STON2_HUMAN
ID STON2_HUMAN Reviewed; 905 AA.
AC Q8WXE9; G3V2T7; Q17R24; Q59H11; Q6NT47; Q96RI7; Q96RU6;
DT 15-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Stonin-2;
DE AltName: Full=Stoned B;
GN Name=STON2; Synonyms=STN2, STNB;
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] (ISOFORM 1), FUNCTION, INTERACTION WITH SYT1 AND
RP WITH THE AP-2 COMPLEX, MUTAGENESIS OF TRP-738 AND LYS-740, AND VARIANT
RP PRO-307.
RC TISSUE=Brain;
RX PubMed=11454741; DOI=10.1093/embo-reports/kve134;
RA Walther K., Krauss M., Diril M.K., Lemke S., Ricotta D., Hoening S.,
RA Kaiser S., Haucke V.;
RT "Human stoned B interacts with AP-2 and synaptotagmin and facilitates
RT clathrin-coated vesicle uncoating.";
RL EMBO Rep. 2:634-640(2001).
RN [2]
RP ERRATUM OF PUBMED:11454741.
RA Walther K., Krauss M., Diril M.K., Lemke S., Ricotta D., Hoening S.,
RA Kaiser S., Haucke V.;
RL EMBO Rep. 3:197-197(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT PRO-307.
RC TISSUE=Spleen;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RT "Homo sapiens protein coding cDNA.";
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-307.
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 NUCLEOTIDE SEQUENCE [MRNA] OF 191-905 (ISOFORM 1), FUNCTION, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH EPS15; EPS15R; ITSN1;
RP SYT1 AND SYT2.
RX PubMed=11381094; DOI=10.1083/jcb.153.5.1111;
RA Martina J.A., Bonangelino C.J., Aguilar R.C., Bonifacino J.S.;
RT "Stonin 2: an adaptor-like protein that interacts with components of the
RT endocytic machinery.";
RL J. Cell Biol. 153:1111-1120(2001).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP FUNCTION IN SYNAPTIC VESICLE RECYCLING, INTERACTION WITH TOR1A AND COPS4,
RP PHOSPHORYLATION, NEDDYLATION, AND UBIQUITINATION.
RX PubMed=21102408; DOI=10.1038/emboj.2010.285;
RA Granata A., Koo S.J., Haucke V., Schiavo G., Warner T.T.;
RT "CSN complex controls the stability of selected synaptic proteins via a
RT torsinA-dependent process.";
RL EMBO J. 30:181-193(2011).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-281; SER-287; SER-302 AND
RP SER-762, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [10]
RP STRUCTURE BY NMR OF 121-215 IN COMPLEX WITH EPS15.
RX PubMed=18200045; DOI=10.1038/sj.emboj.7601980;
RA Rumpf J., Simon B., Jung N., Maritzen T., Haucke V., Sattler M.,
RA Groemping Y.;
RT "Structure of the Eps15-stonin2 complex provides a molecular explanation
RT for EH-domain ligand specificity.";
RL EMBO J. 27:558-569(2008).
CC -!- FUNCTION: Adapter protein involved in endocytic machinery. Involved in
CC the synaptic vesicle recycling. May facilitate clathrin-coated vesicle
CC uncoating. {ECO:0000269|PubMed:11381094, ECO:0000269|PubMed:11454741,
CC ECO:0000269|PubMed:21102408}.
CC -!- SUBUNIT: Interacts with the second C2 domain of synaptotagmins SYT1 and
CC SYT2. Interacts with EPS15, EPS15R and ITSN1. Interacts indirectly with
CC the AP-2 adapter complex. Interacts with TOR1A and COPS4; the
CC interaction controls STON2 protein stability.
CC {ECO:0000269|PubMed:11381094, ECO:0000269|PubMed:11454741,
CC ECO:0000269|PubMed:18200045, ECO:0000269|PubMed:21102408}.
CC -!- INTERACTION:
CC Q8WXE9; P42566: EPS15; NbExp=18; IntAct=EBI-539742, EBI-396684;
CC Q8WXE9; Q15843: NEDD8; NbExp=2; IntAct=EBI-539742, EBI-716247;
CC Q8WXE9; P21707: Syt1; Xeno; NbExp=2; IntAct=EBI-539742, EBI-458098;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11381094}. Membrane
CC {ECO:0000269|PubMed:11381094}. Synapse, synaptosome {ECO:0000250}.
CC Note=Some fraction is membrane-associated.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8WXE9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8WXE9-3; Sequence=VSP_044863;
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:11381094}.
CC -!- DOMAIN: The Asn-Pro-Phe (NPF) motifs, which are found in proteins
CC involved in the endocytic pathway, mediate the interaction with the EH
CC domain of SYT1, SYT2, EPS15, EPS15R and ITSN1.
CC -!- PTM: Phosphorylated in vitro by PKD. {ECO:0000269|PubMed:21102408}.
CC -!- PTM: Neddylated; deneddylated via its interaction with the COP9
CC signalosome (CSN) complex through TOR1A and COPS4.
CC {ECO:0000269|PubMed:21102408}.
CC -!- PTM: Ubiquitinated; leading to its degradation.
CC {ECO:0000269|PubMed:21102408}.
CC -!- SIMILARITY: Belongs to the Stoned B family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK57558.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAK57558.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
CC Sequence=AAK76362.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAD92185.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF380833; AAK76362.1; ALT_FRAME; mRNA.
DR EMBL; AF449430; AAL47008.1; -; mRNA.
DR EMBL; AB208948; BAD92185.1; ALT_INIT; mRNA.
DR EMBL; AL121769; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL136040; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC069389; AAH69389.1; -; mRNA.
DR EMBL; BC117493; AAI17494.1; -; mRNA.
DR EMBL; AF255309; AAK57558.1; ALT_SEQ; mRNA.
DR CCDS; CCDS58332.1; -. [Q8WXE9-3]
DR RefSeq; NP_001243359.1; NM_001256430.1. [Q8WXE9-3]
DR RefSeq; NP_149095.2; NM_033104.3.
DR PDB; 2JXC; NMR; -; B=301-340.
DR PDBsum; 2JXC; -.
DR AlphaFoldDB; Q8WXE9; -.
DR BMRB; Q8WXE9; -.
DR SMR; Q8WXE9; -.
DR BioGRID; 124526; 81.
DR CORUM; Q8WXE9; -.
DR ELM; Q8WXE9; -.
DR IntAct; Q8WXE9; 50.
DR MINT; Q8WXE9; -.
DR STRING; 9606.ENSP00000450857; -.
DR CarbonylDB; Q8WXE9; -.
DR iPTMnet; Q8WXE9; -.
DR PhosphoSitePlus; Q8WXE9; -.
DR BioMuta; STON2; -.
DR DMDM; 34098614; -.
DR EPD; Q8WXE9; -.
DR jPOST; Q8WXE9; -.
DR MassIVE; Q8WXE9; -.
DR MaxQB; Q8WXE9; -.
DR PaxDb; Q8WXE9; -.
DR PeptideAtlas; Q8WXE9; -.
DR PRIDE; Q8WXE9; -.
DR ProteomicsDB; 32734; -.
DR ProteomicsDB; 75021; -. [Q8WXE9-1]
DR ABCD; Q8WXE9; 1 sequenced antibody.
DR Antibodypedia; 164; 29 antibodies from 14 providers.
DR DNASU; 85439; -.
DR Ensembl; ENST00000555447.5; ENSP00000450857.1; ENSG00000140022.14. [Q8WXE9-3]
DR GeneID; 85439; -.
DR KEGG; hsa:85439; -.
DR UCSC; uc001xvk.3; human. [Q8WXE9-1]
DR CTD; 85439; -.
DR DisGeNET; 85439; -.
DR GeneCards; STON2; -.
DR HGNC; HGNC:30652; STON2.
DR HPA; ENSG00000140022; Tissue enriched (brain).
DR MIM; 608467; gene.
DR neXtProt; NX_Q8WXE9; -.
DR OpenTargets; ENSG00000140022; -.
DR PharmGKB; PA143485624; -.
DR VEuPathDB; HostDB:ENSG00000140022; -.
DR eggNOG; KOG2677; Eukaryota.
DR GeneTree; ENSGT00940000159392; -.
DR HOGENOM; CLU_016541_0_0_1; -.
DR InParanoid; Q8WXE9; -.
DR OMA; SQPKDGW; -.
DR OrthoDB; 1059322at2759; -.
DR PhylomeDB; Q8WXE9; -.
DR TreeFam; TF300393; -.
DR PathwayCommons; Q8WXE9; -.
DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR SignaLink; Q8WXE9; -.
DR SIGNOR; Q8WXE9; -.
DR BioGRID-ORCS; 85439; 11 hits in 1081 CRISPR screens.
DR ChiTaRS; STON2; human.
DR EvolutionaryTrace; Q8WXE9; -.
DR GenomeRNAi; 85439; -.
DR Pharos; Q8WXE9; Tbio.
DR PRO; PR:Q8WXE9; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q8WXE9; protein.
DR Bgee; ENSG00000140022; Expressed in medial globus pallidus and 170 other tissues.
DR ExpressionAtlas; Q8WXE9; baseline and differential.
DR Genevisible; Q8WXE9; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030136; C:clathrin-coated vesicle; IBA:GO_Central.
DR GO; GO:0031410; C:cytoplasmic vesicle; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043005; C:neuron projection; IEA:UniProtKB-KW.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0008021; C:synaptic vesicle; IBA:GO_Central.
DR GO; GO:0035615; F:clathrin adaptor activity; IBA:GO_Central.
DR GO; GO:0030100; P:regulation of endocytosis; ISS:UniProtKB.
DR GO; GO:0048488; P:synaptic vesicle endocytosis; IGI:UniProtKB.
DR GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
DR DisProt; DP01368; -.
DR InterPro; IPR036168; AP2_Mu_C_sf.
DR InterPro; IPR028565; MHD.
DR InterPro; IPR012320; SHD_dom.
DR InterPro; IPR031228; STON2.
DR InterPro; IPR017110; Stonin.
DR InterPro; IPR022699; Stonin2_N.
DR PANTHER; PTHR10529:SF345; PTHR10529:SF345; 1.
DR Pfam; PF00928; Adap_comp_sub; 1.
DR Pfam; PF12016; Stonin2_N; 1.
DR PIRSF; PIRSF037099; Stonin; 1.
DR SUPFAM; SSF49447; SSF49447; 1.
DR PROSITE; PS51072; MHD; 1.
DR PROSITE; PS51070; SHD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Endocytosis; Membrane;
KW Phosphoprotein; Reference proteome; Repeat; Synapse; Synaptosome;
KW Ubl conjugation.
FT CHAIN 1..905
FT /note="Stonin-2"
FT /id="PRO_0000185732"
FT DOMAIN 427..560
FT /note="SHD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00403"
FT DOMAIN 568..878
FT /note="MHD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00404"
FT REGION 1..121
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 178..205
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 244..263
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 313..315
FT /note="NPF 1"
FT MOTIF 329..331
FT /note="NPF 2"
FT COMPBIAS 1..17
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 34..57
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 58..74
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 102..121
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 178..193
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 246..260
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 255
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8BZ60"
FT MOD_RES 281
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 287
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 302
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 762
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 872..905
FT /note="VALGSIWLMLPTPFVHPTTLPLLFLLAMLTMFAW -> TTETDNLPNPLYCS
FT CLPHTDLKRGSKRVVKIRWNASLEVPLASSIRTMV (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_044863"
FT VARIANT 307
FT /note="S -> P (in dbSNP:rs3813535)"
FT /evidence="ECO:0000269|PubMed:11454741,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.3"
FT /id="VAR_020182"
FT VARIANT 646
FT /note="R -> H (in dbSNP:rs34323725)"
FT /id="VAR_046643"
FT VARIANT 694
FT /note="T -> A (in dbSNP:rs35689202)"
FT /id="VAR_046644"
FT VARIANT 851
FT /note="S -> A (in dbSNP:rs2241621)"
FT /id="VAR_021912"
FT MUTAGEN 738
FT /note="W->A: Reduces interaction with SYT1."
FT /evidence="ECO:0000269|PubMed:11454741"
FT MUTAGEN 740
FT /note="K->A: Reduces interaction with SYT1."
FT /evidence="ECO:0000269|PubMed:11454741"
FT CONFLICT 121..122
FT /note="TA -> NS (in Ref. 1; AAK76362)"
FT /evidence="ECO:0000305"
FT STRAND 314..317
FT /evidence="ECO:0007829|PDB:2JXC"
FT TURN 318..320
FT /evidence="ECO:0007829|PDB:2JXC"
FT HELIX 334..337
FT /evidence="ECO:0007829|PDB:2JXC"
FT CONFLICT Q8WXE9-3:899
FT /note="V -> L (in Ref. 3; BAD92185)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 905 AA; 101165 MW; 59F5810DEC540CA3 CRC64;
MTTLDHVIAT HQSEWVSFNE EPPFPAHSQG GTEEHLPGLS SSPDQSESSS GENHVVDGGS
QDHSHSEQDD SSEKMGLISE AASPPGSPEQ PPPDLASAIS NWVQFEDDTP WASTSPPHQE
TAETALPLTM PCWTCPSFDS LGRCPLTSES SWTTHSEDTS SPSFGCSYTD LQLINAEEQT
SGQASGADST DNSSSLQEDE EVEMEAISWQ ASSPAMNGHP APPVTSARFP SWVTFDDNEV
SCPLPPVTSP LKPNTPPSAS VIPDVPYNSM GSFKKRDRPK STLMNFSKVQ KLDISSLNRT
PSVTEASPWR ATNPFLNETL QDVQPSPINP FSAFFEEQER RSQNSSISST TGKSQRDSLI
VIYQDAISFD DSSKTQSHSD AVEKLKQLQI DDPDHFGSAT LPDDDPVAWI ELDAHPPGSA
RSQPRDGWPM MLRIPEKKNI MSSRHWGPIF VKLTDTGYLQ LYYEQGLEKP FREFKLEICH
EISEPRLQNY DENGRIHSLR IDRVTYKEKK KYQPKPAVAH TAEREQVIKL GTTNYDDFLS
FIHAVQDRLM DLPVLSMDLS TVGLNYLEEE ITVDVRDEFS GIVSKGDNQI LQHHVLTRIH
ILSFLSGLAE CRLGLNDILV KGNEIVLRQD IMPTTTTKWI KLHECRFHGC VDEDVFHNSR
VILFNPLDAC RFELMRFRTV FAEKTLPFTL RTATSVNGAE VEVQSWLRMS TGFSANRDPL
TQVPCENVMI RYPVPSEWVK NFRRESVLGE KSLKAKVNRG ASFGSTSVSG SEPVMRVTLG
TAKYEHAFNS IVWRINRLPD KNSASGHPHC FFCHLELGSD REVPSRFANH VNVEFSMPTT
SASKASVRSI SVEDKTDVRK WVNYSAHYSY QVALGSIWLM LPTPFVHPTT LPLLFLLAML
TMFAW
