TM100_MOUSE
ID TM100_MOUSE Reviewed; 134 AA.
AC Q9CQG9;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Transmembrane protein 100;
GN Name=Tmem100;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo, and Pancreas;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Thymus;
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 [4]
RP PROTEIN SEQUENCE OF 8-23, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-121, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, AND CONDITIONAL KNOCKOUT.
RX PubMed=20848592; DOI=10.1002/dvg.20674;
RA Moon E.H., Kim M.J., Ko K.S., Kim Y.S., Seo J., Oh S.P., Lee Y.J.;
RT "Generation of mice with a conditional and reporter allele for Tmem100.";
RL Genesis 48:673-678(2010).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, CONDITIONAL KNOCKOUT, TISSUE SPECIFICITY,
RP AND DEVELOPMENTAL STAGE.
RX PubMed=22783020; DOI=10.1073/pnas.1207210109;
RA Somekawa S., Imagawa K., Hayashi H., Sakabe M., Ioka T., Sato G.E.,
RA Inada K., Iwamoto T., Mori T., Uemura S., Nakagawa O., Saito Y.;
RT "Tmem100, an ALK1 receptor signaling-dependent gene essential for arterial
RT endothelium differentiation and vascular morphogenesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12064-12069(2012).
RN [8]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=23485812; DOI=10.1016/j.neuroscience.2013.02.034;
RA Eisenman S.T., Gibbons S.J., Singh R.D., Bernard C.E., Wu J., Sarr M.G.,
RA Kendrick M.L., Larson D.W., Dozois E.J., Shen K.R., Farrugia G.;
RT "Distribution of TMEM100 in the mouse and human gastrointestinal tract--a
RT novel marker of enteric nerves.";
RL Neuroscience 240:117-128(2013).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE,
RP MUTAGENESIS OF 117-LYS--ARG-119, AND INTERACTION WITH TRPA1 AND TRPV1.
RX PubMed=25640077; DOI=10.1016/j.neuron.2014.12.065;
RA Weng H.J., Patel K.N., Jeske N.A., Bierbower S.M., Zou W., Tiwari V.,
RA Zheng Q., Tang Z., Mo G.C., Wang Y., Geng Y., Zhang J., Guan Y.,
RA Akopian A.N., Dong X.;
RT "Tmem100 Is a regulator of TRPA1-TRPV1 complex and contributes to
RT persistent pain.";
RL Neuron 85:833-846(2015).
RN [10]
RP INTERACTION WITH TASOR.
RX PubMed=31112734; DOI=10.1016/j.yexcr.2019.05.018;
RA Gresakova V., Novosadova V., Prochazkova M., Bhargava S., Jenickova I.,
RA Prochazka J., Sedlacek R.;
RT "Fam208a orchestrates interaction protein network essential for early
RT embryonic development and cell division.";
RL Exp. Cell Res. 382:111437-111437(2019).
CC -!- FUNCTION: Plays a role during embryonic arterial endothelium
CC differentiation and vascular morphogenesis through the ACVRL1 receptor-
CC dependent signaling pathway upon stimulation by bone morphogenetic
CC proteins, such as GDF2/BMP9 and BMP10 (PubMed:22783020). Involved in
CC the regulation of nociception, acting as a modulator of the interaction
CC between TRPA1 and TRPV1, two molecular sensors and mediators of pain
CC signals in dorsal root ganglia (DRG) neurons (PubMed:25640077).
CC Mechanistically, it weakens their interaction, thereby releasing the
CC inhibition of TRPA1 by TRPV1 and increasing the single-channel open
CC probability of the TRPA1-TRPV1 complex (PubMed:25640077).
CC {ECO:0000269|PubMed:22783020, ECO:0000269|PubMed:25640077}.
CC -!- SUBUNIT: Interacts (via C-terminus) with TRPA1 and TRPV1
CC (PubMed:25640077). Interacts with TASOR (PubMed:31112734).
CC {ECO:0000269|PubMed:25640077, ECO:0000269|PubMed:31112734}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23485812,
CC ECO:0000269|PubMed:25640077}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:23485812, ECO:0000269|PubMed:25640077}. Membrane
CC {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}. Perikaryon
CC {ECO:0000269|PubMed:23485812}. Cytoplasm, perinuclear region
CC {ECO:0000250}. Endoplasmic reticulum {ECO:0000250}. Note=Colocalized
CC with HSPA5 in the endoplasmic reticulum (ER). Enriched in ER microsome.
CC Colocalized with BMP4 in neural cell bodies and neural fibers of the
CC enteric nervous system (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in dorsal root ganglia. Expressed in
CC neurons as well as nerve fiber bundles connecting ganglia and fibers
CC innervating muscle layer of the gastric body, jejunum, and proximal
CC colon. Expressed in arterial endothelial cells and neurons of the
CC central nervous system and peripheral nervous system (at protein
CC level). Expressed strongly in lung, weakly in brain, heart and muscle.
CC Expressed in enteric neurons and vascular tissue in the muscularis
CC propria of the gastrointestinal tract. {ECO:0000269|PubMed:22783020,
CC ECO:0000269|PubMed:23485812, ECO:0000269|PubMed:25640077}.
CC -!- DEVELOPMENTAL STAGE: Expressed in embryo at 8.5 dpc. Expressed in
CC arterial endothelial cells of the pharyngeal arch artery and
CC endocardium at 9.5 dpc, onward. Expressed in dorsal aorta, pharyngeal
CC arch and primitive internal carotid arteries at 11.5 dpc. Expressed
CC also in intersomitic, mesenchephalic, metencephalic and anterior
CC choroidal arteries at 12.5 dpc. Expressed in the ventral neural tube of
CC the embryo. {ECO:0000269|PubMed:20848592, ECO:0000269|PubMed:22783020}.
CC -!- DISRUPTION PHENOTYPE: Mice die at a mid- or late-gestational period.
CC Show embryonic lethality due to impaired differentiation of arterial
CC endothelium and defects of vascular morphogenesis (PubMed:22783020).
CC Conditional knockout in endothelial cells show similar vascular defects
CC to those observed in global null mice (PubMed:20848592,
CC PubMed:22783020). Conditional knockout mice lacking Tmem100 in dorsal
CC root ganglia (DRG) primary sensory neurons, exhibit normal mechanical
CC sensitivity but reduced acute nocifensive behaviors induced by mustard
CC oil, consistent with a reduction in inflammatory mechanical
CC hyperalgesia and TRPA1- but not TRPV1-mediated pain (PubMed:25640077).
CC {ECO:0000269|PubMed:20848592, ECO:0000269|PubMed:22783020,
CC ECO:0000269|PubMed:25640077}.
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DR EMBL; AK003574; BAB22866.1; -; mRNA.
DR EMBL; AK007878; BAB25325.1; -; mRNA.
DR EMBL; AL645932; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC034841; AAH34841.1; -; mRNA.
DR CCDS; CCDS25239.1; -.
DR RefSeq; NP_080709.1; NM_026433.2.
DR RefSeq; XP_006534093.1; XM_006534030.3.
DR RefSeq; XP_006534094.1; XM_006534031.1.
DR AlphaFoldDB; Q9CQG9; -.
DR SMR; Q9CQG9; -.
DR STRING; 10090.ENSMUSP00000090464; -.
DR iPTMnet; Q9CQG9; -.
DR PhosphoSitePlus; Q9CQG9; -.
DR MaxQB; Q9CQG9; -.
DR PaxDb; Q9CQG9; -.
DR PRIDE; Q9CQG9; -.
DR ProteomicsDB; 260671; -.
DR Antibodypedia; 56967; 173 antibodies from 20 providers.
DR DNASU; 67888; -.
DR Ensembl; ENSMUST00000092788; ENSMUSP00000090464; ENSMUSG00000069763.
DR GeneID; 67888; -.
DR KEGG; mmu:67888; -.
DR UCSC; uc007kwm.1; mouse.
DR CTD; 55273; -.
DR MGI; MGI:1915138; Tmem100.
DR VEuPathDB; HostDB:ENSMUSG00000069763; -.
DR eggNOG; ENOG502RZCB; Eukaryota.
DR GeneTree; ENSGT00940000154322; -.
DR HOGENOM; CLU_141108_0_0_1; -.
DR InParanoid; Q9CQG9; -.
DR OMA; CWKIRQH; -.
DR OrthoDB; 1598239at2759; -.
DR PhylomeDB; Q9CQG9; -.
DR TreeFam; TF332068; -.
DR BioGRID-ORCS; 67888; 3 hits in 73 CRISPR screens.
DR PRO; PR:Q9CQG9; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q9CQG9; protein.
DR Bgee; ENSMUSG00000069763; Expressed in right lung lobe and 226 other tissues.
DR Genevisible; Q9CQG9; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043204; C:perikaryon; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IMP:MGI.
DR GO; GO:0060842; P:arterial endothelial cell differentiation; IMP:MGI.
DR GO; GO:0030509; P:BMP signaling pathway; ISS:UniProtKB.
DR GO; GO:0071773; P:cellular response to BMP stimulus; ISS:UniProtKB.
DR GO; GO:0003197; P:endocardial cushion development; IMP:MGI.
DR GO; GO:0003198; P:epithelial to mesenchymal transition involved in endocardial cushion formation; IMP:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0007219; P:Notch signaling pathway; IMP:MGI.
DR GO; GO:0045603; P:positive regulation of endothelial cell differentiation; IMP:UniProtKB.
DR GO; GO:2001214; P:positive regulation of vasculogenesis; IMP:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; IMP:MGI.
DR GO; GO:0050848; P:regulation of calcium-mediated signaling; IMP:MGI.
DR GO; GO:0051930; P:regulation of sensory perception of pain; IMP:UniProtKB.
DR GO; GO:0001570; P:vasculogenesis; IMP:MGI.
DR InterPro; IPR032536; TMEM100.
DR PANTHER; PTHR16100:SF5; PTHR16100:SF5; 1.
DR Pfam; PF16311; TMEM100; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cytoplasm; Developmental protein; Differentiation;
KW Direct protein sequencing; Endoplasmic reticulum; Membrane; Phosphoprotein;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..134
FT /note="Transmembrane protein 100"
FT /id="PRO_0000240847"
FT TRANSMEM 56..76
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 84..104
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 15
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q569C0"
FT MOD_RES 121
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MUTAGEN 117..119
FT /note="KRR->QQQ: Abolishes interaction with TRPA1.
FT Increases interaction with TRPV1. Enhances interaction
FT between TRPA1 and TRPV1."
FT /evidence="ECO:0000269|PubMed:25640077"
SQ SEQUENCE 134 AA; 14504 MW; 8E7A4C4DEA71FC72 CRC64;
MTEESTKENL GAPKSPTPVT MEKNPKREVV VTTGPLVSEV QLMAATGGAE LSCYRCIIPF
AVVVFITGIV VTAVAYSFNS HGSIISIFGL VLLSSGLFLL ASSALCWKVR QRNKKVKRRE
SQTALVVNQR CLFA