SYNJ1_HUMAN
ID SYNJ1_HUMAN Reviewed; 1573 AA.
AC O43426; O43425; O94984; Q4KMR1;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=Synaptojanin-1;
DE EC=3.1.3.36;
DE AltName: Full=Synaptic inositol 1,4,5-trisphosphate 5-phosphatase 1;
GN Name=SYNJ1; Synonyms=KIAA0910;
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] (ISOFORMS 1 AND 2), AND VARIANT ARG-295.
RC TISSUE=Cerebellum;
RX PubMed=9428629; DOI=10.1016/s0014-5793(97)01451-8;
RA Haffner C., Takei K., Chen H., Ringstad N., Hudson A., Butler M.H.,
RA Salcini A.E., Di Fiore P.P., De Camilli P.;
RT "Synaptojanin 1: localization on coated endocytic intermediates in nerve
RT terminals and interaction of its 170 kDa isoform with Eps15.";
RL FEBS Lett. 419:175-180(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:355-364(1998).
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 GENOMIC DNA].
RX PubMed=10830953; DOI=10.1038/35012518;
RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S.,
RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.;
RT "The DNA sequence of human chromosome 21.";
RL Nature 405:311-319(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Placenta;
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 INTERACTION WITH AMPH; SH3GL1; SH3GL2 AND SH3GL3.
RX PubMed=10542231; DOI=10.1074/jbc.274.45.32001;
RA Cestra G., Castagnoli L., Dente L., Minenkova O., Petrelli A., Migone N.,
RA Hoffmueller U., Schneider-Mergener J., Cesareni G.;
RT "The SH3 domains of endophilin and amphiphysin bind to the proline-rich
RT region of synaptojanin 1 at distinct sites that display an unconventional
RT binding specificity.";
RL J. Biol. Chem. 274:32001-32007(1999).
RN [7]
RP INTERACTION WITH MYO1E.
RX PubMed=17257598; DOI=10.1016/j.febslet.2007.01.021;
RA Krendel M., Osterweil E.K., Mooseker M.S.;
RT "Myosin 1E interacts with synaptojanin-1 and dynamin and is involved in
RT endocytosis.";
RL FEBS Lett. 581:644-650(2007).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-830; THR-1220; SER-1551 AND
RP SER-1565, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-830, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1318, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-830; THR-1220; SER-1292;
RP SER-1345 AND SER-1565, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1220, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [13]
RP FUNCTION, INVOLVEMENT IN DEE53, VARIANT DEE53 CYS-849, CHARACTERIZATION OF
RP VARIANT DEE53 CYS-849, VARIANTS ILE-981 AND SER-1018, AND CHARACTERIZATION
RP OF VARIANTS ILE-981 AND SER-1018.
RX PubMed=27435091; DOI=10.1093/brain/aww180;
RG AR working group of the EuroEPINOMICS RES Consortium;
RA Hardies K., Cai Y., Jardel C., Jansen A.C., Cao M., May P., Djemie T.,
RA Hachon Le Camus C., Keymolen K., Deconinck T., Bhambhani V., Long C.,
RA Sajan S.A., Helbig K.L., Suls A., Balling R., Helbig I., De Jonghe P.,
RA Depienne C., De Camilli P., Weckhuysen S.;
RT "Loss of SYNJ1 dual phosphatase activity leads to early onset refractory
RT seizures and progressive neurological decline.";
RL Brain 139:2420-2430(2016).
RN [14]
RP STRUCTURE BY NMR OF 894-971.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of RNA binding domain in synaptojanin 1.";
RL Submitted (OCT-2006) to the PDB data bank.
RN [15]
RP VARIANT PARK20 GLN-219, AND CHARACTERIZATION OF VARIANT PARK20 GLN-219.
RX PubMed=23804563; DOI=10.1002/humu.22372;
RA Krebs C.E., Karkheiran S., Powell J.C., Cao M., Makarov V., Darvish H.,
RA Di Paolo G., Walker R.H., Shahidi G.A., Buxbaum J.D., De Camilli P.,
RA Yue Z., Paisan-Ruiz C.;
RT "The Sac1 domain of SYNJ1 identified mutated in a family with early-onset
RT progressive Parkinsonism with generalized seizures.";
RL Hum. Mutat. 34:1200-1207(2013).
RN [16]
RP VARIANTS PARK20 GLN-219 AND ARG-1383.
RX PubMed=23804577; DOI=10.1002/humu.22373;
RA Quadri M., Fang M., Picillo M., Olgiati S., Breedveld G.J., Graafland J.,
RA Wu B., Xu F., Erro R., Amboni M., Pappata S., Quarantelli M., Annesi G.,
RA Quattrone A., Chien H.F., Barbosa E.R., Oostra B.A., Barone P., Wang J.,
RA Bonifati V.;
RT "Mutation in the SYNJ1 gene associated with autosomal recessive, early-
RT onset Parkinsonism.";
RL Hum. Mutat. 34:1208-1215(2013).
RN [17]
RP VARIANT PARK20 PRO-420.
RX PubMed=27496670; DOI=10.1016/j.parkreldis.2016.07.014;
RA Kirola L., Behari M., Shishir C., Thelma B.K.;
RT "Identification of a novel homozygous mutation Arg459Pro in SYNJ1 gene of
RT an Indian family with autosomal recessive juvenile Parkinsonism.";
RL Parkinsonism Relat. Disord. 31:124-128(2016).
CC -!- FUNCTION: Phosphatase that acts on various phosphoinositides, including
CC phosphatidylinositol 4-phosphate, phosphatidylinositol (4,5)-
CC bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate
CC (PubMed:27435091). Has a role in clathrin-mediated endocytosis (By
CC similarity). Hydrolyzes PIP2 bound to actin regulatory proteins
CC resulting in the rearrangement of actin filaments downstream of
CC tyrosine kinase and ASH/GRB2 (By similarity).
CC {ECO:0000250|UniProtKB:O18964, ECO:0000250|UniProtKB:Q62910,
CC ECO:0000269|PubMed:27435091}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-
CC bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC inositol 4-phosphate) + phosphate; Xref=Rhea:RHEA:22764,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:58178,
CC ChEBI:CHEBI:58456; EC=3.1.3.36;
CC -!- SUBUNIT: Interacts with ASH/GRB2. Interacts with PACSIN1, PACSIN2 and
CC PACSIN3 (By similarity). Binds AMPH, SH3GL1, SH3GL2 and SH3GL3
CC (PubMed:10542231). Interacts with MYO1E (via SH3 domain)
CC (PubMed:17257598). Interacts with BIN1 and DNM1 (By similarity).
CC {ECO:0000250|UniProtKB:Q62910, ECO:0000250|UniProtKB:Q8CHC4,
CC ECO:0000269|PubMed:10542231, ECO:0000269|PubMed:17257598}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:O18964}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Synaptojanin-170;
CC IsoId=O43426-1; Sequence=Displayed;
CC Name=2; Synonyms=Synaptojanin-145;
CC IsoId=O43426-2; Sequence=VSP_002682, VSP_002683;
CC Name=3;
CC IsoId=O43426-4; Sequence=VSP_041578, VSP_002682, VSP_002683;
CC Name=4;
CC IsoId=O43426-5; Sequence=VSP_035709, VSP_035710, VSP_035711;
CC -!- TISSUE SPECIFICITY: Concentrated at clathrin-coated endocytic
CC intermediates in nerve terminals. Isoform 1 is more enriched than
CC isoform 2 in developing brain as well as non-neuronal cells. Isoform 2
CC is very abundant in nerve terminals.
CC -!- DOMAIN: Binds to EPS15 (a clathrin coat-associated protein) via a C-
CC terminal domain containing three Asn-Pro-Phe (NPF) repeats.
CC {ECO:0000250}.
CC -!- DOMAIN: The C-terminal proline-rich region mediates binding to a
CC variety of SH3 domain-containing proteins including AMPH, SH3GL1,
CC SH3GL2, SH3GL3 and GRB2.
CC -!- DISEASE: Parkinson disease 20, early-onset (PARK20) [MIM:615530]: An
CC early-onset form of Parkinson disease, a complex neurodegenerative
CC disorder characterized by bradykinesia, resting tremor, muscular
CC rigidity and postural instability, as well as by a clinically
CC significant response to treatment with levodopa. The pathology involves
CC the loss of dopaminergic neurons in the substantia nigra and the
CC presence of Lewy bodies (intraneuronal accumulations of aggregated
CC proteins), in surviving neurons in various areas of the brain. PARK20
CC is characterized by young adult-onset of parkinsonism. Additional
CC features may include seizures, cognitive decline, abnormal eye
CC movements, and dystonia. {ECO:0000269|PubMed:23804563,
CC ECO:0000269|PubMed:23804577, ECO:0000269|PubMed:27496670}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Developmental and epileptic encephalopathy 53 (DEE53)
CC [MIM:617389]: A form of epileptic encephalopathy, a heterogeneous group
CC of severe early-onset epilepsies characterized by refractory seizures,
CC neurodevelopmental impairment, and poor prognosis. Development is
CC normal prior to seizure onset, after which cognitive and motor delays
CC become apparent. DEE53 inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:27435091}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the synaptojanin family. {ECO:0000305}.
CC -!- SIMILARITY: In the central section; belongs to the inositol 1,4,5-
CC trisphosphate 5-phosphatase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA74933.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF009039; AAC51921.1; -; mRNA.
DR EMBL; AF009040; AAC51922.1; -; mRNA.
DR EMBL; AB020717; BAA74933.2; ALT_INIT; mRNA.
DR EMBL; AP000275; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP000276; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP000277; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP000278; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP000279; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC098395; AAH98395.1; -; mRNA.
DR CCDS; CCDS33540.2; -. [O43426-2]
DR CCDS; CCDS54483.1; -. [O43426-4]
DR RefSeq; NP_001153774.1; NM_001160302.1. [O43426-4]
DR RefSeq; NP_001153778.1; NM_001160306.1.
DR RefSeq; NP_003886.3; NM_003895.3.
DR RefSeq; NP_982271.2; NM_203446.2. [O43426-2]
DR RefSeq; XP_016883989.1; XM_017028500.1. [O43426-2]
DR PDB; 1W80; X-ray; 1.90 A; P=1477-1488, Q=1458-1469.
DR PDB; 2DNR; NMR; -; A=894-971.
DR PDB; 2VJ0; X-ray; 1.60 A; P=1477-1488.
DR PDB; 7A0V; X-ray; 2.30 A; A/C/E=528-873.
DR PDBsum; 1W80; -.
DR PDBsum; 2DNR; -.
DR PDBsum; 2VJ0; -.
DR PDBsum; 7A0V; -.
DR AlphaFoldDB; O43426; -.
DR SMR; O43426; -.
DR BioGRID; 114388; 58.
DR ELM; O43426; -.
DR IntAct; O43426; 17.
DR MINT; O43426; -.
DR STRING; 9606.ENSP00000409667; -.
DR ChEMBL; CHEMBL4523136; -.
DR DEPOD; SYNJ1; -.
DR GlyGen; O43426; 5 sites, 1 O-linked glycan (5 sites).
DR iPTMnet; O43426; -.
DR MetOSite; O43426; -.
DR PhosphoSitePlus; O43426; -.
DR BioMuta; SYNJ1; -.
DR EPD; O43426; -.
DR jPOST; O43426; -.
DR MassIVE; O43426; -.
DR MaxQB; O43426; -.
DR PaxDb; O43426; -.
DR PeptideAtlas; O43426; -.
DR PRIDE; O43426; -.
DR ProteomicsDB; 48937; -. [O43426-1]
DR ProteomicsDB; 48938; -. [O43426-2]
DR ProteomicsDB; 48939; -. [O43426-4]
DR ProteomicsDB; 48940; -. [O43426-5]
DR Antibodypedia; 2183; 160 antibodies from 27 providers.
DR DNASU; 8867; -.
DR Ensembl; ENST00000357345.7; ENSP00000349903.3; ENSG00000159082.18. [O43426-4]
DR Ensembl; ENST00000674204.1; ENSP00000501504.1; ENSG00000159082.18. [O43426-2]
DR Ensembl; ENST00000674308.1; ENSP00000501426.1; ENSG00000159082.18. [O43426-1]
DR Ensembl; ENST00000674351.1; ENSP00000501530.1; ENSG00000159082.18. [O43426-2]
DR GeneID; 8867; -.
DR KEGG; hsa:8867; -.
DR MANE-Select; ENST00000674351.1; ENSP00000501530.1; NM_203446.3; NP_982271.3. [O43426-2]
DR UCSC; uc002yqf.2; human. [O43426-1]
DR CTD; 8867; -.
DR DisGeNET; 8867; -.
DR GeneCards; SYNJ1; -.
DR HGNC; HGNC:11503; SYNJ1.
DR HPA; ENSG00000159082; Tissue enhanced (brain, retina).
DR MalaCards; SYNJ1; -.
DR MIM; 604297; gene.
DR MIM; 615530; phenotype.
DR MIM; 617389; phenotype.
DR neXtProt; NX_O43426; -.
DR OpenTargets; ENSG00000159082; -.
DR Orphanet; 391411; Atypical juvenile parkinsonism.
DR Orphanet; 442835; Non-specific early-onset epileptic encephalopathy.
DR Orphanet; 2828; Young-onset Parkinson disease.
DR PharmGKB; PA36285; -.
DR VEuPathDB; HostDB:ENSG00000159082; -.
DR eggNOG; KOG0566; Eukaryota.
DR GeneTree; ENSGT00940000157964; -.
DR InParanoid; O43426; -.
DR OMA; EYVRPRM; -.
DR OrthoDB; 359616at2759; -.
DR PhylomeDB; O43426; -.
DR BioCyc; MetaCyc:HS08354-MON; -.
DR PathwayCommons; O43426; -.
DR Reactome; R-HSA-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-HSA-1855183; Synthesis of IP2, IP, and Ins in the cytosol.
DR Reactome; R-HSA-1855204; Synthesis of IP3 and IP4 in the cytosol.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR SignaLink; O43426; -.
DR SIGNOR; O43426; -.
DR BioGRID-ORCS; 8867; 9 hits in 1076 CRISPR screens.
DR ChiTaRS; SYNJ1; human.
DR EvolutionaryTrace; O43426; -.
DR GenomeRNAi; 8867; -.
DR Pharos; O43426; Tchem.
DR PRO; PR:O43426; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; O43426; protein.
DR Bgee; ENSG00000159082; Expressed in Brodmann (1909) area 23 and 191 other tissues.
DR ExpressionAtlas; O43426; baseline and differential.
DR Genevisible; O43426; HS.
DR GO; GO:0030132; C:clathrin coat of coated pit; ISS:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030117; C:membrane coat; ISS:ParkinsonsUK-UCL.
DR GO; GO:0005874; C:microtubule; IEA:Ensembl.
DR GO; GO:0098688; C:parallel fiber to Purkinje cell synapse; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0098793; C:presynapse; IDA:ParkinsonsUK-UCL.
DR GO; GO:0097060; C:synaptic membrane; ISS:BHF-UCL.
DR GO; GO:0043195; C:terminal bouton; ISS:ParkinsonsUK-UCL.
DR GO; GO:0012506; C:vesicle membrane; ISS:ParkinsonsUK-UCL.
DR GO; GO:1990175; F:EH domain binding; IEA:Ensembl.
DR GO; GO:0052658; F:inositol-1,4,5-trisphosphate 5-phosphatase activity; TAS:Reactome.
DR GO; GO:0034596; F:phosphatidylinositol phosphate 4-phosphatase activity; TAS:Reactome.
DR GO; GO:0034595; F:phosphatidylinositol phosphate 5-phosphatase activity; ISS:ParkinsonsUK-UCL.
DR GO; GO:0052629; F:phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity; TAS:Reactome.
DR GO; GO:0043813; F:phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity; TAS:Reactome.
DR GO; GO:0004438; F:phosphatidylinositol-3-phosphatase activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0004439; F:phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0043812; F:phosphatidylinositol-4-phosphate phosphatase activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0008022; F:protein C-terminus binding; IEA:Ensembl.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0017124; F:SH3 domain binding; IBA:GO_Central.
DR GO; GO:0007420; P:brain development; IBA:GO_Central.
DR GO; GO:0046855; P:inositol phosphate dephosphorylation; ISS:ParkinsonsUK-UCL.
DR GO; GO:0043647; P:inositol phosphate metabolic process; TAS:Reactome.
DR GO; GO:0007612; P:learning; IMP:ParkinsonsUK-UCL.
DR GO; GO:0061024; P:membrane organization; TAS:Reactome.
DR GO; GO:0006836; P:neurotransmitter transport; ISS:ParkinsonsUK-UCL.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IDA:ParkinsonsUK-UCL.
DR GO; GO:0046488; P:phosphatidylinositol metabolic process; ISS:ParkinsonsUK-UCL.
DR GO; GO:1904980; P:positive regulation of endosome organization; IMP:ParkinsonsUK-UCL.
DR GO; GO:0014015; P:positive regulation of gliogenesis; IEA:Ensembl.
DR GO; GO:0048260; P:positive regulation of receptor-mediated endocytosis; IEA:Ensembl.
DR GO; GO:0034097; P:response to cytokine; IEA:Ensembl.
DR GO; GO:0032526; P:response to retinoic acid; IEA:Ensembl.
DR GO; GO:0048488; P:synaptic vesicle endocytosis; IGI:ParkinsonsUK-UCL.
DR GO; GO:0016082; P:synaptic vesicle priming; ISS:ParkinsonsUK-UCL.
DR GO; GO:0048489; P:synaptic vesicle transport; ISS:ParkinsonsUK-UCL.
DR GO; GO:0016191; P:synaptic vesicle uncoating; ISS:ParkinsonsUK-UCL.
DR CDD; cd12719; RRM_SYNJ1; 1.
DR Gene3D; 3.30.70.330; -; 1.
DR Gene3D; 3.60.10.10; -; 1.
DR InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR InterPro; IPR005135; Endo/exonuclease/phosphatase.
DR InterPro; IPR000300; IPPc.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR000504; RRM_dom.
DR InterPro; IPR002013; SAC_dom.
DR InterPro; IPR034972; SYNJ1.
DR InterPro; IPR015047; SYNJ1/2_RRM.
DR InterPro; IPR034971; SYNJ1_RRM.
DR PANTHER; PTHR11200:SF158; PTHR11200:SF158; 1.
DR Pfam; PF08952; DUF1866; 1.
DR Pfam; PF03372; Exo_endo_phos; 1.
DR Pfam; PF02383; Syja_N; 1.
DR SMART; SM01165; DUF1866; 1.
DR SMART; SM00128; IPPc; 1.
DR SUPFAM; SSF54928; SSF54928; 1.
DR SUPFAM; SSF56219; SSF56219; 1.
DR PROSITE; PS50102; RRM; 1.
DR PROSITE; PS50275; SAC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Disease variant;
KW Endocytosis; Epilepsy; Hydrolase; Lipid metabolism; Methylation;
KW Neurodegeneration; Parkinson disease; Parkinsonism; Phosphoprotein;
KW Reference proteome; Repeat; RNA-binding.
FT CHAIN 1..1573
FT /note="Synaptojanin-1"
FT /id="PRO_0000209730"
FT DOMAIN 119..442
FT /note="SAC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00183"
FT DOMAIN 902..971
FT /note="RRM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT REPEAT 1396..1398
FT /note="1"
FT REPEAT 1406..1408
FT /note="2"
FT REPEAT 1417..1419
FT /note="3"
FT REGION 500..899
FT /note="Catalytic"
FT /evidence="ECO:0000255"
FT REGION 1029..1322
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1341..1360
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1370..1463
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1396..1419
FT /note="3 X 3 AA repeats of N-P-F"
FT REGION 1535..1573
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1029..1059
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1065..1079
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1095..1134
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1216..1237
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1242..1261
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1269..1291
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1292..1312
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1370..1410
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1443..1463
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1535..1554
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1555..1573
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 820
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CHC4"
FT MOD_RES 830
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 1053
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62910"
FT MOD_RES 1150
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CHC4"
FT MOD_RES 1178
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62910"
FT MOD_RES 1201
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q8CHC4"
FT MOD_RES 1220
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 1292
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1318
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 1345
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1349
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8CHC4"
FT MOD_RES 1551
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1565
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 451
FT /note="K -> KAGK (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_035709"
FT VAR_SEQ 504..511
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_035710"
FT VAR_SEQ 525..1573
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_035711"
FT VAR_SEQ 1144..1159
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10048485"
FT /id="VSP_041578"
FT VAR_SEQ 1306..1311
FT /note="VKTNGI -> QEQPSG (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:10048485,
FT ECO:0000303|PubMed:9428629"
FT /id="VSP_002682"
FT VAR_SEQ 1312..1573
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:10048485,
FT ECO:0000303|PubMed:9428629"
FT /id="VSP_002683"
FT VARIANT 219
FT /note="R -> Q (in PARK20; impairs the phosphatase activity
FT of the enzyme toward phosphatidylinositol-3-phosphate and
FT phosphatidylinositol-4-phosphate; dbSNP:rs398122403)"
FT /evidence="ECO:0000269|PubMed:23804563,
FT ECO:0000269|PubMed:23804577"
FT /id="VAR_070905"
FT VARIANT 295
FT /note="K -> R (in dbSNP:rs2254562)"
FT /evidence="ECO:0000269|PubMed:9428629"
FT /id="VAR_047308"
FT VARIANT 420
FT /note="R -> P (in PARK20; dbSNP:rs1060499619)"
FT /evidence="ECO:0000269|PubMed:27496670"
FT /id="VAR_078803"
FT VARIANT 849
FT /note="Y -> C (in DEE53; decreased inositol phosphate
FT phosphatase activity; dbSNP:rs1057524877)"
FT /evidence="ECO:0000269|PubMed:27435091"
FT /id="VAR_078804"
FT VARIANT 981
FT /note="M -> I (likely benign variant; no effect on inositol
FT phosphate phosphatase activity; dbSNP:rs115683257)"
FT /evidence="ECO:0000269|PubMed:27435091"
FT /id="VAR_078805"
FT VARIANT 1018
FT /note="Y -> S (likely benign variant; no effect on inositol
FT phosphate phosphatase activity)"
FT /evidence="ECO:0000269|PubMed:27435091"
FT /id="VAR_078806"
FT VARIANT 1366
FT /note="V -> A (in dbSNP:rs9980589)"
FT /id="VAR_047309"
FT VARIANT 1383
FT /note="S -> R (in PARK20; unknown pathological
FT significance; the patient also carries a heterozygous PINK1
FT truncating mutation; dbSNP:rs769099271)"
FT /evidence="ECO:0000269|PubMed:23804577"
FT /id="VAR_070906"
FT VARIANT 1547
FT /note="P -> L (in dbSNP:rs2230767)"
FT /id="VAR_049603"
FT CONFLICT 1093..1108
FT /note="Missing (in Ref. 1; BAA74933)"
FT /evidence="ECO:0000305"
FT CONFLICT 1366
FT /note="V -> VNT (in Ref. 1; AAC51922)"
FT /evidence="ECO:0000305"
FT STRAND 531..541
FT /evidence="ECO:0007829|PDB:7A0V"
FT HELIX 559..562
FT /evidence="ECO:0007829|PDB:7A0V"
FT HELIX 565..569
FT /evidence="ECO:0007829|PDB:7A0V"
FT HELIX 572..574
FT /evidence="ECO:0007829|PDB:7A0V"
FT STRAND 575..577
FT /evidence="ECO:0007829|PDB:7A0V"
FT STRAND 583..590
FT /evidence="ECO:0007829|PDB:7A0V"
FT HELIX 597..601
FT /evidence="ECO:0007829|PDB:7A0V"
FT HELIX 606..619
FT /evidence="ECO:0007829|PDB:7A0V"
FT TURN 620..622
FT /evidence="ECO:0007829|PDB:7A0V"
FT STRAND 626..633
FT /evidence="ECO:0007829|PDB:7A0V"
FT STRAND 636..642
FT /evidence="ECO:0007829|PDB:7A0V"
FT HELIX 644..649
FT /evidence="ECO:0007829|PDB:7A0V"
FT STRAND 650..661
FT /evidence="ECO:0007829|PDB:7A0V"
FT TURN 662..665
FT /evidence="ECO:0007829|PDB:7A0V"
FT STRAND 666..678
FT /evidence="ECO:0007829|PDB:7A0V"
FT STRAND 681..689
FT /evidence="ECO:0007829|PDB:7A0V"
FT HELIX 697..710
FT /evidence="ECO:0007829|PDB:7A0V"
FT TURN 714..716
FT /evidence="ECO:0007829|PDB:7A0V"
FT HELIX 719..721
FT /evidence="ECO:0007829|PDB:7A0V"
FT STRAND 722..730
FT /evidence="ECO:0007829|PDB:7A0V"
FT HELIX 739..747
FT /evidence="ECO:0007829|PDB:7A0V"
FT HELIX 751..755
FT /evidence="ECO:0007829|PDB:7A0V"
FT HELIX 759..765
FT /evidence="ECO:0007829|PDB:7A0V"
FT STRAND 790..793
FT /evidence="ECO:0007829|PDB:7A0V"
FT STRAND 796..798
FT /evidence="ECO:0007829|PDB:7A0V"
FT STRAND 806..812
FT /evidence="ECO:0007829|PDB:7A0V"
FT HELIX 815..825
FT /evidence="ECO:0007829|PDB:7A0V"
FT STRAND 845..851
FT /evidence="ECO:0007829|PDB:7A0V"
FT STRAND 856..859
FT /evidence="ECO:0007829|PDB:7A0V"
FT STRAND 862..870
FT /evidence="ECO:0007829|PDB:7A0V"
FT STRAND 895..901
FT /evidence="ECO:0007829|PDB:2DNR"
FT TURN 905..907
FT /evidence="ECO:0007829|PDB:2DNR"
FT HELIX 912..923
FT /evidence="ECO:0007829|PDB:2DNR"
FT STRAND 928..933
FT /evidence="ECO:0007829|PDB:2DNR"
FT STRAND 935..944
FT /evidence="ECO:0007829|PDB:2DNR"
FT HELIX 945..950
FT /evidence="ECO:0007829|PDB:2DNR"
FT HELIX 951..954
FT /evidence="ECO:0007829|PDB:2DNR"
FT STRAND 962..968
FT /evidence="ECO:0007829|PDB:2DNR"
SQ SEQUENCE 1573 AA; 173103 MW; D50B249B1EBFFC18 CRC64;
MAFSKGFRIY HKLDPPPFSL IVETRHKEEC LMFESGAVAV LSSAEKEAIK GTYSKVLDAY
GLLGVLRLNL GDTMLHYLVL VTGCMSVGKI QESEVFRVTS TEFISLRIDS SDEDRISEVR
KVLNSGNFYF AWSASGISLD LSLNAHRSMQ EQTTDNRFFW NQSLHLHLKH YGVNCDDWLL
RLMCGGVEIR TIYAAHKQAK ACLISRLSCE RAGTRFNVRG TNDDGHVANF VETEQVVYLD
DSVSSFIQIR GSVPLFWEQP GLQVGSHRVR MSRGFEANAP AFDRHFRTLK NLYGKQIIVN
LLGSKEGEHM LSKAFQSHLK ASEHAADIQM VNFDYHQMVK GGKAEKLHSV LKPQVQKFLD
YGFFYFNGSE VQRCQSGTVR TNCLDCLDRT NSVQAFLGLE MLAKQLEALG LAEKPQLVTR
FQEVFRSMWS VNGDSISKIY AGTGALEGKA KLKDGARSVT RTIQNNFFDS SKQEAIDVLL
LGNTLNSDLA DKARALLTTG SLRVSEQTLQ SASSKVLKSM CENFYKYSKP KKIRVCVGTW
NVNGGKQFRS IAFKNQTLTD WLLDAPKLAG IQEFQDKRSK PTDIFAIGFE EMVELNAGNI
VSASTTNQKL WAVELQKTIS RDNKYVLLAS EQLVGVCLFV FIRPQHAPFI RDVAVDTVKT
GMGGATGNKG AVAIRMLFHT TSLCFVCSHF AAGQSQVKER NEDFIEIARK LSFPMGRMLF
SHDYVFWCGD FNYRIDLPNE EVKELIRQQN WDSLIAGDQL INQKNAGQVF RGFLEGKVTF
APTYKYDLFS DDYDTSEKCR TPAWTDRVLW RRRKWPFDRS AEDLDLLNAS FQDESKILYT
WTPGTLLHYG RAELKTSDHR PVVALIDIDI FEVEAEERQN IYKEVIAVQG PPDGTVLVSI
KSSLPENNFF DDALIDELLQ QFASFGEVIL IRFVEDKMWV TFLEGSSALN VLSLNGKELL
NRTITIALKS PDWIKNLEEE MSLEKISIAL PSSTSSTLLG EDAEVAADFD MEGDVDDYSA
EVEELLPQHL QPSSSSGLGT SPSSSPRTSP CQSPTISEGP VPSLPIRPSR APSRTPGPPS
AQSSPIDAQP ATPLPQKDPA QPLEPKRPPP PRPVAPPTRP APPQRPPPPS GARSPAPTRK
EFGGIGAPPS PGVARREMEA PKSPGTTRKD NIGRSQPSPQ AGLAGPGPAG YSTARPTIPP
RAGVISAPQS HARASAGRLT PESQSKTSET SKGSTFLPEP LKPQAAFPPQ SSLPPPAQRL
QEPLVPVAAP MPQSGPQPNL ETPPQPPPRS RSSHSLPSEA SSQPQVKTNG ISDGKRESPL
KIDPFEDLSF NLLAVSKAQL SVQTSPVPTP DPKRLIQLPS ATQSNVLSSV SCMPTMPPIP
ARSQSQENMR SSPNPFITGL TRTNPFSDRT AAPGNPFRAK SEESEATSWF SKEEPVTISP
FPSLQPLGHN KSRASSSLDG FKDSFDLQGQ STLKISNPKG WVTFEEEEDF GVKGKSKSAC
SDLLGNQPSS FSGSNLTLND DWNKGTNVSF CVLPSRRPPP PPVPLLPPGT SPPVDPFTTL
ASKASPTLDF TER
