PACN1_RAT
ID PACN1_RAT Reviewed; 441 AA.
AC Q9Z0W5;
DT 13-AUG-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Protein kinase C and casein kinase substrate in neurons protein 1;
DE AltName: Full=Dynamin proline-rich domain-interacting protein;
DE Short=Dynamin PRD-interacting protein;
DE AltName: Full=Synaptic, dynamin-associated protein I;
DE AltName: Full=Syndapin-1;
DE AltName: Full=Syndapin-I;
DE Short=SdpI;
GN Name=Pacsin1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 71-90 AND 412-429,
RP INTERACTION WITH DNM1; SYNJ1 AND WASL, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND MUTAGENESIS OF PRO-434.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=9950691; DOI=10.1091/mbc.10.2.501;
RA Qualmann B., Roos J., DiGregorio P.J., Kelly R.B.;
RT "Syndapin I, a synaptic dynamin-binding protein that associates with the
RT neural Wiskott-Aldrich syndrome protein.";
RL Mol. Biol. Cell 10:501-513(1999).
RN [2]
RP PROTEIN SEQUENCE OF 71-79; 197-215; 252-266; 274-282 AND 389-404, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain, and Hippocampus;
RA Lubec G., Diao W., Kang S.U., Lubec S.;
RL Submitted (SEP-2007) to UniProtKB.
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=11082044; DOI=10.1242/jcs.113.24.4511;
RA Modregger J., Ritter B., Witter B., Paulsson M., Plomann M.;
RT "All three PACSIN isoforms bind to endocytic proteins and inhibit
RT endocytosis.";
RL J. Cell Sci. 113:4511-4521(2000).
RN [4]
RP INTERACTION WITH EHD1 AND EHD3, AND TISSUE SPECIFICITY.
RX PubMed=15930129; DOI=10.1091/mbc.e05-01-0076;
RA Braun A., Pinyol R., Dahlhaus R., Koch D., Fonarev P., Grant B.D.,
RA Kessels M.M., Qualmann B.;
RT "EHD proteins associate with syndapin I and II and such interactions play a
RT crucial role in endosomal recycling.";
RL Mol. Biol. Cell 16:3642-3658(2005).
RN [5]
RP FUNCTION, INTERACTION WITH DNM1, PARTIAL PROTEIN SEQUENCE, SUBCELLULAR
RP LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=16648848; DOI=10.1038/nn1695;
RA Anggono V., Smillie K.J., Graham M.E., Valova V.A., Cousin M.A.,
RA Robinson P.J.;
RT "Syndapin I is the phosphorylation-regulated dynamin I partner in synaptic
RT vesicle endocytosis.";
RL Nat. Neurosci. 9:752-760(2006).
RN [6]
RP INTERACTION WITH COBL AND DBNL.
RX PubMed=17956734; DOI=10.1016/j.cell.2007.08.030;
RA Ahuja R., Pinyol R., Reichenbach N., Custer L., Klingensmith J.,
RA Kessels M.M., Qualmann B.;
RT "Cordon-bleu is an actin nucleation factor and controls neuronal
RT morphology.";
RL Cell 131:337-350(2007).
RN [7]
RP FUNCTION, INTERACTION WITH DNM1, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=17437541; DOI=10.1111/j.1471-4159.2007.04574.x;
RA Anggono V., Robinson P.J.;
RT "Syndapin I and endophilin I bind overlapping proline-rich regions of
RT dynamin I: role in synaptic vesicle endocytosis.";
RL J. Neurochem. 102:931-943(2007).
RN [8]
RP FUNCTION, DOMAIN, SUBCELLULAR LOCATION, AND INTERACTION WITH WASL.
RX PubMed=19846719; DOI=10.1523/jneurosci.3973-09.2009;
RA Dharmalingam E., Haeckel A., Pinyol R., Schwintzer L., Koch D.,
RA Kessels M.M., Qualmann B.;
RT "F-BAR proteins of the syndapin family shape the plasma membrane and are
RT crucial for neuromorphogenesis.";
RL J. Neurosci. 29:13315-13327(2009).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH COBL, AND IDENTIFICATION
RP IN A COMPLEX WITH COBL AND WASL.
RX PubMed=21725280; DOI=10.1038/emboj.2011.207;
RA Schwintzer L., Koch N., Ahuja R., Grimm J., Kessels M.M., Qualmann B.;
RT "The functions of the actin nucleator Cobl in cellular morphogenesis
RT critically depend on syndapin I.";
RL EMBO J. 30:3147-3159(2011).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; SER-346; SER-358; SER-362
RP AND SER-427, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [11]
RP FUNCTION, PHOSPHORYLATION AT SER-76 AND THR-181, IDENTIFICATION BY MASS
RP SPECTROMETRY, SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH DNM1 AND
RP WASL, DOMAIN, MUTAGENESIS OF 62-LYS-LYS-63; SER-76; LYS-127; LYS-130;
RP 154-LYS-LYS-155; THR-181; ASP-276 AND ASP-280, AND TISSUE SPECIFICITY.
RX PubMed=22355135; DOI=10.1073/pnas.1108294109;
RA Quan A., Xue J., Wielens J., Smillie K.J., Anggono V., Parker M.W.,
RA Cousin M.A., Graham M.E., Robinson P.J.;
RT "Phosphorylation of syndapin I F-BAR domain at two helix-capping motifs
RT regulates membrane tubulation.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:3760-3765(2012).
CC -!- FUNCTION: Binds to membranes via its F-BAR domain and mediates membrane
CC tubulation. 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.
CC {ECO:0000269|PubMed:16648848, ECO:0000269|PubMed:17437541,
CC ECO:0000269|PubMed:19846719, ECO:0000269|PubMed:21725280,
CC ECO:0000269|PubMed:22355135}.
CC -!- SUBUNIT: Homodimer. May form heterooligomers with other PACSINs.
CC Interacts with MAPT. Interacts with TRPV4 (By similarity). Interacts
CC (via SH3 domain) with SYNJ1 and WASL. Interacts (via SH3 domain) with
CC DNM1; the interaction is reduced by DNM1 phosphorylation. Interacts
CC with DNM2 and DNM3. Interacts with both COBL and DBNL. Identified in a
CC complex composed of COBL, PACSIN1 and WASL. Interacts with EHD1 and
CC EHD3. {ECO:0000250, ECO:0000269|PubMed:15930129,
CC ECO:0000269|PubMed:16648848, ECO:0000269|PubMed:17437541,
CC ECO:0000269|PubMed:17956734, ECO:0000269|PubMed:19846719,
CC ECO:0000269|PubMed:21725280, ECO:0000269|PubMed:22355135,
CC ECO:0000269|PubMed:9950691}.
CC -!- INTERACTION:
CC Q9Z0W5; D3ZUI5: Cobl; NbExp=6; IntAct=EBI-1550185, EBI-7003590;
CC Q9Z0W5; P21575: Dnm1; NbExp=4; IntAct=EBI-1550185, EBI-80070;
CC Q9Z0W5; Q5NBX1: Cobl; Xeno; NbExp=14; IntAct=EBI-1550185, EBI-1550138;
CC Q9Z0W5; Q5NBX1-1: Cobl; Xeno; NbExp=2; IntAct=EBI-1550185, EBI-16174243;
CC Q9Z0W5; Q9NZQ3: NCKIPSD; Xeno; NbExp=6; IntAct=EBI-1550185, EBI-745080;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell projection. Synapse, synaptosome.
CC Cell projection, ruffle membrane {ECO:0000250}. Membrane; Peripheral
CC membrane protein. Cytoplasmic vesicle membrane {ECO:0000250};
CC Peripheral membrane protein {ECO:0000250}. Synapse {ECO:0000250}.
CC Cytoplasm, cytosol {ECO:0000250}. Cell membrane; Peripheral membrane
CC protein; Cytoplasmic side. Note=Colocalizes with MAPT in axons (By
CC similarity). In primary neuronal cultures, present at a high level in
CC presynaptic nerve terminals and in the cell body. Colocalizes with DNM1
CC at vesicular structures in the cell body and neurites. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Highly expressed in brain (at protein level).
CC {ECO:0000269|PubMed:15930129, ECO:0000269|PubMed:17437541,
CC ECO:0000269|PubMed:22355135, ECO:0000269|PubMed:9950691}.
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|PubMed:22355135}.
CC -!- SIMILARITY: Belongs to the PACSIN family. {ECO:0000305}.
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DR EMBL; AF104402; AAD16887.1; -; mRNA.
DR RefSeq; NP_058990.1; NM_017294.1.
DR AlphaFoldDB; Q9Z0W5; -.
DR SMR; Q9Z0W5; -.
DR BioGRID; 248321; 4.
DR DIP; DIP-39836N; -.
DR ELM; Q9Z0W5; -.
DR IntAct; Q9Z0W5; 7.
DR MINT; Q9Z0W5; -.
DR STRING; 10116.ENSRNOP00000036285; -.
DR iPTMnet; Q9Z0W5; -.
DR PhosphoSitePlus; Q9Z0W5; -.
DR SwissPalm; Q9Z0W5; -.
DR PaxDb; Q9Z0W5; -.
DR PRIDE; Q9Z0W5; -.
DR GeneID; 29704; -.
DR KEGG; rno:29704; -.
DR UCSC; RGD:3247; rat.
DR CTD; 29993; -.
DR RGD; 3247; Pacsin1.
DR eggNOG; KOG2856; Eukaryota.
DR InParanoid; Q9Z0W5; -.
DR OrthoDB; 727724at2759; -.
DR PhylomeDB; Q9Z0W5; -.
DR Reactome; R-RNO-8856828; Clathrin-mediated endocytosis.
DR PRO; PR:Q9Z0W5; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0043679; C:axon terminus; IDA:UniProtKB.
DR GO; GO:0030137; C:COPI-coated vesicle; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
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:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL.
DR GO; GO:0098684; C:photoreceptor ribbon synapse; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0098839; C:postsynaptic density membrane; IDA:SynGO.
DR GO; GO:0098833; C:presynaptic endocytic zone; ISO:RGD.
DR GO; GO:0032587; C:ruffle membrane; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; IDA:BHF-UCL.
DR GO; GO:0043195; C:terminal bouton; HDA:ParkinsonsUK-UCL.
DR GO; GO:0008092; F:cytoskeletal protein binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
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; IDA:RGD.
DR GO; GO:0045806; P:negative regulation of endocytosis; ISO:RGD.
DR GO; GO:0048812; P:neuron projection morphogenesis; IMP:UniProtKB.
DR GO; GO:0097320; P:plasma membrane tubulation; IMP:UniProtKB.
DR GO; GO:1900006; P:positive regulation of dendrite development; IDA:BHF-UCL.
DR GO; GO:0072657; P:protein localization to membrane; ISS:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; IDA:BHF-UCL.
DR GO; GO:0030100; P:regulation of endocytosis; IBA:GO_Central.
DR GO; GO:0099149; P:regulation of postsynaptic neurotransmitter receptor internalization; IDA:SynGO.
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 Cell membrane; Cell projection; Coiled coil; Cytoplasm;
KW Cytoplasmic vesicle; Direct protein sequencing; Endocytosis; Lipid-binding;
KW Membrane; Phosphoprotein; Reference proteome; SH3 domain; Synapse;
KW Synaptosome.
FT CHAIN 1..441
FT /note="Protein kinase C and casein kinase substrate in
FT neurons protein 1"
FT /id="PRO_0000161794"
FT DOMAIN 10..280
FT /note="F-BAR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01077"
FT DOMAIN 382..441
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 310..380
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 23..272
FT /evidence="ECO:0000250"
FT COMPBIAS 328..352
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 76
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:22355135"
FT MOD_RES 181
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:22355135"
FT MOD_RES 343
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61644"
FT MOD_RES 345
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61644"
FT MOD_RES 346
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 358
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 362
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 391
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q61644"
FT MOD_RES 402
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61644"
FT MOD_RES 427
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MUTAGEN 62..63
FT /note="KR->QQ: Reduces membrane-binding. Abolishes membrane
FT tubulation."
FT /evidence="ECO:0000269|PubMed:22355135"
FT MUTAGEN 76
FT /note="S->A: No effect on membrane-binding. Reduces
FT membrane tubulation."
FT /evidence="ECO:0000269|PubMed:22355135"
FT MUTAGEN 127
FT /note="K->Q: Reduces membrane-binding; when associated with
FT Q-130. Abolishes membrane tubulation."
FT /evidence="ECO:0000269|PubMed:22355135"
FT MUTAGEN 130
FT /note="K->Q: Reduces membrane-binding. Abolishes membrane
FT tubulation; when associated with Q-127."
FT /evidence="ECO:0000269|PubMed:22355135"
FT MUTAGEN 154..155
FT /note="KK->QQ: Reduces membrane-binding. Abolishes membrane
FT tubulation."
FT /evidence="ECO:0000269|PubMed:22355135"
FT MUTAGEN 181
FT /note="T->A: No effect on membrane-binding."
FT /evidence="ECO:0000269|PubMed:22355135"
FT MUTAGEN 181
FT /note="T->E: Reduces membrane-binding. Abolishes membrane
FT tubulation."
FT /evidence="ECO:0000269|PubMed:22355135"
FT MUTAGEN 276
FT /note="D->A: Reduces membrane tubulation; when associated
FT with A-280."
FT /evidence="ECO:0000269|PubMed:22355135"
FT MUTAGEN 280
FT /note="D->A: Reduces membrane tubulation; when associated
FT with A-276."
FT /evidence="ECO:0000269|PubMed:22355135"
FT MUTAGEN 434
FT /note="P->L: Abolishes interaction with DNM1, SYNJ1 and
FT WASL."
FT /evidence="ECO:0000269|PubMed:9950691"
SQ SEQUENCE 441 AA; 50449 MW; 585B328850572DF8 CRC64;
MSGPYDEASE EITDSFWEVG NYKRTVKRID DGHRLCNDLM SCVQERAKIE KAYAQQLTDW
AKRWRQLIEK GPQYGSLERA WGAMMTEADK VSELHQEVKN SLLNEDLEKV KNWQKDAYHK
QIMGGFKETK EAEDGFRKAQ KPWAKKMKEL EAAKKAYHLA CKEEKLAMTR EMNSKTEQSV
TPEQQKKLVD KVDKCRQDVQ KTQEKYEKVL EDVGKTTPQY MEGMEQVFEQ CQQFEEKRLV
FLKEVLLDIK RHLNLAENSS YIHVYRELEQ AIRGADAQED LRWFRSTSGP GMPMNWPQFE
EWNPDLPHTA AKKEKQPKKA EGAALSNATG AVESTSQAGD RGSVSSYDRG QAYATEWSDD
ESGNPFGGNE ANGGANPFED DAKGVRVRAL YDYDGQEQDE LSFKAGDELT KLGEEDEQGW
CRGRLDSGQL GLYPANYVEA I
