ITSN1_XENLA
ID ITSN1_XENLA Reviewed; 1705 AA.
AC O42287; A0A1L8HCG8;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 05-DEC-2018, sequence version 2.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Intersectin-1;
GN Name=itsn1;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND INTERACTION WITH EPN1 AND EPN2.
RC TISSUE=Oocyte;
RX PubMed=9813051; DOI=10.1074/jbc.273.47.31401;
RA Yamabhai M., Hoffman N.G., Hardison N.L., McPherson P.S., Castagnoli L.,
RA Cesareni G., Kay B.K.;
RT "Intersectin, a novel adaptor protein with two eps15 homology and five src
RT homology 3 domains.";
RL J. Biol. Chem. 273:31401-31407(1998).
RN [2] {ECO:0000312|Proteomes:UP000186698}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=J {ECO:0000312|Proteomes:UP000186698};
RX PubMed=27762356; DOI=10.1038/nature19840;
RA Session A.M., Uno Y., Kwon T., Chapman J.A., Toyoda A., Takahashi S.,
RA Fukui A., Hikosaka A., Suzuki A., Kondo M., van Heeringen S.J., Quigley I.,
RA Heinz S., Ogino H., Ochi H., Hellsten U., Lyons J.B., Simakov O.,
RA Putnam N., Stites J., Kuroki Y., Tanaka T., Michiue T., Watanabe M.,
RA Bogdanovic O., Lister R., Georgiou G., Paranjpe S.S., van Kruijsbergen I.,
RA Shu S., Carlson J., Kinoshita T., Ohta Y., Mawaribuchi S., Jenkins J.,
RA Grimwood J., Schmutz J., Mitros T., Mozaffari S.V., Suzuki Y., Haramoto Y.,
RA Yamamoto T.S., Takagi C., Heald R., Miller K., Haudenschild C., Kitzman J.,
RA Nakayama T., Izutsu Y., Robert J., Fortriede J., Burns K., Lotay V.,
RA Karimi K., Yasuoka Y., Dichmann D.S., Flajnik M.F., Houston D.W.,
RA Shendure J., DuPasquier L., Vize P.D., Zorn A.M., Ito M., Marcotte E.M.,
RA Wallingford J.B., Ito Y., Asashima M., Ueno N., Matsuda Y., Veenstra G.J.,
RA Fujiyama A., Harland R.M., Taira M., Rokhsar D.S.;
RT "Genome evolution in the allotetraploid frog Xenopus laevis.";
RL Nature 538:336-343(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). Involved in endocytosis of activated egfr, and probably
CC also other growth factor receptors (By similarity).
CC {ECO:0000250|UniProtKB:Q15811, ECO:0000250|UniProtKB:Q9Z0R4}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC -!- SUBUNIT: Binds epn1 and epn2. {ECO:0000269|PubMed:9813051}.
CC -!- SUBCELLULAR LOCATION: Endomembrane system
CC {ECO:0000250|UniProtKB:Q15811}. Synapse, synaptosome
CC {ECO:0000250|UniProtKB:Q9WVE9}. Cell projection, lamellipodium
CC {ECO:0000250|UniProtKB:Q15811}. Cell membrane
CC {ECO:0000250|UniProtKB:Q15811}. Membrane, clathrin-coated pit
CC {ECO:0000250|UniProtKB:Q15811}. Recycling endosome
CC {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=2;
CC Name=1;
CC IsoId=O42287-1; Sequence=Displayed;
CC Name=2; Synonyms=ITSN-s {ECO:0000250|UniProtKB:Q15811};
CC IsoId=O42287-2; Sequence=VSP_059962, VSP_059963;
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DR EMBL; AF032118; AAC73068.1; -; mRNA.
DR EMBL; CM004468; OCT93804.1; -; Genomic_DNA.
DR PIR; T09194; T09194.
DR RefSeq; NP_001080955.1; NM_001087486.1.
DR RefSeq; XP_018100329.1; XM_018244840.1. [O42287-1]
DR AlphaFoldDB; O42287; -.
DR SMR; O42287; -.
DR BioGRID; 98902; 4.
DR STRING; 8355.O42287; -.
DR PRIDE; O42287; -.
DR GeneID; 394300; -.
DR KEGG; xla:394300; -.
DR CTD; 394300; -.
DR Xenbase; XB-GENE-5904211; itsn1.L.
DR OMA; CERATQG; -.
DR OrthoDB; 807060at2759; -.
DR Proteomes; UP000186698; Chromosome 2L.
DR Bgee; 394300; Expressed in egg cell and 19 other tissues.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0043005; C:neuron projection; IEA:UniProtKB-KW.
DR GO; GO:0005635; C:nuclear envelope; ISS:UniProtKB.
DR GO; GO:0055037; C:recycling endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
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:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0006887; P:exocytosis; IEA:UniProtKB-KW.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
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; 1.
DR Pfam; PF07653; SH3_2; 2.
DR Pfam; PF14604; SH3_9; 2.
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 Alternative splicing; Calcium; Cell membrane; Cell projection; Coated pit;
KW Coiled coil; Cytoplasm; Endocytosis; Endosome; Exocytosis; Membrane;
KW Metal-binding; Nucleus; Protein transport; Reference proteome; Repeat;
KW SH3 domain; Synapse; Synaptosome; Transport.
FT CHAIN 1..1705
FT /note="Intersectin-1"
FT /id="PRO_0000080960"
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 220..309
FT /note="EH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00077"
FT DOMAIN 253..288
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 732..793
FT /note="SH3 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 897..955
FT /note="SH3 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 986..1044
FT /note="SH3 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 1058..1122
FT /note="SH3 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 1139..1198
FT /note="SH3 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 1221..1407
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 1446..1555
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 1563..1679
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 322..355
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 325..697
FT /note="KLERQ"
FT REGION 386..433
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 668..708
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 823..851
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 959..978
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 350..687
FT /evidence="ECO:0000255"
FT MOTIF 1088..1111
FT /note="Bipartite nuclear localization signal; in isoform 2"
FT /evidence="ECO:0000250|UniProtKB:Q15811"
FT COMPBIAS 336..355
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 668..700
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 959..975
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 266
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 268
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 270
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 272
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 277
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 1651
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1654
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1657
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT VAR_SEQ 1205..1270
FT /note="WCADLHLLDMLSPTERKRQGYIHELIVTEENYVSDLQLVTETFQKPLLESDL
FT LTEKEVAMIFVNWK -> FRLGVKPAGGIPATGDRPFILFPFRDGPSLLPNAFQAPPLS
FT VVMIKFRCFTAPRFCPDMNVKYINI (in isoform 2)"
FT /id="VSP_059962"
FT VAR_SEQ 1271..1705
FT /note="Missing (in isoform 2)"
FT /id="VSP_059963"
FT CONFLICT 547
FT /note="N -> I (in Ref. 1; AAC73068)"
FT /evidence="ECO:0000305"
FT CONFLICT 654
FT /note="H -> Q (in Ref. 1; AAC73068)"
FT /evidence="ECO:0000305"
FT CONFLICT 683
FT /note="I -> V (in Ref. 1; AAC73068)"
FT /evidence="ECO:0000305"
FT CONFLICT 1073
FT /note="G -> A (in Ref. 1; AAC73068)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1705 AA; 194051 MW; A284C31DACC2F541 CRC64;
MAQFGTPFGG NLDIWAITVE ERAKHDQQFH GLKPTAGYIT GDQARNFFLQ SGLPQPVLAQ
IWALADMNND GRMDQLEFSI AMKLIKLKLQ GYPLPSILPS NMLKQPVAMP AAAVAGFGMS
GIVGIPPLAA VAPVPMPSIP VVGMSPPLVS SVPTVPPLSN GAPAVIQSHP AFAHSATLPK
SSSFGRSVAG SQINTKLQKA QSFDVPAPPL VVEWAVPSSS RLKYRQLFNS QDKTMSGNLT
GPQARTILMQ SSLPQSQLAT IWNLSDIDQD GKLTAEEFIL AMHLIDVAMS GQPLPPILPP
EYIPPSFRRV RSGSGLSIMS SVSVDQRLPE EPEEEEPQNA DKKLPVTFED KKRENFERGN
LELEKRRQAL LEQQRKEQER LAQLERAEQE RKERERQDQE RKRQQDLEKQ LEKQRELERQ
REEERRKEIE RREAAKRELE RQRQLEWERN RRQELLNQRN REQEDIVVLK AKKKTLEFEL
EALNDKKHQL EGKLQDIRCR LTTQRHEIES TNKSRELRIA EITHLQQQLQ ESQQLLGKMI
PEKQSLNDQL KQVQQNSLHR DSLLTLKRAL ETKEIGRQQL RDQLDEVEKE TRAKLQEIDV
FNNQLKELRE LYNKQQFQKQ QDFETEKIKQ KELERKTSEL DKLKEEDKRR MLEHDKLWQD
RVKQEEERYK FQDEEKEKRE ESIQKCEVEK KPEIQEKPNK PFHQPPEPGK LGGQIPWMNT
EKAPLTINQG DVKVVYYRAL YPFDARSHDE ITIEPGDIIM VDESQTGEPG WLGGELKGKT
GWFPANYAER MPESEFPSTT KPAAETTAKP TVHVAPSPVA PAAFTNTSTN SNNWADFSST
WPTNNTDKVE SDNWDTWAAQ PSLTVPSAGQ HRQRSAFTPA TVTGSSPSPV LGQGEKVEGL
QAQALYPWRA KKDNHLNFNK NDVITVLEQQ DMWWFGEVQG QKGWFPKSYV KLISGPLRKS
TSIDSTSSES PASLKRVSSP AFKPAIQGEE YISMYTYESN EQGDLTFQQG DLIVVIKKDG
DWWTGTVGEK TGVFPSNYVR PKDSEAAGSG GKTGSLGKKP EIAQVIASYA ATGPEQLTLA
PGQLILIRKK NPGGWWEGEL QARGKKRQIG WFPANYVKLL SPGTNKSTPT EPPKPTSLPP
TCQVIGMYDY IAQNDDELAF SKGQVINVLN KEDPDWWKGE LNGHVGLFPS NYVKLTTDMD
PSQQWCADLH LLDMLSPTER KRQGYIHELI VTEENYVSDL QLVTETFQKP LLESDLLTEK
EVAMIFVNWK ELIMCNIKLL KALRVRKKMS GEKMPVKMIG DILTAQLPHM QPYIRFCSCQ
LNGAALIQQK TDEVPEFKEF VKRLAMDPRC KGMPLSSFLL KPMQRVTRYP LIIKNIIENT
PENHPDHSHL KQALEKAEEL CSQVNEGVRE KENSDRLEWI QGHVQCEGLS EQLVFNSVTN
CLGPRKFLHS GKLYKAKSNK ELYGFLFNDF LLLTQIIKPL GSSGNDKVFS PKSNLQYKMY
KTPIFLNEVL VKLPTDPSGD EPIFHISHID RVYTLRAESI NERTAWVQKI KAASELYIET
EKKKREKAYL VRSQRATGIG RLMVNIVEGI ELKPCRTHGK SNPYCEITMG SQCHITKTIQ
DTLNPKWNSN CQFFIKDLEQ DVLCITVFER DQFSPDDFLG RTEIRVADIK KDQGSKGPVT
KCLLLHEVPT GEIVVRLDLQ LFDEP
