (PACN1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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:
Protein kinase C and casein kinase substrate in neurons protein 1
Alternative name(s):
Syndapin-1
Gene names
Name:Pacsin1
Synonyms:Pacsin
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length441 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Binds to membranes via its F-BAR domain and mediates membrane tubulation. Plays a role in the reorganization of the microtubule cytoskeleton via its interaction with MAPT; this decreases microtubule stability and inhibits MAPT-induced microtubule polymerization. Plays a role in cellular transport processes by recruiting DNM1, DNM2 and DNM3 to membranes. Plays a role in the reorganization of the actin cytoskeleton and in neuron morphogenesis via its interaction with COBL and WASL, and by recruiting COBL to the cell cortex. Plays a role in the regulation of neurite formation, neurite branching and the regulation of neurite length. Required for normal synaptic vesicle endocytosis; this process retrieves previously released neurotransmitters to accommodate multiple cycles of neurotransmission. Required for normal excitatory and inhibitory synaptic transmission. Ref.4 Ref.8 Ref.9 Ref.10

Subunit structure

Homodimer. May form heterooligomers with other PACSINs. Interacts with both COBL and DBNL. Identified in a complex composed of COBL, PACSIN1 and WASL. Interacts with EHD3 By similarity. Interacts (via SH3 domain) with SYNJ1 and WASL. Interacts (via SH3 domain) with DNM1; the interaction is reduced by DNM1 phosphorylation. Interacts with DNM2 and DNM3. Interacts with MAPT. Interacts with EHD1. Interacts with TRPV4. Ref.4 Ref.5 Ref.6 Ref.8 Ref.9 Ref.10

Subcellular location

Cytoplasm. Cell projection By similarity. Cell junctionsynapsesynaptosome By similarity. Cell projectionruffle membrane. Membrane; Peripheral membrane protein. Cytoplasmic vesicle membrane; Peripheral membrane protein. Cell junctionsynapse. Cytoplasmcytosol. Cell membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Note: In primary neuronal cultures, present at a high level in presynaptic nerve terminals and in the cell body. Colocalizes with DNM1 at vesicular structures in the cell body and neurites By similarity. Colocalizes with MAPT in axons. Ref.8 Ref.10

Tissue specificity

Highly expressed in brain. Detected in hippocampus and dorsal root ganglion neurons. Detected in rod photoreceptor terminals in the outer plexiform layer of the retina (at protein level). In CNS neurons, high levels in the pyramidal cells of the hippocampus, Purkinje cells of the cerebellum and large neurons of the cortex and brain stem. Ref.1 Ref.4 Ref.8 Ref.9

Developmental stage

Expression is seen at embryonic day 17 and is up-regulated developmentally with a correlation to neuronal differentiation.

Domain

The F-BAR domain forms a coiled coil and mediates membrane-binding and membrane tubulation. In the autoinhibited conformation, interaction with the SH3 domain inhibits membrane tubulation mediated by the F-BAR domain. DNM1 binding abolishes autoinhibition. Ref.10

Post-translational modification

Phosphorylated by casein kinase 2 (CK2) and protein kinase C (PKC) Probable.

Disruption phenotype

Mice are born at the expected Mendelian rate, but display a slightly reduced body weight and reduced fertility. Mice display increased synaptic vesicle diameter and impaired compensatory synaptic vesicle endocytosis after high synapse activity. Rod photoreceptor ribbon synapses display an abnormally high number of endosome-like structures and tubular elements after light exposure. Mice display defects in excitatory and inhibitory synaptic transmission in the hippocampus, and display a tendency to seizures when confronted with novelty. Ref.8

Sequence similarities

Belongs to the PACSIN family.

Contains 1 FCH domain.

Contains 1 SH3 domain.

Ontologies

Keywords
   Biological processEndocytosis
   Cellular componentCell junction
Cell membrane
Cell projection
Cytoplasm
Cytoplasmic vesicle
Membrane
Synapse
Synaptosome
   DomainCoiled coil
SH3 domain
   LigandLipid-binding
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processactin filament organization

Inferred from electronic annotation. Source: InterPro

membrane tubulation

Inferred from mutant phenotype Ref.10. Source: UniProtKB

negative regulation of endocytosis

Inferred from direct assay Ref.4. Source: MGI

neuron projection morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

protein localization to membrane

Inferred from mutant phenotype Ref.8. Source: UniProtKB

signal transduction

Traceable author statement Ref.1. Source: MGI

synaptic vesicle endocytosis

Inferred from mutant phenotype Ref.8. Source: UniProtKB

   Cellular_componentCOPI-coated vesicle

Inferred from direct assay Ref.1. Source: MGI

axon terminus

Inferred from sequence or structural similarity. Source: UniProtKB

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

cytoplasm

Inferred from direct assay Ref.10. Source: UniProtKB

cytoplasmic vesicle membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytosol

Inferred from electronic annotation. Source: UniProtKB-SubCell

ruffle membrane

Inferred from direct assay Ref.10. Source: UniProtKB

synapse

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functioncytoskeletal protein binding

Inferred from direct assay Ref.4. Source: MGI

phospholipid binding

Inferred from direct assay Ref.10. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MaptP106375EBI-2255561,EBI-774043
MaptP19332-56EBI-2255561,EBI-8758676From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 441441Protein kinase C and casein kinase substrate in neurons protein 1
PRO_0000161793

Regions

Domain10 – 7364FCH
Domain382 – 44160SH3
Region1 – 304304F-BAR domain
Coiled coil23 – 272250

Amino acid modifications

Modified residue761Phosphoserine By similarity
Modified residue1811Phosphothreonine By similarity
Modified residue3911Phosphotyrosine Ref.7

Experimental info

Mutagenesis122 – 1232IM → FF: Increases membrane tubulation.
Mutagenesis122 – 1232IM → QQ: Abolishes membrane tubulation. No effect on phospholipid binding.
Mutagenesis1271K → E: Abolishes membrane tubulation; when associated with E-130. Ref.10
Mutagenesis1301K → E: Abolishes membrane tubulation; when associated with E-127. Ref.10
Mutagenesis145 – 1484KKMK → EEME: Abolishes membrane tubulation. Ref.10
Mutagenesis4001E → R: Impairs interaction with DNM1.
Mutagenesis4341P → L: Abolishes interaction with DNM1, MAPT, SYNJ1 and WASL. Ref.4 Ref.9 Ref.10

Secondary structure

............................... 441
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q61644 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 21BEB339A14A41F9

FASTA44150,575
        10         20         30         40         50         60 
MSGSYDEASE EITDSFWEVG NYKRTVKRID DGHRLCNDLM SCVQERAKIE KAYAQQLTDW 

        70         80         90        100        110        120 
AKRWRQLIEK GPQYGSLERA WGAMMTEADK VSELHQEVKN SLLNEDLEKV KNWQKDAYHK 

       130        140        150        160        170        180 
QIMGGFKETK EAEDGFRKAQ KPWAKKMKEL EAAKKAYHLA CKEERLAMTR EMNSKTEQSV 

       190        200        210        220        230        240 
TPEQQKKLVD KVDKCRQDVQ KTQEKYEKVL EDVGKTTPQY MEGMEQVFEQ CQQFEEKRLV 

       250        260        270        280        290        300 
FLKEVLLDIK RHLNLAENSS YMHVYRELEQ AIRGADAQED LRWFRSTSGP GMPMNWPQFE 

       310        320        330        340        350        360 
EWNPDLPHTT AKKEKQPKKA EGATLSNATG AVESTSQAGD RGSVSSYDRG QTYATEWSDD 

       370        380        390        400        410        420 
ESGNPFGGNE ANGGANPFED DAKGVRVRAL YDYDGQEQDE LSFKAGDELT KLGEEDEQGW 

       430        440 
CRGRLDSGQL GLYPANYVEA I 

« Hide

References

« Hide 'large scale' references
[1]"PACSIN, a brain protein that is upregulated upon differentiation into neuronal cells."
Plomann M., Lange R., Vopper G., Cremer H., Heinlein U.A.O., Scheff S., Baldwin S.A., Leitges M., Cramer M., Paulsson M., Barthels D.
Eur. J. Biochem. 256:201-211(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Strain: C57BL/6J.
Tissue: Cerebellum.
[2]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Eye.
[3]Lubec G., Kang S.U.
Submitted (APR-2007) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 52-62; 71-79; 319-341 AND 425-441, IDENTIFICATION BY MASS SPECTROMETRY.
Strain: C57BL/6.
Tissue: Brain.
[4]"All three PACSIN isoforms bind to endocytic proteins and inhibit endocytosis."
Modregger J., Ritter B., Witter B., Paulsson M., Plomann M.
J. Cell Sci. 113:4511-4521(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DNM1; SYNJ1 AND WASL, HOMOOLIGOMERIZATION, HETEROOLIGOMERIZATION WITH PACSIN2 AND PACSIN3, TISSUE SPECIFICITY, MUTAGENESIS OF PRO-434.
[5]"EHD proteins associate with syndapin I and II and such interactions play a crucial role in endosomal recycling."
Braun A., Pinyol R., Dahlhaus R., Koch D., Fonarev P., Grant B.D., Kessels M.M., Qualmann B.
Mol. Biol. Cell 16:3642-3658(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EHD1.
[6]"PACSINs bind to the TRPV4 cation channel. PACSIN 3 modulates the subcellular localization of TRPV4."
Cuajungco M.P., Grimm C., Oshima K., D'hoedt D., Nilius B., Mensenkamp A.R., Bindels R.J., Plomann M., Heller S.
J. Biol. Chem. 281:18753-18762(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TRPV4.
[7]"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain."
Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.
J. Proteome Res. 7:311-318(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-391, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Brain.
[8]"Proper synaptic vesicle formation and neuronal network activity critically rely on syndapin I."
Koch D., Spiwoks-Becker I., Sabanov V., Sinning A., Dugladze T., Stellmacher A., Ahuja R., Grimm J., Schuler S., Muller A., Angenstein F., Ahmed T., Diesler A., Moser M., Tom Dieck S., Spessert R., Boeckers T.M., Fassler R. expand/collapse author list , Hubner C.A., Balschun D., Gloveli T., Kessels M.M., Qualmann B.
EMBO J. 30:4955-4969(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE, INTERACTION WITH DNM1; DNM2 AND DNM3, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[9]"PACSIN1, a Tau-interacting protein, regulates axonal elongation and branching by facilitating microtubule instability."
Liu Y., Lv K., Li Z., Yu A.C., Chen J., Teng J.
J. Biol. Chem. 287:39911-39924(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MAPT, MUTAGENESIS OF PRO-434, TISSUE SPECIFICITY.
[10]"Molecular basis for SH3 domain regulation of F-BAR-mediated membrane deformation."
Rao Y., Ma Q., Vahedi-Faridi A., Sundborger A., Pechstein A., Puchkov D., Luo L., Shupliakov O., Saenger W., Haucke V.
Proc. Natl. Acad. Sci. U.S.A. 107:8213-8218(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 1-337, SUBCELLULAR LOCATION, FUNCTION, SUBUNIT, INTERACTION WITH DNM1, MUTAGENESIS OF 122-ILE-MET-123; LYS-127; LYS-130; 145-LYS--LYS-148 AND PRO-434, DOMAIN, IDENTIFICATION BY MASS SPECTROMETRY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X85124 mRNA. Translation: CAA59437.1.
BC014698 mRNA. Translation: AAH14698.1.
RefSeqNP_001273672.1. NM_001286743.1.
NP_001273673.1. NM_001286744.1.
NP_035991.1. NM_011861.3.
NP_848142.1. NM_178365.4.
XP_006524289.1. XM_006524226.1.
XP_006536813.1. XM_006536750.1.
UniGeneMm.4926.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2X3VX-ray2.45A/B/C1-337[»]
2X3WX-ray2.64A/B/C1-337[»]
D382-441[»]
2X3XX-ray3.35A/B/C1-337[»]
D/E382-441[»]
ProteinModelPortalQ61644.
SMRQ61644. Positions 13-304, 385-440.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-53108N.
IntActQ61644. 8 interactions.
MINTMINT-4106465.
STRING10090.ENSMUSP00000110522.

PTM databases

PhosphoSiteQ61644.

2D gel databases

UCD-2DPAGEQ61644.

Proteomic databases

PaxDbQ61644.
PRIDEQ61644.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000045896; ENSMUSP00000044168; ENSMUSG00000040276.
ENSMUST00000097360; ENSMUSP00000094973; ENSMUSG00000040276.
ENSMUST00000114872; ENSMUSP00000110522; ENSMUSG00000040276.
ENSMUST00000114873; ENSMUSP00000110523; ENSMUSG00000040276.
GeneID23969.
KEGGmmu:23969.
UCSCuc008bpj.1. mouse.

Organism-specific databases

CTD29993.
MGIMGI:1345181. Pacsin1.

Phylogenomic databases

eggNOGNOG283356.
GeneTreeENSGT00510000046376.
HOGENOMHOG000007245.
HOVERGENHBG053486.
InParanoidQ61644.
OMAAMTREAN.
OrthoDBEOG75TMBJ.
PhylomeDBQ61644.
TreeFamTF313677.

Gene expression databases

ArrayExpressQ61644.
BgeeQ61644.
GenevestigatorQ61644.

Family and domain databases

InterProIPR001060. FCH_dom.
IPR028518. PACSIN1.
IPR001452. SH3_domain.
[Graphical view]
PANTHERPTHR10959:SF0. PTHR10959:SF0. 1 hit.
PfamPF00611. FCH. 1 hit.
[Graphical view]
PRINTSPR00452. SH3DOMAIN.
SMARTSM00055. FCH. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMSSF50044. SSF50044. 1 hit.
PROSITEPS50133. FCH. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ61644.
NextBio303847.
PROQ61644.
SOURCESearch...

Entry information

Entry namePACN1_MOUSE
AccessionPrimary (citable) accession number: Q61644
Entry history
Integrated into UniProtKB/Swiss-Prot: August 13, 2002
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 109 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot