TACD2_HUMAN
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 03-AUG-2022, entry version 214.
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; 211.
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 GlyGen; P09758; 4 sites, 8 N-linked glycans (3 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; P09758; -.
DR PeptideAtlas; P09758; -.
DR PRIDE; P09758; -.
DR ProteomicsDB; 52267; -.
DR ABCD; P09758; 2 sequenced antibodies.
DR Antibodypedia; 33262; 649 antibodies from 45 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 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; HYEHPTI; -.
DR OrthoDB; 1017141at2759; -.
DR PhylomeDB; P09758; -.
DR TreeFam; TF332767; -.
DR PathwayCommons; P09758; -.
DR SignaLink; P09758; -.
DR BioGRID-ORCS; 4070; 4 hits in 1063 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 152 other tissues.
DR Genevisible; P09758; HS.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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; -; 1.
DR InterPro; IPR043406; EPCAM/Trop-2.
DR InterPro; IPR000716; Thyroglobulin_1.
DR InterPro; IPR036857; Thyroglobulin_1_sf.
DR PANTHER; PTHR14168; PTHR14168; 1.
DR Pfam; PF00086; Thyroglobulin_1; 1.
DR SMART; SM00211; TY; 1.
DR SUPFAM; SSF57610; SSF57610; 1.
DR PROSITE; PS00484; THYROGLOBULIN_1_1; 1.
DR PROSITE; PS51162; THYROGLOBULIN_1_2; 1.
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
