ID TEFF1_HUMAN Reviewed; 380 AA. AC Q8IYR6; Q13086; Q8N3T8; DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2003, sequence version 1. DT 13-SEP-2023, entry version 167. DE RecName: Full=Tomoregulin-1; DE Short=TR-1; DE AltName: Full=H7365; DE AltName: Full=Transmembrane protein with EGF-like and one follistatin-like domain; DE Flags: Precursor; GN Name=TMEFF1; Synonyms=C9orf2; 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). RC TISSUE=Brain; RX PubMed=8752111; DOI=10.1046/j.1471-4159.1996.67031047.x; RA Eib D.W., Martens G.J.M.; RT "A novel transmembrane protein with epidermal growth factor and follistatin RT domains expressed in the hypothalamo-hypophysial axis of Xenopus laevis."; RL J. Neurochem. 67:1047-1055(1996). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Amygdala; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [4] 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 [5] RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND FUNCTION. RX PubMed=12743596; DOI=10.1038/sj.onc.1206351; RA Gery S., Yin D., Xie D., Black K.L., Koeffler H.P.; RT "TMEFF1 and brain tumors."; RL Oncogene 22:2723-2727(2003). RN [6] RP POSSIBLE INTERACTION WITH ST14, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=16407223; DOI=10.1074/jbc.m510687200; RA Ge W., Hu H., Ding K., Sun L., Zheng S.; RT "Protein interaction analysis of ST14 domains and their point and deletion RT mutants."; RL J. Biol. Chem. 281:7406-7412(2006). CC -!- FUNCTION: May inhibit NODAL and BMP signaling during neural patterning CC (By similarity). May be a tumor suppressor in brain cancers. CC {ECO:0000250, ECO:0000269|PubMed:12743596}. CC -!- SUBUNIT: May interact with ST14. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12743596}; CC Single-pass type I membrane protein {ECO:0000269|PubMed:12743596}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q8IYR6-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8IYR6-2; Sequence=VSP_024959; CC -!- TISSUE SPECIFICITY: Expressed predominantly in brain, and at lower CC levels in heart, placenta and skeletal muscle. Down-regulated in brain CC tumors as compared to control brain tissues. CC {ECO:0000269|PubMed:12743596}. CC -!- SIMILARITY: Belongs to the tomoregulin family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA64622.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=CAA58791.1; Type=Frameshift; 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; U19878; AAA64622.1; ALT_FRAME; mRNA. DR EMBL; X83961; CAA58791.1; ALT_FRAME; mRNA. DR EMBL; AL831919; CAD38580.2; -; mRNA. DR EMBL; AL353805; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL354917; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC035056; AAH35056.1; -; mRNA. DR CCDS; CCDS6750.1; -. [Q8IYR6-1] DR PIR; G01639; G01639. DR RefSeq; NP_003683.2; NM_003692.4. [Q8IYR6-1] DR AlphaFoldDB; Q8IYR6; -. DR SMR; Q8IYR6; -. DR BioGRID; 114145; 36. DR IntAct; Q8IYR6; 22. DR MINT; Q8IYR6; -. DR STRING; 9606.ENSP00000364013; -. DR MEROPS; I01.969; -. DR MEROPS; I01.974; -. DR TCDB; 8.A.74.1.4; the tm9 or phg1 targeting receptor (ppg1) family. DR GlyGen; Q8IYR6; 1 site. DR iPTMnet; Q8IYR6; -. DR PhosphoSitePlus; Q8IYR6; -. DR BioMuta; TMEFF1; -. DR DMDM; 74750770; -. DR EPD; Q8IYR6; -. DR MassIVE; Q8IYR6; -. DR PaxDb; Q8IYR6; -. DR PeptideAtlas; Q8IYR6; -. DR ProteomicsDB; 71216; -. [Q8IYR6-1] DR Antibodypedia; 34902; 244 antibodies from 22 providers. DR DNASU; 8577; -. DR Ensembl; ENST00000374879.5; ENSP00000364013.4; ENSG00000241697.5. [Q8IYR6-1] DR GeneID; 8577; -. DR KEGG; hsa:100526694; -. DR KEGG; hsa:8577; -. DR MANE-Select; ENST00000374879.5; ENSP00000364013.4; NM_003692.5; NP_003683.2. DR UCSC; uc004baz.3; human. [Q8IYR6-1] DR AGR; HGNC:11866; -. DR AGR; HGNC:38838; -. DR CTD; 100526694; -. DR CTD; 8577; -. DR DisGeNET; 100526694; -. DR DisGeNET; 8577; -. DR GeneCards; TMEFF1; -. DR HGNC; HGNC:11866; TMEFF1. DR HPA; ENSG00000241697; Tissue enriched (brain). DR MIM; 603421; gene. DR neXtProt; NX_Q8IYR6; -. DR OpenTargets; ENSG00000241697; -. DR OpenTargets; ENSG00000251349; -. DR PharmGKB; PA36567; -. DR VEuPathDB; HostDB:ENSG00000241697; -. DR eggNOG; KOG3649; Eukaryota. DR GeneTree; ENSGT00940000160714; -. DR HOGENOM; CLU_048579_0_0_1; -. DR InParanoid; Q8IYR6; -. DR OMA; DSTCRYG; -. DR OrthoDB; 4320472at2759; -. DR PhylomeDB; Q8IYR6; -. DR TreeFam; TF330868; -. DR PathwayCommons; Q8IYR6; -. DR SignaLink; Q8IYR6; -. DR BioGRID-ORCS; 100526694; 5 hits in 237 CRISPR screens. DR BioGRID-ORCS; 8577; 11 hits in 1139 CRISPR screens. DR Pharos; Q8IYR6; Tbio. DR PRO; PR:Q8IYR6; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; Q8IYR6; Protein. DR Bgee; ENSG00000241697; Expressed in cortical plate and 67 other tissues. DR Genevisible; Q8IYR6; HS. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. 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:SF3; TOMOREGULIN-1; 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; 2. DR PROSITE; PS51465; KAZAL_2; 2. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Developmental protein; Disulfide bond; KW EGF-like domain; Membrane; Reference proteome; Repeat; Signal; KW Transmembrane; Transmembrane helix. FT SIGNAL 1..39 FT /evidence="ECO:0000255" FT CHAIN 40..380 FT /note="Tomoregulin-1" FT /id="PRO_0000286056" FT TOPO_DOM 40..330 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 331..351 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 352..380 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 93..145 FT /note="Kazal-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DOMAIN 184..237 FT /note="Kazal-like 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DOMAIN 271..311 FT /note="EGF-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT REGION 359..380 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 365..380 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT DISULFID 99..129 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 103..122 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 111..143 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 190..221 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 194..214 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 203..235 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 275..288 FT /evidence="ECO:0000250" FT DISULFID 283..299 FT /evidence="ECO:0000250" FT DISULFID 301..310 FT /evidence="ECO:0000250" FT VAR_SEQ 1..65 FT /note="MGAAAAEAPLRLPAAPPLAFCCYTSVLLLFAFSLPGSRASNQPPGGGGGSGG FT DCPGGKGKSINCS -> MLPEQLYFLQSPPEEEPEYHPDASAQ (in isoform 2)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_024959" FT VARIANT 189 FT /note="V -> I (in dbSNP:rs35624603)" FT /id="VAR_032060" FT CONFLICT 7 FT /note="E -> Q (in Ref. 1; AAA64622/CAA58791)" FT /evidence="ECO:0000305" FT CONFLICT 11 FT /note="R -> G (in Ref. 1; AAA64622/CAA58791)" FT /evidence="ECO:0000305" FT CONFLICT 16..23 FT /note="PPLAFCCY -> SARLLLLA (in Ref. 1; AAA64622/CAA58791)" FT /evidence="ECO:0000305" FT CONFLICT 50 FT /note="S -> T (in Ref. 1; AAA64622/CAA58791)" FT /evidence="ECO:0000305" SQ SEQUENCE 380 AA; 40934 MW; 0F95B3469ACD4601 CRC64; MGAAAAEAPL RLPAAPPLAF CCYTSVLLLF AFSLPGSRAS NQPPGGGGGS GGDCPGGKGK SINCSELNVR ESDVRVCDES SCKYGGVCKE DGDGLKCACQ FQCHTNYIPV CGSNGDTYQN ECFLRRAACK HQKEITVIAR GPCYSDNGSG SGEGEEEGSG AEVHRKHSKC GPCKYKAECD EDAENVGCVC NIDCSGYSFN PVCASDGSSY NNPCFVREAS CIKQEQIDIR HLGHCTDTDD TSLLGKKDDG LQYRPDVKDA SDQREDVYIG NHMPCPENLN GYCIHGKCEF IYSTQKASCR CESGYTGQHC EKTDFSILYV VPSRQKLTHV LIAAIIGAVQ IAIIVAIVMC ITRKCPKNNR GRRQKQNLGH FTSDTSSRMV //