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   22-APR-2020, entry version 158.
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=17; 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}. Cell junction, synapse, synaptosome
CC       {ECO:0000250}. 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};
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
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   SMR; Q8WXE9; -.
DR   BioGrid; 124526; 58.
DR   CORUM; Q8WXE9; -.
DR   ELM; Q8WXE9; -.
DR   IntAct; Q8WXE9; 46.
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; -.
DR   Antibodypedia; 164; 22 antibodies.
DR   DNASU; 85439; -.
DR   Ensembl; ENST00000555447; ENSP00000450857; ENSG00000140022. [Q8WXE9-3]
DR   Ensembl; ENST00000614646; ENSP00000477736; ENSG00000140022. [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; Low tissue specificity.
DR   MIM; 608467; gene.
DR   neXtProt; NX_Q8WXE9; -.
DR   OpenTargets; ENSG00000140022; -.
DR   PharmGKB; PA143485624; -.
DR   eggNOG; KOG2677; Eukaryota.
DR   eggNOG; ENOG410XQHF; LUCA.
DR   GeneTree; ENSGT00940000159392; -.
DR   HOGENOM; CLU_016541_0_0_1; -.
DR   InParanoid; Q8WXE9; -.
DR   KO; K20067; -.
DR   OMA; WSATNPF; -.
DR   OrthoDB; 1059322at2759; -.
DR   PhylomeDB; Q8WXE9; -.
DR   TreeFam; TF300393; -.
DR   Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR   Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR   SignaLink; Q8WXE9; -.
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 kidney and 181 other tissues.
DR   ExpressionAtlas; Q8WXE9; baseline and differential.
DR   Genevisible; Q8WXE9; HS.
DR   GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR   GO; GO:0030136; C:clathrin-coated vesicle; IEA:Ensembl.
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-SubCell.
DR   GO; GO:0005730; C:nucleolus; IDA:HPA.
DR   GO; GO:0008021; C:synaptic vesicle; IEA:Ensembl.
DR   GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IEA:Ensembl.
DR   GO; GO:0061024; P:membrane organization; TAS:Reactome.
DR   GO; GO:0030100; P:regulation of endocytosis; ISS:UniProtKB.
DR   GO; GO:0048488; P:synaptic vesicle endocytosis; IGI:UniProtKB.
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; Cell junction; Cytoplasm; Endocytosis;
KW   Membrane; Phosphoprotein; Polymorphism; Reference proteome; Repeat;
KW   Synapse; Synaptosome; 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   MOTIF           313..315
FT                   /note="NPF 1"
FT   MOTIF           329..331
FT                   /note="NPF 2"
FT   MOD_RES         255
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8BZ60"
FT   MOD_RES         281
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:23186163"
FT   MOD_RES         287
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:23186163"
FT   MOD_RES         302
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:23186163"
FT   MOD_RES         762
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|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:0000244|PDB:2JXC"
FT   TURN            318..320
FT                   /evidence="ECO:0000244|PDB:2JXC"
FT   HELIX           334..337
FT                   /evidence="ECO:0000244|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
//