TTYH2_HUMAN
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 03-AUG-2022, entry version 150.
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 GlyGen; Q9BSA4; 2 sites.
DR iPTMnet; Q9BSA4; -.
DR PhosphoSitePlus; Q9BSA4; -.
DR BioMuta; TTYH2; -.
DR DMDM; 296453009; -.
DR jPOST; Q9BSA4; -.
DR MassIVE; Q9BSA4; -.
DR PaxDb; Q9BSA4; -.
DR PeptideAtlas; Q9BSA4; -.
DR PRIDE; Q9BSA4; -.
DR ProteomicsDB; 78869; -. [Q9BSA4-1]
DR ProteomicsDB; 78870; -. [Q9BSA4-2]
DR Antibodypedia; 61709; 26 antibodies from 16 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 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 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 1072 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; PTHR12424; 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
