TEFF1_HUMAN
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 03-AUG-2022, entry version 161.
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};
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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_001185741.1; NM_001198812.1.
DR RefSeq; NP_003683.2; NM_003692.4. [Q8IYR6-1]
DR AlphaFoldDB; Q8IYR6; -.
DR SMR; Q8IYR6; -.
DR BioGRID; 114145; 34.
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 PRIDE; Q8IYR6; -.
DR ProteomicsDB; 71216; -. [Q8IYR6-1]
DR Antibodypedia; 34902; 215 antibodies from 22 providers.
DR DNASU; 8577; -.
DR Ensembl; ENST00000374879.5; ENSP00000364013.4; ENSG00000241697.5. [Q8IYR6-1]
DR GeneID; 100526694; -.
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 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; XNGSGSG; -.
DR OrthoDB; 773030at2759; -.
DR PhylomeDB; Q8IYR6; -.
DR TreeFam; TF330868; -.
DR PathwayCommons; Q8IYR6; -.
DR SignaLink; Q8IYR6; -.
DR BioGRID-ORCS; 100526694; 5 hits in 186 CRISPR screens.
DR BioGRID-ORCS; 8577; 11 hits in 1063 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:0005604; C:basement membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0009887; P:animal organ morphogenesis; IBA:GO_Central.
DR GO; GO:0016358; P:dendrite development; IBA:GO_Central.
DR GO; GO:0008045; P:motor neuron axon guidance; IBA:GO_Central.
DR GO; GO:0009888; P:tissue development; IBA:GO_Central.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR002350; Kazal_dom.
DR InterPro; IPR036058; Kazal_dom_sf.
DR Pfam; PF07648; Kazal_2; 2.
DR SMART; SM00280; KAZAL; 2.
DR SUPFAM; SSF100895; SSF100895; 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
