ID   INSM2_HUMAN             Reviewed;         566 AA.
AC   Q96T92; A1L432; J9Y024; Q8N8K7; Q96Q84;
DT   29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT   18-MAY-2010, sequence version 3.
DT   24-JAN-2024, entry version 154.
DE   RecName: Full=Insulinoma-associated protein 2;
DE   AltName: Full=Zinc finger protein IA-6;
GN   Name=INSM2; Synonyms=IA6; ORFNames=Nbla106;
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 [MRNA], AND VARIANT GLY-206.
RA   Cai T., Notkins A.L.;
RT   "A novel insulinoma-associated gene IA-6 with C2H2-type zinc finger motifs
RT   expressed in neuroendocrine tissues.";
RL   Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLY-206.
RA   Halford S., Broadgate S.L.;
RT   "Insm2 is expressed in the developing mammalian retina.";
RL   Submitted (JUL-2012) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-206.
RC   TISSUE=Neuroblastoma;
RX   PubMed=12880961; DOI=10.1016/s0304-3835(03)00085-5;
RA   Ohira M., Morohashi A., Nakamura Y., Isogai E., Furuya K., Hamano S.,
RA   Machida T., Aoyama M., Fukumura M., Miyazaki K., Suzuki Y., Sugano S.,
RA   Hirato J., Nakagawara A.;
RT   "Neuroblastoma oligo-capping cDNA project: toward the understanding of the
RT   genesis and biology of neuroblastoma.";
RL   Cancer Lett. 197:63-68(2003).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
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   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12508121; DOI=10.1038/nature01348;
RA   Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA   Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA   Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA   Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA   Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA   Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA   Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA   Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA   Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA   Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA   Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA   Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA   Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA   Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA   Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA   Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA   Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA   Waterston R., Hood L., Weissenbach J.;
RT   "The DNA sequence and analysis of human chromosome 14.";
RL   Nature 421:601-607(2003).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLY-206.
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   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-206.
RC   TISSUE=Brain;
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   [8]
RP   DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RX   PubMed=21343251; DOI=10.1210/en.2010-1065;
RA   Cai T., Chen X., Wang R., Xu H., You Y., Zhang T., Lan M.S., Notkins A.L.;
RT   "Expression of insulinoma-associated 2 (INSM2) in pancreatic islet cells is
RT   regulated by the transcription factors Ngn3 and NeuroD1.";
RL   Endocrinology 152:1961-1969(2011).
CC   -!- FUNCTION: May function as a growth suppressor or tumor suppressor in
CC       liver cells and in certain neurons. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Expressed in heart, liver, skeletal muscle, kidney
CC       and pancreas, and, to a lesser extent, in brain, lung and spleen. In
CC       the pancreas, expressed in islet cells, including insulin- and
CC       glucagon-producing alpha- and beta-cells, but not in acinar cells (at
CC       protein level). Detected in adrenal glands, particularly in the deeper
CC       layer of the cortex (at protein level). {ECO:0000269|PubMed:21343251}.
CC   -!- DEVELOPMENTAL STAGE: Expressed in the islet-like cells of the
CC       developing pancreas and epithelial cells of the duodenum from
CC       gestational weeks 8 to 20 (at protein level).
CC       {ECO:0000269|PubMed:21343251}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAK49393.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; AF260323; AAK49393.1; ALT_FRAME; mRNA.
DR   EMBL; JX403968; AFS33107.1; -; mRNA.
DR   EMBL; AB037912; BAB69042.1; -; mRNA.
DR   EMBL; AK096639; BAC04830.1; -; mRNA.
DR   EMBL; AL160231; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471078; EAW65872.1; -; Genomic_DNA.
DR   EMBL; BC130377; AAI30378.1; -; mRNA.
DR   EMBL; BC130379; AAI30380.1; -; mRNA.
DR   CCDS; CCDS9657.1; -.
DR   RefSeq; NP_115983.3; NM_032594.3.
DR   AlphaFoldDB; Q96T92; -.
DR   BioGRID; 124201; 4.
DR   IntAct; Q96T92; 1.
DR   STRING; 9606.ENSP00000306523; -.
DR   iPTMnet; Q96T92; -.
DR   PhosphoSitePlus; Q96T92; -.
DR   BioMuta; INSM2; -.
DR   DMDM; 296439326; -.
DR   MassIVE; Q96T92; -.
DR   PaxDb; 9606-ENSP00000306523; -.
DR   PeptideAtlas; Q96T92; -.
DR   ProteomicsDB; 78217; -.
DR   Antibodypedia; 23212; 112 antibodies from 21 providers.
DR   DNASU; 84684; -.
DR   Ensembl; ENST00000307169.4; ENSP00000306523.3; ENSG00000168348.4.
DR   GeneID; 84684; -.
DR   KEGG; hsa:84684; -.
DR   MANE-Select; ENST00000307169.4; ENSP00000306523.3; NM_032594.4; NP_115983.3.
DR   UCSC; uc001wth.1; human.
DR   AGR; HGNC:17539; -.
DR   CTD; 84684; -.
DR   DisGeNET; 84684; -.
DR   GeneCards; INSM2; -.
DR   HGNC; HGNC:17539; INSM2.
DR   HPA; ENSG00000168348; Tissue enhanced (brain, retina).
DR   MIM; 614027; gene.
DR   neXtProt; NX_Q96T92; -.
DR   OpenTargets; ENSG00000168348; -.
DR   PharmGKB; PA134899231; -.
DR   VEuPathDB; HostDB:ENSG00000168348; -.
DR   eggNOG; KOG3993; Eukaryota.
DR   GeneTree; ENSGT00940000162391; -.
DR   HOGENOM; CLU_033476_1_0_1; -.
DR   InParanoid; Q96T92; -.
DR   OMA; EIFMCPY; -.
DR   OrthoDB; 5316972at2759; -.
DR   PhylomeDB; Q96T92; -.
DR   TreeFam; TF320538; -.
DR   PathwayCommons; Q96T92; -.
DR   SignaLink; Q96T92; -.
DR   BioGRID-ORCS; 84684; 18 hits in 1166 CRISPR screens.
DR   GenomeRNAi; 84684; -.
DR   Pharos; Q96T92; Tbio.
DR   PRO; PR:Q96T92; -.
DR   Proteomes; UP000005640; Chromosome 14.
DR   RNAct; Q96T92; Protein.
DR   Bgee; ENSG00000168348; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 55 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0017053; C:transcription repressor complex; IBA:GO_Central.
DR   GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IBA:GO_Central.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR   GO; GO:0010564; P:regulation of cell cycle process; IBA:GO_Central.
DR   Gene3D; 3.30.160.60; Classic Zinc Finger; 3.
DR   InterPro; IPR042972; INSM1/2.
DR   InterPro; IPR036236; Znf_C2H2_sf.
DR   InterPro; IPR013087; Znf_C2H2_type.
DR   PANTHER; PTHR15065; INSULINOMA-ASSOCIATED 1; 1.
DR   PANTHER; PTHR15065:SF6; INSULINOMA-ASSOCIATED PROTEIN 2; 1.
DR   Pfam; PF00096; zf-C2H2; 2.
DR   SMART; SM00355; ZnF_C2H2; 5.
DR   SUPFAM; SSF57667; beta-beta-alpha zinc fingers; 2.
DR   PROSITE; PS00028; ZINC_FINGER_C2H2_1; 4.
DR   PROSITE; PS50157; ZINC_FINGER_C2H2_2; 3.
DR   Genevisible; Q96T92; HS.
PE   1: Evidence at protein level;
KW   Cytoplasm; DNA-binding; Metal-binding; Nucleus; Reference proteome; Repeat;
KW   Transcription; Transcription regulation; Zinc; Zinc-finger.
FT   CHAIN           1..566
FT                   /note="Insulinoma-associated protein 2"
FT                   /id="PRO_0000331576"
FT   ZN_FING         263..283
FT                   /note="C2H2-type 1; atypical"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         291..313
FT                   /note="C2H2-type 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         426..448
FT                   /note="C2H2-type 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         470..492
FT                   /note="C2H2-type 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         525..548
FT                   /note="C2H2-type 5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   REGION          1..20
FT                   /note="SNAG domain"
FT                   /evidence="ECO:0000250"
FT   REGION          32..117
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          310..418
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        327..345
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        354..373
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VARIANT         206
FT                   /note="D -> G (in dbSNP:rs1958260)"
FT                   /evidence="ECO:0000269|PubMed:12880961,
FT                   ECO:0000269|PubMed:15489334, ECO:0000269|Ref.1,
FT                   ECO:0000269|Ref.2, ECO:0000269|Ref.6"
FT                   /id="VAR_070885"
FT   CONFLICT        198
FT                   /note="E -> G (in Ref. 3; BAB69042)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        330
FT                   /note="G -> E (in Ref. 4; BAC04830)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        390
FT                   /note="L -> V (in Ref. 1; AAK49393)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   566 AA;  59491 MW;  3603B8ACC8920631 CRC64;
     MPRGFLVKRT KRTGGLYRVR LAERVFPLLG PQGAPPFLEE APSASLPGAE RATPPTREEP
     GKGLTAEAAR EQSGSPCRAA GVSPGTGGRE GAEWRAGGRE GPGPSPSPSP SPAKPAGAEL
     RRAFLERCLS SPVSAESFPG GAAAVAAFSC SVAPAAAPTP GEQFLLPLRA PFPEPALQPD
     PAPLSAALQS LKRAAGGERR GKAPTDCASG PAAAGIKKPK AMRKLSFADE VTTSPVLGLK
     IKEEEPGAPS RGLGGSRTPL GEFICQLCKE QYADPFALAQ HRCSRIVRVE YRCPECDKVF
     SCPANLASHR RWHKPRPAAA NAATVSSADG KPPSSSSSSS RDSGAIASFL AEGKENSRIE
     RTADQHPQAR DSSGADQHPD SAPRQGLQVL THPEPPLPQG PYTEGVLGRR VPVPGSTSGG
     RGSEIFVCPY CHKKFRRQAY LRKHLSTHEA GSARALAPGF GSERGAPLAF ACPLCGAHFP
     TADIREKHRL WHAVREELLL PALAGAPPET SGPSGPSDGS AQQIFSCKHC PSTFFSSPGL
     TRHINKCHPS ESRQVLLLQM PLRPGC
//