Q9BY11 (PACN1_HUMAN) 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:	KIAA1379

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	444 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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 By similarity. Binds to membranes via its F-BAR domain and mediates membrane tubulation. Ref.6 Ref.7
Subunit structure	May form heterooligomers with other PACSINs. Interacts with MAPT 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 both COBL and DBNL. Identified in a complex composed of COBL, PACSIN1 and WASL By similarity. Homodimer. Ref.6
Subcellular location	Cytoplasm By similarity. Cell projection By similarity. Cell junction › synapse › synaptosome By similarity. Cell projection › ruffle membrane By similarity. Membrane; Peripheral membrane protein. Cytoplasmic vesicle membrane; Peripheral membrane protein By similarity. Cell junction › synapse By similarity. Cytoplasm › cytosol By similarity. Cell membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Note: Colocalizes with MAPT in axons. 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. Associates with membranes via its F-BAR domain. Ref.6
Tissue specificity	Highly expressed in brain and, at much lower levels, in heart and pancreas. Ref.1
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 By similarity. Ref.6 Ref.7
Post-translational modification	Phosphorylated by casein kinase 2 (CK2) and protein kinase C (PKC) Probable.
Sequence similarities	Belongs to the PACSIN family. Contains 1 FCH domain. Contains 1 SH3 domain.
Sequence caution	The sequence BAA92617.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Endocytosis
Cellular component	Cell junction Cell membrane Cell projection Cytoplasm Cytoplasmic vesicle Membrane Synapse Synaptosome
Coding sequence diversity	Polymorphism
Domain	Coiled coil SH3 domain
Ligand	Lipid-binding
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	endocytosis Non-traceable author statement. Source: UniProtKB establishment of protein localization to plasma membrane Inferred from sequence or structural similarity. Source: BHF-UCL membrane tubulation Inferred from direct assay Ref.6. Source: UniProtKB negative regulation of endocytosis Inferred from electronic annotation. Source: Compara neuron projection morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of dendrite development Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular_component	COPI-coated vesicle Inferred from electronic annotation. Source: Compara axon terminus Inferred from sequence or structural similarity. Source: UniProtKB perinuclear region of cytoplasm Inferred from sequence or structural similarity. Source: BHF-UCL ruffle membrane Inferred from sequence or structural similarity. Source: UniProtKB synapse Inferred from sequence or structural similarity. Source: BHF-UCL
Molecular_function	phospholipid binding Inferred from direct assay Ref.6. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 444

444

Protein kinase C and casein kinase substrate in neurons protein 1

PRO_0000161792

Regions

Domain

13 – 76

64

FCH

Domain

385 – 444

60

SH3

Region

1 – 307

307

F-BAR domain

Coiled coil

147 – 168

22

Coiled coil

184 – 220

37

Amino acid modifications

Modified residue

79

1

Phosphoserine By similarity

Modified residue

184

1

Phosphothreonine By similarity

Modified residue

394

1

Phosphotyrosine By similarity

Natural variations

Natural variant

334

1

A → V.
Corresponds to variant rs41312309 [ dbSNP | Ensembl ].

VAR_053554

Experimental info

Mutagenesis

125

1

I → E: Reduces membrane-binding. Abolishes membrane tubulation. Ref.6

Mutagenesis

126

1

M → E: Reduces membrane-binding. Abolishes membrane tubulation. Ref.6

Secondary structure

1

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444

Helix Strand Turn

Details...

Turn

22 – 25

4

Helix

26 – 73

48

Helix

78 – 107

30

Helix

109 – 120

12

Beta strand

127 – 129

3

Helix

130 – 170

41

Turn

176 – 179

4

Helix

193 – 256

64

Helix

258 – 260

3

Turn

262 – 264

3

Helix

265 – 275

11

Helix

280 – 291

12

Sequences

	Sequence		Length	Mass (Da)
	Q9BY11 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 6AAF801873770975	FASTA	444	50,966
	10 20 30 40 50 60 MSSSYDEASL APEETTDSFW EVGNYKRTVK RIDDGHRLCN DLMNCVQERA KIEKAYGQQL 70 80 90 100 110 120 TDWAKRWRQL IEKGPQYGSL ERAWGAIMTE ADKVSELHQE VKNNLLNEDL EKVKNWQKDA 130 140 150 160 170 180 YHKQIMGGFK ETKEAEDGFR KAQKPWAKKM KELEAAKKAY HLACKEEKLA MTREMNSKTE 190 200 210 220 230 240 QSVTPEQQKK LQDKVDKCKQ DVQKTQEKYE KVLEDVGKTT PQYMENMEQV FEQCQQFEEK 250 260 270 280 290 300 RLVFLKEVLL DIKRHLNLAE NSSYIHVYRE LEQAIRGADA QEDLRWFRST SGPGMPMNWP 310 320 330 340 350 360 QFEEWNPDLP HTTTKKEKQP KKAEGVALTN ATGAVESTSQ AGDRGSVSSY DRGQPYATEW 370 380 390 400 410 420 SDDESGNPFG GSETNGGANP FEDDSKGVRV RALYDYDGQE QDELSFKAGD ELTKLGEEDE 430 440 QGWCRGRLDS GQLGLYPANY VEAI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"PACSIN 3 is a novel SH3 domain cytoplasmic adapter protein of the pacsin-syndapin-FAP52 gene family." Sumoy L., Pluvinet R., Andreu N., Estivill X., Escarceller M. Gene 262:199-205(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[2]	"Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O. DNA Res. 7:65-73(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones." Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T. DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Amygdala.
[5]	"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: Brain.
[6]	"Molecular mechanism of membrane constriction and tubulation mediated by the F-BAR protein Pacsin/Syndapin." Wang Q., Navarro M.V., Peng G., Molinelli E., Goh S.L., Judson B.L., Rajashankar K.R., Sondermann H. Proc. Natl. Acad. Sci. U.S.A. 106:12700-12705(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.77 ANGSTROMS) OF 1-325, FUNCTION, LIPID-BINDING, SUBUNIT, SUBCELLULAR LOCATION, MUTAGENESIS OF ILE-125 AND MET-126, DOMAIN.
[7]	"Rigidity of wedge loop in PACSIN 3 protein is a key factor in dictating diameters of tubules." Bai X., Meng G., Luo M., Zheng X. J. Biol. Chem. 287:22387-22396(2012) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 14-308, FUNCTION, DOMAIN.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF242529 mRNA. Translation: AAK29206.1.
AB037800 mRNA. Translation: BAA92617.2. Different initiation.
AL834211 mRNA. Translation: CAD38895.1.
BC040228 mRNA. Translation: AAH40228.1.

IPI

IPI00011515.

RefSeq

NP_001186512.1. NM_001199583.2.
NP_065855.1. NM_020804.4.

UniGene

Hs.520087.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3HAH	X-ray	2.77	A/B	1-325	[»]
3HAI	X-ray	2.88	A/B/C/D	1-308	[»]
3Q84	X-ray	2.80	A/B/G/H/M/N	14-308	[»]
3QNI	X-ray	2.80	A/B	1-307	[»]

ProteinModelPortal

Q9BY11.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9BY11. 16 interactions.

STRING

9606.ENSP00000244458.

PTM databases

PhosphoSite

Q9BY11.

Polymorphism databases

DMDM

22256962.

Proteomic databases

PaxDb

Q9BY11.

PRIDE

Q9BY11.

Protocols and materials databases

DNASU

29993.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000244458; ENSP00000244458; ENSG00000124507.
ENST00000538621; ENSP00000439639; ENSG00000124507.

GeneID

29993.

KEGG

hsa:29993.

UCSC

uc003ojo.3. human.

Organism-specific databases

CTD

29993.

GeneCards

GC06P034562.

HGNC

HGNC:8570. PACSIN1.

HPA

CAB009929.
HPA028852.

MIM

606512. gene.

neXtProt

NX_Q9BY11.

PharmGKB

PA32896.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG283356.

HOGENOM

HOG000007245.

HOVERGEN

HBG053486.

InParanoid

Q9BY11.

OMA

PDSLGWC.

OrthoDB

EOG4QVCC5.

PhylomeDB

Q9BY11.

Gene expression databases

ArrayExpress

Q9BY11.

Bgee

Q9BY11.

CleanEx

HS_PACSIN1.

Genevestigator

Q9BY11.

GermOnline

ENSG00000124507. Homo sapiens.

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

Q9BY11.

GenomeRNAi

29993.

NextBio

52788.

SOURCE

Search...

Entry information

Entry name

PACN1_HUMAN

Accession

Primary (citable) accession number: Q9BY11
Secondary accession number(s): Q9P2G8

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 2002
Last sequence update:	June 1, 2001
Last modified:	May 1, 2013
This is version 95 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.