ID   TACD2_HUMAN             Reviewed;         323 AA.
AC   P09758; Q15658; Q6FG48; Q7Z7Q4; Q96QD2;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   13-NOV-2007, sequence version 3.
DT   27-MAR-2024, entry version 223.
DE   RecName: Full=Tumor-associated calcium signal transducer 2;
DE   AltName: Full=Cell surface glycoprotein Trop-2;
DE   AltName: Full=Membrane component chromosome 1 surface marker 1;
DE   AltName: Full=Pancreatic carcinoma marker protein GA733-1;
DE   Flags: Precursor;
GN   Name=TACSTD2; Synonyms=GA733-1, M1S1, TROP2;
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 [GENOMIC DNA], AND VARIANT ASP-147.
RC   TISSUE=Placenta;
RX   PubMed=2911574; DOI=10.1073/pnas.86.1.27;
RA   Linnenbach A.J., Wojcierowski J., Wu S., Pyrc J.J., Ross A.H.,
RA   Dietzschold B., Speicher D., Koprowski H.;
RT   "Sequence investigation of the major gastrointestinal tumor-associated
RT   antigen gene family, GA733.";
RL   Proc. Natl. Acad. Sci. U.S.A. 86:27-31(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLU-216.
RC   TISSUE=Placenta;
RX   PubMed=8382772; DOI=10.1128/mcb.13.3.1507-1515.1993;
RA   Linnenbach A.J., Seng B.A., Wu S., Robbins S., Scollon M., Pyrc J.J.,
RA   Druck T., Huebner K.;
RT   "Retroposition in a family of carcinoma-associated antigen genes.";
RL   Mol. Cell. Biol. 13:1507-1515(1993).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=7665234; DOI=10.1002/ijc.2910620520;
RA   Fornaro M., Dell'Arciprete R., Stella S., Bucci C., Nutini M., Capri M.G.,
RA   Alberti S.;
RT   "Cloning of the gene encoding Trop-2, a cell-surface glycoprotein expressed
RT   by human carcinomas.";
RL   Int. J. Cancer 62:610-618(1995).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA   Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA   LaBaer J.;
RT   "Cloning of human full open reading frames in Gateway(TM) system entry
RT   vector (pDONR201).";
RL   Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA   Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA   Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA   Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA   Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA   Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA   Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA   Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA   Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA   McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA   Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA   White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA   Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA   Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA   Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLU-216.
RC   TISSUE=Pancreas;
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   INVOLVEMENT IN GDLD.
RX   PubMed=10192395; DOI=10.1038/7759;
RA   Tsujikawa M., Kurahashi H., Tanaka T., Nishida K., Shimomura Y., Tano Y.,
RA   Nakamura Y.;
RT   "Identification of the gene responsible for gelatinous drop-like corneal
RT   dystrophy.";
RL   Nat. Genet. 21:420-423(1999).
RN   [9]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [10]
RP   VARIANT ALA-173.
RX   PubMed=11687514;
RA   Tasa G., Kals J., Muru K., Juronen E., Piirsoo A., Veromann S., Janes S.,
RA   Mikelsaar A.V., Lang A.;
RT   "A novel mutation in the M1S1 gene responsible for gelatinous droplike
RT   corneal dystrophy.";
RL   Invest. Ophthalmol. Vis. Sci. 42:2762-2764(2001).
CC   -!- FUNCTION: May function as a growth factor receptor.
CC   -!- INTERACTION:
CC       P09758; Q8IUG1: KRTAP1-3; NbExp=3; IntAct=EBI-4324738, EBI-11749135;
CC       P09758; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-4324738, EBI-10171774;
CC       P09758; Q701N4: KRTAP5-2; NbExp=3; IntAct=EBI-4324738, EBI-11958178;
CC       P09758; Q5TA81: LCE2C; NbExp=3; IntAct=EBI-4324738, EBI-11973993;
CC   -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC   -!- TISSUE SPECIFICITY: Placenta, pancreatic carcinoma cell lines.
CC   -!- PTM: The N-terminus is blocked.
CC   -!- DISEASE: Corneal dystrophy, gelatinous drop-like (GDLD) [MIM:204870]: A
CC       form of lattice corneal dystrophy, a class of inherited stromal
CC       amyloidoses characterized by pathognomonic branching lattice figures in
CC       the cornea. GDLD is an autosomal recessive disorder characterized by
CC       severe corneal amyloidosis leading to blindness. Clinical
CC       manifestations, which appear in the first decade of life, include
CC       blurred vision, photophobia, and foreign-body sensation. By the third
CC       decade, raised, yellowish-gray, gelatinous masses severely impair
CC       visual acuity. {ECO:0000269|PubMed:10192395}. Note=The disease is
CC       caused by variants affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the EPCAM family. {ECO:0000305}.
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DR   EMBL; X13425; CAA31781.1; -; mRNA.
DR   EMBL; J04152; AAA52505.1; -; Genomic_DNA.
DR   EMBL; X77753; CAA54799.1; -; mRNA.
DR   EMBL; X77754; CAA54801.1; -; mRNA.
DR   EMBL; BT007255; AAP35919.1; -; mRNA.
DR   EMBL; CR542260; CAG47056.1; -; mRNA.
DR   EMBL; AL035411; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC009409; AAH09409.1; -; mRNA.
DR   CCDS; CCDS609.1; -.
DR   PIR; A48149; A48149.
DR   RefSeq; NP_002344.2; NM_002353.2.
DR   PDB; 2MAE; NMR; -; A=298-323.
DR   PDB; 2MVK; NMR; -; A=298-323.
DR   PDB; 2MVL; NMR; -; A=298-323.
DR   PDB; 7E5M; X-ray; 3.20 A; A/B=33-268.
DR   PDB; 7E5N; X-ray; 3.20 A; A/B/C/D=1-323.
DR   PDB; 7PEE; X-ray; 2.81 A; A/B/C/D=31-274.
DR   PDBsum; 2MAE; -.
DR   PDBsum; 2MVK; -.
DR   PDBsum; 2MVL; -.
DR   PDBsum; 7E5M; -.
DR   PDBsum; 7E5N; -.
DR   PDBsum; 7PEE; -.
DR   AlphaFoldDB; P09758; -.
DR   BMRB; P09758; -.
DR   SMR; P09758; -.
DR   BioGRID; 110248; 213.
DR   IntAct; P09758; 14.
DR   STRING; 9606.ENSP00000360269; -.
DR   ChEMBL; CHEMBL3856163; -.
DR   DrugBank; DB12893; Sacituzumab govitecan.
DR   GlyConnect; 1865; 8 N-Linked glycans (3 sites).
DR   GlyCosmos; P09758; 4 sites, 8 glycans.
DR   GlyGen; P09758; 6 sites, 8 N-linked glycans (3 sites), 2 O-linked glycans (2 sites).
DR   iPTMnet; P09758; -.
DR   MetOSite; P09758; -.
DR   PhosphoSitePlus; P09758; -.
DR   BioMuta; TACSTD2; -.
DR   DMDM; 160113102; -.
DR   CPTAC; CPTAC-1510; -.
DR   EPD; P09758; -.
DR   jPOST; P09758; -.
DR   MassIVE; P09758; -.
DR   MaxQB; P09758; -.
DR   PaxDb; 9606-ENSP00000360269; -.
DR   PeptideAtlas; P09758; -.
DR   ProteomicsDB; 52267; -.
DR   Pumba; P09758; -.
DR   ABCD; P09758; 2 sequenced antibodies.
DR   Antibodypedia; 33262; 848 antibodies from 46 providers.
DR   CPTC; P09758; 3 antibodies.
DR   DNASU; 4070; -.
DR   Ensembl; ENST00000371225.4; ENSP00000360269.2; ENSG00000184292.7.
DR   GeneID; 4070; -.
DR   KEGG; hsa:4070; -.
DR   MANE-Select; ENST00000371225.4; ENSP00000360269.2; NM_002353.3; NP_002344.2.
DR   UCSC; uc001cyz.5; human.
DR   AGR; HGNC:11530; -.
DR   CTD; 4070; -.
DR   DisGeNET; 4070; -.
DR   GeneCards; TACSTD2; -.
DR   HGNC; HGNC:11530; TACSTD2.
DR   HPA; ENSG00000184292; Tissue enhanced (esophagus, salivary gland, skin).
DR   MalaCards; TACSTD2; -.
DR   MIM; 137290; gene.
DR   MIM; 204870; phenotype.
DR   neXtProt; NX_P09758; -.
DR   OpenTargets; ENSG00000184292; -.
DR   Orphanet; 98957; Gelatinous drop-like corneal dystrophy.
DR   PharmGKB; PA36305; -.
DR   VEuPathDB; HostDB:ENSG00000184292; -.
DR   eggNOG; ENOG502QVSU; Eukaryota.
DR   GeneTree; ENSGT00390000018245; -.
DR   HOGENOM; CLU_075326_0_0_1; -.
DR   InParanoid; P09758; -.
DR   OMA; CTCATNK; -.
DR   OrthoDB; 5305981at2759; -.
DR   PhylomeDB; P09758; -.
DR   TreeFam; TF332767; -.
DR   PathwayCommons; P09758; -.
DR   SignaLink; P09758; -.
DR   SIGNOR; P09758; -.
DR   BioGRID-ORCS; 4070; 4 hits in 1143 CRISPR screens.
DR   ChiTaRS; TACSTD2; human.
DR   GeneWiki; TACSTD2; -.
DR   GenomeRNAi; 4070; -.
DR   Pharos; P09758; Tclin.
DR   PRO; PR:P09758; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; P09758; Protein.
DR   Bgee; ENSG00000184292; Expressed in palpebral conjunctiva and 153 other cell types or tissues.
DR   GO; GO:0009925; C:basal plasma membrane; ISS:UniProtKB.
DR   GO; GO:0005829; C:cytosol; TAS:ProtInc.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0016328; C:lateral plasma membrane; ISS:UniProtKB.
DR   GO; GO:0016020; C:membrane; TAS:ProtInc.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0090191; P:negative regulation of branching involved in ureteric bud morphogenesis; ISS:UniProtKB.
DR   GO; GO:2000146; P:negative regulation of cell motility; ISS:UniProtKB.
DR   GO; GO:0010633; P:negative regulation of epithelial cell migration; ISS:UniProtKB.
DR   GO; GO:1900028; P:negative regulation of ruffle assembly; ISS:UniProtKB.
DR   GO; GO:0051497; P:negative regulation of stress fiber assembly; ISS:UniProtKB.
DR   GO; GO:1900025; P:negative regulation of substrate adhesion-dependent cell spreading; ISS:UniProtKB.
DR   GO; GO:2000738; P:positive regulation of stem cell differentiation; IBA:GO_Central.
DR   GO; GO:0050678; P:regulation of epithelial cell proliferation; IEA:Ensembl.
DR   GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR   GO; GO:0060675; P:ureteric bud morphogenesis; IEA:Ensembl.
DR   GO; GO:0007601; P:visual perception; TAS:ProtInc.
DR   CDD; cd00191; TY; 1.
DR   Gene3D; 4.10.800.10; Thyroglobulin type-1; 1.
DR   InterPro; IPR049420; EPCAM-Trop-2_C.
DR   InterPro; IPR043406; EPCAM/Trop-2.
DR   InterPro; IPR041630; EpCAM_N.
DR   InterPro; IPR000716; Thyroglobulin_1.
DR   InterPro; IPR036857; Thyroglobulin_1_sf.
DR   PANTHER; PTHR14168; TUMOR-ASSOCIATED CALCIUM SIGNAL TRANSDUCER; 1.
DR   PANTHER; PTHR14168:SF5; TUMOR-ASSOCIATED CALCIUM SIGNAL TRANSDUCER 2; 1.
DR   Pfam; PF21283; EPCAM-Trop-2_C; 1.
DR   Pfam; PF18635; EpCAM_N; 1.
DR   Pfam; PF00086; Thyroglobulin_1; 1.
DR   SMART; SM00211; TY; 1.
DR   SUPFAM; SSF57610; Thyroglobulin type-1 domain; 1.
DR   PROSITE; PS00484; THYROGLOBULIN_1_1; 1.
DR   PROSITE; PS51162; THYROGLOBULIN_1_2; 1.
DR   Genevisible; P09758; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Amyloid; Amyloidosis; Corneal dystrophy; Disulfide bond;
KW   Glycoprotein; Membrane; Reference proteome; Sensory transduction; Signal;
KW   Transmembrane; Transmembrane helix; Tumor antigen; Vision.
FT   SIGNAL          1..26
FT                   /evidence="ECO:0000255"
FT   CHAIN           27..323
FT                   /note="Tumor-associated calcium signal transducer 2"
FT                   /id="PRO_0000022468"
FT   TOPO_DOM        27..274
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        275..297
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        298..323
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          70..145
FT                   /note="Thyroglobulin type-1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00500"
FT   CARBOHYD        33
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        120
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        168
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        208
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        73..108
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00500"
FT   DISULFID        119..125
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00500"
FT   DISULFID        127..145
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00500"
FT   VARIANT         147
FT                   /note="E -> D (in dbSNP:rs1062964)"
FT                   /evidence="ECO:0000269|PubMed:2911574"
FT                   /id="VAR_051407"
FT   VARIANT         173
FT                   /note="D -> A (in dbSNP:rs35075952)"
FT                   /evidence="ECO:0000269|PubMed:11687514"
FT                   /id="VAR_012451"
FT   VARIANT         216
FT                   /note="D -> E (in dbSNP:rs14008)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:8382772"
FT                   /id="VAR_016981"
FT   CONFLICT        220
FT                   /note="G -> D (in Ref. 5; CAG47056)"
FT                   /evidence="ECO:0000305"
FT   STRAND          41..46
FT                   /evidence="ECO:0007829|PDB:7PEE"
FT   HELIX           49..51
FT                   /evidence="ECO:0007829|PDB:7PEE"
FT   STRAND          54..57
FT                   /evidence="ECO:0007829|PDB:7PEE"
FT   TURN            58..60
FT                   /evidence="ECO:0007829|PDB:7PEE"
FT   HELIX           72..80
FT                   /evidence="ECO:0007829|PDB:7PEE"
FT   STRAND          97..99
FT                   /evidence="ECO:0007829|PDB:7PEE"
FT   STRAND          112..114
FT                   /evidence="ECO:0007829|PDB:7E5M"
FT   STRAND          116..120
FT                   /evidence="ECO:0007829|PDB:7PEE"
FT   TURN            121..123
FT                   /evidence="ECO:0007829|PDB:7PEE"
FT   STRAND          124..129
FT                   /evidence="ECO:0007829|PDB:7PEE"
FT   STRAND          151..160
FT                   /evidence="ECO:0007829|PDB:7PEE"
FT   HELIX           169..182
FT                   /evidence="ECO:0007829|PDB:7PEE"
FT   HELIX           188..190
FT                   /evidence="ECO:0007829|PDB:7PEE"
FT   STRAND          191..197
FT                   /evidence="ECO:0007829|PDB:7PEE"
FT   STRAND          200..206
FT                   /evidence="ECO:0007829|PDB:7PEE"
FT   HELIX           209..211
FT                   /evidence="ECO:0007829|PDB:7PEE"
FT   HELIX           219..230
FT                   /evidence="ECO:0007829|PDB:7PEE"
FT   STRAND          237..239
FT                   /evidence="ECO:0007829|PDB:7PEE"
FT   STRAND          253..264
FT                   /evidence="ECO:0007829|PDB:7PEE"
FT   HELIX           299..317
FT                   /evidence="ECO:0007829|PDB:2MAE"
SQ   SEQUENCE   323 AA;  35709 MW;  C8081FBE1D0B9F73 CRC64;
     MARGPGLAPP PLRLPLLLLV LAAVTGHTAA QDNCTCPTNK MTVCSPDGPG GRCQCRALGS
     GMAVDCSTLT SKCLLLKARM SAPKNARTLV RPSEHALVDN DGLYDPDCDP EGRFKARQCN
     QTSVCWCVNS VGVRRTDKGD LSLRCDELVR THHILIDLRH RPTAGAFNHS DLDAELRRLF
     RERYRLHPKF VAAVHYEQPT IQIELRQNTS QKAAGDVDIG DAAYYFERDI KGESLFQGRG
     GLDLRVRGEP LQVERTLIYY LDEIPPKFSM KRLTAGLIAV IVVVVVALVA GMAVLVITNR
     RKSGKYKKVE IKELGELRKE PSL
//