TMX3_HUMAN
ID TMX3_HUMAN Reviewed; 454 AA.
AC Q96JJ7; B3KV75; Q52LT7; Q8N5J0; Q9NWJ9;
DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2005, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Protein disulfide-isomerase TMX3;
DE EC=5.3.4.1;
DE AltName: Full=Thioredoxin domain-containing protein 10;
DE AltName: Full=Thioredoxin-related transmembrane protein 3;
DE Flags: Precursor;
GN Name=TMX3; Synonyms=KIAA1830, TXNDC10;
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 1).
RC TISSUE=Brain;
RX PubMed=11347906; DOI=10.1093/dnares/8.2.85;
RA Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 8:85-95(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon, and Tongue;
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 1).
RC TISSUE=Skeletal muscle;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP SER-61.
RC TISSUE=Brain, and Skin;
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 FUNCTION, ENZYME ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, INDUCTION, AND GLYCOSYLATION.
RX PubMed=15623505; DOI=10.1074/jbc.m413924200;
RA Haugstetter J., Blicher T., Ellgaard L.;
RT "Identification and characterization of a novel thioredoxin-related
RT transmembrane protein of the endoplasmic reticulum.";
RL J. Biol. Chem. 280:8371-8380(2005).
RN [6]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-258.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- FUNCTION: Probable disulfide isomerase, which participates in the
CC folding of proteins containing disulfide bonds. May act as a dithiol
CC oxidase. {ECO:0000269|PubMed:15623505}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Catalyzes the rearrangement of -S-S- bonds in proteins.;
CC EC=5.3.4.1; Evidence={ECO:0000269|PubMed:15623505};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Redox potential:
CC E(0) is -157 mV. {ECO:0000269|PubMed:15623505};
CC -!- INTERACTION:
CC Q96JJ7; Q13643: FHL3; NbExp=3; IntAct=EBI-2514069, EBI-741101;
CC Q96JJ7-2; P27797: CALR; NbExp=3; IntAct=EBI-25833898, EBI-1049597;
CC Q96JJ7-2; P36957: DLST; NbExp=3; IntAct=EBI-25833898, EBI-351007;
CC Q96JJ7-2; Q8TDX7: NEK7; NbExp=3; IntAct=EBI-25833898, EBI-1055945;
CC Q96JJ7-2; P16284: PECAM1; NbExp=3; IntAct=EBI-25833898, EBI-716404;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:15623505}; Single-pass membrane protein
CC {ECO:0000269|PubMed:15623505}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96JJ7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96JJ7-2; Sequence=VSP_013748, VSP_013749;
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in brain, testis, lung,
CC skin, kidney, uterus, bone, stomach, liver, prostate, placenta, eye and
CC muscle. {ECO:0000269|PubMed:15623505}.
CC -!- INDUCTION: Not up-regulated by unfolded protein response (UPR).
CC {ECO:0000269|PubMed:15623505}.
CC -!- DOMAIN: The di-lysine motif confers endoplasmic reticulum localization
CC for type I membrane proteins. {ECO:0000250}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:15623505,
CC ECO:0000269|PubMed:19159218}.
CC -!- SIMILARITY: Belongs to the protein disulfide isomerase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA91381.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB47459.1; Type=Erroneous initiation; Note=Extended N-terminus.; 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; AB058733; BAB47459.1; ALT_INIT; mRNA.
DR EMBL; AK000800; BAA91381.1; ALT_INIT; mRNA.
DR EMBL; AK122715; BAG53687.1; -; mRNA.
DR EMBL; BX647846; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC032325; AAH32325.1; -; mRNA.
DR EMBL; BC093792; AAH93792.1; -; mRNA.
DR EMBL; BC093794; AAH93794.1; -; mRNA.
DR CCDS; CCDS32840.1; -. [Q96JJ7-1]
DR CCDS; CCDS86680.1; -. [Q96JJ7-2]
DR RefSeq; NP_061895.3; NM_019022.3. [Q96JJ7-1]
DR AlphaFoldDB; Q96JJ7; -.
DR SMR; Q96JJ7; -.
DR BioGRID; 119991; 117.
DR IntAct; Q96JJ7; 41.
DR MINT; Q96JJ7; -.
DR STRING; 9606.ENSP00000299608; -.
DR TCDB; 8.A.88.2.3; the calciquestrin (casq) family.
DR GlyConnect; 1656; 2 N-Linked glycans (1 site).
DR GlyGen; Q96JJ7; 2 sites, 4 N-linked glycans (1 site).
DR iPTMnet; Q96JJ7; -.
DR PhosphoSitePlus; Q96JJ7; -.
DR SwissPalm; Q96JJ7; -.
DR BioMuta; TMX3; -.
DR DMDM; 78103208; -.
DR EPD; Q96JJ7; -.
DR jPOST; Q96JJ7; -.
DR MassIVE; Q96JJ7; -.
DR MaxQB; Q96JJ7; -.
DR PaxDb; Q96JJ7; -.
DR PeptideAtlas; Q96JJ7; -.
DR PRIDE; Q96JJ7; -.
DR ProteomicsDB; 76972; -. [Q96JJ7-1]
DR ProteomicsDB; 76973; -. [Q96JJ7-2]
DR TopDownProteomics; Q96JJ7-1; -. [Q96JJ7-1]
DR Antibodypedia; 2580; 110 antibodies from 21 providers.
DR DNASU; 54495; -.
DR Ensembl; ENST00000299608.7; ENSP00000299608.2; ENSG00000166479.10. [Q96JJ7-1]
DR Ensembl; ENST00000562706.5; ENSP00000457262.1; ENSG00000166479.10. [Q96JJ7-2]
DR GeneID; 54495; -.
DR KEGG; hsa:54495; -.
DR MANE-Select; ENST00000299608.7; ENSP00000299608.2; NM_019022.5; NP_061895.3.
DR UCSC; uc002lkf.4; human. [Q96JJ7-1]
DR CTD; 54495; -.
DR DisGeNET; 54495; -.
DR GeneCards; TMX3; -.
DR HGNC; HGNC:24718; TMX3.
DR HPA; ENSG00000166479; Low tissue specificity.
DR MIM; 616102; gene.
DR neXtProt; NX_Q96JJ7; -.
DR OpenTargets; ENSG00000166479; -.
DR PharmGKB; PA164726632; -.
DR VEuPathDB; HostDB:ENSG00000166479; -.
DR eggNOG; KOG4277; Eukaryota.
DR GeneTree; ENSGT00930000151022; -.
DR HOGENOM; CLU_040429_1_0_1; -.
DR InParanoid; Q96JJ7; -.
DR OMA; MWRGNPV; -.
DR OrthoDB; 746938at2759; -.
DR PhylomeDB; Q96JJ7; -.
DR TreeFam; TF313807; -.
DR PathwayCommons; Q96JJ7; -.
DR Reactome; R-HSA-114608; Platelet degranulation.
DR SignaLink; Q96JJ7; -.
DR BioGRID-ORCS; 54495; 9 hits in 1079 CRISPR screens.
DR ChiTaRS; TMX3; human.
DR GeneWiki; TMX3; -.
DR GenomeRNAi; 54495; -.
DR Pharos; Q96JJ7; Tbio.
DR PRO; PR:Q96JJ7; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q96JJ7; protein.
DR Bgee; ENSG00000166479; Expressed in calcaneal tendon and 181 other tissues.
DR ExpressionAtlas; Q96JJ7; baseline and differential.
DR Genevisible; Q96JJ7; HS.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:WormBase.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0031092; C:platelet alpha granule membrane; TAS:Reactome.
DR GO; GO:0003756; F:protein disulfide isomerase activity; IBA:GO_Central.
DR GO; GO:0015035; F:protein-disulfide reductase activity; IDA:WormBase.
DR GO; GO:0018171; P:peptidyl-cysteine oxidation; IDA:WormBase.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR InterPro; IPR017937; Thioredoxin_CS.
DR InterPro; IPR013766; Thioredoxin_domain.
DR Pfam; PF00085; Thioredoxin; 1.
DR SUPFAM; SSF52833; SSF52833; 2.
DR PROSITE; PS00194; THIOREDOXIN_1; 1.
DR PROSITE; PS51352; THIOREDOXIN_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disulfide bond; Endoplasmic reticulum; Glycoprotein;
KW Isomerase; Membrane; Redox-active center; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..454
FT /note="Protein disulfide-isomerase TMX3"
FT /id="PRO_0000034185"
FT TOPO_DOM 25..375
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 376..396
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 397..454
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 25..128
FT /note="Thioredoxin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT REGION 412..454
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 451..454
FT /note="Di-lysine motif"
FT COMPBIAS 412..428
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 258
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 313
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 53..56
FT /note="Redox-active"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT VAR_SEQ 191..195
FT /note="YVTLK -> VIFKI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013748"
FT VAR_SEQ 196..454
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013749"
FT VARIANT 61
FT /note="P -> S (in dbSNP:rs11557684)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_022451"
SQ SEQUENCE 454 AA; 51872 MW; 37EBA0C70ED84A9B CRC64;
MAAWKSWTAL RLCATVVVLD MVVCKGFVED LDESFKENRN DDIWLVDFYA PWCGHCKKLE
PIWNEVGLEM KSIGSPVKVG KMDATSYSSI ASEFGVRGYP TIKLLKGDLA YNYRGPRTKD
DIIEFAHRVS GALIRPLPSQ QMFEHMQKRH RVFFVYVGGE SPLKEKYIDA ASELIVYTYF
FSASEEVVPE YVTLKEMPAV LVFKDETYFV YDEYEDGDLS SWINRERFQN YLAMDGFLLY
ELGDTGKLVA LAVIDEKNTS VEHTRLKSII QEVARDYRDL FHRDFQFGHM DGNDYINTLL
MDELTVPTVV VLNTSNQQYF LLDRQIKNVE DMVQFINNIL DGTVEAQGGD SILQRLKRIV
FDAKSTIVSI FKSSPLMGCF LFGLPLGVIS IMCYGIYTAD TDGGYIEERY EVSKSENENQ
EQIEESKEQQ EPSSGGSVVP TVQEPKDVLE KKKD
