TMM25_HUMAN
ID TMM25_HUMAN Reviewed; 366 AA.
AC Q86YD3; A8K8J4; B0YJA6; B0YJA7; B0YJA9; G5E9U4; Q6UW89; Q86UA7; Q8NBL5;
AC Q96KA6; Q96MW9;
DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Transmembrane protein 25;
DE Flags: Precursor;
GN Name=TMEM25; ORFNames=UNQ2531/PRO6030;
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 [LARGE SCALE MRNA] (ISOFORM 2).
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3; 4 AND 2).
RC TISSUE=Embryo, and Testis;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5), AND VARIANT ARG-342.
RC TISSUE=Placenta;
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP ARG-342.
RC TISSUE=Brain, and Ovary;
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 [8]
RP PROTEIN SEQUENCE OF 27-41.
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 [9]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=31424425; DOI=10.1172/jci122599;
RA Zhang H., Tian X., Lu X., Xu D., Guo Y., Dong Z., Li Y., Ma Y., Chen C.,
RA Yang Y., Yang M., Yang Y., Liu F., Zhou R., He M., Xiao F., Wang X.;
RT "TMEM25 modulates neuronal excitability and NMDA receptor subunit NR2B
RT degradation.";
RL J. Clin. Invest. 129:3864-3876(2019).
CC -!- FUNCTION: In neurons, modulates the degradation of NMDA receptor GRIN2B
CC subunit. Plays a role in the regulation of neuronal excitability.
CC {ECO:0000269|PubMed:31424425}.
CC -!- SUBUNIT: Interacts with GRIN2B. {ECO:0000250|UniProtKB:Q9DCF1}.
CC -!- INTERACTION:
CC Q86YD3; O76003: GLRX3; NbExp=4; IntAct=EBI-10260688, EBI-374781;
CC Q86YD3; P53611: RABGGTB; NbExp=3; IntAct=EBI-10260688, EBI-536715;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane {ECO:0000305}; Single-
CC pass type I membrane protein {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Cell membrane {ECO:0000305}; Single-
CC pass type I membrane protein {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Secreted {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Late endosome {ECO:0000250|UniProtKB:Q9DCF1}.
CC Lysosome {ECO:0000250|UniProtKB:Q9DCF1}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q86YD3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86YD3-2; Sequence=VSP_012940;
CC Name=3;
CC IsoId=Q86YD3-3; Sequence=VSP_012939, VSP_012940;
CC Name=4;
CC IsoId=Q86YD3-4; Sequence=VSP_012941;
CC Name=5;
CC IsoId=Q86YD3-5; Sequence=VSP_012940, VSP_045635, VSP_012941;
CC -!- TISSUE SPECIFICITY: Expressed throughout the brain with higher levels
CC in the pyramidal cell layer of the hippocampal CA1 and CA3 regions.
CC Also highly expressed within the hippocampal dentate gyrus region and
CC cerebellum and in scattered neurons in the cerebral cortex.
CC {ECO:0000269|PubMed:31424425}.
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DR EMBL; AY358919; AAQ89278.1; -; mRNA.
DR EMBL; AK027305; BAB55029.1; -; mRNA.
DR EMBL; AK056325; BAB71151.1; -; mRNA.
DR EMBL; AK292359; BAF85048.1; -; mRNA.
DR EMBL; AK075437; BAC11620.1; -; mRNA.
DR EMBL; EF445037; ACA06084.1; -; Genomic_DNA.
DR EMBL; EF445037; ACA06085.1; -; Genomic_DNA.
DR EMBL; EF445037; ACA06086.1; -; Genomic_DNA.
DR EMBL; EF445037; ACA06087.1; -; Genomic_DNA.
DR EMBL; AP000941; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471065; EAW67388.1; -; Genomic_DNA.
DR EMBL; CH471065; EAW67389.1; -; Genomic_DNA.
DR EMBL; CH471065; EAW67393.1; -; Genomic_DNA.
DR EMBL; BC042896; AAH42896.1; -; mRNA.
DR EMBL; BC051841; AAH51841.1; -; mRNA.
DR CCDS; CCDS44745.1; -. [Q86YD3-4]
DR CCDS; CCDS44746.1; -. [Q86YD3-5]
DR CCDS; CCDS44747.1; -. [Q86YD3-2]
DR CCDS; CCDS44748.1; -. [Q86YD3-3]
DR CCDS; CCDS8398.1; -. [Q86YD3-1]
DR RefSeq; NP_001137506.1; NM_001144034.1. [Q86YD3-2]
DR RefSeq; NP_001137507.1; NM_001144035.1. [Q86YD3-2]
DR RefSeq; NP_001137508.1; NM_001144036.1. [Q86YD3-3]
DR RefSeq; NP_001137509.1; NM_001144037.1. [Q86YD3-4]
DR RefSeq; NP_001137510.1; NM_001144038.1. [Q86YD3-5]
DR RefSeq; NP_001305684.1; NM_001318755.1.
DR RefSeq; NP_001305686.1; NM_001318757.1.
DR RefSeq; NP_116169.2; NM_032780.3. [Q86YD3-1]
DR RefSeq; XP_016873911.1; XM_017018422.1. [Q86YD3-1]
DR AlphaFoldDB; Q86YD3; -.
DR BioGRID; 124311; 146.
DR IntAct; Q86YD3; 60.
DR MINT; Q86YD3; -.
DR STRING; 9606.ENSP00000315635; -.
DR TCDB; 8.A.23.3.1; the basigin (basigin) family.
DR GlyGen; Q86YD3; 5 sites.
DR iPTMnet; Q86YD3; -.
DR PhosphoSitePlus; Q86YD3; -.
DR BioMuta; TMEM25; -.
DR jPOST; Q86YD3; -.
DR MassIVE; Q86YD3; -.
DR PaxDb; Q86YD3; -.
DR PeptideAtlas; Q86YD3; -.
DR PRIDE; Q86YD3; -.
DR ProteomicsDB; 34043; -.
DR ProteomicsDB; 70400; -. [Q86YD3-1]
DR ProteomicsDB; 70401; -. [Q86YD3-2]
DR ProteomicsDB; 70402; -. [Q86YD3-3]
DR ProteomicsDB; 70403; -. [Q86YD3-4]
DR Antibodypedia; 2512; 93 antibodies from 19 providers.
DR DNASU; 84866; -.
DR Ensembl; ENST00000313236.10; ENSP00000315635.5; ENSG00000149582.16. [Q86YD3-1]
DR Ensembl; ENST00000354064.11; ENSP00000278959.8; ENSG00000149582.16. [Q86YD3-3]
DR Ensembl; ENST00000354284.8; ENSP00000346237.4; ENSG00000149582.16. [Q86YD3-4]
DR Ensembl; ENST00000359862.8; ENSP00000352924.4; ENSG00000149582.16. [Q86YD3-2]
DR Ensembl; ENST00000411589.6; ENSP00000411882.2; ENSG00000149582.16. [Q86YD3-2]
DR Ensembl; ENST00000442938.6; ENSP00000416071.2; ENSG00000149582.16. [Q86YD3-5]
DR Ensembl; ENST00000524725.5; ENSP00000431205.1; ENSG00000149582.16. [Q86YD3-2]
DR GeneID; 84866; -.
DR KEGG; hsa:84866; -.
DR MANE-Select; ENST00000313236.10; ENSP00000315635.5; NM_032780.4; NP_116169.2.
DR UCSC; uc001pth.4; human. [Q86YD3-1]
DR CTD; 84866; -.
DR DisGeNET; 84866; -.
DR GeneCards; TMEM25; -.
DR HGNC; HGNC:25890; TMEM25.
DR HPA; ENSG00000149582; Low tissue specificity.
DR MIM; 613934; gene.
DR neXtProt; NX_Q86YD3; -.
DR OpenTargets; ENSG00000149582; -.
DR PharmGKB; PA134919013; -.
DR VEuPathDB; HostDB:ENSG00000149582; -.
DR eggNOG; KOG4555; Eukaryota.
DR GeneTree; ENSGT01040000240433; -.
DR InParanoid; Q86YD3; -.
DR OMA; CVCLGRW; -.
DR OrthoDB; 914115at2759; -.
DR PhylomeDB; Q86YD3; -.
DR TreeFam; TF333068; -.
DR PathwayCommons; Q86YD3; -.
DR SignaLink; Q86YD3; -.
DR BioGRID-ORCS; 84866; 10 hits in 1071 CRISPR screens.
DR ChiTaRS; TMEM25; human.
DR GeneWiki; TMEM25; -.
DR GenomeRNAi; 84866; -.
DR Pharos; Q86YD3; Tdark.
DR PRO; PR:Q86YD3; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q86YD3; protein.
DR Bgee; ENSG00000149582; Expressed in right hemisphere of cerebellum and 125 other tissues.
DR ExpressionAtlas; Q86YD3; baseline and differential.
DR Genevisible; Q86YD3; HS.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005770; C:late endosome; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0090394; P:negative regulation of excitatory postsynaptic potential; ISS:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; ISS:UniProtKB.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR013162; CD80_C2-set.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR042864; TMEM25.
DR PANTHER; PTHR47224; PTHR47224; 1.
DR Pfam; PF08205; C2-set_2; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Direct protein sequencing;
KW Disulfide bond; Endosome; Glycoprotein; Immunoglobulin domain; Lysosome;
KW Membrane; Reference proteome; Secreted; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..26
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 27..366
FT /note="Transmembrane protein 25"
FT /id="PRO_0000014984"
FT TOPO_DOM 27..232
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 233..253
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 254..366
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 30..123
FT /note="Ig-like"
FT REGION 299..335
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 106
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 162
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 175
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 192
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 205
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 52..107
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 24..128
FT /note="GWGELEPQIDGQTWAERALRENERHAFTCRVAGGPGTPRLAWYLDGQLQEAS
FT TSRLLSVGGEAFSGGTSTFTVTAHRAQHELNCSLQDPRSGRSANASVILNVQF -> V
FT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_012939"
FT VAR_SEQ 225..268
FT /note="Missing (in isoform 2, isoform 3 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:12975309,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16303743"
FT /id="VSP_012940"
FT VAR_SEQ 313
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:16303743"
FT /id="VSP_045635"
FT VAR_SEQ 344..366
FT /note="FIRLPVLGYIYRVSSVSSDEIWL -> RRNQDKDA (in isoform 4
FT and isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:16303743"
FT /id="VSP_012941"
FT VARIANT 25
FT /note="W -> C (in dbSNP:rs35915434)"
FT /id="VAR_033623"
FT VARIANT 342
FT /note="Q -> R (in dbSNP:rs12289253)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:16303743"
FT /id="VAR_021391"
FT CONFLICT 277
FT /note="I -> V (in Ref. 3; BAC11620)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 366 AA; 39285 MW; 82B06A7B55A10129 CRC64;
MALPPGPAAL RHTLLLLPAL LSSGWGELEP QIDGQTWAER ALRENERHAF TCRVAGGPGT
PRLAWYLDGQ LQEASTSRLL SVGGEAFSGG TSTFTVTAHR AQHELNCSLQ DPRSGRSANA
SVILNVQFKP EIAQVGAKYQ EAQGPGLLVV LFALVRANPP ANVTWIDQDG PVTVNTSDFL
VLDAQNYPWL TNHTVQLQLR SLAHNLSVVA TNDVGVTSAS LPAPGLLATR VEVPLLGIVV
AAGLALGTLV GFSTLVACLV CRKEKKTKGP SRHPSLISSD SNNLKLNNVR LPRENMSLPS
NLQLNDLTPD SRAVKPADRQ MAQNNSRPEL LDPEPGGLLT SQGFIRLPVL GYIYRVSSVS
SDEIWL
