Q61644 (PACN1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein kinase C and casein kinase substrate in neurons protein 1

Alternative name(s):
Syndapin 1

Gene names

Name:	Pacsin1
Synonyms:	Pacsin

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	441 AA.
Sequence status	Complete.
Protein existence	Evidence 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 accomodate multiple cycles of neurotransmission. Required for normal excitatory and inhibitory synaptic transmission. Ref.4 Ref.6 Ref.7 Ref.8
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 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. Ref.4 Ref.6 Ref.7 Ref.8
Subcellular location	Cytoplasm. Cell projection By similarity. Cell junction › synapse › synaptosome By similarity. Cell projection › ruffle membrane. Membrane; Peripheral membrane protein. Cytoplasmic vesicle membrane; Peripheral membrane protein. Cell junction › synapse. Cytoplasm › cytosol. 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.6 Ref.8
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.6 Ref.7
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.8
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.6
Sequence similarities	Belongs to the PACSIN family. Contains 1 FCH domain. Contains 1 SH3 domain.

Ontologies

Keywords
Biological process	Endocytosis
Cellular component	Cell junction Cell membrane Cell projection Cytoplasm Cytoplasmic vesicle Membrane Synapse Synaptosome
Domain	Coiled coil SH3 domain
Ligand	Lipid-binding
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	endocytosis Inferred from electronic annotation. Source: UniProtKB-KW membrane tubulation Inferred from mutant phenotype Ref.8. 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 signal transduction Traceable author statement Ref.1. Source: MGI
Cellular_component	COPI-coated vesicle Inferred from direct assay Ref.1. Source: MGI axon terminus Inferred from sequence or structural similarity. Source: UniProtKB ruffle membrane Inferred from direct assay Ref.8. Source: UniProtKB
Molecular_function	cytoskeletal protein binding Inferred from direct assay Ref.4. Source: MGI phospholipid binding Inferred from direct assay Ref.8. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 441

441

Protein kinase C and casein kinase substrate in neurons protein 1

PRO_0000161793

Regions

Domain

10 – 73

64

FCH

Domain

382 – 441

60

SH3

Region

1 – 304

304

F-BAR domain

Coiled coil

144 – 165

22

Coiled coil

183 – 217

35

Amino acid modifications

Modified residue

76

1

Phosphoserine By similarity

Modified residue

181

1

Phosphothreonine By similarity

Modified residue

391

1

Phosphotyrosine Ref.5

Experimental info

Mutagenesis

122 – 123

2

IM → FF: Increases membrane tubulation.

Mutagenesis

122 – 123

2

IM → QQ: Abolishes membrane tubulation. No effect on phospholipid binding.

Mutagenesis

127

1

K → E: Abolishes membrane tubulation; when associated with E-130. Ref.8

Mutagenesis

130

1

K → E: Abolishes membrane tubulation; when associated with E-127. Ref.8

Mutagenesis

145 – 148

4

KKMK → EEME: Abolishes membrane tubulation. Ref.8

Mutagenesis

400

1

E → R: Impairs interaction with DNM1.

Mutagenesis

434

1

P → L: Abolishes interaction with DNM1, MAPT, SYNJ1 and WASL. Ref.4 Ref.7 Ref.8

Secondary structure

1

.

.

.

.

.

.

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.

.

.

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.

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.

.

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441

Helix Strand Turn

Details...

Turn

19 – 22

4

Helix

23 – 70

48

Helix

75 – 104

30

Helix

106 – 117

12

Helix

127 – 175

49

Beta strand

176 – 178

3

Helix

182 – 253

72

Helix

255 – 257

3

Helix

260 – 274

15

Helix

277 – 288

12

Sequences

	Sequence		Length	Mass (Da)
	Q61644 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 21BEB339A14A41F9	FASTA	441	50,575
	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

References

	« Hide 'large scale' referencesShow '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, 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]	"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, MASS SPECTROMETRY. Tissue: Brain.
[6]	"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. , 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.
[7]	"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.
[8]	"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, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X85124 mRNA. Translation: CAA59437.1.
BC014698 mRNA. Translation: AAH14698.1.

IPI

IPI00123613.

RefSeq

NP_035991.1. NM_011861.2.
NP_848142.1. NM_178365.3.

UniGene

Mm.4926.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2X3V	X-ray	2.45	A/B/C	1-337	[»]
2X3W	X-ray	2.64	A/B/C	1-337	[»]
			D	382-441	[»]
2X3X	X-ray	3.35	A/B/C	1-337	[»]
			D/E	382-441	[»]

ProteinModelPortal

Q61644.

SMR

Q61644. Positions 13-304, 385-440.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-53108N.

IntAct

Q61644. 2 interactions.

STRING

10090.ENSMUSP00000110522.

PTM databases

PhosphoSite

Q61644.

2D gel databases

UCD-2DPAGE

Q61644.

Proteomic databases

PaxDb

Q61644.

PRIDE

Q61644.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000045896; ENSMUSP00000044168; ENSMUSG00000040276.
ENSMUST00000097360; ENSMUSP00000094973; ENSMUSG00000040276.
ENSMUST00000114872; ENSMUSP00000110522; ENSMUSG00000040276.
ENSMUST00000114873; ENSMUSP00000110523; ENSMUSG00000040276.

GeneID

23969.

KEGG

mmu:23969.

Organism-specific databases

CTD

29993.

MGI

MGI:1345181. Pacsin1.

Phylogenomic databases

eggNOG

NOG283356.

GeneTree

ENSGT00510000046376.

HOGENOM

HOG000007245.

HOVERGEN

HBG053486.

InParanoid

Q61644.

OMA

PDSLGWC.

OrthoDB

EOG4QVCC5.

Gene expression databases

ArrayExpress

Q61644.

Bgee

Q61644.

Genevestigator

Q61644.

GermOnline

ENSMUSG00000040276. Mus musculus.

Family and domain databases

InterPro

IPR001060. FCH_dom.
IPR001452. SH3_domain.
[Graphical view]

Pfam

PF00611. FCH. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]

PRINTS

PR00452. SH3DOMAIN.

SMART

SM00055. FCH. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]

SUPFAM

SSF50044. SH3. 1 hit.

PROSITE

PS50133. FCH. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q61644.

NextBio

303847.

SOURCE

Search...

Entry information

Entry name

PACN1_MOUSE

Accession

Primary (citable) accession number: Q61644

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 2002
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 98 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program