Full text data of ERBB2IP
ERBB2IP
(ERBIN, KIAA1225, LAP2)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Protein LAP2 (Densin-180-like protein; Erbb2-interacting protein; Erbin)
Protein LAP2 (Densin-180-like protein; Erbb2-interacting protein; Erbin)
UniProt
Q96RT1
ID LAP2_HUMAN Reviewed; 1412 AA.
AC Q96RT1; A0AVR1; B4E3F1; B7ZLV9; E7EQW9; E9PCR8; Q1RMD0; Q86W38;
read moreAC Q9NR18; Q9NW48; Q9ULJ5;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 22-JAN-2014, entry version 127.
DE RecName: Full=Protein LAP2;
DE AltName: Full=Densin-180-like protein;
DE AltName: Full=Erbb2-interacting protein;
DE Short=Erbin;
GN Name=ERBB2IP; Synonyms=ERBIN, KIAA1225, LAP2;
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 [MRNA] (ISOFORM 2), INTERACTION WITH ERBB2, TISSUE
RP SPECIFICITY, SUBCELLULAR LOCATION, AND FUNCTION.
RC TISSUE=B-cell;
RX PubMed=10878805; DOI=10.1038/35017038;
RA Borg J.-P., Marchetto S., Le Bivic A., Ollendorff V.,
RA Jaulin-Bastard F., Saito H., Fournier E., Adelaide J., Margolis B.,
RA Birnbaum D.;
RT "ERBIN: a basolateral PDZ protein that interacts with the mammalian
RT ERBB2/HER2 receptor.";
RL Nat. Cell Biol. 2:407-414(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4; 5; 6 AND 7),
RP INTERACTION WITH BPAG1; DST AND ITGB4, SUBCELLULAR LOCATION, AND
RP VARIANT GLU-1207.
RX PubMed=11375975; DOI=10.1074/jbc.M011005200;
RA Favre B., Fontao L., Koster J., Shafaatian R., Jaunin F.,
RA Saurat J.-H., Sonnenberg A., Borradori L.;
RT "The hemidesmosomal protein bullous pemphigoid antigen 1 and the
RT integrin beta 4 subunit bind to ERBIN. Molecular cloning of multiple
RT alternative splice variants of ERBIN and analysis of their tissue
RT expression.";
RL J. Biol. Chem. 276:32427-32436(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=10574462; DOI=10.1093/dnares/6.5.337;
RA Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XV.
RT The complete sequences of 100 new cDNA clones from brain which code
RT for large proteins in vitro.";
RL DNA Res. 6:337-345(1999).
RN [4]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 601-1206 (ISOFORM 1).
RC TISSUE=Teratocarcinoma, and Uterus;
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=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T.,
RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
RA Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 8 AND 9), AND
RP VARIANTS LEU-274 AND VAL-313.
RC TISSUE=Cerebellum, and Skin;
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 INTERACTION WITH DELTA CATENIN AND ARVCF.
RX PubMed=11821434; DOI=10.1074/jbc.M200818200;
RA Laura R.P., Witt A.S., Held H.A., Gerstner R., Deshayes K.,
RA Koehler M.F.T., Kosik K.S., Sidhu S.S., Lasky L.A.;
RT "The Erbin PDZ domain binds with high affinity and specificity to the
RT carboxyl termini of delta-catenin and ARVCF.";
RL J. Biol. Chem. 277:12906-12914(2002).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-920, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=15144186; DOI=10.1021/ac035352d;
RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,
RA Peters E.C.;
RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites
RT from human T cells using immobilized metal affinity chromatography and
RT tandem mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-972, AND MASS
RP SPECTROMETRY.
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-440, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-569; SER-857; THR-917
RP AND SER-1286, AND 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-872; THR-917; SER-931
RP AND SER-1158, AND MASS SPECTROMETRY.
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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-569; SER-602 AND
RP SER-603, AND MASS SPECTROMETRY.
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 [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) OF 1321-1412 IN COMPLEX WITH
RP ERBB2 C-TERMINUS.
RX PubMed=12444095; DOI=10.1074/jbc.C200571200;
RA Birrane G., Chung J., Ladias J.A.;
RT "Novel mode of ligand recognition by the Erbin PDZ domain.";
RL J. Biol. Chem. 278:1399-1402(2003).
RN [18]
RP STRUCTURE BY NMR OF 1314-1412 IN COMPLEX WITH PHAGE-DERIVED PEPTIDE.
RX PubMed=12446668; DOI=10.1074/jbc.M209751200;
RA Skelton N.J., Koehler M.F.T., Zobel K., Wong W.L., Yeh S.,
RA Pisabarro M.T., Yin J.P., Lasky L.A., Sidhu S.S.;
RT "Origins of PDZ domain ligand specificity. Structure determination and
RT mutagenesis of the Erbin PDZ domain.";
RL J. Biol. Chem. 278:7645-7654(2003).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.0 ANGSTROMS) OF 1314-1412.
RX PubMed=16737969; DOI=10.1074/jbc.M602901200;
RA Appleton B.A., Zhang Y., Wu P., Yin J.P., Hunziker W., Skelton N.J.,
RA Sidhu S.S., Wiesmann C.;
RT "Comparative structural analysis of the erbin PDZ domain and the first
RT PDZ domain of ZO-1. Insights into determinants of PDZ domain
RT specificity.";
RL J. Biol. Chem. 281:22312-22320(2006).
CC -!- FUNCTION: Acts as an adapter for the receptor ERBB2, in epithelia.
CC By binding the unphosphorylated 'Tyr-1248' of receptor ERBB2, it
CC may contribute to stabilize this unphosphorylated state.
CC -!- SUBUNIT: Interacts with ERBB2, BPAG1 and ITGB4. May favor the
CC localization of ERBB2, by restricting its presence to the
CC basolateral membrane of epithelial cells. Also found to interact
CC with ARVCF and delta catenin. Interacts (via C-terminus) with DST
CC Isoform 3 (via N-terminus).
CC -!- INTERACTION:
CC Q99569:PKP4; NbExp=3; IntAct=EBI-8449250, EBI-726447;
CC -!- SUBCELLULAR LOCATION: Cell junction, hemidesmosome. Nucleus
CC membrane (By similarity). Note=Found in hemidesmosomes, which are
CC cell-substrate adhesion complexes in stratified epithelia. In
CC transfected cells, either diffusely distributed over the cytoplasm
CC or concentrated at the basolateral membrane. Colocalizes with the
CC adrenergic receptors, ADREN1A and ADREN1B, at the nuclear membrane
CC of cardiac myocytes (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=9;
CC Name=1;
CC IsoId=Q96RT1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96RT1-2; Sequence=VSP_010802;
CC Name=3;
CC IsoId=Q96RT1-3; Sequence=VSP_010802, VSP_010804;
CC Name=4;
CC IsoId=Q96RT1-4; Sequence=VSP_010802, VSP_010807;
CC Name=5;
CC IsoId=Q96RT1-5; Sequence=VSP_010802, VSP_010803;
CC Name=6;
CC IsoId=Q96RT1-6; Sequence=VSP_010802, VSP_010806;
CC Name=7;
CC IsoId=Q96RT1-7; Sequence=VSP_010802, VSP_010803, VSP_010804,
CC VSP_010805;
CC Name=8;
CC IsoId=Q96RT1-8; Sequence=VSP_044536;
CC Note=No experimental confirmation available;
CC Name=9;
CC IsoId=Q96RT1-9; Sequence=VSP_047389, VSP_010802;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Highly expressed in brain, heart, kidney,
CC muscle and stomach, followed by liver, spleen and intestine.
CC -!- SIMILARITY: Belongs to the LAP (LRR and PDZ) protein family.
CC -!- SIMILARITY: Contains 17 LRR (leucine-rich) repeats.
CC -!- SIMILARITY: Contains 1 PDZ (DHR) domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH50692.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence;
CC Sequence=BAA91538.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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DR EMBL; AF263744; AAF77048.1; -; mRNA.
DR EMBL; AF276423; AAK69431.1; -; mRNA.
DR EMBL; AB033051; BAA86539.2; -; mRNA.
DR EMBL; AK001180; BAA91538.1; ALT_INIT; mRNA.
DR EMBL; AK304693; BAG65463.1; -; mRNA.
DR EMBL; AC010359; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC025442; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC050692; AAH50692.1; ALT_SEQ; mRNA.
DR EMBL; BC115012; AAI15013.1; -; mRNA.
DR EMBL; BC126464; AAI26465.1; -; mRNA.
DR EMBL; BC144075; AAI44076.1; -; mRNA.
DR RefSeq; NP_001006600.1; NM_001006600.2.
DR RefSeq; NP_001240626.1; NM_001253697.1.
DR RefSeq; NP_001240627.1; NM_001253698.1.
DR RefSeq; NP_001240628.1; NM_001253699.1.
DR RefSeq; NP_001240630.1; NM_001253701.1.
DR RefSeq; NP_061165.1; NM_018695.3.
DR UniGene; Hs.591774; -.
DR UniGene; Hs.597241; -.
DR PDB; 1MFG; X-ray; 1.25 A; A=1321-1412.
DR PDB; 1MFL; X-ray; 1.88 A; A=1321-1412.
DR PDB; 1N7T; NMR; -; A=1314-1412.
DR PDB; 2H3L; X-ray; 1.00 A; A/B=1314-1412.
DR PDB; 2QBW; X-ray; 1.80 A; A=1318-1410.
DR PDB; 3CH8; X-ray; 1.90 A; A=1318-1410.
DR PDBsum; 1MFG; -.
DR PDBsum; 1MFL; -.
DR PDBsum; 1N7T; -.
DR PDBsum; 2H3L; -.
DR PDBsum; 2QBW; -.
DR PDBsum; 3CH8; -.
DR ProteinModelPortal; Q96RT1; -.
DR SMR; Q96RT1; 10-453, 1283-1412.
DR IntAct; Q96RT1; 13.
DR MINT; MINT-199447; -.
DR STRING; 9606.ENSP00000370330; -.
DR PhosphoSite; Q96RT1; -.
DR DMDM; 116242614; -.
DR PaxDb; Q96RT1; -.
DR PRIDE; Q96RT1; -.
DR Ensembl; ENST00000284037; ENSP00000284037; ENSG00000112851.
DR Ensembl; ENST00000380935; ENSP00000370322; ENSG00000112851.
DR Ensembl; ENST00000380936; ENSP00000370323; ENSG00000112851.
DR Ensembl; ENST00000380938; ENSP00000370325; ENSG00000112851.
DR Ensembl; ENST00000380939; ENSP00000370326; ENSG00000112851.
DR Ensembl; ENST00000380943; ENSP00000370330; ENSG00000112851.
DR Ensembl; ENST00000506030; ENSP00000426632; ENSG00000112851.
DR Ensembl; ENST00000508515; ENSP00000422015; ENSG00000112851.
DR Ensembl; ENST00000511297; ENSP00000422766; ENSG00000112851.
DR GeneID; 55914; -.
DR KEGG; hsa:55914; -.
DR UCSC; uc003jul.2; human.
DR CTD; 55914; -.
DR GeneCards; GC05P065258; -.
DR HGNC; HGNC:15842; ERBB2IP.
DR HPA; HPA048606; -.
DR MIM; 606944; gene.
DR neXtProt; NX_Q96RT1; -.
DR PharmGKB; PA27845; -.
DR eggNOG; COG4886; -.
DR HOGENOM; HOG000060229; -.
DR HOVERGEN; HBG052305; -.
DR InParanoid; Q96RT1; -.
DR KO; K12796; -.
DR OMA; SDEEMKM; -.
DR OrthoDB; EOG72C501; -.
DR PhylomeDB; Q96RT1; -.
DR Reactome; REACT_111102; Signal Transduction.
DR SignaLink; Q96RT1; -.
DR ChiTaRS; ERBB2IP; human.
DR EvolutionaryTrace; Q96RT1; -.
DR GeneWiki; Erbin_(protein); -.
DR GenomeRNAi; 55914; -.
DR NextBio; 61305; -.
DR PRO; PR:Q96RT1; -.
DR ArrayExpress; Q96RT1; -.
DR Bgee; Q96RT1; -.
DR CleanEx; HS_ERBB2IP; -.
DR Genevestigator; Q96RT1; -.
DR GO; GO:0009925; C:basal plasma membrane; NAS:UniProtKB.
DR GO; GO:0005604; C:basement membrane; TAS:ProtInc.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0030056; C:hemidesmosome; IDA:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005176; F:ErbB-2 class receptor binding; TAS:UniProtKB.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; NAS:UniProtKB.
DR GO; GO:0045175; P:basal protein localization; NAS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; NAS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; NAS:UniProtKB.
DR GO; GO:0016049; P:cell growth; NAS:UniProtKB.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:UniProtKB.
DR GO; GO:0045197; P:establishment or maintenance of epithelial cell apical/basal polarity; NAS:UniProtKB.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; NAS:UniProtKB.
DR GO; GO:0045104; P:intermediate filament cytoskeleton organization; NAS:UniProtKB.
DR GO; GO:0006605; P:protein targeting; IEA:Ensembl.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR025875; Leu-rich_rpt_4.
DR InterPro; IPR001478; PDZ.
DR Pfam; PF12799; LRR_4; 2.
DR Pfam; PF00595; PDZ; 1.
DR SMART; SM00228; PDZ; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR PROSITE; PS51450; LRR; 15.
DR PROSITE; PS50106; PDZ; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell junction; Complete proteome;
KW Leucine-rich repeat; Membrane; Nucleus; Phosphoprotein; Polymorphism;
KW Reference proteome; Repeat.
FT CHAIN 1 1412 Protein LAP2.
FT /FTId=PRO_0000188301.
FT REPEAT 23 44 LRR 1.
FT REPEAT 47 68 LRR 2.
FT REPEAT 70 91 LRR 3.
FT REPEAT 93 114 LRR 4.
FT REPEAT 116 137 LRR 5.
FT REPEAT 139 161 LRR 6.
FT REPEAT 162 183 LRR 7.
FT REPEAT 185 206 LRR 8.
FT REPEAT 208 229 LRR 9.
FT REPEAT 231 252 LRR 10.
FT REPEAT 254 275 LRR 11.
FT REPEAT 277 298 LRR 12.
FT REPEAT 300 321 LRR 13.
FT REPEAT 323 344 LRR 14.
FT REPEAT 346 367 LRR 15.
FT REPEAT 369 391 LRR 16.
FT REPEAT 392 413 LRR 17.
FT DOMAIN 1321 1410 PDZ.
FT COMPBIAS 930 934 Poly-Ser.
FT MOD_RES 440 440 Phosphoserine.
FT MOD_RES 569 569 Phosphoserine.
FT MOD_RES 602 602 Phosphoserine.
FT MOD_RES 603 603 Phosphoserine.
FT MOD_RES 715 715 Phosphoserine (By similarity).
FT MOD_RES 857 857 Phosphoserine.
FT MOD_RES 872 872 Phosphoserine.
FT MOD_RES 917 917 Phosphothreonine.
FT MOD_RES 920 920 Phosphotyrosine.
FT MOD_RES 931 931 Phosphoserine.
FT MOD_RES 972 972 Phosphotyrosine.
FT MOD_RES 1104 1104 Phosphotyrosine (By similarity).
FT MOD_RES 1158 1158 Phosphoserine.
FT MOD_RES 1286 1286 Phosphoserine.
FT VAR_SEQ 531 534 Missing (in isoform 9).
FT /FTId=VSP_047389.
FT VAR_SEQ 1212 1252 Missing (in isoform 2, isoform 3, isoform
FT 4, isoform 5, isoform 6, isoform 7 and
FT isoform 9).
FT /FTId=VSP_010802.
FT VAR_SEQ 1212 1252 KHPQTSSSGDPCQDGIFISGQQNYSSATLSHKDVPPDSLMK
FT -> SMLSRSFNSNFTTVSSFHCGSSRDLHGSQGSLALSVAD
FT RRGSGGHIFR (in isoform 8).
FT /FTId=VSP_044536.
FT VAR_SEQ 1253 1267 Missing (in isoform 5 and isoform 7).
FT /FTId=VSP_010803.
FT VAR_SEQ 1268 1278 Missing (in isoform 3 and isoform 7).
FT /FTId=VSP_010804.
FT VAR_SEQ 1279 1321 Missing (in isoform 7).
FT /FTId=VSP_010805.
FT VAR_SEQ 1322 1352 Missing (in isoform 6).
FT /FTId=VSP_010806.
FT VAR_SEQ 1353 1377 Missing (in isoform 4).
FT /FTId=VSP_010807.
FT VARIANT 274 274 S -> L (in dbSNP:rs3213837).
FT /FTId=VAR_019346.
FT VARIANT 313 313 A -> V (in dbSNP:rs191137999).
FT /FTId=VAR_068905.
FT VARIANT 746 746 K -> E (in dbSNP:rs16894812).
FT /FTId=VAR_028304.
FT VARIANT 914 914 K -> R (in dbSNP:rs34521887).
FT /FTId=VAR_046673.
FT VARIANT 1089 1089 G -> V (in dbSNP:rs35601230).
FT /FTId=VAR_046674.
FT VARIANT 1112 1112 S -> L (in dbSNP:rs3805466).
FT /FTId=VAR_019347.
FT VARIANT 1207 1207 K -> E.
FT /FTId=VAR_019348.
FT CONFLICT 271 271 T -> P (in Ref. 7; AAI15013).
FT CONFLICT 547 547 D -> G (in Ref. 7; AAI15013).
FT CONFLICT 805 805 E -> G (in Ref. 5; BAA91538).
FT CONFLICT 813 813 Y -> C (in Ref. 2; AAK69431).
FT CONFLICT 848 848 G -> C (in Ref. 5; BAG65463).
FT CONFLICT 1047 1047 R -> S (in Ref. 5; BAG65463).
FT CONFLICT 1205 1205 E -> G (in Ref. 7; AAI15013).
FT CONFLICT 1267 1267 Q -> P (in Ref. 7; AAI15013).
FT CONFLICT 1328 1328 K -> R (in Ref. 7; AAI15013).
FT STRAND 1318 1327
FT STRAND 1329 1331
FT STRAND 1333 1338
FT TURN 1339 1342
FT STRAND 1346 1348
FT STRAND 1353 1359
FT TURN 1364 1368
FT STRAND 1374 1378
FT HELIX 1388 1397
FT STRAND 1400 1410
SQ SEQUENCE 1412 AA; 158298 MW; 304DFC81578CF671 CRC64;
MTTKRSLFVR LVPCRCLRGE EETVTTLDYS HCSLEQVPKE IFTFEKTLEE LYLDANQIEE
LPKQLFNCQS LHKLSLPDND LTTLPASIAN LINLRELDVS KNGIQEFPEN IKNCKVLTIV
EASVNPISKL PDGFSQLLNL TQLYLNDAFL EFLPANFGRL TKLQILELRE NQLKMLPKTM
NRLTQLERLD LGSNEFTEVP EVLEQLSGLK EFWMDANRLT FIPGFIGSLK QLTYLDVSKN
NIEMVEEGIS TCENLQDLLL SSNSLQQLPE TIGSLKNITT LKIDENQLMY LPDSIGGLIS
VEELDCSFNE VEALPSSIGQ LTNLRTFAAD HNYLQQLPPE IGSWKNITVL FLHSNKLETL
PEEMGDMQKL KVINLSDNRL KNLPFSFTKL QQLTAMWLSD NQSKPLIPLQ KETDSETQKM
VLTNYMFPQQ PRTEDVMFIS DNESFNPSLW EEQRKQRAQV AFECDEDKDE REAPPREGNL
KRYPTPYPDE LKNMVKTVQT IVHRLKDEET NEDSGRDLKP HEDQQDINKD VGVKTSESTT
TVKSKVDERE KYMIGNSVQK ISEPEAEISP GSLPVTANMK ASENLKHIVN HDDVFEESEE
LSSDEEMKMA EMRPPLIETS INQPKVVALS NNKKDDTKET DSLSDEVTHN SNQNNSNCSS
PSRMSDSVSL NTDSSQDTSL CSPVKQTHID INSKIRQEDE NFNSLLQNGD ILNSSTEEKF
KAHDKKDFNL PEYDLNVEER LVLIEKSVDS TATADDTHKL DHINMNLNKL ITNDTFQPEI
MERSKTQDIV LGTSFLSINS KEETEHLENG NKYPNLESVN KVNGHSEETS QSPNRTEPHD
SDCSVDLGIS KSTEDLSPQK SGPVGSVVKS HSITNMEIGG LKIYDILSDN GPQQPSTTVK
ITSAVDGKNI VRSKSATLLY DQPLQVFTGS SSSSDLISGT KAIFKFDSNH NPEEPNIIRG
PTSGPQSAPQ IYGPPQYNIQ YSSSAAVKDT LWHSKQNPQI DHASFPPQLL PRSESTENQS
YAKHSANMNF SNHNNVRANT AYHLHQRLGP ARHGEMWAIS PNDRLIPAVT RSTIQRQSSV
SSTASVNLGD PGSTRRAQIP EGDYLSYREF HSAGRTPPMM PGSQRPLSAR TYSIDGPNAS
RPQSARPSIN EIPERTMSVS DFNYSRTSPS KRPNARVGSE HSLLDPPGKS KVPRDWREQV
LRHIEAKKLE KKHPQTSSSG DPCQDGIFIS GQQNYSSATL SHKDVPPDSL MKMPLSNGQM
GQPLRPQANY SQIHHPPQAS VARHPSREQL IDYLMLKVAH QPPYTQPHCS PRQGHELAKQ
EIRVRVEKDP ELGFSISGGV GGRGNPFRPD DDGIFVTRVQ PEGPASKLLQ PGDKIIQANG
YSFINIEHGQ AVSLLKTFQN TVELIIVREV SS
//
ID LAP2_HUMAN Reviewed; 1412 AA.
AC Q96RT1; A0AVR1; B4E3F1; B7ZLV9; E7EQW9; E9PCR8; Q1RMD0; Q86W38;
read moreAC Q9NR18; Q9NW48; Q9ULJ5;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 22-JAN-2014, entry version 127.
DE RecName: Full=Protein LAP2;
DE AltName: Full=Densin-180-like protein;
DE AltName: Full=Erbb2-interacting protein;
DE Short=Erbin;
GN Name=ERBB2IP; Synonyms=ERBIN, KIAA1225, LAP2;
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 [MRNA] (ISOFORM 2), INTERACTION WITH ERBB2, TISSUE
RP SPECIFICITY, SUBCELLULAR LOCATION, AND FUNCTION.
RC TISSUE=B-cell;
RX PubMed=10878805; DOI=10.1038/35017038;
RA Borg J.-P., Marchetto S., Le Bivic A., Ollendorff V.,
RA Jaulin-Bastard F., Saito H., Fournier E., Adelaide J., Margolis B.,
RA Birnbaum D.;
RT "ERBIN: a basolateral PDZ protein that interacts with the mammalian
RT ERBB2/HER2 receptor.";
RL Nat. Cell Biol. 2:407-414(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4; 5; 6 AND 7),
RP INTERACTION WITH BPAG1; DST AND ITGB4, SUBCELLULAR LOCATION, AND
RP VARIANT GLU-1207.
RX PubMed=11375975; DOI=10.1074/jbc.M011005200;
RA Favre B., Fontao L., Koster J., Shafaatian R., Jaunin F.,
RA Saurat J.-H., Sonnenberg A., Borradori L.;
RT "The hemidesmosomal protein bullous pemphigoid antigen 1 and the
RT integrin beta 4 subunit bind to ERBIN. Molecular cloning of multiple
RT alternative splice variants of ERBIN and analysis of their tissue
RT expression.";
RL J. Biol. Chem. 276:32427-32436(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=10574462; DOI=10.1093/dnares/6.5.337;
RA Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XV.
RT The complete sequences of 100 new cDNA clones from brain which code
RT for large proteins in vitro.";
RL DNA Res. 6:337-345(1999).
RN [4]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 601-1206 (ISOFORM 1).
RC TISSUE=Teratocarcinoma, and Uterus;
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=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T.,
RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
RA Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 8 AND 9), AND
RP VARIANTS LEU-274 AND VAL-313.
RC TISSUE=Cerebellum, and Skin;
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 INTERACTION WITH DELTA CATENIN AND ARVCF.
RX PubMed=11821434; DOI=10.1074/jbc.M200818200;
RA Laura R.P., Witt A.S., Held H.A., Gerstner R., Deshayes K.,
RA Koehler M.F.T., Kosik K.S., Sidhu S.S., Lasky L.A.;
RT "The Erbin PDZ domain binds with high affinity and specificity to the
RT carboxyl termini of delta-catenin and ARVCF.";
RL J. Biol. Chem. 277:12906-12914(2002).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-920, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=15144186; DOI=10.1021/ac035352d;
RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,
RA Peters E.C.;
RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites
RT from human T cells using immobilized metal affinity chromatography and
RT tandem mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-972, AND MASS
RP SPECTROMETRY.
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-440, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-569; SER-857; THR-917
RP AND SER-1286, AND 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-872; THR-917; SER-931
RP AND SER-1158, AND MASS SPECTROMETRY.
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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-569; SER-602 AND
RP SER-603, AND MASS SPECTROMETRY.
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 [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) OF 1321-1412 IN COMPLEX WITH
RP ERBB2 C-TERMINUS.
RX PubMed=12444095; DOI=10.1074/jbc.C200571200;
RA Birrane G., Chung J., Ladias J.A.;
RT "Novel mode of ligand recognition by the Erbin PDZ domain.";
RL J. Biol. Chem. 278:1399-1402(2003).
RN [18]
RP STRUCTURE BY NMR OF 1314-1412 IN COMPLEX WITH PHAGE-DERIVED PEPTIDE.
RX PubMed=12446668; DOI=10.1074/jbc.M209751200;
RA Skelton N.J., Koehler M.F.T., Zobel K., Wong W.L., Yeh S.,
RA Pisabarro M.T., Yin J.P., Lasky L.A., Sidhu S.S.;
RT "Origins of PDZ domain ligand specificity. Structure determination and
RT mutagenesis of the Erbin PDZ domain.";
RL J. Biol. Chem. 278:7645-7654(2003).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.0 ANGSTROMS) OF 1314-1412.
RX PubMed=16737969; DOI=10.1074/jbc.M602901200;
RA Appleton B.A., Zhang Y., Wu P., Yin J.P., Hunziker W., Skelton N.J.,
RA Sidhu S.S., Wiesmann C.;
RT "Comparative structural analysis of the erbin PDZ domain and the first
RT PDZ domain of ZO-1. Insights into determinants of PDZ domain
RT specificity.";
RL J. Biol. Chem. 281:22312-22320(2006).
CC -!- FUNCTION: Acts as an adapter for the receptor ERBB2, in epithelia.
CC By binding the unphosphorylated 'Tyr-1248' of receptor ERBB2, it
CC may contribute to stabilize this unphosphorylated state.
CC -!- SUBUNIT: Interacts with ERBB2, BPAG1 and ITGB4. May favor the
CC localization of ERBB2, by restricting its presence to the
CC basolateral membrane of epithelial cells. Also found to interact
CC with ARVCF and delta catenin. Interacts (via C-terminus) with DST
CC Isoform 3 (via N-terminus).
CC -!- INTERACTION:
CC Q99569:PKP4; NbExp=3; IntAct=EBI-8449250, EBI-726447;
CC -!- SUBCELLULAR LOCATION: Cell junction, hemidesmosome. Nucleus
CC membrane (By similarity). Note=Found in hemidesmosomes, which are
CC cell-substrate adhesion complexes in stratified epithelia. In
CC transfected cells, either diffusely distributed over the cytoplasm
CC or concentrated at the basolateral membrane. Colocalizes with the
CC adrenergic receptors, ADREN1A and ADREN1B, at the nuclear membrane
CC of cardiac myocytes (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=9;
CC Name=1;
CC IsoId=Q96RT1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96RT1-2; Sequence=VSP_010802;
CC Name=3;
CC IsoId=Q96RT1-3; Sequence=VSP_010802, VSP_010804;
CC Name=4;
CC IsoId=Q96RT1-4; Sequence=VSP_010802, VSP_010807;
CC Name=5;
CC IsoId=Q96RT1-5; Sequence=VSP_010802, VSP_010803;
CC Name=6;
CC IsoId=Q96RT1-6; Sequence=VSP_010802, VSP_010806;
CC Name=7;
CC IsoId=Q96RT1-7; Sequence=VSP_010802, VSP_010803, VSP_010804,
CC VSP_010805;
CC Name=8;
CC IsoId=Q96RT1-8; Sequence=VSP_044536;
CC Note=No experimental confirmation available;
CC Name=9;
CC IsoId=Q96RT1-9; Sequence=VSP_047389, VSP_010802;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Highly expressed in brain, heart, kidney,
CC muscle and stomach, followed by liver, spleen and intestine.
CC -!- SIMILARITY: Belongs to the LAP (LRR and PDZ) protein family.
CC -!- SIMILARITY: Contains 17 LRR (leucine-rich) repeats.
CC -!- SIMILARITY: Contains 1 PDZ (DHR) domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH50692.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence;
CC Sequence=BAA91538.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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DR EMBL; AF263744; AAF77048.1; -; mRNA.
DR EMBL; AF276423; AAK69431.1; -; mRNA.
DR EMBL; AB033051; BAA86539.2; -; mRNA.
DR EMBL; AK001180; BAA91538.1; ALT_INIT; mRNA.
DR EMBL; AK304693; BAG65463.1; -; mRNA.
DR EMBL; AC010359; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC025442; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC050692; AAH50692.1; ALT_SEQ; mRNA.
DR EMBL; BC115012; AAI15013.1; -; mRNA.
DR EMBL; BC126464; AAI26465.1; -; mRNA.
DR EMBL; BC144075; AAI44076.1; -; mRNA.
DR RefSeq; NP_001006600.1; NM_001006600.2.
DR RefSeq; NP_001240626.1; NM_001253697.1.
DR RefSeq; NP_001240627.1; NM_001253698.1.
DR RefSeq; NP_001240628.1; NM_001253699.1.
DR RefSeq; NP_001240630.1; NM_001253701.1.
DR RefSeq; NP_061165.1; NM_018695.3.
DR UniGene; Hs.591774; -.
DR UniGene; Hs.597241; -.
DR PDB; 1MFG; X-ray; 1.25 A; A=1321-1412.
DR PDB; 1MFL; X-ray; 1.88 A; A=1321-1412.
DR PDB; 1N7T; NMR; -; A=1314-1412.
DR PDB; 2H3L; X-ray; 1.00 A; A/B=1314-1412.
DR PDB; 2QBW; X-ray; 1.80 A; A=1318-1410.
DR PDB; 3CH8; X-ray; 1.90 A; A=1318-1410.
DR PDBsum; 1MFG; -.
DR PDBsum; 1MFL; -.
DR PDBsum; 1N7T; -.
DR PDBsum; 2H3L; -.
DR PDBsum; 2QBW; -.
DR PDBsum; 3CH8; -.
DR ProteinModelPortal; Q96RT1; -.
DR SMR; Q96RT1; 10-453, 1283-1412.
DR IntAct; Q96RT1; 13.
DR MINT; MINT-199447; -.
DR STRING; 9606.ENSP00000370330; -.
DR PhosphoSite; Q96RT1; -.
DR DMDM; 116242614; -.
DR PaxDb; Q96RT1; -.
DR PRIDE; Q96RT1; -.
DR Ensembl; ENST00000284037; ENSP00000284037; ENSG00000112851.
DR Ensembl; ENST00000380935; ENSP00000370322; ENSG00000112851.
DR Ensembl; ENST00000380936; ENSP00000370323; ENSG00000112851.
DR Ensembl; ENST00000380938; ENSP00000370325; ENSG00000112851.
DR Ensembl; ENST00000380939; ENSP00000370326; ENSG00000112851.
DR Ensembl; ENST00000380943; ENSP00000370330; ENSG00000112851.
DR Ensembl; ENST00000506030; ENSP00000426632; ENSG00000112851.
DR Ensembl; ENST00000508515; ENSP00000422015; ENSG00000112851.
DR Ensembl; ENST00000511297; ENSP00000422766; ENSG00000112851.
DR GeneID; 55914; -.
DR KEGG; hsa:55914; -.
DR UCSC; uc003jul.2; human.
DR CTD; 55914; -.
DR GeneCards; GC05P065258; -.
DR HGNC; HGNC:15842; ERBB2IP.
DR HPA; HPA048606; -.
DR MIM; 606944; gene.
DR neXtProt; NX_Q96RT1; -.
DR PharmGKB; PA27845; -.
DR eggNOG; COG4886; -.
DR HOGENOM; HOG000060229; -.
DR HOVERGEN; HBG052305; -.
DR InParanoid; Q96RT1; -.
DR KO; K12796; -.
DR OMA; SDEEMKM; -.
DR OrthoDB; EOG72C501; -.
DR PhylomeDB; Q96RT1; -.
DR Reactome; REACT_111102; Signal Transduction.
DR SignaLink; Q96RT1; -.
DR ChiTaRS; ERBB2IP; human.
DR EvolutionaryTrace; Q96RT1; -.
DR GeneWiki; Erbin_(protein); -.
DR GenomeRNAi; 55914; -.
DR NextBio; 61305; -.
DR PRO; PR:Q96RT1; -.
DR ArrayExpress; Q96RT1; -.
DR Bgee; Q96RT1; -.
DR CleanEx; HS_ERBB2IP; -.
DR Genevestigator; Q96RT1; -.
DR GO; GO:0009925; C:basal plasma membrane; NAS:UniProtKB.
DR GO; GO:0005604; C:basement membrane; TAS:ProtInc.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0030056; C:hemidesmosome; IDA:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005176; F:ErbB-2 class receptor binding; TAS:UniProtKB.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; NAS:UniProtKB.
DR GO; GO:0045175; P:basal protein localization; NAS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; NAS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; NAS:UniProtKB.
DR GO; GO:0016049; P:cell growth; NAS:UniProtKB.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:UniProtKB.
DR GO; GO:0045197; P:establishment or maintenance of epithelial cell apical/basal polarity; NAS:UniProtKB.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; NAS:UniProtKB.
DR GO; GO:0045104; P:intermediate filament cytoskeleton organization; NAS:UniProtKB.
DR GO; GO:0006605; P:protein targeting; IEA:Ensembl.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR025875; Leu-rich_rpt_4.
DR InterPro; IPR001478; PDZ.
DR Pfam; PF12799; LRR_4; 2.
DR Pfam; PF00595; PDZ; 1.
DR SMART; SM00228; PDZ; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR PROSITE; PS51450; LRR; 15.
DR PROSITE; PS50106; PDZ; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell junction; Complete proteome;
KW Leucine-rich repeat; Membrane; Nucleus; Phosphoprotein; Polymorphism;
KW Reference proteome; Repeat.
FT CHAIN 1 1412 Protein LAP2.
FT /FTId=PRO_0000188301.
FT REPEAT 23 44 LRR 1.
FT REPEAT 47 68 LRR 2.
FT REPEAT 70 91 LRR 3.
FT REPEAT 93 114 LRR 4.
FT REPEAT 116 137 LRR 5.
FT REPEAT 139 161 LRR 6.
FT REPEAT 162 183 LRR 7.
FT REPEAT 185 206 LRR 8.
FT REPEAT 208 229 LRR 9.
FT REPEAT 231 252 LRR 10.
FT REPEAT 254 275 LRR 11.
FT REPEAT 277 298 LRR 12.
FT REPEAT 300 321 LRR 13.
FT REPEAT 323 344 LRR 14.
FT REPEAT 346 367 LRR 15.
FT REPEAT 369 391 LRR 16.
FT REPEAT 392 413 LRR 17.
FT DOMAIN 1321 1410 PDZ.
FT COMPBIAS 930 934 Poly-Ser.
FT MOD_RES 440 440 Phosphoserine.
FT MOD_RES 569 569 Phosphoserine.
FT MOD_RES 602 602 Phosphoserine.
FT MOD_RES 603 603 Phosphoserine.
FT MOD_RES 715 715 Phosphoserine (By similarity).
FT MOD_RES 857 857 Phosphoserine.
FT MOD_RES 872 872 Phosphoserine.
FT MOD_RES 917 917 Phosphothreonine.
FT MOD_RES 920 920 Phosphotyrosine.
FT MOD_RES 931 931 Phosphoserine.
FT MOD_RES 972 972 Phosphotyrosine.
FT MOD_RES 1104 1104 Phosphotyrosine (By similarity).
FT MOD_RES 1158 1158 Phosphoserine.
FT MOD_RES 1286 1286 Phosphoserine.
FT VAR_SEQ 531 534 Missing (in isoform 9).
FT /FTId=VSP_047389.
FT VAR_SEQ 1212 1252 Missing (in isoform 2, isoform 3, isoform
FT 4, isoform 5, isoform 6, isoform 7 and
FT isoform 9).
FT /FTId=VSP_010802.
FT VAR_SEQ 1212 1252 KHPQTSSSGDPCQDGIFISGQQNYSSATLSHKDVPPDSLMK
FT -> SMLSRSFNSNFTTVSSFHCGSSRDLHGSQGSLALSVAD
FT RRGSGGHIFR (in isoform 8).
FT /FTId=VSP_044536.
FT VAR_SEQ 1253 1267 Missing (in isoform 5 and isoform 7).
FT /FTId=VSP_010803.
FT VAR_SEQ 1268 1278 Missing (in isoform 3 and isoform 7).
FT /FTId=VSP_010804.
FT VAR_SEQ 1279 1321 Missing (in isoform 7).
FT /FTId=VSP_010805.
FT VAR_SEQ 1322 1352 Missing (in isoform 6).
FT /FTId=VSP_010806.
FT VAR_SEQ 1353 1377 Missing (in isoform 4).
FT /FTId=VSP_010807.
FT VARIANT 274 274 S -> L (in dbSNP:rs3213837).
FT /FTId=VAR_019346.
FT VARIANT 313 313 A -> V (in dbSNP:rs191137999).
FT /FTId=VAR_068905.
FT VARIANT 746 746 K -> E (in dbSNP:rs16894812).
FT /FTId=VAR_028304.
FT VARIANT 914 914 K -> R (in dbSNP:rs34521887).
FT /FTId=VAR_046673.
FT VARIANT 1089 1089 G -> V (in dbSNP:rs35601230).
FT /FTId=VAR_046674.
FT VARIANT 1112 1112 S -> L (in dbSNP:rs3805466).
FT /FTId=VAR_019347.
FT VARIANT 1207 1207 K -> E.
FT /FTId=VAR_019348.
FT CONFLICT 271 271 T -> P (in Ref. 7; AAI15013).
FT CONFLICT 547 547 D -> G (in Ref. 7; AAI15013).
FT CONFLICT 805 805 E -> G (in Ref. 5; BAA91538).
FT CONFLICT 813 813 Y -> C (in Ref. 2; AAK69431).
FT CONFLICT 848 848 G -> C (in Ref. 5; BAG65463).
FT CONFLICT 1047 1047 R -> S (in Ref. 5; BAG65463).
FT CONFLICT 1205 1205 E -> G (in Ref. 7; AAI15013).
FT CONFLICT 1267 1267 Q -> P (in Ref. 7; AAI15013).
FT CONFLICT 1328 1328 K -> R (in Ref. 7; AAI15013).
FT STRAND 1318 1327
FT STRAND 1329 1331
FT STRAND 1333 1338
FT TURN 1339 1342
FT STRAND 1346 1348
FT STRAND 1353 1359
FT TURN 1364 1368
FT STRAND 1374 1378
FT HELIX 1388 1397
FT STRAND 1400 1410
SQ SEQUENCE 1412 AA; 158298 MW; 304DFC81578CF671 CRC64;
MTTKRSLFVR LVPCRCLRGE EETVTTLDYS HCSLEQVPKE IFTFEKTLEE LYLDANQIEE
LPKQLFNCQS LHKLSLPDND LTTLPASIAN LINLRELDVS KNGIQEFPEN IKNCKVLTIV
EASVNPISKL PDGFSQLLNL TQLYLNDAFL EFLPANFGRL TKLQILELRE NQLKMLPKTM
NRLTQLERLD LGSNEFTEVP EVLEQLSGLK EFWMDANRLT FIPGFIGSLK QLTYLDVSKN
NIEMVEEGIS TCENLQDLLL SSNSLQQLPE TIGSLKNITT LKIDENQLMY LPDSIGGLIS
VEELDCSFNE VEALPSSIGQ LTNLRTFAAD HNYLQQLPPE IGSWKNITVL FLHSNKLETL
PEEMGDMQKL KVINLSDNRL KNLPFSFTKL QQLTAMWLSD NQSKPLIPLQ KETDSETQKM
VLTNYMFPQQ PRTEDVMFIS DNESFNPSLW EEQRKQRAQV AFECDEDKDE REAPPREGNL
KRYPTPYPDE LKNMVKTVQT IVHRLKDEET NEDSGRDLKP HEDQQDINKD VGVKTSESTT
TVKSKVDERE KYMIGNSVQK ISEPEAEISP GSLPVTANMK ASENLKHIVN HDDVFEESEE
LSSDEEMKMA EMRPPLIETS INQPKVVALS NNKKDDTKET DSLSDEVTHN SNQNNSNCSS
PSRMSDSVSL NTDSSQDTSL CSPVKQTHID INSKIRQEDE NFNSLLQNGD ILNSSTEEKF
KAHDKKDFNL PEYDLNVEER LVLIEKSVDS TATADDTHKL DHINMNLNKL ITNDTFQPEI
MERSKTQDIV LGTSFLSINS KEETEHLENG NKYPNLESVN KVNGHSEETS QSPNRTEPHD
SDCSVDLGIS KSTEDLSPQK SGPVGSVVKS HSITNMEIGG LKIYDILSDN GPQQPSTTVK
ITSAVDGKNI VRSKSATLLY DQPLQVFTGS SSSSDLISGT KAIFKFDSNH NPEEPNIIRG
PTSGPQSAPQ IYGPPQYNIQ YSSSAAVKDT LWHSKQNPQI DHASFPPQLL PRSESTENQS
YAKHSANMNF SNHNNVRANT AYHLHQRLGP ARHGEMWAIS PNDRLIPAVT RSTIQRQSSV
SSTASVNLGD PGSTRRAQIP EGDYLSYREF HSAGRTPPMM PGSQRPLSAR TYSIDGPNAS
RPQSARPSIN EIPERTMSVS DFNYSRTSPS KRPNARVGSE HSLLDPPGKS KVPRDWREQV
LRHIEAKKLE KKHPQTSSSG DPCQDGIFIS GQQNYSSATL SHKDVPPDSL MKMPLSNGQM
GQPLRPQANY SQIHHPPQAS VARHPSREQL IDYLMLKVAH QPPYTQPHCS PRQGHELAKQ
EIRVRVEKDP ELGFSISGGV GGRGNPFRPD DDGIFVTRVQ PEGPASKLLQ PGDKIIQANG
YSFINIEHGQ AVSLLKTFQN TVELIIVREV SS
//
MIM
606944
*RECORD*
*FIELD* NO
606944
*FIELD* TI
*606944 ERBB2 INTERACTING PROTEIN; ERBB2IP
;;DENSIN-180-LIKE PROTEIN; ERBIN
*FIELD* TX
read more
CLONING
In a yeast 2-hybrid screen of a mouse kidney cDNA library with the 9
C-terminal residues of Erbb2 (164870) as bait, Borg et al. (2000) cloned
Erbb2ip, which they called Erbin. They cloned human ERBB2IP by RT-PCR of
a human B-lymphocyte cell line. The deduced 1,371-amino acid protein
contains 16 canonical LRR (leucine-rich repeat) motifs at the N
terminus, followed by an LRR-like domain, proline-rich stretches that
may represent binding sites for SH3 and WW domains, and a C-terminal PDZ
domain. Northern blot analysis revealed a 7.2-kb transcript in most
human and mouse tissues. Western blot analysis indicated a 180-kD
doublet in all tissues tested.
Favre et al. (2001) cloned ERBB2IP in a yeast 2-hybrid screen of a human
keratinocyte cDNA library with the N terminus of bullous pemphigoid
antigen-1 (BPAG1; 113810) as bait. They observed several splice
variants. ERBB2IP was expressed as a doublet of about 6.9 to 7.4 kb in
human keratinocytes and in a keratinocyte cell line. Semiquantitative
RT-PCR indicated numerous transcripts expressed in most tissues. Western
blot analysis showed a 200-kD in differentiated cells but not in
undifferentiated keratinocytes.
Huang et al. (2001) cloned Erbb2ip from mouse muscle, brain, and heart
cDNA libraries in a yeast 2-hybrid screen using Erbb2 as bait. Erbb2ip
was expressed as a 180-kD protein in brain, skeletal muscle, primary
muscle cultures, and muscle cell lines. Erbb2ip expression was found at
a similar level in myoblasts and myotubes, suggesting that expression is
not differentially regulated in muscle. By immunolocalization studies,
they colocalized Erbb2ip with the acetylcholine receptor at the
neuromuscular junction. Both Erbb2 and Erbb2ip were also found in
synaptosomes from adult mouse brain and copurified with postsynaptic
densities.
GENE FUNCTION
Using coimmunoprecipitation, mutation analysis, and GST pull-down
experiments, Borg et al. (2000) determined that ERBB2IP interacts with
nonactivated ERBB2 and that the interaction requires the PDZ domain of
ERBB2IP. They further showed by immunolocalization studies that the 2
proteins colocalize to the basolateral surface of polarized human colon
carcinoma cells and that mutation of the PDZ domain of ERBB2IP causes
mislocalization of ERBB2 in stably transfected canine kidney cells.
By mutation analysis and in vitro binding assays, Favre et al. (2001)
determined that ERBB2IP interacts specifically with BPAG1 and integrin
beta-4 (147557).
Huang et al. (2001) found that mouse Erbb2ip associates with Psd95
(602887). Mutation analysis indicated that the interaction is dependent
upon the PDZ domain of Psd95.
GENE STRUCTURE
Favre et al. (2001) determined that the ERBB2IP gene contains at least
26 exons. Sequence comparison of ERBB2IP variants indicated that the
variants are likely caused by alternate splicing between exons 21 and
26.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the ERBB2IP
gene to chromosome 5 (TMAP WI-31186). Favre et al. (2001) stated that
sequence analysis places the ERBB2IP gene on the long arm of chromosome
5 between D5S427 and D5S647.
*FIELD* RF
1. Borg, J.-P.; Marchetto, S.; Le Bivic, A.; Ollendorff, V.; Jaulin-Bastard,
F.; Saito, H.; Fournier, E.; Adelaide, J.; Margolis, B.; Birnbaum,
D.: ERBIN: a basolateral PDZ protein that interacts with the mammalian
ERBB2/HER2 receptor. Nature Cell Biol. 2: 407-414, 2000.
2. Favre, B.; Fontao, L.; Koster, J.; Shafaatian, R.; Jaunin, F.;
Saurat, J.-H.; Sonnenberg, A.; Borradori, L.: The hemidesmosomal
protein bullous pemphigoid antigen 1 and the integrin beta-4 subunit
bind to ERBIN: molecular cloning of multiple alternative splice variants
of ERBIN and analysis of their tissue expression. J. Biol. Chem. 276:
32427-32436, 2001.
3. Huang, Y. Z.; Wang, Q.; Xiong, W. C.; Mei, L.: Erbin is a protein
concentrated at postsynaptic membranes that interacts with PSD-95. J.
Biol. Chem. 276: 19318-19326, 2001.
*FIELD* CD
Patricia A. Hartz: 5/14/2002
*FIELD* ED
carol: 05/15/2002
carol: 5/15/2002
*RECORD*
*FIELD* NO
606944
*FIELD* TI
*606944 ERBB2 INTERACTING PROTEIN; ERBB2IP
;;DENSIN-180-LIKE PROTEIN; ERBIN
*FIELD* TX
read more
CLONING
In a yeast 2-hybrid screen of a mouse kidney cDNA library with the 9
C-terminal residues of Erbb2 (164870) as bait, Borg et al. (2000) cloned
Erbb2ip, which they called Erbin. They cloned human ERBB2IP by RT-PCR of
a human B-lymphocyte cell line. The deduced 1,371-amino acid protein
contains 16 canonical LRR (leucine-rich repeat) motifs at the N
terminus, followed by an LRR-like domain, proline-rich stretches that
may represent binding sites for SH3 and WW domains, and a C-terminal PDZ
domain. Northern blot analysis revealed a 7.2-kb transcript in most
human and mouse tissues. Western blot analysis indicated a 180-kD
doublet in all tissues tested.
Favre et al. (2001) cloned ERBB2IP in a yeast 2-hybrid screen of a human
keratinocyte cDNA library with the N terminus of bullous pemphigoid
antigen-1 (BPAG1; 113810) as bait. They observed several splice
variants. ERBB2IP was expressed as a doublet of about 6.9 to 7.4 kb in
human keratinocytes and in a keratinocyte cell line. Semiquantitative
RT-PCR indicated numerous transcripts expressed in most tissues. Western
blot analysis showed a 200-kD in differentiated cells but not in
undifferentiated keratinocytes.
Huang et al. (2001) cloned Erbb2ip from mouse muscle, brain, and heart
cDNA libraries in a yeast 2-hybrid screen using Erbb2 as bait. Erbb2ip
was expressed as a 180-kD protein in brain, skeletal muscle, primary
muscle cultures, and muscle cell lines. Erbb2ip expression was found at
a similar level in myoblasts and myotubes, suggesting that expression is
not differentially regulated in muscle. By immunolocalization studies,
they colocalized Erbb2ip with the acetylcholine receptor at the
neuromuscular junction. Both Erbb2 and Erbb2ip were also found in
synaptosomes from adult mouse brain and copurified with postsynaptic
densities.
GENE FUNCTION
Using coimmunoprecipitation, mutation analysis, and GST pull-down
experiments, Borg et al. (2000) determined that ERBB2IP interacts with
nonactivated ERBB2 and that the interaction requires the PDZ domain of
ERBB2IP. They further showed by immunolocalization studies that the 2
proteins colocalize to the basolateral surface of polarized human colon
carcinoma cells and that mutation of the PDZ domain of ERBB2IP causes
mislocalization of ERBB2 in stably transfected canine kidney cells.
By mutation analysis and in vitro binding assays, Favre et al. (2001)
determined that ERBB2IP interacts specifically with BPAG1 and integrin
beta-4 (147557).
Huang et al. (2001) found that mouse Erbb2ip associates with Psd95
(602887). Mutation analysis indicated that the interaction is dependent
upon the PDZ domain of Psd95.
GENE STRUCTURE
Favre et al. (2001) determined that the ERBB2IP gene contains at least
26 exons. Sequence comparison of ERBB2IP variants indicated that the
variants are likely caused by alternate splicing between exons 21 and
26.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the ERBB2IP
gene to chromosome 5 (TMAP WI-31186). Favre et al. (2001) stated that
sequence analysis places the ERBB2IP gene on the long arm of chromosome
5 between D5S427 and D5S647.
*FIELD* RF
1. Borg, J.-P.; Marchetto, S.; Le Bivic, A.; Ollendorff, V.; Jaulin-Bastard,
F.; Saito, H.; Fournier, E.; Adelaide, J.; Margolis, B.; Birnbaum,
D.: ERBIN: a basolateral PDZ protein that interacts with the mammalian
ERBB2/HER2 receptor. Nature Cell Biol. 2: 407-414, 2000.
2. Favre, B.; Fontao, L.; Koster, J.; Shafaatian, R.; Jaunin, F.;
Saurat, J.-H.; Sonnenberg, A.; Borradori, L.: The hemidesmosomal
protein bullous pemphigoid antigen 1 and the integrin beta-4 subunit
bind to ERBIN: molecular cloning of multiple alternative splice variants
of ERBIN and analysis of their tissue expression. J. Biol. Chem. 276:
32427-32436, 2001.
3. Huang, Y. Z.; Wang, Q.; Xiong, W. C.; Mei, L.: Erbin is a protein
concentrated at postsynaptic membranes that interacts with PSD-95. J.
Biol. Chem. 276: 19318-19326, 2001.
*FIELD* CD
Patricia A. Hartz: 5/14/2002
*FIELD* ED
carol: 05/15/2002
carol: 5/15/2002