ITSN1_RAT
ID ITSN1_RAT Reviewed; 1713 AA.
AC Q9WVE9; D3ZV52; F1M823; Q9WVE1;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 05-DEC-2018, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Intersectin-1;
DE AltName: Full=EH domain and SH3 domain regulator of endocytosis 1;
GN Name=Itsn1; Synonyms=Ehsh1 {ECO:0000303|PubMed:10373452}, Itsn;
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] (ISOFORMS 2 AND 3), SUBCELLULAR LOCATION,
RP INTERACTION WITH DYNAMIN; SNAP23 AND SNAP25, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=10373452; DOI=10.1074/jbc.274.26.18446;
RA Okamoto M., Schoch S., Suedhof T.C.;
RT "EHSH1/intersectin, a protein that contains EH and SH3 domains and binds to
RT dynamin and SNAP-25. A protein connection between exocytosis and
RT endocytosis?";
RL J. Biol. Chem. 274:18446-18454(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH WASL.
RX PubMed=11584276; DOI=10.1038/ncb1001-927;
RA Hussain N.K., Jenna S., Glogauer M., Quinn C.C., Wasiak S., Guipponi M.,
RA Antonarakis S.E., Kay B.K., Stossel T.P., Lamarche-Vane N., McPherson P.S.;
RT "Endocytic protein intersectin-l regulates actin assembly via Cdc42 and N-
RT WASP.";
RL Nat. Cell Biol. 3:927-932(2001).
RN [5]
RP FUNCTION, INTERACTION WITH FCHO2, IDENTIFICATION BY MASS SPECTROMETRY,
RP IDENTIFICATION IN A COMPLEX WITH FCHO2; DNM1 AND EPS15, SUBCELLULAR
RP LOCATION, AND SUBUNIT.
RX PubMed=20448150; DOI=10.1126/science.1188462;
RA Henne W.M., Boucrot E., Meinecke M., Evergren E., Vallis Y., Mittal R.,
RA McMahon H.T.;
RT "FCHo proteins are nucleators of clathrin-mediated endocytosis.";
RL Science 328:1281-1284(2010).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203; SER-334; SER-335;
RP SER-685; SER-894; SER-896; SER-970; SER-1129 AND THR-1136, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [7]
RP FUNCTION.
RX PubMed=23633571; DOI=10.1073/pnas.1219234110;
RA Sakaba T., Kononenko N.L., Bacetic J., Pechstein A., Schmoranzer J.,
RA Yao L., Barth H., Shupliakov O., Kobler O., Aktories K., Haucke V.;
RT "Fast neurotransmitter release regulated by the endocytic scaffold
RT intersectin.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:8266-8271(2013).
RN [8]
RP INTERACTION WITH PRRT2, AND SUBCELLULAR LOCATION.
RX PubMed=26797119; DOI=10.1074/jbc.m115.683888;
RA Rossi P., Sterlini B., Castroflorio E., Marte A., Onofri F., Valtorta F.,
RA Maragliano L., Corradi A., Benfenati F.;
RT "A Novel Topology of Proline-rich Transmembrane Protein 2 (PRRT2): hints
RT for an intracellular function at the synapse.";
RL J. Biol. Chem. 291:6111-6123(2016).
CC -!- FUNCTION: Adapter protein that provides a link between the endocytic
CC membrane traffic and the actin assembly machinery. Acts as guanine
CC nucleotide exchange factor (GEF) for CDC42, and thereby stimulates
CC actin nucleation mediated by WASL and the ARP2/3 complex (By
CC similarity). Plays a role in the assembly and maturation of clathrin-
CC coated vesicles (PubMed:20448150). Recruits FCHSD2 to clathrin-coated
CC pits (By similarity). Involved in endocytosis of activated EGFR, and
CC probably also other growth factor receptors (By similarity). Involved
CC in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor
CC (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR may
CC involve association with DAB2 (By similarity). Promotes ubiquitination
CC and subsequent degradation of EGFR, and thereby contributes to the
CC down-regulation of EGFR-dependent signaling pathways. In chromaffin
CC cells, required for normal exocytosis of catecholamines (By
CC similarity). Required for rapid replenishment of release-ready synaptic
CC vesicles at presynaptic active zones (PubMed:23633571). Inhibits
CC ARHGAP31 activity toward RAC1 (By similarity).
CC {ECO:0000250|UniProtKB:Q15811, ECO:0000250|UniProtKB:Q9Z0R4,
CC ECO:0000269|PubMed:20448150, ECO:0000269|PubMed:23633571}.
CC -!- FUNCTION: [Isoform 1]: Plays a role in synaptic vesicle endocytosis in
CC brain neurons. {ECO:0000250|UniProtKB:Q9Z0R4}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC -!- SUBUNIT: Interacts (via DH domain) with CDC42. Interacts (via SH3
CC domain 1) with WASL (By similarity). Interacts with dynamin, SNAP25 and
CC SNAP23 (PubMed:10373452). Interacts with clathrin-associated proteins
CC and other components of the endocytic machinery, such as SPIN90, EPS15,
CC EPN1, EPN2, STON2, FCHO1, FCHO2 and DAB2 (PubMed:20448150). Interacts
CC (via SH3 domains) with REPS1 and SGIP1. Interacts with ARHGAP31.
CC Interacts with ADAM15 (By similarity). Interacts with PRRT2
CC (PubMed:26797119). Interacts (via SH3 domain 4) with FCHSD2 (via SH3
CC domain 2). Interacts (via SH3 domain 1) with DENND2B (By similarity).
CC Interacts (via SH3 domains) with CBL (By similarity). Isoform 2:
CC Interacts with CBL and DNM1. Isoform 2: Interacts with LMNA. Isoform 2:
CC Interacts with importin subunit KPNA1; this is likely to mediate its
CC import into the nucleus (By similarity). {ECO:0000250|UniProtKB:Q15811,
CC ECO:0000250|UniProtKB:Q9Z0R4, ECO:0000269|PubMed:10373452,
CC ECO:0000269|PubMed:20448150, ECO:0000269|PubMed:26797119}.
CC -!- SUBCELLULAR LOCATION: Endomembrane system
CC {ECO:0000250|UniProtKB:Q15811}. Synapse, synaptosome
CC {ECO:0000269|PubMed:10373452, ECO:0000269|PubMed:26797119}. Cell
CC projection, lamellipodium {ECO:0000250|UniProtKB:Q15811}. Cell membrane
CC {ECO:0000250|UniProtKB:Q15811}. Membrane, clathrin-coated pit
CC {ECO:0000269|PubMed:11584276, ECO:0000269|PubMed:20448150}. Recycling
CC endosome {ECO:0000250|UniProtKB:Q15811}. Endosome
CC {ECO:0000250|UniProtKB:Q9Z0R4}. Cytoplasmic vesicle
CC {ECO:0000250|UniProtKB:Q9Z0R4}. Note=Colocalizes with SGIP1 at the
CC plasma membrane in structures corresponding most probably to clathrin-
CC coated pits. Colocalizes with RAB13 on cytoplasmic vesicles that are
CC most likely recycling endosomes. {ECO:0000250|UniProtKB:Q15811}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000250|UniProtKB:Q15811}. Nucleus envelope
CC {ECO:0000250|UniProtKB:Q15811}. Note=Shuttles between the cytoplasm and
CC nucleus in an XPO1/CRM1-dependent manner.
CC {ECO:0000250|UniProtKB:Q15811}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9WVE9-3; Sequence=Displayed;
CC Name=2; Synonyms=ITSN-s {ECO:0000250|UniProtKB:Q15811};
CC IsoId=Q9WVE9-1; Sequence=VSP_059959, VSP_059961;
CC Name=3;
CC IsoId=Q9WVE9-2; Sequence=VSP_059959, VSP_059960, VSP_059961;
CC -!- TISSUE SPECIFICITY: Detected in brain, spleen, lung, liver and heart
CC (at protein level). Ubiquitous. Detected in brain, spleen, lung, liver,
CC skeletal muscle and kidney. {ECO:0000269|PubMed:10373452}.
CC -!- DOMAIN: SH3-1 and SH3-4 bind to ARHGAP31 (By similarity). SH3-3, SH3-4
CC and SH3-5, but not SH3-1 and SH3-2 domains, bind to dynamin.
CC {ECO:0000250}.
CC -!- DOMAIN: The KLERQ domain binds to SNAP-25 and SNAP-23.
CC -!- DOMAIN: In an autoinhibited form the SH3 domain 5 may bind
CC intramolecularly to the DH domain, thus blocking the CDC42-binding
CC site. {ECO:0000250|UniProtKB:Q9Z0R4}.
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DR EMBL; AF127798; AAD30271.1; -; mRNA.
DR EMBL; AF132672; AAD31026.1; -; mRNA.
DR EMBL; AC123507; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC142009; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH473989; EDM10741.1; -; Genomic_DNA.
DR RefSeq; NP_001129568.1; NM_001136096.1. [Q9WVE9-3]
DR RefSeq; NP_062100.1; NM_019227.1. [Q9WVE9-1]
DR PDB; 3HS9; X-ray; 2.15 A; P=844-855.
DR PDBsum; 3HS9; -.
DR AlphaFoldDB; Q9WVE9; -.
DR SMR; Q9WVE9; -.
DR BioGRID; 248132; 5.
DR IntAct; Q9WVE9; 4.
DR MINT; Q9WVE9; -.
DR STRING; 10116.ENSRNOP00000045513; -.
DR iPTMnet; Q9WVE9; -.
DR PhosphoSitePlus; Q9WVE9; -.
DR PaxDb; Q9WVE9; -.
DR PRIDE; Q9WVE9; -.
DR Ensembl; ENSRNOT00000096792; ENSRNOP00000095645; ENSRNOG00000002001. [Q9WVE9-3]
DR GeneID; 29491; -.
DR KEGG; rno:29491; -.
DR UCSC; RGD:2935; rat. [Q9WVE9-3]
DR CTD; 6453; -.
DR RGD; 2935; Itsn1.
DR eggNOG; KOG1029; Eukaryota.
DR GeneTree; ENSGT00940000157065; -.
DR HOGENOM; CLU_002819_2_0_1; -.
DR InParanoid; Q9WVE9; -.
DR OMA; WEGELQX; -.
DR OrthoDB; 807060at2759; -.
DR PhylomeDB; Q9WVE9; -.
DR Reactome; R-RNO-193648; NRAGE signals death through JNK.
DR Reactome; R-RNO-3928662; EPHB-mediated forward signaling.
DR Reactome; R-RNO-416482; G alpha (12/13) signalling events.
DR Reactome; R-RNO-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-RNO-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-RNO-9013148; CDC42 GTPase cycle.
DR Reactome; R-RNO-9013406; RHOQ GTPase cycle.
DR Reactome; R-RNO-9013408; RHOG GTPase cycle.
DR EvolutionaryTrace; Q9WVE9; -.
DR PRO; PR:Q9WVE9; -.
DR Proteomes; UP000002494; Chromosome 11.
DR Proteomes; UP000234681; Chromosome 11.
DR Bgee; ENSRNOG00000002001; Expressed in skeletal muscle tissue and 18 other tissues.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0097440; C:apical dendrite; IDA:RGD.
DR GO; GO:0044305; C:calyx of Held; ISO:RGD.
DR GO; GO:0005905; C:clathrin-coated pit; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0043197; C:dendritic spine; IDA:RGD.
DR GO; GO:0030139; C:endocytic vesicle; ISO:RGD.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0097708; C:intracellular vesicle; IDA:RGD.
DR GO; GO:0030027; C:lamellipodium; ISO:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005635; C:nuclear envelope; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0098871; C:postsynaptic actin cytoskeleton; IDA:SynGO.
DR GO; GO:0098833; C:presynaptic endocytic zone; ISO:RGD.
DR GO; GO:0055037; C:recycling endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; IDA:RGD.
DR GO; GO:0043195; C:terminal bouton; HDA:ParkinsonsUK-UCL.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IEA:InterPro.
DR GO; GO:0019209; F:kinase activator activity; ISO:RGD.
DR GO; GO:0060090; F:molecular adaptor activity; ISO:RGD.
DR GO; GO:0070064; F:proline-rich region binding; ISO:RGD.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0150007; P:clathrin-dependent synaptic vesicle endocytosis; IBA:GO_Central.
DR GO; GO:0006897; P:endocytosis; IBA:GO_Central.
DR GO; GO:0016197; P:endosomal transport; IBA:GO_Central.
DR GO; GO:0006887; P:exocytosis; IEA:UniProtKB-KW.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:RGD.
DR GO; GO:2001288; P:positive regulation of caveolin-mediated endocytosis; IMP:RGD.
DR GO; GO:0060999; P:positive regulation of dendritic spine development; IMP:RGD.
DR GO; GO:0060124; P:positive regulation of growth hormone secretion; IMP:RGD.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISO:RGD.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:1905274; P:regulation of modification of postsynaptic actin cytoskeleton; IDA:SynGO.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; ISO:RGD.
DR GO; GO:0048488; P:synaptic vesicle endocytosis; ISO:RGD.
DR CDD; cd00052; EH; 2.
DR CDD; cd00160; RhoGEF; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR000219; DH-domain.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR000261; EH_dom.
DR InterPro; IPR001331; GDS_CDC24_CS.
DR InterPro; IPR032140; INTAP.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF12763; EF-hand_4; 2.
DR Pfam; PF16617; INTAP; 1.
DR Pfam; PF16652; PH_13; 1.
DR Pfam; PF00621; RhoGEF; 1.
DR Pfam; PF00018; SH3_1; 2.
DR Pfam; PF07653; SH3_2; 2.
DR Pfam; PF14604; SH3_9; 1.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00239; C2; 1.
DR SMART; SM00054; EFh; 2.
DR SMART; SM00027; EH; 2.
DR SMART; SM00233; PH; 1.
DR SMART; SM00325; RhoGEF; 1.
DR SMART; SM00326; SH3; 5.
DR SUPFAM; SSF47473; SSF47473; 2.
DR SUPFAM; SSF48065; SSF48065; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF50044; SSF50044; 5.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS00741; DH_1; 1.
DR PROSITE; PS50010; DH_2; 1.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 2.
DR PROSITE; PS50031; EH; 2.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50002; SH3; 5.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Cell membrane;
KW Cell projection; Coated pit; Coiled coil; Cytoplasm; Cytoplasmic vesicle;
KW Endocytosis; Endosome; Exocytosis; Membrane; Metal-binding; Nucleus;
KW Phosphoprotein; Protein transport; Reference proteome; Repeat; SH3 domain;
KW Synapse; Synaptosome; Transport.
FT CHAIN 1..1713
FT /note="Intersectin-1"
FT /id="PRO_0000080959"
FT DOMAIN 21..109
FT /note="EH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00077"
FT DOMAIN 53..88
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 221..310
FT /note="EH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00077"
FT DOMAIN 254..289
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 737..798
FT /note="SH3 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 905..963
FT /note="SH3 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 994..1052
FT /note="SH3 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 1066..1130
FT /note="SH3 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 1147..1206
FT /note="SH3 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 1229..1415
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 1454..1563
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 1571..1687
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 310..354
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 326..702
FT /note="KLERQ"
FT REGION 629..723
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 826..862
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1066..1130
FT /note="Required for interaction with FCHSD2"
FT /evidence="ECO:0000250|UniProtKB:Q15811"
FT COILED 351..670
FT /evidence="ECO:0000255"
FT MOTIF 1096..1119
FT /note="Bipartite nuclear localization signal; in isoform 2"
FT /evidence="ECO:0000250|UniProtKB:Q15811"
FT COMPBIAS 314..329
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 330..354
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 629..709
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 829..862
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 66
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 68
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 70
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 72
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 77
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 267
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 269
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 271
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 273
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 278
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 1659
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1662
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1665
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT MOD_RES 203
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 318
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0R4"
FT MOD_RES 334
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 335
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 685
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 889
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0R4"
FT MOD_RES 893
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15811"
FT MOD_RES 894
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 896
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 970
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 976
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0R4"
FT MOD_RES 987
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15811"
FT MOD_RES 1129
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1136
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT VAR_SEQ 766
FT /note="V -> VKGEWV (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_059959"
FT VAR_SEQ 998..1068
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_059960"
FT VAR_SEQ 1213..1713
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_059961"
FT CONFLICT 781
FT /note="L -> P (in Ref. 1; AAD30271/AAD31026)"
FT /evidence="ECO:0000305"
FT CONFLICT 1019
FT /note="D -> H (in Ref. 1; AAD30271)"
FT /evidence="ECO:0000305"
FT CONFLICT 1065
FT /note="G -> E (in Ref. 1; AAD30271)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1713 AA; 194197 MW; DF5ED07492F716BA CRC64;
MAQFPTPFGG SLDIWAITVE ERAKHDQQFQ SLKPISGFIT GDQARNFFFQ SGLPQPVLAQ
IWALADMNKD GRMDQVEFSI AMKLIKLKLQ GYQLPPALPP VMKQQPAAIS SAPAFGIGGM
AGMPPLTAVA PVPMGSIPVV GMSPPLVSSV PQAAVPPLAN GAPPVIQPLP AFAHPAATLP
KSSSFSRSGP GSQLNTKLQK AQSFDVASAP AAAEWAVPQS SRLKYRQLFN SHDKTMSGHL
TGPQARTILM QSSLPQAQLA SIWNLSDIDQ DGKLTAEEFI LAMHLIDVAM SGQPLPPVLP
PEYIPPSFRR VRSGSGMSVI SSSSADQRLP EEPSSEDEQQ VEKKLPVTFE DKKRENFERG
NLELEKRRQA LLEQQRKEQE RLAQLERAEQ ERKERERQEQ ERKRQLELEK QLEKQRELER
QREEERRKEI ERREAAKREL ERQRQLEWER NRRQELLTQR NKDQEGIVVL KARRKTLEFE
LEALNDKKHQ LEGKLQDIRC RLATQRQEIE STNKSRELRI AEITHLQQQL QESQQMLGRL
IPEKQILSDQ LKQVQQNSLH RDSLLTLKRA LEAKELARQQ LREQLDEVEK ETRSKLQEID
VFNNQLKELR EIHSKQQLQK QRSIEAERLK QKEQERKSLE LEKQKEEGQR RVQERDKQWQ
EHVQQEEQQR PRKPHEEDKL KREDSVKKKE AEERAKPEVQ DKQSRLFHPH QEPAKPAQAP
WPTTEKGPLT ISAQESAKVV YYRALYPFES RSHDEITIQP GDIVMVDESQ TGEPGWLGGE
LKGKTGWFPA NYAEKIPENE IPTPAKPVTD LTSAPAPKLA LRETPAPLPV TSSEPSTTPN
NWADFSSTWP SSTNEKPETD NWDTWAAQPS LTVPSAGQLR QRSAFTPATA TGSSPSPVLG
QGEKVEGLQA QALYPWRAKK DNHLNFNKSD VITVLEQQDM WWFGEVQGQK GWFPKSYVKL
ISGPVRKSTS IDTGPTEAPS SLKRVASPAA KPAIPGEEFV AMYTYESSEH GDLTFQQGDV
IVVTKKDGDW WTGTVGETSG VFPSNYVRLK DSEGSGTAGK TGSLGKKPEI AQVIASYTAT
GPEQLTLAPG QLILIRKKNP GGWWEGELQA RGKKRQIGWF PANYVKLLSP GTSKITPTEL
PKTAVQPAVC QVIGMYDYTA QNDDELAFSK GQIINVLSKE DPDWWKGEVS GQVGLFPSNY
VKLTTDMDPS QQWCSDLHLL DMLTPTERKR QGYIHELIVT EENYVNDLQL VTEIFQKPLT
ESELLTEKEV AMIFVNWKEL IMCNIKLLKA LRVRKKMSGE KMPVKMIGDI LSAQLPHMQP
YIRFCSCQLN GAALIQQKTD EAPDFKEFVK RLAMDPRCKG MPLSSFILKP MQRVTRYPLI
IKNILENTPE NHPDHSHLKH ALEKAEELCS QVNEGVREKE NSDRLEWIQA HVQCEGLSEQ
LVFNSVTNCL GPRKFLHSGK LYKAKSNKEL YGFLFNDFLL LTQITKPLGS SSTDKVFSPK
SNLQYKMYKT PIFLNEVLVK LPTDPSGDEP IFHISHIDRV YTLRAESINE RTAWVQKIKA
ASELYIETEK KKREKAYLVR SQRATGIGRL MVNVVEGIEL KPCRSHGKSN PYCEVTMGSQ
CHITKTIQDT LNPKWNSNCQ FFIRDLEQEV LCITVFERDQ FSPDDFLGRT EIRVADIKKD
QGSKGPVTKC LLLHEVPTGE IVVRLDLQLF DEP
