PACN1_HUMAN
ID PACN1_HUMAN Reviewed; 444 AA.
AC Q9BY11; Q9P2G8;
DT 13-AUG-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Protein kinase C and casein kinase substrate in neurons protein 1;
DE AltName: Full=Syndapin-1;
GN Name=PACSIN1; Synonyms=KIAA1379;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=11179684; DOI=10.1016/s0378-1119(00)00531-x;
RA Sumoy L., Pluvinet R., Andreu N., Estivill X., Escarceller M.;
RT "PACSIN 3 is a novel SH3 domain cytoplasmic adapter protein of the pacsin-
RT syndapin-FAP52 gene family.";
RL Gene 262:199-205(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVI. The
RT complete sequences of 150 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:65-73(2000).
RN [3]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Amygdala;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION, INTERACTION WITH DNM1, SUBCELLULAR LOCATION, AND DOMAIN.
RX PubMed=23236520; DOI=10.1371/journal.pone.0051628;
RA Goh S.L., Wang Q., Byrnes L.J., Sondermann H.;
RT "Versatile membrane deformation potential of activated pacsin.";
RL PLoS ONE 7:E51628-E51628(2012).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.77 ANGSTROMS) OF 1-325, FUNCTION, LIPID-BINDING,
RP SUBUNIT, SUBCELLULAR LOCATION, MUTAGENESIS OF ILE-125 AND MET-126, AND
RP DOMAIN.
RX PubMed=19549836; DOI=10.1073/pnas.0902974106;
RA Wang Q., Navarro M.V., Peng G., Molinelli E., Goh S.L., Judson B.L.,
RA Rajashankar K.R., Sondermann H.;
RT "Molecular mechanism of membrane constriction and tubulation mediated by
RT the F-BAR protein Pacsin/Syndapin.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:12700-12705(2009).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 14-308, FUNCTION, AND DOMAIN.
RX PubMed=22573331; DOI=10.1074/jbc.m112.358960;
RA Bai X., Meng G., Luo M., Zheng X.;
RT "Rigidity of wedge loop in PACSIN 3 protein is a key factor in dictating
RT diameters of tubules.";
RL J. Biol. Chem. 287:22387-22396(2012).
CC -!- FUNCTION: Plays a role in the reorganization of the microtubule
CC cytoskeleton via its interaction with MAPT; this decreases microtubule
CC stability and inhibits MAPT-induced microtubule polymerization. Plays a
CC role in cellular transport processes by recruiting DNM1, DNM2 and DNM3
CC to membranes. Plays a role in the reorganization of the actin
CC cytoskeleton and in neuron morphogenesis via its interaction with COBL
CC and WASL, and by recruiting COBL to the cell cortex. Plays a role in
CC the regulation of neurite formation, neurite branching and the
CC regulation of neurite length. Required for normal synaptic vesicle
CC endocytosis; this process retrieves previously released
CC neurotransmitters to accommodate multiple cycles of neurotransmission.
CC Required for normal excitatory and inhibitory synaptic transmission (By
CC similarity). Binds to membranes via its F-BAR domain and mediates
CC membrane tubulation. {ECO:0000250, ECO:0000269|PubMed:19549836,
CC ECO:0000269|PubMed:22573331, ECO:0000269|PubMed:23236520}.
CC -!- SUBUNIT: May form heterooligomers with other PACSINs. Interacts with
CC MAPT. Interacts with TRPV4 (By similarity). Interacts (via SH3 domain)
CC with SYNJ1 and WASL. Interacts with DNM2 and DNM3. Interacts with both
CC COBL and DBNL. Identified in a complex composed of COBL, PACSIN1 and
CC WASL. Interacts with EHD1 and EHD3 (By similarity). Homodimer.
CC Interacts (via SH3 domain) with DNM1; the interaction is reduced by
CC DNM1 phosphorylation. {ECO:0000250, ECO:0000269|PubMed:19549836,
CC ECO:0000269|PubMed:23236520}.
CC -!- INTERACTION:
CC Q9BY11; O14672: ADAM10; NbExp=2; IntAct=EBI-721769, EBI-1536151;
CC Q9BY11; Q8TAB7: CCDC26; NbExp=3; IntAct=EBI-721769, EBI-10271580;
CC Q9BY11; O75128: COBL; NbExp=3; IntAct=EBI-721769, EBI-3446582;
CC Q9BY11; P48023: FASLG; NbExp=4; IntAct=EBI-721769, EBI-495538;
CC Q9BY11; P42858: HTT; NbExp=3; IntAct=EBI-721769, EBI-466029;
CC Q9BY11; O00746: NME4; NbExp=3; IntAct=EBI-721769, EBI-744871;
CC Q9BY11; Q9UNF0: PACSIN2; NbExp=10; IntAct=EBI-721769, EBI-742503;
CC Q9BY11; Q9UKS6: PACSIN3; NbExp=8; IntAct=EBI-721769, EBI-77926;
CC Q9BY11; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-721769, EBI-742388;
CC Q9BY11; Q9NUX5: POT1; NbExp=2; IntAct=EBI-721769, EBI-752420;
CC Q9BY11; Q8IYM2: SLFN12; NbExp=3; IntAct=EBI-721769, EBI-2822550;
CC Q9BY11; Q9UMY4: SNX12; NbExp=3; IntAct=EBI-721769, EBI-1752602;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell projection
CC {ECO:0000250}. Synapse, synaptosome {ECO:0000250}. Cell projection,
CC ruffle membrane {ECO:0000250}. Membrane; Peripheral membrane protein.
CC Cytoplasmic vesicle membrane {ECO:0000250}; Peripheral membrane protein
CC {ECO:0000250}. Synapse {ECO:0000250}. Cytoplasm, cytosol {ECO:0000250}.
CC Cell membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250};
CC Cytoplasmic side {ECO:0000250}. Note=Colocalizes with MAPT in axons. In
CC primary neuronal cultures, present at a high level in presynaptic nerve
CC terminals and in the cell body. Colocalizes with DNM1 at vesicular
CC structures in the cell body and neurites (By similarity). Associates
CC with membranes via its F-BAR domain. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Highly expressed in brain and, at much lower
CC levels, in heart and pancreas. {ECO:0000269|PubMed:11179684}.
CC -!- DOMAIN: The F-BAR domain forms a coiled coil and mediates membrane-
CC binding and membrane tubulation. In the autoinhibited conformation,
CC interaction with the SH3 domain inhibits membrane tubulation mediated
CC by the F-BAR domain. DNM1 binding abolishes autoinhibition (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated by casein kinase 2 (CK2) and protein kinase C
CC (PKC). {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the PACSIN family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA92617.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF242529; AAK29206.1; -; mRNA.
DR EMBL; AB037800; BAA92617.2; ALT_INIT; mRNA.
DR EMBL; AL834211; CAD38895.1; -; mRNA.
DR EMBL; BC040228; AAH40228.1; -; mRNA.
DR CCDS; CCDS4793.1; -.
DR RefSeq; NP_001186512.1; NM_001199583.2.
DR RefSeq; NP_065855.1; NM_020804.4.
DR RefSeq; XP_011512843.1; XM_011514541.1.
DR PDB; 3HAH; X-ray; 2.77 A; A/B=1-325.
DR PDB; 3HAI; X-ray; 2.88 A; A/B/C/D=1-308.
DR PDB; 3Q84; X-ray; 2.80 A; A/B/G/H/M/N=14-308.
DR PDB; 3QNI; X-ray; 2.80 A; A/B=1-307.
DR PDBsum; 3HAH; -.
DR PDBsum; 3HAI; -.
DR PDBsum; 3Q84; -.
DR PDBsum; 3QNI; -.
DR AlphaFoldDB; Q9BY11; -.
DR SMR; Q9BY11; -.
DR BioGRID; 119018; 52.
DR IntAct; Q9BY11; 47.
DR MINT; Q9BY11; -.
DR STRING; 9606.ENSP00000484060; -.
DR iPTMnet; Q9BY11; -.
DR PhosphoSitePlus; Q9BY11; -.
DR SwissPalm; Q9BY11; -.
DR BioMuta; PACSIN1; -.
DR DMDM; 22256962; -.
DR EPD; Q9BY11; -.
DR jPOST; Q9BY11; -.
DR MassIVE; Q9BY11; -.
DR MaxQB; Q9BY11; -.
DR PaxDb; Q9BY11; -.
DR PeptideAtlas; Q9BY11; -.
DR PRIDE; Q9BY11; -.
DR ProteomicsDB; 79560; -.
DR ABCD; Q9BY11; 1 sequenced antibody.
DR Antibodypedia; 4091; 264 antibodies from 34 providers.
DR DNASU; 29993; -.
DR Ensembl; ENST00000244458.7; ENSP00000244458.2; ENSG00000124507.11.
DR Ensembl; ENST00000538621.2; ENSP00000439639.1; ENSG00000124507.11.
DR Ensembl; ENST00000620693.4; ENSP00000484060.1; ENSG00000124507.11.
DR GeneID; 29993; -.
DR KEGG; hsa:29993; -.
DR MANE-Select; ENST00000244458.7; ENSP00000244458.2; NM_020804.5; NP_065855.1.
DR UCSC; uc003ojo.5; human.
DR CTD; 29993; -.
DR DisGeNET; 29993; -.
DR GeneCards; PACSIN1; -.
DR HGNC; HGNC:8570; PACSIN1.
DR HPA; ENSG00000124507; Group enriched (brain, retina).
DR MIM; 606512; gene.
DR neXtProt; NX_Q9BY11; -.
DR OpenTargets; ENSG00000124507; -.
DR PharmGKB; PA32896; -.
DR VEuPathDB; HostDB:ENSG00000124507; -.
DR eggNOG; KOG2856; Eukaryota.
DR GeneTree; ENSGT00950000182973; -.
DR HOGENOM; CLU_030752_0_0_1; -.
DR InParanoid; Q9BY11; -.
DR OMA; WAAIMTE; -.
DR OrthoDB; 727724at2759; -.
DR PhylomeDB; Q9BY11; -.
DR TreeFam; TF313677; -.
DR PathwayCommons; Q9BY11; -.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR SignaLink; Q9BY11; -.
DR SIGNOR; Q9BY11; -.
DR BioGRID-ORCS; 29993; 9 hits in 1068 CRISPR screens.
DR ChiTaRS; PACSIN1; human.
DR EvolutionaryTrace; Q9BY11; -.
DR GeneWiki; PACSIN1; -.
DR GenomeRNAi; 29993; -.
DR Pharos; Q9BY11; Tbio.
DR PRO; PR:Q9BY11; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9BY11; protein.
DR Bgee; ENSG00000124507; Expressed in right frontal lobe and 177 other tissues.
DR ExpressionAtlas; Q9BY11; baseline and differential.
DR Genevisible; Q9BY11; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0043679; C:axon terminus; ISS:UniProtKB.
DR GO; GO:0030137; C:COPI-coated vesicle; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:LIFEdb.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:BHF-UCL.
DR GO; GO:0098684; C:photoreceptor ribbon synapse; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; ISS:BHF-UCL.
DR GO; GO:0098833; C:presynaptic endocytic zone; IEA:Ensembl.
DR GO; GO:0032587; C:ruffle membrane; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; ISS:BHF-UCL.
DR GO; GO:0008092; F:cytoskeletal protein binding; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0005543; F:phospholipid binding; IDA:UniProtKB.
DR GO; GO:0007015; P:actin filament organization; IEA:InterPro.
DR GO; GO:0007010; P:cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0045806; P:negative regulation of endocytosis; IEA:Ensembl.
DR GO; GO:0048812; P:neuron projection morphogenesis; ISS:UniProtKB.
DR GO; GO:0097320; P:plasma membrane tubulation; IDA:UniProtKB.
DR GO; GO:1900006; P:positive regulation of dendrite development; ISS:BHF-UCL.
DR GO; GO:0072657; P:protein localization to membrane; ISS:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISS:BHF-UCL.
DR GO; GO:0030100; P:regulation of endocytosis; IBA:GO_Central.
DR GO; GO:0048488; P:synaptic vesicle endocytosis; ISS:UniProtKB.
DR CDD; cd07680; F-BAR_PACSIN1; 1.
DR CDD; cd11998; SH3_PACSIN1-2; 1.
DR Gene3D; 1.20.1270.60; -; 1.
DR InterPro; IPR027267; AH/BAR_dom_sf.
DR InterPro; IPR031160; F_BAR.
DR InterPro; IPR001060; FCH_dom.
DR InterPro; IPR028518; PACSIN1.
DR InterPro; IPR035743; PACSIN1/PACSIN2_SH3.
DR InterPro; IPR037454; PACSIN1_F-BAR.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR23065:SF16; PTHR23065:SF16; 1.
DR Pfam; PF00611; FCH; 1.
DR Pfam; PF14604; SH3_9; 1.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00055; FCH; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF103657; SSF103657; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS51741; F_BAR; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cell projection; Coiled coil; Cytoplasm;
KW Cytoplasmic vesicle; Endocytosis; Lipid-binding; Membrane; Phosphoprotein;
KW Reference proteome; SH3 domain; Synapse; Synaptosome.
FT CHAIN 1..444
FT /note="Protein kinase C and casein kinase substrate in
FT neurons protein 1"
FT /id="PRO_0000161792"
FT DOMAIN 13..283
FT /note="F-BAR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01077"
FT DOMAIN 385..444
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 175..194
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 309..386
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 26..275
FT COMPBIAS 309..323
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 331..355
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0W5"
FT MOD_RES 79
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0W5"
FT MOD_RES 184
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0W5"
FT MOD_RES 346
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61644"
FT MOD_RES 348
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61644"
FT MOD_RES 349
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0W5"
FT MOD_RES 361
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61644"
FT MOD_RES 365
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0W5"
FT MOD_RES 394
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q61644"
FT MOD_RES 405
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61644"
FT MOD_RES 430
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61644"
FT VARIANT 334
FT /note="A -> V (in dbSNP:rs41312309)"
FT /id="VAR_053554"
FT MUTAGEN 125
FT /note="I->E: Reduces membrane-binding. Abolishes membrane
FT tubulation."
FT /evidence="ECO:0000269|PubMed:19549836"
FT MUTAGEN 126
FT /note="M->E: Reduces membrane-binding. Abolishes membrane
FT tubulation."
FT /evidence="ECO:0000269|PubMed:19549836"
FT TURN 22..25
FT /evidence="ECO:0007829|PDB:3HAH"
FT HELIX 26..73
FT /evidence="ECO:0007829|PDB:3HAH"
FT HELIX 78..107
FT /evidence="ECO:0007829|PDB:3HAH"
FT HELIX 109..120
FT /evidence="ECO:0007829|PDB:3HAH"
FT STRAND 127..129
FT /evidence="ECO:0007829|PDB:3HAH"
FT HELIX 130..170
FT /evidence="ECO:0007829|PDB:3HAH"
FT TURN 176..179
FT /evidence="ECO:0007829|PDB:3HAI"
FT HELIX 193..256
FT /evidence="ECO:0007829|PDB:3HAH"
FT HELIX 258..260
FT /evidence="ECO:0007829|PDB:3HAH"
FT TURN 262..264
FT /evidence="ECO:0007829|PDB:3HAH"
FT HELIX 265..275
FT /evidence="ECO:0007829|PDB:3HAH"
FT HELIX 280..291
FT /evidence="ECO:0007829|PDB:3HAH"
SQ SEQUENCE 444 AA; 50966 MW; 6AAF801873770975 CRC64;
MSSSYDEASL APEETTDSFW EVGNYKRTVK RIDDGHRLCN DLMNCVQERA KIEKAYGQQL
TDWAKRWRQL IEKGPQYGSL ERAWGAIMTE ADKVSELHQE VKNNLLNEDL EKVKNWQKDA
YHKQIMGGFK ETKEAEDGFR KAQKPWAKKM KELEAAKKAY HLACKEEKLA MTREMNSKTE
QSVTPEQQKK LQDKVDKCKQ DVQKTQEKYE KVLEDVGKTT PQYMENMEQV FEQCQQFEEK
RLVFLKEVLL DIKRHLNLAE NSSYIHVYRE LEQAIRGADA QEDLRWFRST SGPGMPMNWP
QFEEWNPDLP HTTTKKEKQP KKAEGVALTN ATGAVESTSQ AGDRGSVSSY DRGQPYATEW
SDDESGNPFG GSETNGGANP FEDDSKGVRV RALYDYDGQE QDELSFKAGD ELTKLGEEDE
QGWCRGRLDS GQLGLYPANY VEAI
