ID TEFF2_HUMAN Reviewed; 374 AA. AC Q9UIK5; Q2FA44; Q4ZFW4; Q53H90; Q53RE1; Q8N2R5; Q9NR15; Q9NSS5; Q9P2Y9; AC Q9UK65; DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 27-MAR-2024, entry version 180. DE RecName: Full=Tomoregulin-2; DE Short=TR-2; DE AltName: Full=Hyperplastic polyposis protein 1; DE AltName: Full=Transmembrane protein with EGF-like and two follistatin-like domains; DE Flags: Precursor; GN Name=TMEFF2; Synonyms=HPP1, TENB2, TPEF; ORFNames=UNQ178/PRO204; 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), FUNCTION, AND TISSUE SPECIFICITY. RC TISSUE=Brain; RX PubMed=10903839; DOI=10.1006/geno.2000.6228; RA Horie M., Mitsumoto Y., Kyushiki H., Kanemoto N., Watanabe A., RA Taniguchi Y., Nishino N., Okamoto T., Kondo M., Mori T., Noguchi K., RA Nakamura Y., Takahashi E., Tanigami A.; RT "Identification and characterization of TMEFF2, a novel survival factor for RT hippocampal and mesencephalic neurons."; RL Genomics 67:146-152(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [GENOMIC DNA] RP OF 1-57, INDUCTION, AND TISSUE SPECIFICITY. RC TISSUE=Brain; RX PubMed=10987305; RA Liang G., Robertson K.D., Talmadge C., Sumegi J., Jones P.A.; RT "The gene for a novel transmembrane protein containing epidermal growth RT factor and follistatin domains is frequently hypermethylated in human tumor RT cells."; RL Cancer Res. 60:4907-4912(2000). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), GLYCOSYLATION, AND TISSUE RP SPECIFICITY. RC TISSUE=Prostatic carcinoma; RX PubMed=11668495; DOI=10.1002/ijc.1450; RA Glynne-Jones E., Harper M.E., Seery L.T., James R., Anglin I., Morgan H.E., RA Taylor K.M., Gee J.M., Nicholson R.I.; RT "TENB2, a proteoglycan identified in prostate cancer that is associated RT with disease progression and androgen independence."; RL Int. J. Cancer 94:178-184(2001). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND TISSUE SPECIFICITY. RX PubMed=16439095; DOI=10.1016/j.ygeno.2005.12.004; RA Quayle S.N., Sadar M.D.; RT "A truncated isoform of TMEFF2 encodes a secreted protein in prostate RT cancer cells."; RL Genomics 87:633-637(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Embryo; 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; 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 [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; 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 [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [12] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-360. RX PubMed=10600548; DOI=10.1006/bbrc.1999.1873; RA Uchida T., Wada K., Akamatsu T., Yonezawa M., Noguchi H., Mizoguchi A., RA Kasuga M., Sakamoto C.; RT "A novel epidermal growth factor-like molecule containing two follistatin RT modules stimulates tyrosine phosphorylation of erbB-4 in MKN28 gastric RT cancer cells."; RL Biochem. Biophys. Res. Commun. 266:593-602(1999). RN [13] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-57, TISSUE SPECIFICITY, AND RP INDUCTION. RC TISSUE=Colon; RX PubMed=11120884; DOI=10.1073/pnas.98.1.265; RA Young J., Biden K.G., Simms L.A., Huggard P., Karamatic R., Eyre H.J., RA Sutherland G.R., Herath N., Barker M., Anderson G.J., Fitzpatrick D.R., RA Ramm G.A., Jass J.R., Leggett B.A.; RT "HPP1: a transmembrane protein-encoding gene commonly methylated in RT colorectal polyps and cancers."; RL Proc. Natl. Acad. Sci. U.S.A. 98:265-270(2001). RN [14] RP PROTEIN SEQUENCE OF 41-55. RX PubMed=15340161; DOI=10.1110/ps.04682504; RA Zhang Z., Henzel W.J.; RT "Signal peptide prediction based on analysis of experimentally verified RT cleavage sites."; RL Protein Sci. 13:2819-2824(2004). RN [15] RP TISSUE SPECIFICITY. RX PubMed=16805794; DOI=10.1111/j.1471-4159.2006.03801.x; RA Siegel D.A., Davies P., Dobrenis K., Huang M.; RT "Tomoregulin-2 is found extensively in plaques in Alzheimer's disease RT brain."; RL J. Neurochem. 98:34-44(2006). RN [16] RP CLEAVAGE, AND FUNCTION. RX PubMed=17942404; DOI=10.1074/jbc.m702170200; RA Ali N., Knaeuper V.; RT "Phorbol ester-induced shedding of the prostate cancer marker transmembrane RT protein with epidermal growth factor and two follistatin motifs 2 is RT mediated by the disintegrin and metalloproteinase-17."; RL J. Biol. Chem. 282:37378-37388(2007). RN [17] RP GLYCOSYLATION AT ASN-204. RX PubMed=19139490; DOI=10.1074/mcp.m800504-mcp200; RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B., RA Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L., RA Ying W.T., He S.M., Qian X.H.; RT "A strategy for precise and large scale identification of core fucosylated RT glycoproteins."; RL Mol. Cell. Proteomics 8:913-923(2009). CC -!- FUNCTION: May be a survival factor for hippocampal and mesencephalic CC neurons. The shedded form up-regulates cancer cell proliferation, CC probably by promoting ERK1/2 phosphorylation. CC {ECO:0000269|PubMed:10903839, ECO:0000269|PubMed:17942404}. CC -!- INTERACTION: CC Q9UIK5; PRO_0000000090 [P05067]: APP; NbExp=3; IntAct=EBI-11423693, EBI-21194918; CC Q9UIK5; O75031: HSF2BP; NbExp=3; IntAct=EBI-11423693, EBI-7116203; CC Q9UIK5; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-11423693, EBI-22310682; CC Q9UIK5; Q7Z5B4-5: RIC3; NbExp=3; IntAct=EBI-11423693, EBI-12375429; CC Q9UIK5; Q96Q45-2: TMEM237; NbExp=3; IntAct=EBI-11423693, EBI-10982110; CC Q9UIK5; P34981: TRHR; NbExp=3; IntAct=EBI-11423693, EBI-18055230; CC Q9UIK5; Q9Y5Z9: UBIAD1; NbExp=3; IntAct=EBI-11423693, EBI-2819725; CC Q9UIK5; Q96MV8: ZDHHC15; NbExp=3; IntAct=EBI-11423693, EBI-12837904; CC Q9UIK5-2; P55212: CASP6; NbExp=3; IntAct=EBI-25835153, EBI-718729; CC Q9UIK5-2; O75400-2: PRPF40A; NbExp=3; IntAct=EBI-25835153, EBI-5280197; CC Q9UIK5-2; P62826: RAN; NbExp=3; IntAct=EBI-25835153, EBI-286642; CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Membrane {ECO:0000305}; Single-pass CC type I membrane protein {ECO:0000305}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Membrane {ECO:0000305}; Single-pass CC type I membrane protein {ECO:0000305}. CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Secreted. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9UIK5-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9UIK5-2; Sequence=VSP_014312, VSP_014313; CC Name=3; Synonyms=TMEFF2-S; CC IsoId=Q9UIK5-3; Sequence=VSP_024973, VSP_024974; CC -!- TISSUE SPECIFICITY: Highly expressed in adult and fetal brain, spinal CC cord and prostate. Expressed in all brain regions except the pituitary CC gland, with highest levels in amygdala and corpus callosum. Expressed CC in the pericryptal myofibroblasts and other stromal cells of normal CC colonic mucosa. Expressed in prostate carcinoma. Down-regulated in CC colorectal cancer. Present in Alzheimer disease plaques (at protein CC level). Isoform 3 is expressed weakly in testis and at high levels in CC normal and cancerous prostate. {ECO:0000269|PubMed:10903839, CC ECO:0000269|PubMed:10987305, ECO:0000269|PubMed:11120884, CC ECO:0000269|PubMed:11668495, ECO:0000269|PubMed:16439095, CC ECO:0000269|PubMed:16805794}. CC -!- INDUCTION: Down-regulated in tumor cell lines in response to a high CC level of methylation in the 5' region. The CpG island methylation CC correlates with TMEFF2 silencing in tumor cell lines. CC {ECO:0000269|PubMed:10987305, ECO:0000269|PubMed:11120884}. CC -!- PTM: O-glycosylated; contains chondroitin sulfate glycosaminoglycans. CC {ECO:0000269|PubMed:11668495}. CC -!- PTM: A soluble form (TMEFF2-ECD) is produced by proteolytic shedding. CC This shedding can be induced by phorbol ester or pro-inflammatory CC cytokines such as TNFalpha, and is mediated by ADAM17. CC -!- SIMILARITY: Belongs to the tomoregulin family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA90820.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Mitochondrial contamination starting in position 361.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB017269; BAA87897.1; -; mRNA. DR EMBL; AF242221; AAG49451.1; -; Genomic_DNA. DR EMBL; AF242222; AAG49452.1; -; mRNA. DR EMBL; AF179274; AAD55776.2; -; mRNA. DR EMBL; DQ133599; AAZ43216.1; -; mRNA. DR EMBL; AY358907; AAQ89266.1; -; mRNA. DR EMBL; AK074507; BAC11030.1; -; mRNA. DR EMBL; CR457390; CAG33671.1; -; mRNA. DR EMBL; AK222691; BAD96411.1; -; mRNA. DR EMBL; AL157430; CAB75654.1; -; mRNA. DR EMBL; AC092644; AAY14874.1; -; Genomic_DNA. DR EMBL; AC098617; AAX88893.1; -; Genomic_DNA. DR EMBL; BC008973; AAH08973.1; -; mRNA. DR EMBL; AB004064; BAA90820.1; ALT_TERM; mRNA. DR EMBL; AF264150; AAF91397.1; -; Genomic_DNA. DR CCDS; CCDS2314.1; -. [Q9UIK5-1] DR CCDS; CCDS82547.1; -. [Q9UIK5-3] DR CCDS; CCDS82548.1; -. [Q9UIK5-2] DR PIR; T46914; T46914. DR RefSeq; NP_001292063.1; NM_001305134.1. [Q9UIK5-2] DR RefSeq; NP_001292074.1; NM_001305145.1. [Q9UIK5-3] DR RefSeq; NP_057276.2; NM_016192.3. [Q9UIK5-1] DR AlphaFoldDB; Q9UIK5; -. DR SMR; Q9UIK5; -. DR BioGRID; 117189; 12. DR IntAct; Q9UIK5; 14. DR MINT; Q9UIK5; -. DR STRING; 9606.ENSP00000272771; -. DR MEROPS; I01.969; -. DR MEROPS; I01.978; -. DR GlyCosmos; Q9UIK5; 3 sites, No reported glycans. DR GlyGen; Q9UIK5; 3 sites. DR iPTMnet; Q9UIK5; -. DR PhosphoSitePlus; Q9UIK5; -. DR SwissPalm; Q9UIK5; -. DR BioMuta; TMEFF2; -. DR DMDM; 71153590; -. DR MassIVE; Q9UIK5; -. DR PaxDb; 9606-ENSP00000272771; -. DR PeptideAtlas; Q9UIK5; -. DR ProteomicsDB; 84539; -. [Q9UIK5-1] DR ProteomicsDB; 84540; -. [Q9UIK5-2] DR ProteomicsDB; 84541; -. [Q9UIK5-3] DR Antibodypedia; 2895; 441 antibodies from 31 providers. DR DNASU; 23671; -. DR Ensembl; ENST00000272771.10; ENSP00000272771.5; ENSG00000144339.12. [Q9UIK5-1] DR Ensembl; ENST00000392314.5; ENSP00000376128.1; ENSG00000144339.12. [Q9UIK5-2] DR Ensembl; ENST00000409056.3; ENSP00000386871.3; ENSG00000144339.12. [Q9UIK5-3] DR GeneID; 23671; -. DR KEGG; hsa:23671; -. DR MANE-Select; ENST00000272771.10; ENSP00000272771.5; NM_016192.4; NP_057276.2. DR UCSC; uc002utc.4; human. [Q9UIK5-1] DR AGR; HGNC:11867; -. DR CTD; 23671; -. DR DisGeNET; 23671; -. DR GeneCards; TMEFF2; -. DR HGNC; HGNC:11867; TMEFF2. DR HPA; ENSG00000144339; Tissue enhanced (brain, prostate, seminal vesicle). DR MIM; 605734; gene. DR neXtProt; NX_Q9UIK5; -. DR OpenTargets; ENSG00000144339; -. DR PharmGKB; PA36568; -. DR VEuPathDB; HostDB:ENSG00000144339; -. DR eggNOG; KOG3649; Eukaryota. DR GeneTree; ENSGT00940000156056; -. DR HOGENOM; CLU_048579_1_0_1; -. DR InParanoid; Q9UIK5; -. DR OMA; DCFCWLL; -. DR OrthoDB; 4320472at2759; -. DR PhylomeDB; Q9UIK5; -. DR TreeFam; TF330868; -. DR PathwayCommons; Q9UIK5; -. DR SignaLink; Q9UIK5; -. DR BioGRID-ORCS; 23671; 7 hits in 1065 CRISPR screens. DR ChiTaRS; TMEFF2; human. DR GeneWiki; TMEFF2; -. DR GenomeRNAi; 23671; -. DR Pharos; Q9UIK5; Tbio. DR PRO; PR:Q9UIK5; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q9UIK5; Protein. DR Bgee; ENSG00000144339; Expressed in middle temporal gyrus and 148 other cell types or tissues. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; NAS:UniProtKB. DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central. DR GO; GO:0030336; P:negative regulation of cell migration; IDA:MGI. DR GO; GO:0045720; P:negative regulation of integrin biosynthetic process; IMP:MGI. DR GO; GO:0051497; P:negative regulation of stress fiber assembly; IDA:MGI. DR GO; GO:0044319; P:wound healing, spreading of cells; IDA:MGI. DR CDD; cd00104; KAZAL_FS; 2. DR Gene3D; 3.30.60.30; -; 2. DR Gene3D; 2.10.25.10; Laminin; 1. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR002350; Kazal_dom. DR InterPro; IPR036058; Kazal_dom_sf. DR PANTHER; PTHR21632:SF5; TRANSMEMBRANE PROTEIN WITH EGF LIKE AND TWO FOLLISTATIN LIKE DOMAINS 2; 1. DR PANTHER; PTHR21632; UNCHARACTERIZED; 1. DR Pfam; PF07648; Kazal_2; 2. DR SMART; SM00280; KAZAL; 2. DR SUPFAM; SSF57196; EGF/Laminin; 1. DR SUPFAM; SSF100895; Kazal-type serine protease inhibitors; 2. DR PROSITE; PS00022; EGF_1; 1. DR PROSITE; PS01186; EGF_2; 1. DR PROSITE; PS50026; EGF_3; 1. DR PROSITE; PS51465; KAZAL_2; 2. DR Genevisible; Q9UIK5; HS. PE 1: Evidence at protein level; KW Alternative splicing; Direct protein sequencing; Disulfide bond; KW EGF-like domain; Glycoprotein; Membrane; Proteoglycan; Reference proteome; KW Repeat; Secreted; Signal; Transmembrane; Transmembrane helix. FT SIGNAL 1..40 FT /evidence="ECO:0000269|PubMed:15340161" FT CHAIN 41..374 FT /note="Tomoregulin-2" FT /id="PRO_0000016587" FT TOPO_DOM 41..320 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 321..341 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 342..374 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 85..137 FT /note="Kazal-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DOMAIN 176..229 FT /note="Kazal-like 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DOMAIN 261..301 FT /note="EGF-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT REGION 303..320 FT /note="Required for shedding" FT REGION 353..374 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 355..374 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 55 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 204 FT /note="N-linked (GlcNAc...) (complex) asparagine; atypical" FT /evidence="ECO:0000269|PubMed:19139490" FT CARBOHYD 230 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 91..121 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 95..114 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 103..135 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 182..213 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 186..206 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 195..227 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 265..278 FT /evidence="ECO:0000250" FT DISULFID 273..289 FT /evidence="ECO:0000250" FT DISULFID 291..300 FT /evidence="ECO:0000250" FT VAR_SEQ 147..175 FT /note="VHEGSGETSQKETSTCDICQFGAECDEDA -> GRSCLFTYLKIYWWILLCI FT FTYVCSISDI (in isoform 3)" FT /evidence="ECO:0000303|PubMed:16439095" FT /id="VSP_024973" FT VAR_SEQ 176..374 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:16439095" FT /id="VSP_024974" FT VAR_SEQ 344..346 FT /note="KCP -> AKL (in isoform 2)" FT /evidence="ECO:0000303|PubMed:17974005, ECO:0000303|Ref.7" FT /id="VSP_014312" FT VAR_SEQ 347..374 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:17974005, ECO:0000303|Ref.7" FT /id="VSP_014313" FT CONFLICT 28 FT /note="M -> V (in Ref. 8; BAD96411)" FT /evidence="ECO:0000305" FT CONFLICT 63 FT /note="E -> G (in Ref. 6; BAC11030)" FT /evidence="ECO:0000305" FT CONFLICT 222 FT /note="M -> T (in Ref. 8; BAD96411)" FT /evidence="ECO:0000305" FT CONFLICT 339 FT /note="L -> H (in Ref. 8; BAD96411)" FT /evidence="ECO:0000305" SQ SEQUENCE 374 AA; 41428 MW; 44452F680FEBDCDB CRC64; MVLWESPRQC SSWTLCEGFC WLLLLPVMLL IVARPVKLAA FPTSLSDCQT PTGWNCSGYD DRENDLFLCD TNTCKFDGEC LRIGDTVTCV CQFKCNNDYV PVCGSNGESY QNECYLRQAA CKQQSEILVV SEGSCATDAG SGSGDGVHEG SGETSQKETS TCDICQFGAE CDEDAEDVWC VCNIDCSQTN FNPLCASDGK SYDNACQIKE ASCQKQEKIE VMSLGRCQDN TTTTTKSEDG HYARTDYAEN ANKLEESARE HHIPCPEHYN GFCMHGKCEH SINMQEPSCR CDAGYTGQHC EKKDYSVLYV VPGPVRFQYV LIAAVIGTIQ IAVICVVVLC ITRKCPRSNR IHRQKQNTGH YSSDNTTRAS TRLI //