TM119_MOUSE
ID TM119_MOUSE Reviewed; 280 AA.
AC Q8R138; Q8BP14;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Transmembrane protein 119;
DE AltName: Full=Osteoblast induction factor;
DE Short=OBIF;
DE Flags: Precursor;
GN Name=Tmem119;
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, and NOD; TISSUE=Muellerian duct;
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 MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [3]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=20025746; DOI=10.1186/1471-213x-9-70;
RA Kanamoto T., Mizuhashi K., Terada K., Minami T., Yoshikawa H., Furukawa T.;
RT "Isolation and characterization of a novel plasma membrane protein,
RT osteoblast induction factor (obif), associated with osteoblast
RT differentiation.";
RL BMC Dev. Biol. 9:70-70(2009).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [5]
RP FUNCTION, INDUCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH SMAD1;
RP SMAD5 AND RUNX2.
RX PubMed=21239498; DOI=10.1074/jbc.m110.179127;
RA Hisa I., Inoue Y., Hendy G.N., Canaff L., Kitazawa R., Kitazawa S.,
RA Komori T., Sugimoto T., Seino S., Kaji H.;
RT "Parathyroid hormone-responsive Smad3-related factor, Tmem119, promotes
RT osteoblast differentiation and interacts with the bone morphogenetic
RT protein-Runx2 pathway.";
RL J. Biol. Chem. 286:9787-9796(2011).
RN [6]
RP FUNCTION.
RX PubMed=22579779; DOI=10.1016/j.bone.2012.04.017;
RA Tanaka K., Inoue Y., Hendy G.N., Canaff L., Katagiri T., Kitazawa R.,
RA Komori T., Sugimoto T., Seino S., Kaji H.;
RT "Interaction of Tmem119 and the bone morphogenetic protein pathway in the
RT commitment of myoblastic into osteoblastic cells.";
RL Bone 51:158-167(2012).
RN [7]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=22416756; DOI=10.1111/j.1440-169x.2012.01333.x;
RA Mizuhashi K., Kanamoto T., Ito M., Moriishi T., Muranishi Y., Omori Y.,
RA Terada K., Komori T., Furukawa T.;
RT "OBIF, an osteoblast induction factor, plays an essential role in bone
RT formation in association with osteoblastogenesis.";
RL Dev. Growth Differ. 54:474-480(2012).
RN [8]
RP FUNCTION.
RX PubMed=24362451; DOI=10.1007/s00223-013-9828-1;
RA Tanaka K., Kaji H., Yamaguchi T., Kanazawa I., Canaff L., Hendy G.N.,
RA Sugimoto T.;
RT "Involvement of the osteoinductive factors, Tmem119 and BMP-2, and the ER
RT stress response PERK-eIF2alpha-ATF4 pathway in the commitment of myoblastic
RT into osteoblastic cells.";
RL Calcif. Tissue Int. 94:454-464(2014).
RN [9]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, GLYCOSYLATION AT
RP SER-36, AND MUTAGENESIS OF SER-36; SER-43; THR-54; THR-60 AND THR-67.
RX PubMed=26207632; DOI=10.1371/journal.pone.0133704;
RA Mizuhashi K., Chaya T., Kanamoto T., Omori Y., Furukawa T.;
RT "Obif, a transmembrane protein, is required for bone mineralization and
RT spermatogenesis in mice.";
RL PLoS ONE 10:E0133704-E0133704(2015).
CC -!- FUNCTION: Plays an important role in bone formation and normal bone
CC mineralization (PubMed:26207632, PubMed:22416756, PubMed:20025746).
CC Promotes the differentiation of myoblasts into osteoblasts
CC (PubMed:22416756, PubMed:20025746, PubMed:22579779). May induce the
CC commitment and differentiation of myoblasts into osteoblasts through an
CC enhancement of BMP2 production and interaction with the BMP-RUNX2
CC pathway (PubMed:21239498, PubMed:22579779). Up-regulates the expression
CC of ATF4 which plays a central role in osteoblast differentiation
CC (PubMed:24362451). Essential for normal spermatogenesis and late
CC testicular differentiation (PubMed:26207632).
CC {ECO:0000269|PubMed:20025746, ECO:0000269|PubMed:21239498,
CC ECO:0000269|PubMed:22416756, ECO:0000269|PubMed:22579779,
CC ECO:0000269|PubMed:24362451, ECO:0000269|PubMed:26207632}.
CC -!- SUBUNIT: Interacts with SMAD1, SMAD5 and RUNX2.
CC {ECO:0000269|PubMed:21239498}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20025746};
CC Single-pass type I membrane protein {ECO:0000255}. Cytoplasm
CC {ECO:0000269|PubMed:21239498}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:21239498}.
CC -!- TISSUE SPECIFICITY: Expressed in spermatocytes and spermatids in the
CC developing testis (at protein level). Expressed in the brain, heart,
CC lung, spleen, skeletal muscle, ovary, testis and epididymis
CC (PubMed:26207632). Predominantly expressed in osteoblasts
CC (PubMed:20025746). {ECO:0000269|PubMed:20025746,
CC ECO:0000269|PubMed:26207632}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in early and late stage
CC osteoblasts of developing embryos (at protein level).
CC {ECO:0000269|PubMed:20025746}.
CC -!- INDUCTION: By parathyroid hormone (PTH) in osteoblasts (at protein
CC level). {ECO:0000269|PubMed:21239498}.
CC -!- DISRUPTION PHENOTYPE: Mice show a significant decrease in bone
CC formation and bone mineralization and the mineralization defect is
CC independent of calcium and phosphate metabolisms. Testis is smaller,
CC sperm number is significantly decreased and testicular differentiation
CC is perturbed (PubMed:26207632). Significantly reduced cortical
CC thickness in the mid-shaft of the femur at postnatal day 14 (P14), and
CC progressive bone hypoplasia after 8 weeks (PubMed:22416756).
CC {ECO:0000269|PubMed:22416756, ECO:0000269|PubMed:26207632}.
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DR EMBL; AK078473; BAC37292.1; -; mRNA.
DR EMBL; AK170712; BAE41970.1; -; mRNA.
DR EMBL; BC025600; AAH25600.1; -; mRNA.
DR CCDS; CCDS19554.1; -.
DR RefSeq; NP_666274.1; NM_146162.2.
DR RefSeq; XP_006530350.1; XM_006530287.3.
DR AlphaFoldDB; Q8R138; -.
DR IntAct; Q8R138; 1.
DR MINT; Q8R138; -.
DR STRING; 10090.ENSMUSP00000070551; -.
DR GlyGen; Q8R138; 1 site.
DR iPTMnet; Q8R138; -.
DR PhosphoSitePlus; Q8R138; -.
DR jPOST; Q8R138; -.
DR MaxQB; Q8R138; -.
DR PaxDb; Q8R138; -.
DR PeptideAtlas; Q8R138; -.
DR PRIDE; Q8R138; -.
DR ProteomicsDB; 259523; -.
DR Antibodypedia; 55081; 30 antibodies from 12 providers.
DR Ensembl; ENSMUST00000067853; ENSMUSP00000070551; ENSMUSG00000054675.
DR GeneID; 231633; -.
DR KEGG; mmu:231633; -.
DR UCSC; uc008yyq.1; mouse.
DR CTD; 338773; -.
DR MGI; MGI:2385228; Tmem119.
DR VEuPathDB; HostDB:ENSMUSG00000054675; -.
DR eggNOG; ENOG502S283; Eukaryota.
DR GeneTree; ENSGT00390000017134; -.
DR HOGENOM; CLU_086693_0_0_1; -.
DR InParanoid; Q8R138; -.
DR OMA; EEPCSGV; -.
DR OrthoDB; 1284233at2759; -.
DR PhylomeDB; Q8R138; -.
DR TreeFam; TF336958; -.
DR BioGRID-ORCS; 231633; 4 hits in 71 CRISPR screens.
DR ChiTaRS; Tmem119; mouse.
DR PRO; PR:Q8R138; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q8R138; protein.
DR Bgee; ENSMUSG00000054675; Expressed in vault of skull and 187 other tissues.
DR ExpressionAtlas; Q8R138; baseline and differential.
DR Genevisible; Q8R138; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0031214; P:biomineral tissue development; IEA:UniProtKB-KW.
DR GO; GO:0001958; P:endochondral ossification; IMP:ARUK-UCL.
DR GO; GO:0045779; P:negative regulation of bone resorption; IMP:ARUK-UCL.
DR GO; GO:0010832; P:negative regulation of myotube differentiation; IDA:ARUK-UCL.
DR GO; GO:0001649; P:osteoblast differentiation; IDA:MGI.
DR GO; GO:1903012; P:positive regulation of bone development; IMP:UniProtKB.
DR GO; GO:0030501; P:positive regulation of bone mineralization; IMP:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:ARUK-UCL.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IDA:ARUK-UCL.
DR GO; GO:0033690; P:positive regulation of osteoblast proliferation; IDA:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:ARUK-UCL.
DR GO; GO:0048515; P:spermatid differentiation; IMP:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IMP:UniProtKB.
DR InterPro; IPR031453; TMEM119.
DR PANTHER; PTHR28645; PTHR28645; 1.
DR Pfam; PF15724; TMEM119; 1.
PE 1: Evidence at protein level;
KW Biomineralization; Cell membrane; Cytoplasm; Differentiation;
KW Endoplasmic reticulum; Glycoprotein; Membrane; Osteogenesis;
KW Phosphoprotein; Reference proteome; Signal; Spermatogenesis; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..280
FT /note="Transmembrane protein 119"
FT /id="PRO_0000251221"
FT TOPO_DOM 21..91
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 92..112
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 113..280
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 38..73
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 133..162
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 181..280
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 48..71
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 248..267
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 269
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4V9L6"
FT CARBOHYD 36
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000269|PubMed:26207632"
FT MUTAGEN 36
FT /note="S->A: Loss of glycosylation. No effect on osteoblast
FT mineralization. Loss of glycosylation; when associated with
FT A-43; A-54; A-60 AND A-67."
FT /evidence="ECO:0000269|PubMed:26207632"
FT MUTAGEN 43
FT /note="S->A: No loss of glycosylation. Loss of
FT glycosylation; when associated with A-36; A-54; A-60 AND A-
FT 67."
FT /evidence="ECO:0000269|PubMed:26207632"
FT MUTAGEN 54
FT /note="T->A: No loss of glycosylation. Loss of
FT glycosylation; when associated with A-36; A-43; A-60 AND A-
FT 67."
FT /evidence="ECO:0000269|PubMed:26207632"
FT MUTAGEN 60
FT /note="T->A: No loss of glycosylation. Loss of
FT glycosylation; when associated with A-36; A-43; A-54 AND A-
FT 67."
FT /evidence="ECO:0000269|PubMed:26207632"
FT MUTAGEN 67
FT /note="T->A: No loss of glycosylation. Loss of
FT glycosylation; when associated with A-36; A-43; A-54 AND A-
FT 60."
FT /evidence="ECO:0000269|PubMed:26207632"
FT CONFLICT 78
FT /note="L -> H (in Ref. 1; BAC37292)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 280 AA; 29401 MW; CBC0F96107F75C29 CRC64;
MVPWFLLSLL LLARPVPGVA YSVSLPASFL EDVAGSGEAE GSSASSPSLP PPGTPAFSPT
PERPQPTALD GPVPPTNLLE GIMDFFRQYV MLIAVVGSLT FLIMFIVCAA LITRQKHKAT
AYYPSSFPEK KYVDQRDRAG GPRTFSEVPD RAPDSRHEEG LDTSHQLQAD ILAATQNLRS
PARALPGNGE GAKPVKGGSE EEEEEVLSGQ EEAQEAPVCG VTEEKLGVPE ESVSAEAEGV
PATSEGQGEA EGSFSLAQES QGATGPPESP CACNRVSPSV
