ID   TTYH2_HUMAN             Reviewed;         534 AA.
AC   Q9BSA4; B3KX97; Q3B7H8; Q3B7R9; Q6AWB4; Q8NBB7; Q96PK1;
DT   04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT   18-MAY-2010, sequence version 3.
DT   22-FEB-2023, entry version 152.
DE   RecName: Full=Protein tweety homolog 2;
DE            Short=hTTY2;
GN   Name=TTYH2; Synonyms=C17orf29;
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] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX   PubMed=11597145; DOI=10.1006/geno.2001.6629;
RA   Rae F.K., Hooper J.D., Eyre H.J., Sutherland G.R., Nicol D.L.,
RA   Clements J.A.;
RT   "TTYH2, a human homologue of the Drosophila melanogaster gene tweety, is
RT   located on 17q24 and upregulated in renal cell carcinoma.";
RL   Genomics 77:200-207(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE
RP   [LARGE SCALE MRNA] OF 97-534 (ISOFORM 1), AND VARIANTS ALA-265 AND GLU-423.
RC   TISSUE=Hippocampus;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16625196; DOI=10.1038/nature04689;
RA   Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA   Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA   Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA   Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA   DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA   Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA   Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA   LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA   Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA   Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA   Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA   Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA   Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT   "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT   human lineage.";
RL   Nature 440:1045-1049(2006).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS THR-262;
RP   ALA-265 AND GLU-423.
RC   TISSUE=Lymph;
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   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 269-534 (ISOFORM 1).
RC   TISSUE=Cervix;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [6]
RP   FUNCTION.
RX   PubMed=15010458; DOI=10.1074/jbc.m313813200;
RA   Suzuki M., Mizuno A.;
RT   "A novel human Cl(-) channel family related to Drosophila flightless
RT   locus.";
RL   J. Biol. Chem. 279:22461-22468(2004).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-199, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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., Mann M.;
RT   "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT   networks.";
RL   Cell 127:635-648(2006).
RN   [8]
RP   TISSUE SPECIFICITY.
RX   PubMed=17569141; DOI=10.3748/wjg.v13.i19.2717;
RA   Toiyama Y., Mizoguchi A., Kimura K., Hiro J., Inoue Y., Tutumi T., Miki C.,
RA   Kusunoki M.;
RT   "TTYH2, a human homologue of the Drosophila melanogaster gene tweety, is
RT   up-regulated in colon carcinoma and involved in cell proliferation and cell
RT   aggregation.";
RL   World J. Gastroenterol. 13:2717-2721(2007).
CC   -!- FUNCTION: Probable large-conductance Ca(2+)-activated chloride channel.
CC       May play a role in Ca(2+) signal transduction. May be involved in cell
CC       proliferation and cell aggregation. {ECO:0000269|PubMed:15010458}.
CC   -!- INTERACTION:
CC       Q9BSA4; P53618: COPB1; NbExp=7; IntAct=EBI-3959652, EBI-359063;
CC       Q9BSA4; A5PKU2: TUSC5; NbExp=3; IntAct=EBI-3959652, EBI-11988865;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane
CC       protein {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9BSA4-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9BSA4-2; Sequence=VSP_040567;
CC   -!- TISSUE SPECIFICITY: Expressed at higher level in brain and testis and
CC       at lower levels in heart, ovary, spleen and peripheral blood
CC       leukocytes. Up-regulated in 13 of 16 renal cell carcinoma samples
CC       examined. Up-regulated in colon carcinoma.
CC       {ECO:0000269|PubMed:11597145, ECO:0000269|PubMed:17569141}.
CC   -!- SIMILARITY: Belongs to the tweety family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH05168.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC       Sequence=BAC03579.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AF319952; AAL16784.1; -; mRNA.
DR   EMBL; AK126955; BAG54409.1; -; mRNA.
DR   EMBL; AK091085; BAC03579.1; ALT_INIT; mRNA.
DR   EMBL; AC100786; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC005168; AAH05168.1; ALT_INIT; mRNA.
DR   EMBL; BC107492; AAI07493.1; -; mRNA.
DR   EMBL; BC107602; AAI07603.1; -; mRNA.
DR   EMBL; BX647912; CAH10576.1; -; mRNA.
DR   CCDS; CCDS32717.1; -. [Q9BSA4-1]
DR   CCDS; CCDS45770.1; -. [Q9BSA4-2]
DR   RefSeq; NP_116035.5; NM_032646.5. [Q9BSA4-1]
DR   RefSeq; NP_443101.1; NM_052869.1. [Q9BSA4-2]
DR   PDB; 7P54; EM; 3.30 A; A/B=2-534.
DR   PDB; 7P5M; EM; 3.92 A; A/B=2-534.
DR   PDBsum; 7P54; -.
DR   PDBsum; 7P5M; -.
DR   AlphaFoldDB; Q9BSA4; -.
DR   SMR; Q9BSA4; -.
DR   BioGRID; 125087; 25.
DR   IntAct; Q9BSA4; 8.
DR   MINT; Q9BSA4; -.
DR   STRING; 9606.ENSP00000269346; -.
DR   TCDB; 1.A.48.1.3; the anion channel tweety (tweety) family.
DR   GlyCosmos; Q9BSA4; 2 sites, No reported glycans.
DR   GlyGen; Q9BSA4; 2 sites.
DR   iPTMnet; Q9BSA4; -.
DR   PhosphoSitePlus; Q9BSA4; -.
DR   SwissPalm; Q9BSA4; -.
DR   BioMuta; TTYH2; -.
DR   DMDM; 296453009; -.
DR   jPOST; Q9BSA4; -.
DR   MassIVE; Q9BSA4; -.
DR   PaxDb; Q9BSA4; -.
DR   PeptideAtlas; Q9BSA4; -.
DR   ProteomicsDB; 78869; -. [Q9BSA4-1]
DR   ProteomicsDB; 78870; -. [Q9BSA4-2]
DR   Antibodypedia; 61709; 27 antibodies from 17 providers.
DR   DNASU; 94015; -.
DR   Ensembl; ENST00000269346.9; ENSP00000269346.4; ENSG00000141540.11. [Q9BSA4-1]
DR   Ensembl; ENST00000441391.6; ENSP00000394576.2; ENSG00000141540.11. [Q9BSA4-2]
DR   GeneID; 94015; -.
DR   KEGG; hsa:94015; -.
DR   MANE-Select; ENST00000269346.9; ENSP00000269346.4; NM_032646.6; NP_116035.5.
DR   UCSC; uc002jkc.4; human. [Q9BSA4-1]
DR   AGR; HGNC:13877; -.
DR   CTD; 94015; -.
DR   DisGeNET; 94015; -.
DR   GeneCards; TTYH2; -.
DR   HGNC; HGNC:13877; TTYH2.
DR   HPA; ENSG00000141540; Tissue enriched (brain).
DR   MIM; 608855; gene.
DR   neXtProt; NX_Q9BSA4; -.
DR   OpenTargets; ENSG00000141540; -.
DR   PharmGKB; PA37823; -.
DR   VEuPathDB; HostDB:ENSG00000141540; -.
DR   eggNOG; KOG4433; Eukaryota.
DR   GeneTree; ENSGT00950000183060; -.
DR   HOGENOM; CLU_023758_0_1_1; -.
DR   InParanoid; Q9BSA4; -.
DR   OMA; HYSGEFP; -.
DR   OrthoDB; 5393599at2759; -.
DR   PhylomeDB; Q9BSA4; -.
DR   TreeFam; TF319025; -.
DR   PathwayCommons; Q9BSA4; -.
DR   Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR   SignaLink; Q9BSA4; -.
DR   BioGRID-ORCS; 94015; 18 hits in 1152 CRISPR screens.
DR   ChiTaRS; TTYH2; human.
DR   GenomeRNAi; 94015; -.
DR   Pharos; Q9BSA4; Tbio.
DR   PRO; PR:Q9BSA4; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; Q9BSA4; protein.
DR   Bgee; ENSG00000141540; Expressed in inferior vagus X ganglion and 176 other tissues.
DR   ExpressionAtlas; Q9BSA4; baseline and differential.
DR   Genevisible; Q9BSA4; HS.
DR   GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0005229; F:intracellular calcium activated chloride channel activity; IBA:GO_Central.
DR   GO; GO:0072320; F:volume-sensitive chloride channel activity; IBA:GO_Central.
DR   CDD; cd07912; Tweety_N; 1.
DR   InterPro; IPR006990; Tweety.
DR   PANTHER; PTHR12424:SF6; PROTEIN TWEETY HOMOLOG 2; 1.
DR   PANTHER; PTHR12424; TWEETY-RELATED; 1.
DR   Pfam; PF04906; Tweety; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Calcium; Cell membrane; Chloride;
KW   Chloride channel; Glycoprotein; Ion channel; Ion transport; Membrane;
KW   Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix;
KW   Transport.
FT   CHAIN           1..534
FT                   /note="Protein tweety homolog 2"
FT                   /id="PRO_0000312246"
FT   TOPO_DOM        1..44
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        45..65
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        66..87
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        88..108
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        109..213
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        214..234
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        235..240
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        241..261
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        262..388
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        389..409
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        410..534
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         199
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:17081983"
FT   MOD_RES         504
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q3TH73"
FT   CARBOHYD        31
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        283
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         1..321
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_040567"
FT   VARIANT         11
FT                   /note="P -> H (in dbSNP:rs11538875)"
FT                   /id="VAR_037460"
FT   VARIANT         85
FT                   /note="H -> D (in dbSNP:rs11538876)"
FT                   /id="VAR_037461"
FT   VARIANT         262
FT                   /note="A -> T (in dbSNP:rs35682745)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_037462"
FT   VARIANT         265
FT                   /note="S -> A (in dbSNP:rs35999669)"
FT                   /evidence="ECO:0000269|PubMed:14702039,
FT                   ECO:0000269|PubMed:15489334"
FT                   /id="VAR_037463"
FT   VARIANT         409
FT                   /note="A -> E (in dbSNP:rs9892705)"
FT                   /id="VAR_057791"
FT   VARIANT         419
FT                   /note="T -> I (in dbSNP:rs12600564)"
FT                   /id="VAR_037464"
FT   VARIANT         423
FT                   /note="D -> E (in dbSNP:rs9899862)"
FT                   /evidence="ECO:0000269|PubMed:14702039,
FT                   ECO:0000269|PubMed:15489334"
FT                   /id="VAR_037465"
FT   CONFLICT        4
FT                   /note="A -> S (in Ref. 1; AAL16784)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        181
FT                   /note="V -> I (in Ref. 1; AAL16784 and 2; BAC03579)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        388
FT                   /note="G -> V (in Ref. 2; BAG54409)"
FT                   /evidence="ECO:0000305"
FT   HELIX           12..18
FT                   /evidence="ECO:0007829|PDB:7P54"
FT   STRAND          25..27
FT                   /evidence="ECO:0007829|PDB:7P54"
FT   HELIX           39..71
FT                   /evidence="ECO:0007829|PDB:7P54"
FT   HELIX           89..160
FT                   /evidence="ECO:0007829|PDB:7P54"
FT   TURN            161..163
FT                   /evidence="ECO:0007829|PDB:7P54"
FT   HELIX           165..186
FT                   /evidence="ECO:0007829|PDB:7P54"
FT   HELIX           192..236
FT                   /evidence="ECO:0007829|PDB:7P54"
FT   HELIX           239..275
FT                   /evidence="ECO:0007829|PDB:7P54"
FT   HELIX           277..284
FT                   /evidence="ECO:0007829|PDB:7P54"
FT   STRAND          285..289
FT                   /evidence="ECO:0007829|PDB:7P54"
FT   HELIX           291..298
FT                   /evidence="ECO:0007829|PDB:7P54"
FT   STRAND          302..304
FT                   /evidence="ECO:0007829|PDB:7P54"
FT   HELIX           309..336
FT                   /evidence="ECO:0007829|PDB:7P54"
FT   HELIX           342..364
FT                   /evidence="ECO:0007829|PDB:7P54"
FT   HELIX           367..382
FT                   /evidence="ECO:0007829|PDB:7P54"
FT   HELIX           385..408
FT                   /evidence="ECO:0007829|PDB:7P54"
FT   HELIX           410..415
FT                   /evidence="ECO:0007829|PDB:7P54"
SQ   SEQUENCE   534 AA;  58772 MW;  CD59065DD53B309C CRC64;
     MQAARVDYIA PWWVVWLHSV PHVGLRLQPV NSTFSPGDES YQESLLFLGL VAAVCLGLNL
     IFLVAYLVCA CHCRRDDAVQ TKQHHSCCIT WTAVVAGLIC CAAVGVGFYG NSETNDGAYQ
     LMYSLDDANH TFSGIDALVS GTTQKMKVDL EQHLARLSEI FAARGDYLQT LKFIQQMAGS
     VVVQLSGLPV WREVTMELTK LSDQTGYVEY YRWLSYLLLF ILDLVICLIA CLGLAKRSKC
     LLASMLCCGA LSLLLSWASL AADGSAAVAT SDFCVAPDTF ILNVTEGQIS TEVTRYYLYC
     SQSGSSPFQQ TLTTFQRALT TMQIQVAGLL QFAVPLFSTA EEDLLAIQLL LNSSESSLHQ
     LTAMVDCRGL HKDYLDALAG ICYDGLQGLL YLGLFSFLAA LAFSTMICAG PRAWKHFTTR
     NRDYDDIDDD DPFNPQAWRM AAHSPPRGQL HSFCSYSSGL GSQTSLQPPA QTISNAPVSE
     YMNQAMLFGR NPRYENVPLI GRASPPPTYS PSMRATYLSV ADEHLRHYGN QFPA
//