Full text data of ITSN1
ITSN1
(ITSN, SH3D1A)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Intersectin-1 (SH3 domain-containing protein 1A; SH3P17)
Intersectin-1 (SH3 domain-containing protein 1A; SH3P17)
UniProt
Q15811
ID ITSN1_HUMAN Reviewed; 1721 AA.
AC Q15811; A7Y322; A8CTX8; A8CTY3; A8CTY7; A8D7D0; A8DCP3; B4DTM2;
read moreAC E7ERJ1; E9PE44; E9PG01; E9PHV2; O95216; Q0PW94; Q0PW95; Q14BD3;
AC Q1ED40; Q20BK3; Q9UET5; Q9UK60; Q9UNK1; Q9UNK2; Q9UQ92;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 22-JAN-2014, entry version 149.
DE RecName: Full=Intersectin-1;
DE AltName: Full=SH3 domain-containing protein 1A;
DE AltName: Full=SH3P17;
GN Name=ITSN1; Synonyms=ITSN, SH3D1A;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), AND
RP VARIANT ASN-1137.
RC TISSUE=Fetal brain;
RX PubMed=9799604; DOI=10.1006/geno.1998.5521;
RA Guipponi M., Scott H.S., Chen H., Schebesta A., Rossier C.,
RA Antonarakis S.E.;
RT "Two isoforms of a human intersectin (ITSN) protein are produced by
RT brain-specific alternative splicing in a stop codon.";
RL Genomics 53:369-376(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX PubMed=10482960; DOI=10.1038/sj.ejhg.5200356;
RA Pucharcos C., Fuentes J.-J., Casas C., de la Luna S., Alcantara S.,
RA Arbones M.L., Soriano E., Estivill X., Pritchard M.;
RT "Alu-splice cloning of human intersectin (ITSN), a putative
RT multivalent binding protein expressed in proliferating and
RT differentiating neurons and overexpressed in Down syndrome.";
RL Eur. J. Hum. Genet. 7:704-712(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 6; 7; 8; 9; 10; 11 AND 12),
RP VARIANT ASN-1137, AND ALTERNATIVE SPLICING.
RC TISSUE=Brain, and Lung;
RX PubMed=19777371; DOI=10.1007/s11033-009-9824-8;
RA Kropyvko S., Gerasymchuk D., Skrypkina I., Dergai M., Dergai O.,
RA Nikolaienko O., Rynditch A., Tsyba L.;
RT "Structural diversity and differential expression of novel human
RT intersectin 1 isoforms.";
RL Mol. Biol. Rep. 37:2789-2796(2010).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
RC TISSUE=Kidney;
RX PubMed=21712076; DOI=10.1016/j.gene.2011.06.021;
RA Dergai M., Skrypkina I., Dergai O., Tsyba L., Novokhatska O.,
RA Filonenko V., Drobot L., Rynditch A.;
RT "Identification and characterization of a novel mammalian isoform of
RT the endocytic adaptor ITSN1.";
RL Gene 485:120-129(2011).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7).
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
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.,
RA Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y.,
RA Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K.,
RA Polley A., Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D.,
RA Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W.,
RA Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S.,
RA Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E.,
RA Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P.,
RA Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H.,
RA Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E.,
RA Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F.,
RA Lehrach H., Reinhardt R., Yaspo M.-L.;
RT "The DNA sequence of human chromosome 21.";
RL Nature 405:311-319(2000).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Embryonic stem cell;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 620-1721 (ISOFORM 3).
RC TISSUE=Bone marrow;
RX PubMed=9630982; DOI=10.1038/nbt0696-741;
RA Sparks A.B., Hoffman N.G., McConnell S.J., Fowlkes D.M., Kay B.K.;
RT "Cloning of ligand targets: systematic isolation of SH3 domain-
RT containing proteins.";
RL Nat. Biotechnol. 14:741-744(1996).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 963-1721 (ISOFORM 3).
RC TISSUE=Brain;
RA Tsyba L.O., Kvasha S.M., Skripkina I.Y., Anoprienko O.V., Slavov D.,
RA Tassone F., Rynditch A.V., Gardiner K.;
RT "Mouse homologs of human chromosome 21 genes.";
RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP ALTERNATIVE SPLICING.
RC TISSUE=Brain, and Fetal liver;
RX PubMed=11690630; DOI=10.1016/S0167-4781(01)00276-7;
RA Pucharcos C., Casas C., Nadal M., Estivill X., de la Luna S.;
RT "The human intersectin genes and their spliced variants are
RT differentially expressed.";
RL Biochim. Biophys. Acta 1521:1-11(2001).
RN [11]
RP GENE MAPPING.
RX PubMed=9465890;
RA Chen H., Antonarakis S.E.;
RT "The SH3D1A gene maps to human chromosome 21q22.1-->q22.2.";
RL Cytogenet. Cell Genet. 78:213-215(1997).
RN [12]
RP FUNCTION, INTERACTION WITH ARHGAP31, AND SUBCELLULAR LOCATION.
RX PubMed=11744688; DOI=10.1074/jbc.M105516200;
RA Jenna S., Hussain N.K., Danek E.I., Triki I., Wasiak S.,
RA McPherson P.S., Lamarche-Vane N.;
RT "The activity of the GTPase-activating protein CdGAP is regulated by
RT the endocytic protein intersectin.";
RL J. Biol. Chem. 277:6366-6373(2002).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-902 AND SER-904, AND
RP MASS SPECTROMETRY.
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 [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [15]
RP INTERACTION WITH ADAM15.
RX PubMed=19718658; DOI=10.1002/jcb.22317;
RA Kleino I., Ortiz R.M., Yritys M., Huovila A.P., Saksela K.;
RT "Alternative splicing of ADAM15 regulates its interactions with
RT cellular SH3 proteins.";
RL J. Cell. Biochem. 108:877-885(2009).
RN [16]
RP IDENTIFICATION BY 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 [17]
RP INTERACTION WITH REPS1 AND SGIP1, AND SUBCELLULAR LOCATION.
RX PubMed=20946875; DOI=10.1016/j.bbrc.2010.10.045;
RA Dergai O., Novokhatska O., Dergai M., Skrypkina I., Tsyba L.,
RA Moreau J., Rynditch A.;
RT "Intersectin 1 forms complexes with SGIP1 and Reps1 in clathrin-coated
RT pits.";
RL Biochem. Biophys. Res. Commun. 402:408-413(2010).
RN [18]
RP IDENTIFICATION BY 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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [19]
RP INTERACTION WITH FCHO2.
RX PubMed=20448150; DOI=10.1126/science.1188462;
RA Henne W.M., Boucrot E., Meinecke M., Evergren E., Vallis Y.,
RA Mittal R., McMahon H.T.;
RT "FCHo proteins are nucleators of clathrin-mediated endocytosis.";
RL Science 328:1281-1284(2010).
RN [20]
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.,
RA Buerckstuemmer T., 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 [21]
RP FUNCTION, AND INTERACTION WITH DAB2.
RX PubMed=22648170; DOI=10.1091/mbc.E11-12-1007;
RA Teckchandani A., Mulkearns E.E., Randolph T.W., Toida N., Cooper J.A.;
RT "The clathrin adaptor Dab2 recruits EH domain scaffold proteins to
RT regulate integrin beta1 endocytosis.";
RL Mol. Biol. Cell 23:2905-2916(2012).
RN [22]
RP INTERACTION WITH FCHO1.
RX PubMed=22484487; DOI=10.1038/ncb2473;
RA Umasankar P.K., Sanker S., Thieman J.R., Chakraborty S., Wendland B.,
RA Tsang M., Traub L.M.;
RT "Distinct and separable activities of the endocytic clathrin-coat
RT components Fcho1/2 and AP-2 in developmental patterning.";
RL Nat. Cell Biol. 14:488-501(2012).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1229-1581 IN COMPLEX WITH
RP CDC42, AND MUTAGENESIS OF MET-1369 AND LEU-1376.
RX PubMed=12006984; DOI=10.1038/nsb796;
RA Snyder J.T., Worthylake D.K., Rossman K.L., Betts L., Pruitt W.M.,
RA Siderovski D.P., Der C.J., Sondek J.;
RT "Structural basis for the selective activation of Rho GTPases by Dbl
RT exchange factors.";
RL Nat. Struct. Biol. 9:468-475(2002).
CC -!- FUNCTION: Adapter protein that may provide indirect link between
CC the endocytic membrane traffic and the actin assembly machinery.
CC May regulate the formation of clathrin-coated vesicles. Involved
CC in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor
CC (TFR); internalization of ITGB1 as DAB2-dependent cargo but not
CC TFR may involve association with DAB2. Isoform 1 could be involved
CC in brain-specific synaptic vesicle recycling. Inhibits ARHGAP31
CC activity toward RAC1.
CC -!- SUBUNIT: Interacts with dynamin, CDC42, SNAP25 and SNAP23.
CC Clusters several dynamin in a manner that is regulated by
CC alternative splicing. Interacts with clathrin-associated proteins
CC and other components of the endocytic machinery, such as SPIN90,
CC EPS15, EPN1, EPN2, STON2, FCHO1, FCHO2 and DAB2. Interacts (via
CC SH3 domains) with REPS1 and SGIP1. Interacts with ARHGAP31.
CC Interacts with ADAM15.
CC -!- INTERACTION:
CC P22681:CBL; NbExp=12; IntAct=EBI-602041, EBI-518228;
CC P60953-1:CDC42; NbExp=2; IntAct=EBI-602041, EBI-3625591;
CC Q9NRI5:DISC1; NbExp=3; IntAct=EBI-602041, EBI-529989;
CC P50570:DNM2; NbExp=2; IntAct=EBI-602041, EBI-346547;
CC Q3UQN2:Fcho2 (xeno); NbExp=3; IntAct=EBI-602041, EBI-6094986;
CC O15357:INPPL1; NbExp=9; IntAct=EBI-8052395, EBI-1384248;
CC Q925Q9:Sh3kbp1 (xeno); NbExp=4; IntAct=EBI-8052395, EBI-8020091;
CC -!- SUBCELLULAR LOCATION: Endomembrane system (By similarity). Cell
CC junction, synapse, synaptosome (By similarity). Cell projection,
CC lamellipodium. Membrane, clathrin-coated pit. Note=Colocalizes
CC with SGIP1 at the plasma membrane in structures corresponding most
CC problably to clathrin-coated pits (Probable).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=13;
CC Comment=Additional isoforms seem to exist. Alternative splicing
CC affects domains involved in protein recognition and thus may
CC play a role in selecting specific interactions;
CC Name=1; Synonyms=Long, ITSN-l;
CC IsoId=Q15811-1; Sequence=Displayed;
CC Name=2; Synonyms=Short, ITSN-s;
CC IsoId=Q15811-2; Sequence=VSP_004295;
CC Name=3; Synonyms=Short 2, SH3P17;
CC IsoId=Q15811-3; Sequence=VSP_004293, VSP_004294, VSP_004295;
CC Name=4;
CC IsoId=Q15811-4; Sequence=VSP_004294;
CC Name=5; Synonyms=ITSN1-22a;
CC IsoId=Q15811-5; Sequence=VSP_004293, VSP_047460, VSP_047461;
CC Name=6; Synonyms=Long form variant 4, Short form variant 11;
CC IsoId=Q15811-6; Sequence=VSP_004293, VSP_053320, VSP_053321;
CC Note=Contains a premature stop codon, potentially subjected to
CC NMD;
CC Name=7; Synonyms=Short form variant 5;
CC IsoId=Q15811-7; Sequence=VSP_004293, VSP_004295;
CC Name=8; Synonyms=Long form variant 2;
CC IsoId=Q15811-8; Sequence=VSP_004293;
CC Name=9; Synonyms=Long form variant 3;
CC IsoId=Q15811-9; Sequence=VSP_004293, VSP_053322;
CC Name=10; Synonyms=Short form variant 2;
CC IsoId=Q15811-10; Sequence=VSP_053317, VSP_004293, VSP_004295;
CC Name=11; Synonyms=Short form variant 3;
CC IsoId=Q15811-11; Sequence=VSP_053317, VSP_004294, VSP_004295;
CC Name=12; Synonyms=Short form variant 10;
CC IsoId=Q15811-12; Sequence=VSP_053317, VSP_004293, VSP_004294,
CC VSP_004295;
CC Name=13; Synonyms=Short form variant 14;
CC IsoId=Q15811-13; Sequence=VSP_004293, VSP_053318, VSP_053319;
CC Note=Contains a premature stop codon, potentially subjected to
CC NMD;
CC -!- TISSUE SPECIFICITY: Isoform 2 is ubiquitous in adult and fetal
CC tissues with high expression in skeletal muscle, heart, spleen,
CC ovary, testis and all fetal tissues tested and low expression in
CC thymus, blood, lung, liver and pancreas. Isoform 1 is expressed
CC almost exclusively in the brain, in all brain regions. Not
CC expressed in the spinal cord.
CC -!- DOMAIN: SH3-3, SH3-4 and SH3-5, but not SH3-1 and SH3-2 domains,
CC bind to dynamin (By similarity). SH3-1 and SH3-4 bind to ARHGAP31.
CC -!- DOMAIN: The KLERQ domain binds to SNAP-25 and SNAP-23 (By
CC similarity).
CC -!- SIMILARITY: Contains 1 C2 domain.
CC -!- SIMILARITY: Contains 1 DH (DBL-homology) domain.
CC -!- SIMILARITY: Contains 2 EF-hand domains.
CC -!- SIMILARITY: Contains 2 EH domains.
CC -!- SIMILARITY: Contains 1 PH domain.
CC -!- SIMILARITY: Contains 5 SH3 domains.
CC -!- CAUTION: Studies in clathrin-mediated endocytosis of ITGB1 and TFR
CC used a siRNA mixture of ISTN1 and ISTN2, and a Dab2 mutant with
CC impaired binding to EH domain-containing proteins EPS15 and ITSN1
CC suggesting a partially overlapping role of the EH domain-
CC containing proteins (PubMed:22648170).
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC50592.1; Type=Erroneous initiation;
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DR EMBL; AF064244; AAC78611.1; -; mRNA.
DR EMBL; AF064247; AAC80437.1; -; Genomic_DNA.
DR EMBL; AF064245; AAC80437.1; JOINED; Genomic_DNA.
DR EMBL; AF064246; AAC80437.1; JOINED; Genomic_DNA.
DR EMBL; AF064243; AAC78610.1; -; mRNA.
DR EMBL; AF114488; AAD29953.1; -; mRNA.
DR EMBL; AF114487; AAD29952.1; -; mRNA.
DR EMBL; DQ679756; ABG74697.1; -; mRNA.
DR EMBL; DQ679757; ABG74698.1; -; mRNA.
DR EMBL; EU117382; ABV21755.1; -; mRNA.
DR EMBL; EU140799; ABV58335.1; -; mRNA.
DR EMBL; EU140800; ABV58336.1; -; mRNA.
DR EMBL; EU120733; ABV24866.1; -; mRNA.
DR EMBL; EU120734; ABV24867.1; -; mRNA.
DR EMBL; EU120735; ABV24868.1; -; mRNA.
DR EMBL; EU152331; ABV69555.1; -; mRNA.
DR EMBL; DQ386455; ABD72328.1; -; mRNA.
DR EMBL; AK300274; BAG62034.1; -; mRNA.
DR EMBL; AP000308; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP000309; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP000310; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP000311; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP000312; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP000313; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC117560; AAI17561.1; -; mRNA.
DR EMBL; BC116186; AAI16187.1; -; mRNA.
DR EMBL; U61166; AAC50592.1; ALT_INIT; mRNA.
DR EMBL; AF180522; AAD53183.1; -; mRNA.
DR RefSeq; NP_001001132.1; NM_001001132.1.
DR RefSeq; NP_003015.2; NM_003024.2.
DR RefSeq; XP_005261083.1; XM_005261026.1.
DR RefSeq; XP_005261084.1; XM_005261027.1.
DR RefSeq; XP_005261086.1; XM_005261029.1.
DR RefSeq; XP_005261088.1; XM_005261031.1.
DR RefSeq; XP_005261089.1; XM_005261032.1.
DR UniGene; Hs.160324; -.
DR PDB; 1KI1; X-ray; 2.30 A; B/D=1229-1581.
DR PDB; 2KGR; NMR; -; A=210-312.
DR PDB; 2KHN; NMR; -; A=1-111.
DR PDB; 3FIA; X-ray; 1.45 A; A=2-111.
DR PDB; 3QBV; X-ray; 2.65 A; B/D=1229-1579.
DR PDB; 4IIM; X-ray; 1.80 A; A/B=916-970.
DR PDBsum; 1KI1; -.
DR PDBsum; 2KGR; -.
DR PDBsum; 2KHN; -.
DR PDBsum; 3FIA; -.
DR PDBsum; 3QBV; -.
DR PDBsum; 4IIM; -.
DR ProteinModelPortal; Q15811; -.
DR SMR; Q15811; 1-111, 210-312, 745-835, 916-1581, 1595-1718.
DR DIP; DIP-33609N; -.
DR IntAct; Q15811; 43.
DR MINT; MINT-130199; -.
DR STRING; 9606.ENSP00000370719; -.
DR PhosphoSite; Q15811; -.
DR DMDM; 116242596; -.
DR PaxDb; Q15811; -.
DR PRIDE; Q15811; -.
DR Ensembl; ENST00000379960; ENSP00000369294; ENSG00000205726.
DR Ensembl; ENST00000381291; ENSP00000370691; ENSG00000205726.
DR Ensembl; ENST00000381318; ENSP00000370719; ENSG00000205726.
DR Ensembl; ENST00000399326; ENSP00000382265; ENSG00000205726.
DR Ensembl; ENST00000399338; ENSP00000382275; ENSG00000205726.
DR Ensembl; ENST00000399349; ENSP00000382286; ENSG00000205726.
DR Ensembl; ENST00000399352; ENSP00000382289; ENSG00000205726.
DR Ensembl; ENST00000399353; ENSP00000382290; ENSG00000205726.
DR Ensembl; ENST00000399367; ENSP00000382301; ENSG00000205726.
DR Ensembl; ENST00000437442; ENSP00000387377; ENSG00000205726.
DR GeneID; 6453; -.
DR KEGG; hsa:6453; -.
DR UCSC; uc002ytb.1; human.
DR CTD; 6453; -.
DR GeneCards; GC21P035014; -.
DR HGNC; HGNC:6183; ITSN1.
DR HPA; HPA018007; -.
DR MIM; 602442; gene.
DR neXtProt; NX_Q15811; -.
DR PharmGKB; PA29981; -.
DR eggNOG; COG5422; -.
DR HOVERGEN; HBG052159; -.
DR InParanoid; Q15811; -.
DR OMA; VMVKGEW; -.
DR Reactome; REACT_111102; Signal Transduction.
DR SignaLink; Q15811; -.
DR EvolutionaryTrace; Q15811; -.
DR GeneWiki; ITSN1; -.
DR GenomeRNAi; 6453; -.
DR NextBio; 25083; -.
DR PRO; PR:Q15811; -.
DR ArrayExpress; Q15811; -.
DR Bgee; Q15811; -.
DR CleanEx; HS_ITSN1; -.
DR Genevestigator; Q15811; -.
DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR GO; GO:0005905; C:coated pit; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030139; C:endocytic vesicle; IEA:Ensembl.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0043005; C:neuron projection; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; NAS:UniProtKB.
DR GO; GO:0019209; F:kinase activator activity; IEA:Ensembl.
DR GO; GO:0005543; F:phospholipid binding; IEA:InterPro.
DR GO; GO:0032947; F:protein complex scaffold; IDA:UniProtKB.
DR GO; GO:0005089; F:Rho guanyl-nucleotide exchange factor activity; IEA:InterPro.
DR GO; GO:0097190; P:apoptotic signaling pathway; TAS:Reactome.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
DR GO; GO:0043065; P:positive regulation of apoptotic process; TAS:Reactome.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling cascade; IEA:Ensembl.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; TAS:Reactome.
DR GO; GO:0048488; P:synaptic vesicle endocytosis; TAS:ProtInc.
DR Gene3D; 1.10.238.10; -; 2.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR000008; C2_dom.
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; EPS15_homology.
DR InterPro; IPR001331; GDS_CDC24_CS.
DR InterPro; IPR011993; PH_like_dom.
DR InterPro; IPR001849; Pleckstrin_homology.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF00621; RhoGEF; 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; 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 junction;
KW Cell projection; Coated pit; Coiled coil; Complete proteome;
KW Endocytosis; Membrane; Metal-binding; Phosphoprotein; Polymorphism;
KW Reference proteome; Repeat; SH3 domain; Synapse; Synaptosome.
FT CHAIN 1 1721 Intersectin-1.
FT /FTId=PRO_0000080957.
FT DOMAIN 21 109 EH 1.
FT DOMAIN 53 88 EF-hand 1.
FT DOMAIN 221 310 EH 2.
FT DOMAIN 254 289 EF-hand 2.
FT DOMAIN 740 806 SH3 1.
FT DOMAIN 913 971 SH3 2.
FT DOMAIN 1002 1060 SH3 3.
FT DOMAIN 1074 1138 SH3 4.
FT DOMAIN 1155 1214 SH3 5.
FT DOMAIN 1237 1423 DH.
FT DOMAIN 1462 1571 PH.
FT DOMAIN 1583 1679 C2.
FT CA_BIND 66 77 1 (Potential).
FT CA_BIND 267 278 2 (Potential).
FT REGION 326 702 KLERQ.
FT COILED 351 705 Potential.
FT MOD_RES 203 203 Phosphoserine (By similarity).
FT MOD_RES 902 902 Phosphoserine.
FT MOD_RES 904 904 Phosphoserine.
FT MOD_RES 1137 1137 Phosphoserine (By similarity).
FT VAR_SEQ 116 152 Missing (in isoform 10, isoform 11 and
FT isoform 12).
FT /FTId=VSP_053317.
FT VAR_SEQ 770 774 Missing (in isoform 3, isoform 5, isoform
FT 6, isoform 7, isoform 8, isoform 9,
FT isoform 10, isoform 12 and isoform 13).
FT /FTId=VSP_004293.
FT VAR_SEQ 910 1025 GEKVEGLQAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWW
FT FGEVQGQKGWFPKSYVKLISGPIRKSTSMDSGSSESPASLK
FT RVASPAAKPVVSGEEFIAMYTYESSEQGDLTFQQ -> PDF
FT LLHPSMRLGHMQPRIVLLFPDPLQCSTSRLLPMLRPRPGVP
FT FLRSPSCQSPSHPSRPISDAAPSVKFTLMPPGRIHPCFLFI
FT PAVNSRNSFLVYFILPGGTLGCFYLCLPHYL (in
FT isoform 5).
FT /FTId=VSP_047460.
FT VAR_SEQ 910 919 GEKVEGLQAQ -> HGFWFFRESC (in isoform 13).
FT /FTId=VSP_053318.
FT VAR_SEQ 920 1721 Missing (in isoform 13).
FT /FTId=VSP_053319.
FT VAR_SEQ 1006 1076 Missing (in isoform 3, isoform 4, isoform
FT 11 and isoform 12).
FT /FTId=VSP_004294.
FT VAR_SEQ 1006 1020 EFIAMYTYESSEQGD -> GLWNCWENREFRKKT (in
FT isoform 6).
FT /FTId=VSP_053320.
FT VAR_SEQ 1021 1721 Missing (in isoform 6).
FT /FTId=VSP_053321.
FT VAR_SEQ 1026 1721 Missing (in isoform 5).
FT /FTId=VSP_047461.
FT VAR_SEQ 1221 1721 Missing (in isoform 2, isoform 3, isoform
FT 7, isoform 10, isoform 11 and isoform
FT 12).
FT /FTId=VSP_004295.
FT VAR_SEQ 1392 1447 Missing (in isoform 9).
FT /FTId=VSP_053322.
FT VARIANT 1137 1137 S -> N (in dbSNP:rs187895245).
FT /FTId=VAR_070011.
FT MUTAGEN 1369 1369 M->L: Decreases specificity for CDC42;
FT when associated with I-1376.
FT MUTAGEN 1376 1376 L->I: Decreases specificity for CDC42;
FT when associated with L-1369.
FT CONFLICT 114 114 A -> P (in Ref. 1; AAC78610/AAC78611 and
FT 3; ABG74697/ABG74698).
FT CONFLICT 863 863 E -> G (in Ref. 4; ABD72328).
FT CONFLICT 1088 1088 T -> A (in Ref. 9; AAD53183).
FT CONFLICT 1109 1109 G -> R (in Ref. 9; AAD53183).
FT CONFLICT 1361 1361 A -> E (in Ref. 1; AAC78611 and 8;
FT AAC50592).
FT CONFLICT 1367 1367 K -> R (in Ref. 7; AAI16187).
FT CONFLICT 1474 1474 S -> N (in Ref. 1; AAC78611 and 8;
FT AAC50592).
FT TURN 12 14
FT HELIX 19 31
FT STRAND 35 37
FT STRAND 38 40
FT HELIX 41 48
FT HELIX 49 51
FT HELIX 55 65
FT STRAND 70 73
FT HELIX 75 89
FT HELIX 100 102
FT STRAND 215 217
FT HELIX 219 230
FT STRAND 239 241
FT HELIX 242 250
FT HELIX 256 266
FT STRAND 272 275
FT HELIX 276 290
FT HELIX 301 303
FT TURN 306 309
FT STRAND 916 922
FT STRAND 939 945
FT STRAND 947 954
FT STRAND 957 962
FT HELIX 963 965
FT STRAND 966 969
FT HELIX 1233 1262
FT HELIX 1264 1269
FT STRAND 1271 1273
FT HELIX 1275 1282
FT HELIX 1285 1306
FT STRAND 1308 1310
FT HELIX 1316 1322
FT HELIX 1323 1327
FT HELIX 1328 1349
FT HELIX 1351 1361
FT HELIX 1364 1366
FT HELIX 1371 1374
FT HELIX 1377 1393
FT HELIX 1403 1437
FT STRAND 1451 1454
FT STRAND 1456 1460
FT STRAND 1463 1466
FT STRAND 1472 1474
FT STRAND 1479 1493
FT STRAND 1511 1513
FT HELIX 1522 1524
FT STRAND 1525 1528
FT STRAND 1531 1533
FT STRAND 1541 1544
FT STRAND 1547 1550
FT HELIX 1556 1577
SQ SEQUENCE 1721 AA; 195422 MW; FC4DE644D8BEA2BE CRC64;
MAQFPTPFGG SLDIWAITVE ERAKHDQQFH SLKPISGFIT GDQARNFFFQ SGLPQPVLAQ
IWALADMNND GRMDQVEFSI AMKLIKLKLQ GYQLPSALPP VMKQQPVAIS SAPAFGMGGI
ASMPPLTAVA PVPMGSIPVV GMSPTLVSSV PTAAVPPLAN GAPPVIQPLP AFAHPAATLP
KSSSFSRSGP GSQLNTKLQK AQSFDVASVP PVAEWAVPQS SRLKYRQLFN SHDKTMSGHL
TGPQARTILM QSSLPQAQLA SIWNLSDIDQ DGKLTAEEFI LAMHLIDVAM SGQPLPPVLP
PEYIPPSFRR VRSGSGISVI SSTSVDQRLP EEPVLEDEQQ QLEKKLPVTF EDKKRENFER
GNLELEKRRQ ALLEQQRKEQ ERLAQLERAE QERKERERQE QERKRQLELE KQLEKQRELE
RQREEERRKE IERREAAKRE LERQRQLEWE RNRRQELLNQ RNKEQEDIVV LKAKKKTLEF
ELEALNDKKH QLEGKLQDIR CRLTTQRQEI ESTNKSRELR IAEITHLQQQ LQESQQMLGR
LIPEKQILND QLKQVQQNSL HRDSLVTLKR ALEAKELARQ HLRDQLDEVE KETRSKLQEI
DIFNNQLKEL REIHNKQQLQ KQKSMEAERL KQKEQERKII ELEKQKEEAQ RRAQERDKQW
LEHVQQEDEH QRPRKLHEEE KLKREESVKK KDGEEKGKQE AQDKLGRLFH QHQEPAKPAV
QAPWSTAEKG PLTISAQENV KVVYYRALYP FESRSHDEIT IQPGDIVMVK GEWVDESQTG
EPGWLGGELK GKTGWFPANY AEKIPENEVP APVKPVTDST SAPAPKLALR ETPAPLAVTS
SEPSTTPNNW ADFSSTWPTS TNEKPETDNW DAWAAQPSLT VPSAGQLRQR SAFTPATATG
SSPSPVLGQG EKVEGLQAQA LYPWRAKKDN HLNFNKNDVI TVLEQQDMWW FGEVQGQKGW
FPKSYVKLIS GPIRKSTSMD SGSSESPASL KRVASPAAKP VVSGEEFIAM YTYESSEQGD
LTFQQGDVIL VTKKDGDWWT GTVGDKAGVF PSNYVRLKDS EGSGTAGKTG SLGKKPEIAQ
VIASYTATGP EQLTLAPGQL ILIRKKNPGG WWEGELQARG KKRQIGWFPA NYVKLLSPGT
SKITPTEPPK STALAAVCQV IGMYDYTAQN DDELAFNKGQ IINVLNKEDP DWWKGEVNGQ
VGLFPSNYVK LTTDMDPSQQ WCSDLHLLDM LTPTERKRQG YIHELIVTEE NYVNDLQLVT
EIFQKPLMES ELLTEKEVAM IFVNWKELIM CNIKLLKALR VRKKMSGEKM PVKMIGDILS
AQLPHMQPYI RFCSRQLNGA ALIQQKTDEA PDFKEFVKRL AMDPRCKGMP LSSFILKPMQ
RVTRYPLIIK NILENTPENH PDHSHLKHAL EKAEELCSQV NEGVREKENS DRLEWIQAHV
QCEGLSEQLV FNSVTNCLGP RKFLHSGKLY KAKSNKELYG FLFNDFLLLT QITKPLGSSG
TDKVFSPKSN LQYKMYKTPI FLNEVLVKLP TDPSGDEPIF HISHIDRVYT LRAESINERT
AWVQKIKAAS ELYIETEKKK REKAYLVRSQ RATGIGRLMV NVVEGIELKP CRSHGKSNPY
CEVTMGSQCH ITKTIQDTLN PKWNSNCQFF IRDLEQEVLC ITVFERDQFS PDDFLGRTEI
RVADIKKDQG SKGPVTKCLL LHEVPTGEIV VRLDLQLFDE P
//
ID ITSN1_HUMAN Reviewed; 1721 AA.
AC Q15811; A7Y322; A8CTX8; A8CTY3; A8CTY7; A8D7D0; A8DCP3; B4DTM2;
read moreAC E7ERJ1; E9PE44; E9PG01; E9PHV2; O95216; Q0PW94; Q0PW95; Q14BD3;
AC Q1ED40; Q20BK3; Q9UET5; Q9UK60; Q9UNK1; Q9UNK2; Q9UQ92;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 22-JAN-2014, entry version 149.
DE RecName: Full=Intersectin-1;
DE AltName: Full=SH3 domain-containing protein 1A;
DE AltName: Full=SH3P17;
GN Name=ITSN1; Synonyms=ITSN, SH3D1A;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), AND
RP VARIANT ASN-1137.
RC TISSUE=Fetal brain;
RX PubMed=9799604; DOI=10.1006/geno.1998.5521;
RA Guipponi M., Scott H.S., Chen H., Schebesta A., Rossier C.,
RA Antonarakis S.E.;
RT "Two isoforms of a human intersectin (ITSN) protein are produced by
RT brain-specific alternative splicing in a stop codon.";
RL Genomics 53:369-376(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX PubMed=10482960; DOI=10.1038/sj.ejhg.5200356;
RA Pucharcos C., Fuentes J.-J., Casas C., de la Luna S., Alcantara S.,
RA Arbones M.L., Soriano E., Estivill X., Pritchard M.;
RT "Alu-splice cloning of human intersectin (ITSN), a putative
RT multivalent binding protein expressed in proliferating and
RT differentiating neurons and overexpressed in Down syndrome.";
RL Eur. J. Hum. Genet. 7:704-712(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 6; 7; 8; 9; 10; 11 AND 12),
RP VARIANT ASN-1137, AND ALTERNATIVE SPLICING.
RC TISSUE=Brain, and Lung;
RX PubMed=19777371; DOI=10.1007/s11033-009-9824-8;
RA Kropyvko S., Gerasymchuk D., Skrypkina I., Dergai M., Dergai O.,
RA Nikolaienko O., Rynditch A., Tsyba L.;
RT "Structural diversity and differential expression of novel human
RT intersectin 1 isoforms.";
RL Mol. Biol. Rep. 37:2789-2796(2010).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
RC TISSUE=Kidney;
RX PubMed=21712076; DOI=10.1016/j.gene.2011.06.021;
RA Dergai M., Skrypkina I., Dergai O., Tsyba L., Novokhatska O.,
RA Filonenko V., Drobot L., Rynditch A.;
RT "Identification and characterization of a novel mammalian isoform of
RT the endocytic adaptor ITSN1.";
RL Gene 485:120-129(2011).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7).
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
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.,
RA Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y.,
RA Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K.,
RA Polley A., Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D.,
RA Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W.,
RA Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S.,
RA Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E.,
RA Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P.,
RA Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H.,
RA Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E.,
RA Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F.,
RA Lehrach H., Reinhardt R., Yaspo M.-L.;
RT "The DNA sequence of human chromosome 21.";
RL Nature 405:311-319(2000).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Embryonic stem cell;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 620-1721 (ISOFORM 3).
RC TISSUE=Bone marrow;
RX PubMed=9630982; DOI=10.1038/nbt0696-741;
RA Sparks A.B., Hoffman N.G., McConnell S.J., Fowlkes D.M., Kay B.K.;
RT "Cloning of ligand targets: systematic isolation of SH3 domain-
RT containing proteins.";
RL Nat. Biotechnol. 14:741-744(1996).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 963-1721 (ISOFORM 3).
RC TISSUE=Brain;
RA Tsyba L.O., Kvasha S.M., Skripkina I.Y., Anoprienko O.V., Slavov D.,
RA Tassone F., Rynditch A.V., Gardiner K.;
RT "Mouse homologs of human chromosome 21 genes.";
RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP ALTERNATIVE SPLICING.
RC TISSUE=Brain, and Fetal liver;
RX PubMed=11690630; DOI=10.1016/S0167-4781(01)00276-7;
RA Pucharcos C., Casas C., Nadal M., Estivill X., de la Luna S.;
RT "The human intersectin genes and their spliced variants are
RT differentially expressed.";
RL Biochim. Biophys. Acta 1521:1-11(2001).
RN [11]
RP GENE MAPPING.
RX PubMed=9465890;
RA Chen H., Antonarakis S.E.;
RT "The SH3D1A gene maps to human chromosome 21q22.1-->q22.2.";
RL Cytogenet. Cell Genet. 78:213-215(1997).
RN [12]
RP FUNCTION, INTERACTION WITH ARHGAP31, AND SUBCELLULAR LOCATION.
RX PubMed=11744688; DOI=10.1074/jbc.M105516200;
RA Jenna S., Hussain N.K., Danek E.I., Triki I., Wasiak S.,
RA McPherson P.S., Lamarche-Vane N.;
RT "The activity of the GTPase-activating protein CdGAP is regulated by
RT the endocytic protein intersectin.";
RL J. Biol. Chem. 277:6366-6373(2002).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-902 AND SER-904, AND
RP MASS SPECTROMETRY.
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 [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [15]
RP INTERACTION WITH ADAM15.
RX PubMed=19718658; DOI=10.1002/jcb.22317;
RA Kleino I., Ortiz R.M., Yritys M., Huovila A.P., Saksela K.;
RT "Alternative splicing of ADAM15 regulates its interactions with
RT cellular SH3 proteins.";
RL J. Cell. Biochem. 108:877-885(2009).
RN [16]
RP IDENTIFICATION BY 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 [17]
RP INTERACTION WITH REPS1 AND SGIP1, AND SUBCELLULAR LOCATION.
RX PubMed=20946875; DOI=10.1016/j.bbrc.2010.10.045;
RA Dergai O., Novokhatska O., Dergai M., Skrypkina I., Tsyba L.,
RA Moreau J., Rynditch A.;
RT "Intersectin 1 forms complexes with SGIP1 and Reps1 in clathrin-coated
RT pits.";
RL Biochem. Biophys. Res. Commun. 402:408-413(2010).
RN [18]
RP IDENTIFICATION BY 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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [19]
RP INTERACTION WITH FCHO2.
RX PubMed=20448150; DOI=10.1126/science.1188462;
RA Henne W.M., Boucrot E., Meinecke M., Evergren E., Vallis Y.,
RA Mittal R., McMahon H.T.;
RT "FCHo proteins are nucleators of clathrin-mediated endocytosis.";
RL Science 328:1281-1284(2010).
RN [20]
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.,
RA Buerckstuemmer T., 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 [21]
RP FUNCTION, AND INTERACTION WITH DAB2.
RX PubMed=22648170; DOI=10.1091/mbc.E11-12-1007;
RA Teckchandani A., Mulkearns E.E., Randolph T.W., Toida N., Cooper J.A.;
RT "The clathrin adaptor Dab2 recruits EH domain scaffold proteins to
RT regulate integrin beta1 endocytosis.";
RL Mol. Biol. Cell 23:2905-2916(2012).
RN [22]
RP INTERACTION WITH FCHO1.
RX PubMed=22484487; DOI=10.1038/ncb2473;
RA Umasankar P.K., Sanker S., Thieman J.R., Chakraborty S., Wendland B.,
RA Tsang M., Traub L.M.;
RT "Distinct and separable activities of the endocytic clathrin-coat
RT components Fcho1/2 and AP-2 in developmental patterning.";
RL Nat. Cell Biol. 14:488-501(2012).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1229-1581 IN COMPLEX WITH
RP CDC42, AND MUTAGENESIS OF MET-1369 AND LEU-1376.
RX PubMed=12006984; DOI=10.1038/nsb796;
RA Snyder J.T., Worthylake D.K., Rossman K.L., Betts L., Pruitt W.M.,
RA Siderovski D.P., Der C.J., Sondek J.;
RT "Structural basis for the selective activation of Rho GTPases by Dbl
RT exchange factors.";
RL Nat. Struct. Biol. 9:468-475(2002).
CC -!- FUNCTION: Adapter protein that may provide indirect link between
CC the endocytic membrane traffic and the actin assembly machinery.
CC May regulate the formation of clathrin-coated vesicles. Involved
CC in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor
CC (TFR); internalization of ITGB1 as DAB2-dependent cargo but not
CC TFR may involve association with DAB2. Isoform 1 could be involved
CC in brain-specific synaptic vesicle recycling. Inhibits ARHGAP31
CC activity toward RAC1.
CC -!- SUBUNIT: Interacts with dynamin, CDC42, SNAP25 and SNAP23.
CC Clusters several dynamin in a manner that is regulated by
CC alternative splicing. Interacts with clathrin-associated proteins
CC and other components of the endocytic machinery, such as SPIN90,
CC EPS15, EPN1, EPN2, STON2, FCHO1, FCHO2 and DAB2. Interacts (via
CC SH3 domains) with REPS1 and SGIP1. Interacts with ARHGAP31.
CC Interacts with ADAM15.
CC -!- INTERACTION:
CC P22681:CBL; NbExp=12; IntAct=EBI-602041, EBI-518228;
CC P60953-1:CDC42; NbExp=2; IntAct=EBI-602041, EBI-3625591;
CC Q9NRI5:DISC1; NbExp=3; IntAct=EBI-602041, EBI-529989;
CC P50570:DNM2; NbExp=2; IntAct=EBI-602041, EBI-346547;
CC Q3UQN2:Fcho2 (xeno); NbExp=3; IntAct=EBI-602041, EBI-6094986;
CC O15357:INPPL1; NbExp=9; IntAct=EBI-8052395, EBI-1384248;
CC Q925Q9:Sh3kbp1 (xeno); NbExp=4; IntAct=EBI-8052395, EBI-8020091;
CC -!- SUBCELLULAR LOCATION: Endomembrane system (By similarity). Cell
CC junction, synapse, synaptosome (By similarity). Cell projection,
CC lamellipodium. Membrane, clathrin-coated pit. Note=Colocalizes
CC with SGIP1 at the plasma membrane in structures corresponding most
CC problably to clathrin-coated pits (Probable).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=13;
CC Comment=Additional isoforms seem to exist. Alternative splicing
CC affects domains involved in protein recognition and thus may
CC play a role in selecting specific interactions;
CC Name=1; Synonyms=Long, ITSN-l;
CC IsoId=Q15811-1; Sequence=Displayed;
CC Name=2; Synonyms=Short, ITSN-s;
CC IsoId=Q15811-2; Sequence=VSP_004295;
CC Name=3; Synonyms=Short 2, SH3P17;
CC IsoId=Q15811-3; Sequence=VSP_004293, VSP_004294, VSP_004295;
CC Name=4;
CC IsoId=Q15811-4; Sequence=VSP_004294;
CC Name=5; Synonyms=ITSN1-22a;
CC IsoId=Q15811-5; Sequence=VSP_004293, VSP_047460, VSP_047461;
CC Name=6; Synonyms=Long form variant 4, Short form variant 11;
CC IsoId=Q15811-6; Sequence=VSP_004293, VSP_053320, VSP_053321;
CC Note=Contains a premature stop codon, potentially subjected to
CC NMD;
CC Name=7; Synonyms=Short form variant 5;
CC IsoId=Q15811-7; Sequence=VSP_004293, VSP_004295;
CC Name=8; Synonyms=Long form variant 2;
CC IsoId=Q15811-8; Sequence=VSP_004293;
CC Name=9; Synonyms=Long form variant 3;
CC IsoId=Q15811-9; Sequence=VSP_004293, VSP_053322;
CC Name=10; Synonyms=Short form variant 2;
CC IsoId=Q15811-10; Sequence=VSP_053317, VSP_004293, VSP_004295;
CC Name=11; Synonyms=Short form variant 3;
CC IsoId=Q15811-11; Sequence=VSP_053317, VSP_004294, VSP_004295;
CC Name=12; Synonyms=Short form variant 10;
CC IsoId=Q15811-12; Sequence=VSP_053317, VSP_004293, VSP_004294,
CC VSP_004295;
CC Name=13; Synonyms=Short form variant 14;
CC IsoId=Q15811-13; Sequence=VSP_004293, VSP_053318, VSP_053319;
CC Note=Contains a premature stop codon, potentially subjected to
CC NMD;
CC -!- TISSUE SPECIFICITY: Isoform 2 is ubiquitous in adult and fetal
CC tissues with high expression in skeletal muscle, heart, spleen,
CC ovary, testis and all fetal tissues tested and low expression in
CC thymus, blood, lung, liver and pancreas. Isoform 1 is expressed
CC almost exclusively in the brain, in all brain regions. Not
CC expressed in the spinal cord.
CC -!- DOMAIN: SH3-3, SH3-4 and SH3-5, but not SH3-1 and SH3-2 domains,
CC bind to dynamin (By similarity). SH3-1 and SH3-4 bind to ARHGAP31.
CC -!- DOMAIN: The KLERQ domain binds to SNAP-25 and SNAP-23 (By
CC similarity).
CC -!- SIMILARITY: Contains 1 C2 domain.
CC -!- SIMILARITY: Contains 1 DH (DBL-homology) domain.
CC -!- SIMILARITY: Contains 2 EF-hand domains.
CC -!- SIMILARITY: Contains 2 EH domains.
CC -!- SIMILARITY: Contains 1 PH domain.
CC -!- SIMILARITY: Contains 5 SH3 domains.
CC -!- CAUTION: Studies in clathrin-mediated endocytosis of ITGB1 and TFR
CC used a siRNA mixture of ISTN1 and ISTN2, and a Dab2 mutant with
CC impaired binding to EH domain-containing proteins EPS15 and ITSN1
CC suggesting a partially overlapping role of the EH domain-
CC containing proteins (PubMed:22648170).
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC50592.1; Type=Erroneous initiation;
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DR EMBL; AF064244; AAC78611.1; -; mRNA.
DR EMBL; AF064247; AAC80437.1; -; Genomic_DNA.
DR EMBL; AF064245; AAC80437.1; JOINED; Genomic_DNA.
DR EMBL; AF064246; AAC80437.1; JOINED; Genomic_DNA.
DR EMBL; AF064243; AAC78610.1; -; mRNA.
DR EMBL; AF114488; AAD29953.1; -; mRNA.
DR EMBL; AF114487; AAD29952.1; -; mRNA.
DR EMBL; DQ679756; ABG74697.1; -; mRNA.
DR EMBL; DQ679757; ABG74698.1; -; mRNA.
DR EMBL; EU117382; ABV21755.1; -; mRNA.
DR EMBL; EU140799; ABV58335.1; -; mRNA.
DR EMBL; EU140800; ABV58336.1; -; mRNA.
DR EMBL; EU120733; ABV24866.1; -; mRNA.
DR EMBL; EU120734; ABV24867.1; -; mRNA.
DR EMBL; EU120735; ABV24868.1; -; mRNA.
DR EMBL; EU152331; ABV69555.1; -; mRNA.
DR EMBL; DQ386455; ABD72328.1; -; mRNA.
DR EMBL; AK300274; BAG62034.1; -; mRNA.
DR EMBL; AP000308; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP000309; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP000310; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP000311; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP000312; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP000313; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC117560; AAI17561.1; -; mRNA.
DR EMBL; BC116186; AAI16187.1; -; mRNA.
DR EMBL; U61166; AAC50592.1; ALT_INIT; mRNA.
DR EMBL; AF180522; AAD53183.1; -; mRNA.
DR RefSeq; NP_001001132.1; NM_001001132.1.
DR RefSeq; NP_003015.2; NM_003024.2.
DR RefSeq; XP_005261083.1; XM_005261026.1.
DR RefSeq; XP_005261084.1; XM_005261027.1.
DR RefSeq; XP_005261086.1; XM_005261029.1.
DR RefSeq; XP_005261088.1; XM_005261031.1.
DR RefSeq; XP_005261089.1; XM_005261032.1.
DR UniGene; Hs.160324; -.
DR PDB; 1KI1; X-ray; 2.30 A; B/D=1229-1581.
DR PDB; 2KGR; NMR; -; A=210-312.
DR PDB; 2KHN; NMR; -; A=1-111.
DR PDB; 3FIA; X-ray; 1.45 A; A=2-111.
DR PDB; 3QBV; X-ray; 2.65 A; B/D=1229-1579.
DR PDB; 4IIM; X-ray; 1.80 A; A/B=916-970.
DR PDBsum; 1KI1; -.
DR PDBsum; 2KGR; -.
DR PDBsum; 2KHN; -.
DR PDBsum; 3FIA; -.
DR PDBsum; 3QBV; -.
DR PDBsum; 4IIM; -.
DR ProteinModelPortal; Q15811; -.
DR SMR; Q15811; 1-111, 210-312, 745-835, 916-1581, 1595-1718.
DR DIP; DIP-33609N; -.
DR IntAct; Q15811; 43.
DR MINT; MINT-130199; -.
DR STRING; 9606.ENSP00000370719; -.
DR PhosphoSite; Q15811; -.
DR DMDM; 116242596; -.
DR PaxDb; Q15811; -.
DR PRIDE; Q15811; -.
DR Ensembl; ENST00000379960; ENSP00000369294; ENSG00000205726.
DR Ensembl; ENST00000381291; ENSP00000370691; ENSG00000205726.
DR Ensembl; ENST00000381318; ENSP00000370719; ENSG00000205726.
DR Ensembl; ENST00000399326; ENSP00000382265; ENSG00000205726.
DR Ensembl; ENST00000399338; ENSP00000382275; ENSG00000205726.
DR Ensembl; ENST00000399349; ENSP00000382286; ENSG00000205726.
DR Ensembl; ENST00000399352; ENSP00000382289; ENSG00000205726.
DR Ensembl; ENST00000399353; ENSP00000382290; ENSG00000205726.
DR Ensembl; ENST00000399367; ENSP00000382301; ENSG00000205726.
DR Ensembl; ENST00000437442; ENSP00000387377; ENSG00000205726.
DR GeneID; 6453; -.
DR KEGG; hsa:6453; -.
DR UCSC; uc002ytb.1; human.
DR CTD; 6453; -.
DR GeneCards; GC21P035014; -.
DR HGNC; HGNC:6183; ITSN1.
DR HPA; HPA018007; -.
DR MIM; 602442; gene.
DR neXtProt; NX_Q15811; -.
DR PharmGKB; PA29981; -.
DR eggNOG; COG5422; -.
DR HOVERGEN; HBG052159; -.
DR InParanoid; Q15811; -.
DR OMA; VMVKGEW; -.
DR Reactome; REACT_111102; Signal Transduction.
DR SignaLink; Q15811; -.
DR EvolutionaryTrace; Q15811; -.
DR GeneWiki; ITSN1; -.
DR GenomeRNAi; 6453; -.
DR NextBio; 25083; -.
DR PRO; PR:Q15811; -.
DR ArrayExpress; Q15811; -.
DR Bgee; Q15811; -.
DR CleanEx; HS_ITSN1; -.
DR Genevestigator; Q15811; -.
DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR GO; GO:0005905; C:coated pit; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030139; C:endocytic vesicle; IEA:Ensembl.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0043005; C:neuron projection; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; NAS:UniProtKB.
DR GO; GO:0019209; F:kinase activator activity; IEA:Ensembl.
DR GO; GO:0005543; F:phospholipid binding; IEA:InterPro.
DR GO; GO:0032947; F:protein complex scaffold; IDA:UniProtKB.
DR GO; GO:0005089; F:Rho guanyl-nucleotide exchange factor activity; IEA:InterPro.
DR GO; GO:0097190; P:apoptotic signaling pathway; TAS:Reactome.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
DR GO; GO:0043065; P:positive regulation of apoptotic process; TAS:Reactome.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling cascade; IEA:Ensembl.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; TAS:Reactome.
DR GO; GO:0048488; P:synaptic vesicle endocytosis; TAS:ProtInc.
DR Gene3D; 1.10.238.10; -; 2.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR000008; C2_dom.
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; EPS15_homology.
DR InterPro; IPR001331; GDS_CDC24_CS.
DR InterPro; IPR011993; PH_like_dom.
DR InterPro; IPR001849; Pleckstrin_homology.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF00621; RhoGEF; 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; 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 junction;
KW Cell projection; Coated pit; Coiled coil; Complete proteome;
KW Endocytosis; Membrane; Metal-binding; Phosphoprotein; Polymorphism;
KW Reference proteome; Repeat; SH3 domain; Synapse; Synaptosome.
FT CHAIN 1 1721 Intersectin-1.
FT /FTId=PRO_0000080957.
FT DOMAIN 21 109 EH 1.
FT DOMAIN 53 88 EF-hand 1.
FT DOMAIN 221 310 EH 2.
FT DOMAIN 254 289 EF-hand 2.
FT DOMAIN 740 806 SH3 1.
FT DOMAIN 913 971 SH3 2.
FT DOMAIN 1002 1060 SH3 3.
FT DOMAIN 1074 1138 SH3 4.
FT DOMAIN 1155 1214 SH3 5.
FT DOMAIN 1237 1423 DH.
FT DOMAIN 1462 1571 PH.
FT DOMAIN 1583 1679 C2.
FT CA_BIND 66 77 1 (Potential).
FT CA_BIND 267 278 2 (Potential).
FT REGION 326 702 KLERQ.
FT COILED 351 705 Potential.
FT MOD_RES 203 203 Phosphoserine (By similarity).
FT MOD_RES 902 902 Phosphoserine.
FT MOD_RES 904 904 Phosphoserine.
FT MOD_RES 1137 1137 Phosphoserine (By similarity).
FT VAR_SEQ 116 152 Missing (in isoform 10, isoform 11 and
FT isoform 12).
FT /FTId=VSP_053317.
FT VAR_SEQ 770 774 Missing (in isoform 3, isoform 5, isoform
FT 6, isoform 7, isoform 8, isoform 9,
FT isoform 10, isoform 12 and isoform 13).
FT /FTId=VSP_004293.
FT VAR_SEQ 910 1025 GEKVEGLQAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWW
FT FGEVQGQKGWFPKSYVKLISGPIRKSTSMDSGSSESPASLK
FT RVASPAAKPVVSGEEFIAMYTYESSEQGDLTFQQ -> PDF
FT LLHPSMRLGHMQPRIVLLFPDPLQCSTSRLLPMLRPRPGVP
FT FLRSPSCQSPSHPSRPISDAAPSVKFTLMPPGRIHPCFLFI
FT PAVNSRNSFLVYFILPGGTLGCFYLCLPHYL (in
FT isoform 5).
FT /FTId=VSP_047460.
FT VAR_SEQ 910 919 GEKVEGLQAQ -> HGFWFFRESC (in isoform 13).
FT /FTId=VSP_053318.
FT VAR_SEQ 920 1721 Missing (in isoform 13).
FT /FTId=VSP_053319.
FT VAR_SEQ 1006 1076 Missing (in isoform 3, isoform 4, isoform
FT 11 and isoform 12).
FT /FTId=VSP_004294.
FT VAR_SEQ 1006 1020 EFIAMYTYESSEQGD -> GLWNCWENREFRKKT (in
FT isoform 6).
FT /FTId=VSP_053320.
FT VAR_SEQ 1021 1721 Missing (in isoform 6).
FT /FTId=VSP_053321.
FT VAR_SEQ 1026 1721 Missing (in isoform 5).
FT /FTId=VSP_047461.
FT VAR_SEQ 1221 1721 Missing (in isoform 2, isoform 3, isoform
FT 7, isoform 10, isoform 11 and isoform
FT 12).
FT /FTId=VSP_004295.
FT VAR_SEQ 1392 1447 Missing (in isoform 9).
FT /FTId=VSP_053322.
FT VARIANT 1137 1137 S -> N (in dbSNP:rs187895245).
FT /FTId=VAR_070011.
FT MUTAGEN 1369 1369 M->L: Decreases specificity for CDC42;
FT when associated with I-1376.
FT MUTAGEN 1376 1376 L->I: Decreases specificity for CDC42;
FT when associated with L-1369.
FT CONFLICT 114 114 A -> P (in Ref. 1; AAC78610/AAC78611 and
FT 3; ABG74697/ABG74698).
FT CONFLICT 863 863 E -> G (in Ref. 4; ABD72328).
FT CONFLICT 1088 1088 T -> A (in Ref. 9; AAD53183).
FT CONFLICT 1109 1109 G -> R (in Ref. 9; AAD53183).
FT CONFLICT 1361 1361 A -> E (in Ref. 1; AAC78611 and 8;
FT AAC50592).
FT CONFLICT 1367 1367 K -> R (in Ref. 7; AAI16187).
FT CONFLICT 1474 1474 S -> N (in Ref. 1; AAC78611 and 8;
FT AAC50592).
FT TURN 12 14
FT HELIX 19 31
FT STRAND 35 37
FT STRAND 38 40
FT HELIX 41 48
FT HELIX 49 51
FT HELIX 55 65
FT STRAND 70 73
FT HELIX 75 89
FT HELIX 100 102
FT STRAND 215 217
FT HELIX 219 230
FT STRAND 239 241
FT HELIX 242 250
FT HELIX 256 266
FT STRAND 272 275
FT HELIX 276 290
FT HELIX 301 303
FT TURN 306 309
FT STRAND 916 922
FT STRAND 939 945
FT STRAND 947 954
FT STRAND 957 962
FT HELIX 963 965
FT STRAND 966 969
FT HELIX 1233 1262
FT HELIX 1264 1269
FT STRAND 1271 1273
FT HELIX 1275 1282
FT HELIX 1285 1306
FT STRAND 1308 1310
FT HELIX 1316 1322
FT HELIX 1323 1327
FT HELIX 1328 1349
FT HELIX 1351 1361
FT HELIX 1364 1366
FT HELIX 1371 1374
FT HELIX 1377 1393
FT HELIX 1403 1437
FT STRAND 1451 1454
FT STRAND 1456 1460
FT STRAND 1463 1466
FT STRAND 1472 1474
FT STRAND 1479 1493
FT STRAND 1511 1513
FT HELIX 1522 1524
FT STRAND 1525 1528
FT STRAND 1531 1533
FT STRAND 1541 1544
FT STRAND 1547 1550
FT HELIX 1556 1577
SQ SEQUENCE 1721 AA; 195422 MW; FC4DE644D8BEA2BE CRC64;
MAQFPTPFGG SLDIWAITVE ERAKHDQQFH SLKPISGFIT GDQARNFFFQ SGLPQPVLAQ
IWALADMNND GRMDQVEFSI AMKLIKLKLQ GYQLPSALPP VMKQQPVAIS SAPAFGMGGI
ASMPPLTAVA PVPMGSIPVV GMSPTLVSSV PTAAVPPLAN GAPPVIQPLP AFAHPAATLP
KSSSFSRSGP GSQLNTKLQK AQSFDVASVP PVAEWAVPQS SRLKYRQLFN SHDKTMSGHL
TGPQARTILM QSSLPQAQLA SIWNLSDIDQ DGKLTAEEFI LAMHLIDVAM SGQPLPPVLP
PEYIPPSFRR VRSGSGISVI SSTSVDQRLP EEPVLEDEQQ QLEKKLPVTF EDKKRENFER
GNLELEKRRQ ALLEQQRKEQ ERLAQLERAE QERKERERQE QERKRQLELE KQLEKQRELE
RQREEERRKE IERREAAKRE LERQRQLEWE RNRRQELLNQ RNKEQEDIVV LKAKKKTLEF
ELEALNDKKH QLEGKLQDIR CRLTTQRQEI ESTNKSRELR IAEITHLQQQ LQESQQMLGR
LIPEKQILND QLKQVQQNSL HRDSLVTLKR ALEAKELARQ HLRDQLDEVE KETRSKLQEI
DIFNNQLKEL REIHNKQQLQ KQKSMEAERL KQKEQERKII ELEKQKEEAQ RRAQERDKQW
LEHVQQEDEH QRPRKLHEEE KLKREESVKK KDGEEKGKQE AQDKLGRLFH QHQEPAKPAV
QAPWSTAEKG PLTISAQENV KVVYYRALYP FESRSHDEIT IQPGDIVMVK GEWVDESQTG
EPGWLGGELK GKTGWFPANY AEKIPENEVP APVKPVTDST SAPAPKLALR ETPAPLAVTS
SEPSTTPNNW ADFSSTWPTS TNEKPETDNW DAWAAQPSLT VPSAGQLRQR SAFTPATATG
SSPSPVLGQG EKVEGLQAQA LYPWRAKKDN HLNFNKNDVI TVLEQQDMWW FGEVQGQKGW
FPKSYVKLIS GPIRKSTSMD SGSSESPASL KRVASPAAKP VVSGEEFIAM YTYESSEQGD
LTFQQGDVIL VTKKDGDWWT GTVGDKAGVF PSNYVRLKDS EGSGTAGKTG SLGKKPEIAQ
VIASYTATGP EQLTLAPGQL ILIRKKNPGG WWEGELQARG KKRQIGWFPA NYVKLLSPGT
SKITPTEPPK STALAAVCQV IGMYDYTAQN DDELAFNKGQ IINVLNKEDP DWWKGEVNGQ
VGLFPSNYVK LTTDMDPSQQ WCSDLHLLDM LTPTERKRQG YIHELIVTEE NYVNDLQLVT
EIFQKPLMES ELLTEKEVAM IFVNWKELIM CNIKLLKALR VRKKMSGEKM PVKMIGDILS
AQLPHMQPYI RFCSRQLNGA ALIQQKTDEA PDFKEFVKRL AMDPRCKGMP LSSFILKPMQ
RVTRYPLIIK NILENTPENH PDHSHLKHAL EKAEELCSQV NEGVREKENS DRLEWIQAHV
QCEGLSEQLV FNSVTNCLGP RKFLHSGKLY KAKSNKELYG FLFNDFLLLT QITKPLGSSG
TDKVFSPKSN LQYKMYKTPI FLNEVLVKLP TDPSGDEPIF HISHIDRVYT LRAESINERT
AWVQKIKAAS ELYIETEKKK REKAYLVRSQ RATGIGRLMV NVVEGIELKP CRSHGKSNPY
CEVTMGSQCH ITKTIQDTLN PKWNSNCQFF IRDLEQEVLC ITVFERDQFS PDDFLGRTEI
RVADIKKDQG SKGPVTKCLL LHEVPTGEIV VRLDLQLFDE P
//
MIM
602442
*RECORD*
*FIELD* NO
602442
*FIELD* TI
*602442 INTERSECTIN 1; ITSN1
;;ITSN;;
SH3 DOMAIN PROTEIN 1A; SH3D1A;;
SRC HOMOLOGY 3 DOMAIN-CONTAINING PROTEIN;;
read moreSH3P17
*FIELD* TX
DESCRIPTION
Intersectin-1 is an evolutionarily conserved, multidomain protein that
functions in clathrin-associated endocytosis and as a mediator of MAPK
signaling pathways (Tsyba et al., 2004).
CLONING
Chen and Antonarakis (1997) used exon trapping to identify portions of
genes on human chromosome 21. A BLAST search of databases revealed that
1 trapped sequence was identical to a region of the GenBank entry for
the Src homology 3 (SH3) domain-containing gene SH3D1A, formerly called
SH3P17 by Sparks et al. (1996).
By Alu-splice PCR, Pucharcos et al. (1999) trapped 2 exons and
subsequently identified the full-length cDNA of the ITSN gene. The gene
has the potential to code for at least 2 different protein isoforms by
alternative splicing (ITSN-L and ITSN-S). Intersectin exists with a high
degree of similarity in flies, frogs, and mammals, suggesting a
conserved role in higher eukaryotes. ITSN mRNAs were detected in all
adult and fetal tissues tested in human and mouse, with the longer
isoform present in the brain. In situ hybridization studies in the
developing mouse brain showed ITSN expression in both proliferating and
differentiating neurons. Pucharcos et al. (1999) determined the genomic
structure of ITSN using chromosome 21 sequences deposited in the public
databases. The protein contains several known motifs which implicate
ITSN in clathrin-mediated endocytosis and synaptic vesicle recycling.
The expression pattern of intersectin in mouse brain, its presumed
function, and its overexpression in brains from Down syndrome patients,
suggested intersectin may contribute in a gene dosage-dependent manner
to some of the abnormalities of Down syndrome.
Pucharcos et al. (2000) determined by Western blot analysis that the
short and long isoforms of ITSN1 encode 138- and 195-kD proteins,
respectively, as predicted. Immunofluorescence microscopy demonstrated
sparse punctate expression throughout the cytoplasm for both ITSN1 and
ITSN2 (604464), with ITSN1 having a more marked perinuclear pattern and
a concentration in Golgi-like structures.
Tsyba et al. (2004) noted that ITSN1 has a complex domain structure.
Both ITSN1 isoforms have 2 N-terminal Eps15 (600051) homology (EH)
domains, followed by a coiled-coil domain and 5 Src (190090) homology-3
(SH3) domains. In addition, the long isoform has a C-terminal extension
containing a Dbl (311030) homology (DH), or RhoGEF (see 601855), domain,
a pleckstrin (173570) homology (PH) domain, and a putative
calcium-interaction domain. Tsyba et al. (2004) identified 8 additional
alternative splicing events that affect mouse and human ITSN1
transcripts. These splicing events decrease the EH domain spacing,
introduce an insertion in the first SH3 domain, delete the DH domain, or
create frameshifts that truncate the open reading frames at several
points. Tsyba et al. (2004) concluded that alternative splicing
contributes to the regulation of ITSN1 protein functions by creating
diversity in domain composition among protein isoforms.
GENE FUNCTION
Pucharcos et al. (2000) found that overexpression of either of the ITSN2
isoforms or ITSN1 resulted in the inhibition of transferrin uptake and
the blockage of clathrin-mediated endocytosis.
Morphologic changes in neuronal dendritic spines are believed to be
caused by dynamic regulation of actin polymerization. Irie and Yamaguchi
(2002) found that the EphB2 receptor tyrosine kinase (600997) physically
associates with intersectin-1 in cooperation with the actin-regulating
protein N-WASP (605056), which in turn activates the Rho family GTPase
Cdc42 (116952) and spine morphogenesis.
He et al. (2007) showed that mammalian Wnk1 (605232) and Wnk4 (601844)
interacted with Itsn1 and that these interactions were crucial for
stimulation of Romk1 (KCNJ1; 600359) endocytosis. Stimulation of Romk1
endocytosis by Wnk1 and Wnk4 required their proline-rich motifs, but it
did not require their kinase activities. Pseudohypoaldosteronism II
(PHA2B; 614491)-causing mutations in Wnk4 enhanced the interactions of
Wnk4 with Itsn1 and Romk1, leading to increased endocytosis of Romk1.
GENE STRUCTURE
Tsyba et al. (2004) determined that the ITSN1 gene contains 41 exons.
Exon 1 is noncoding, and the initiator methionine is located in exon 2.
MAPPING
By hybridization and PCR, Chen and Antonarakis (1997) mapped the SH3D1A
gene to YACs and cosmids within 21q22.1-q22.2, between DNA markers
D21S319 and D21S65.
*FIELD* RF
1. Chen, H.; Antonarakis, S. E.: The SH3D1A gene maps to human chromosome
21q22.1-q22.2. Cytogenet. Cell Genet. 78: 213-215, 1997.
2. He, G.; Wang, H.-R.; Huang, S.-K.; Huang, C.-L.: Intersectin links
WNK kinases to endocytosis of ROMK1. J. Clin. Invest. 117: 1078-1087,
2007.
3. Irie, F.; Yamaguchi, Y.: EphB receptors regulate dendritic spine
development via intersectin, Cdc42 and N-WASP. Nature Neurosci. 5:
1117-1118, 2002.
4. Pucharcos, C.; Estivill, X.; de la Luna, S.: Intersectin 2, a
new multimodular protein involved in clathrin-mediated endocytosis. FEBS
Lett. 478: 43-51, 2000.
5. Pucharcos, C.; Fuentes, J.-J.; Casas, C.; de la Luna, S.; Alcantara,
S.; Arbones, M. L.; Soriano, E.; Estivill, X.; Prichard, M.: Alu-splice
cloning of human intersectin (ITSN), a putative multivalent binding
protein expressed in proliferating and differentiating neurons and
overexpressed in Down syndrome. Europ. J. Hum. Genet. 7: 704-712,
1999.
6. Sparks, A. B.; Hoffman, N. G.; McConnell, S. J.; Fowlkes, D. M.;
Kay, B. K.: Cloning of ligand targets: systematic isolation of SH3
domain-containing proteins. Nature Biotech. 14: 741-744, 1996.
7. Tsyba, L.; Skrypkina, I.; Rynditch, A.; Nikolaienko, O.; Ferenets,
G.; Fortna, A.; Gardiner, K.: Alternative splicing of mammalian intersectin
1: domain associations and tissue specificities. Genomics 84: 106-113,
2004.
*FIELD* CN
Patricia A. Hartz - updated: 10/18/2007
Patricia A. Hartz - updated: 8/11/2004
Cassandra L. Kniffin - updated: 3/21/2003
Paul J. Converse - updated: 2/16/2001
Victor A. McKusick - updated: 11/8/1999
*FIELD* CD
Victor A. McKusick: 3/16/1998
*FIELD* ED
alopez: 02/27/2012
mgross: 10/18/2007
terry: 10/18/2007
mgross: 8/25/2004
terry: 8/11/2004
ckniffin: 3/21/2003
tkritzer: 3/14/2003
ckniffin: 3/5/2003
mgross: 2/21/2001
mcapotos: 2/20/2001
terry: 2/16/2001
alopez: 11/12/1999
terry: 11/8/1999
carol: 11/25/1998
carol: 6/26/1998
psherman: 3/16/1998
*RECORD*
*FIELD* NO
602442
*FIELD* TI
*602442 INTERSECTIN 1; ITSN1
;;ITSN;;
SH3 DOMAIN PROTEIN 1A; SH3D1A;;
SRC HOMOLOGY 3 DOMAIN-CONTAINING PROTEIN;;
read moreSH3P17
*FIELD* TX
DESCRIPTION
Intersectin-1 is an evolutionarily conserved, multidomain protein that
functions in clathrin-associated endocytosis and as a mediator of MAPK
signaling pathways (Tsyba et al., 2004).
CLONING
Chen and Antonarakis (1997) used exon trapping to identify portions of
genes on human chromosome 21. A BLAST search of databases revealed that
1 trapped sequence was identical to a region of the GenBank entry for
the Src homology 3 (SH3) domain-containing gene SH3D1A, formerly called
SH3P17 by Sparks et al. (1996).
By Alu-splice PCR, Pucharcos et al. (1999) trapped 2 exons and
subsequently identified the full-length cDNA of the ITSN gene. The gene
has the potential to code for at least 2 different protein isoforms by
alternative splicing (ITSN-L and ITSN-S). Intersectin exists with a high
degree of similarity in flies, frogs, and mammals, suggesting a
conserved role in higher eukaryotes. ITSN mRNAs were detected in all
adult and fetal tissues tested in human and mouse, with the longer
isoform present in the brain. In situ hybridization studies in the
developing mouse brain showed ITSN expression in both proliferating and
differentiating neurons. Pucharcos et al. (1999) determined the genomic
structure of ITSN using chromosome 21 sequences deposited in the public
databases. The protein contains several known motifs which implicate
ITSN in clathrin-mediated endocytosis and synaptic vesicle recycling.
The expression pattern of intersectin in mouse brain, its presumed
function, and its overexpression in brains from Down syndrome patients,
suggested intersectin may contribute in a gene dosage-dependent manner
to some of the abnormalities of Down syndrome.
Pucharcos et al. (2000) determined by Western blot analysis that the
short and long isoforms of ITSN1 encode 138- and 195-kD proteins,
respectively, as predicted. Immunofluorescence microscopy demonstrated
sparse punctate expression throughout the cytoplasm for both ITSN1 and
ITSN2 (604464), with ITSN1 having a more marked perinuclear pattern and
a concentration in Golgi-like structures.
Tsyba et al. (2004) noted that ITSN1 has a complex domain structure.
Both ITSN1 isoforms have 2 N-terminal Eps15 (600051) homology (EH)
domains, followed by a coiled-coil domain and 5 Src (190090) homology-3
(SH3) domains. In addition, the long isoform has a C-terminal extension
containing a Dbl (311030) homology (DH), or RhoGEF (see 601855), domain,
a pleckstrin (173570) homology (PH) domain, and a putative
calcium-interaction domain. Tsyba et al. (2004) identified 8 additional
alternative splicing events that affect mouse and human ITSN1
transcripts. These splicing events decrease the EH domain spacing,
introduce an insertion in the first SH3 domain, delete the DH domain, or
create frameshifts that truncate the open reading frames at several
points. Tsyba et al. (2004) concluded that alternative splicing
contributes to the regulation of ITSN1 protein functions by creating
diversity in domain composition among protein isoforms.
GENE FUNCTION
Pucharcos et al. (2000) found that overexpression of either of the ITSN2
isoforms or ITSN1 resulted in the inhibition of transferrin uptake and
the blockage of clathrin-mediated endocytosis.
Morphologic changes in neuronal dendritic spines are believed to be
caused by dynamic regulation of actin polymerization. Irie and Yamaguchi
(2002) found that the EphB2 receptor tyrosine kinase (600997) physically
associates with intersectin-1 in cooperation with the actin-regulating
protein N-WASP (605056), which in turn activates the Rho family GTPase
Cdc42 (116952) and spine morphogenesis.
He et al. (2007) showed that mammalian Wnk1 (605232) and Wnk4 (601844)
interacted with Itsn1 and that these interactions were crucial for
stimulation of Romk1 (KCNJ1; 600359) endocytosis. Stimulation of Romk1
endocytosis by Wnk1 and Wnk4 required their proline-rich motifs, but it
did not require their kinase activities. Pseudohypoaldosteronism II
(PHA2B; 614491)-causing mutations in Wnk4 enhanced the interactions of
Wnk4 with Itsn1 and Romk1, leading to increased endocytosis of Romk1.
GENE STRUCTURE
Tsyba et al. (2004) determined that the ITSN1 gene contains 41 exons.
Exon 1 is noncoding, and the initiator methionine is located in exon 2.
MAPPING
By hybridization and PCR, Chen and Antonarakis (1997) mapped the SH3D1A
gene to YACs and cosmids within 21q22.1-q22.2, between DNA markers
D21S319 and D21S65.
*FIELD* RF
1. Chen, H.; Antonarakis, S. E.: The SH3D1A gene maps to human chromosome
21q22.1-q22.2. Cytogenet. Cell Genet. 78: 213-215, 1997.
2. He, G.; Wang, H.-R.; Huang, S.-K.; Huang, C.-L.: Intersectin links
WNK kinases to endocytosis of ROMK1. J. Clin. Invest. 117: 1078-1087,
2007.
3. Irie, F.; Yamaguchi, Y.: EphB receptors regulate dendritic spine
development via intersectin, Cdc42 and N-WASP. Nature Neurosci. 5:
1117-1118, 2002.
4. Pucharcos, C.; Estivill, X.; de la Luna, S.: Intersectin 2, a
new multimodular protein involved in clathrin-mediated endocytosis. FEBS
Lett. 478: 43-51, 2000.
5. Pucharcos, C.; Fuentes, J.-J.; Casas, C.; de la Luna, S.; Alcantara,
S.; Arbones, M. L.; Soriano, E.; Estivill, X.; Prichard, M.: Alu-splice
cloning of human intersectin (ITSN), a putative multivalent binding
protein expressed in proliferating and differentiating neurons and
overexpressed in Down syndrome. Europ. J. Hum. Genet. 7: 704-712,
1999.
6. Sparks, A. B.; Hoffman, N. G.; McConnell, S. J.; Fowlkes, D. M.;
Kay, B. K.: Cloning of ligand targets: systematic isolation of SH3
domain-containing proteins. Nature Biotech. 14: 741-744, 1996.
7. Tsyba, L.; Skrypkina, I.; Rynditch, A.; Nikolaienko, O.; Ferenets,
G.; Fortna, A.; Gardiner, K.: Alternative splicing of mammalian intersectin
1: domain associations and tissue specificities. Genomics 84: 106-113,
2004.
*FIELD* CN
Patricia A. Hartz - updated: 10/18/2007
Patricia A. Hartz - updated: 8/11/2004
Cassandra L. Kniffin - updated: 3/21/2003
Paul J. Converse - updated: 2/16/2001
Victor A. McKusick - updated: 11/8/1999
*FIELD* CD
Victor A. McKusick: 3/16/1998
*FIELD* ED
alopez: 02/27/2012
mgross: 10/18/2007
terry: 10/18/2007
mgross: 8/25/2004
terry: 8/11/2004
ckniffin: 3/21/2003
tkritzer: 3/14/2003
ckniffin: 3/5/2003
mgross: 2/21/2001
mcapotos: 2/20/2001
terry: 2/16/2001
alopez: 11/12/1999
terry: 11/8/1999
carol: 11/25/1998
carol: 6/26/1998
psherman: 3/16/1998