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ISL2_HUMAN
ID   ISL2_HUMAN              Reviewed;         359 AA.
AC   Q96A47; B3KM37;
DT   15-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   03-AUG-2022, entry version 167.
DE   RecName: Full=Insulin gene enhancer protein ISL-2;
DE            Short=Islet-2;
GN   Name=ISL2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Embryo;
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., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., 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., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   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   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Eye;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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   [5]
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., Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT   refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-279, AND IDENTIFICATION BY
RP   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   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-154 AND SER-157, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma, and Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
CC   -!- FUNCTION: Transcriptional factor that defines subclasses of motoneurons
CC       that segregate into columns in the spinal cord and select distinct axon
CC       pathways. {ECO:0000250}.
CC   -!- SUBUNIT: Interacts with LHX4. {ECO:0000250}.
CC   -!- INTERACTION:
CC       Q96A47; Q86U70-2: LDB1; NbExp=3; IntAct=EBI-18560216, EBI-11979761;
CC       Q96A47; Q969G2: LHX4; NbExp=4; IntAct=EBI-18560216, EBI-2865388;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108}.
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DR   EMBL; AK001022; BAG50849.1; -; mRNA.
DR   EMBL; CH471136; EAW99220.1; -; Genomic_DNA.
DR   EMBL; BC011967; AAH11967.1; -; mRNA.
DR   EMBL; BC012136; AAH12136.1; -; mRNA.
DR   CCDS; CCDS10290.1; -.
DR   RefSeq; NP_665804.1; NM_145805.2.
DR   AlphaFoldDB; Q96A47; -.
DR   SMR; Q96A47; -.
DR   BioGRID; 122318; 38.
DR   IntAct; Q96A47; 17.
DR   MINT; Q96A47; -.
DR   STRING; 9606.ENSP00000290759; -.
DR   iPTMnet; Q96A47; -.
DR   PhosphoSitePlus; Q96A47; -.
DR   BioMuta; ISL2; -.
DR   DMDM; 20978495; -.
DR   EPD; Q96A47; -.
DR   jPOST; Q96A47; -.
DR   MassIVE; Q96A47; -.
DR   MaxQB; Q96A47; -.
DR   PaxDb; Q96A47; -.
DR   PeptideAtlas; Q96A47; -.
DR   PRIDE; Q96A47; -.
DR   ProteomicsDB; 75911; -.
DR   Antibodypedia; 27431; 227 antibodies from 29 providers.
DR   DNASU; 64843; -.
DR   Ensembl; ENST00000290759.9; ENSP00000290759.4; ENSG00000159556.10.
DR   GeneID; 64843; -.
DR   KEGG; hsa:64843; -.
DR   MANE-Select; ENST00000290759.9; ENSP00000290759.4; NM_145805.3; NP_665804.1.
DR   UCSC; uc002bbw.2; human.
DR   CTD; 64843; -.
DR   DisGeNET; 64843; -.
DR   GeneCards; ISL2; -.
DR   HGNC; HGNC:18524; ISL2.
DR   HPA; ENSG00000159556; Tissue enhanced (pituitary gland, prostate, vagina).
DR   MIM; 609481; gene.
DR   neXtProt; NX_Q96A47; -.
DR   OpenTargets; ENSG00000159556; -.
DR   PharmGKB; PA38566; -.
DR   VEuPathDB; HostDB:ENSG00000159556; -.
DR   eggNOG; KOG0490; Eukaryota.
DR   GeneTree; ENSGT00940000153731; -.
DR   HOGENOM; CLU_027802_2_0_1; -.
DR   InParanoid; Q96A47; -.
DR   OMA; QMRDMAV; -.
DR   OrthoDB; 948890at2759; -.
DR   PhylomeDB; Q96A47; -.
DR   TreeFam; TF315442; -.
DR   PathwayCommons; Q96A47; -.
DR   SignaLink; Q96A47; -.
DR   SIGNOR; Q96A47; -.
DR   BioGRID-ORCS; 64843; 14 hits in 1100 CRISPR screens.
DR   GenomeRNAi; 64843; -.
DR   Pharos; Q96A47; Tbio.
DR   PRO; PR:Q96A47; -.
DR   Proteomes; UP000005640; Chromosome 15.
DR   RNAct; Q96A47; protein.
DR   Bgee; ENSG00000159556; Expressed in esophagogastric junction muscularis propria and 64 other tissues.
DR   ExpressionAtlas; Q96A47; baseline and differential.
DR   Genevisible; Q96A47; HS.
DR   GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR   GO; GO:0003677; F:DNA binding; ISS:BHF-UCL.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR   GO; GO:0007409; P:axonogenesis; IBA:GO_Central.
DR   GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl.
DR   GO; GO:0048666; P:neuron development; TAS:BHF-UCL.
DR   GO; GO:0048665; P:neuron fate specification; IBA:GO_Central.
DR   GO; GO:0048935; P:peripheral nervous system neuron development; TAS:BHF-UCL.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0031290; P:retinal ganglion cell axon guidance; IEA:Ensembl.
DR   GO; GO:0021520; P:spinal cord motor neuron cell fate specification; IEA:Ensembl.
DR   GO; GO:0021524; P:visceral motor neuron differentiation; IEA:Ensembl.
DR   CDD; cd00086; homeodomain; 1.
DR   InterPro; IPR009057; Homeobox-like_sf.
DR   InterPro; IPR017970; Homeobox_CS.
DR   InterPro; IPR001356; Homeobox_dom.
DR   InterPro; IPR001781; Znf_LIM.
DR   Pfam; PF00046; Homeodomain; 1.
DR   Pfam; PF00412; LIM; 2.
DR   SMART; SM00389; HOX; 1.
DR   SMART; SM00132; LIM; 2.
DR   SUPFAM; SSF46689; SSF46689; 1.
DR   PROSITE; PS00027; HOMEOBOX_1; 1.
DR   PROSITE; PS50071; HOMEOBOX_2; 1.
DR   PROSITE; PS00478; LIM_DOMAIN_1; 2.
DR   PROSITE; PS50023; LIM_DOMAIN_2; 2.
PE   1: Evidence at protein level;
KW   Developmental protein; DNA-binding; Homeobox; LIM domain; Metal-binding;
KW   Nucleus; Phosphoprotein; Reference proteome; Repeat; Zinc.
FT   CHAIN           1..359
FT                   /note="Insulin gene enhancer protein ISL-2"
FT                   /id="PRO_0000075752"
FT   DOMAIN          25..86
FT                   /note="LIM zinc-binding 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT   DOMAIN          87..149
FT                   /note="LIM zinc-binding 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT   DNA_BIND        191..250
FT                   /note="Homeobox"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   REGION          151..191
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          272..301
FT                   /note="LIM-binding domain (LID)"
FT                   /evidence="ECO:0000250"
FT   REGION          326..359
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         154
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         157
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         279
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19690332"
SQ   SEQUENCE   359 AA;  39768 MW;  2162FB3D430EE4BE CRC64;
     MVDIIFHYPF LGAMGDHSKK KPGTAMCVGC GSQIHDQFIL RVSPDLEWHA ACLKCAECSQ
     YLDETCTCFV RDGKTYCKRD YVRLFGIKCA KCQVGFSSSD LVMRARDSVY HIECFRCSVC
     SRQLLPGDEF SLREHELLCR ADHGLLLERA AAGSPRSPGP LPGARGLHLP DAGSGRQPAL
     RPHVHKQTEK TTRVRTVLNE KQLHTLRTCY AANPRPDALM KEQLVEMTGL SPRVIRVWFQ
     NKRCKDKKKS ILMKQLQQQQ HSDKTSLQGL TGTPLVAGSP IRHENAVQGS AVEVQTYQPP
     WKALSEFALQ SDLDQPAFQQ LVSFSESGSL GNSSGSDVTS LSSQLPDTPN SMVPSPVET
 
 
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