TXND3_HUMAN
ID TXND3_HUMAN Reviewed; 588 AA.
AC Q8N427; Q9NZH1;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 2.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Thioredoxin domain-containing protein 3;
DE AltName: Full=NM23-H8;
DE AltName: Full=NME/NM23 family member 8;
DE AltName: Full=Spermatid-specific thioredoxin-2;
DE Short=Sptrx-2;
GN Name=NME8; Synonyms=SPTRX2, TXNDC3;
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].
RX PubMed=11768308; DOI=10.1023/a:1005584929050;
RA Lacombe M.-L.L., Milon L., Munier A., Mehus J.G., Lambeth D.O.;
RT "The human Nm23/nucleoside diphosphate kinases.";
RL J. Bioenerg. Biomembr. 32:247-258(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11737268; DOI=10.1046/j.1365-2443.2001.00484.x;
RA Sadek C.M., Damdimopoulos A.E., Pelto-Huikko M., Gustafsson J.-A.,
RA Spyrou G., Miranda-Vizuete A.;
RT "Sptrx-2, a fusion protein composed of one thioredoxin and three tandemly
RT repeated NDP-kinase domains is expressed in human testis germ cells.";
RL Genes Cells 6:1077-1090(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ARG-208 AND THR-493.
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 INVOLVEMENT IN CILD6.
RX PubMed=17360648; DOI=10.1073/pnas.0611405104;
RA Duriez B., Duquesnoy P., Escudier E., Bridoux A.-M., Escalier D., Rayet I.,
RA Marcos E., Vojtek A.-M., Bercher J.-F., Amselem S.;
RT "A common variant in combination with a nonsense mutation in a member of
RT the thioredoxin family causes primary ciliary dyskinesia.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:3336-3341(2007).
RN [6]
RP VARIANT [LARGE SCALE ANALYSIS] THR-289.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Probably required during the final stages of sperm tail
CC maturation in the testis and/or epididymis, where extensive disulfide
CC bonding of fibrous sheath (FS) proteins occurs. May be involved in the
CC reduction of disulfide bonds within the sperm FS components. In vitro,
CC it has neither NDP kinase nor reducing activity on disulfide bonds.
CC -!- SUBUNIT: Monomer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11737268}.
CC -!- TISSUE SPECIFICITY: Testis-specific. Expressed only in primary
CC spermatocytes and round spermatids. {ECO:0000269|PubMed:11737268}.
CC -!- DEVELOPMENTAL STAGE: Restricted to spermiogenesis, starting at the
CC pachytene spermatocyte level and peaking at the round and elongating
CC spermatid stage.
CC -!- DOMAIN: Contains 3 inactive NDK domains that each lack the active His
CC residue, suggesting that they have no NDP kinase activity.
CC -!- DISEASE: Ciliary dyskinesia, primary, 6 (CILD6) [MIM:610852]: A
CC disorder characterized by abnormalities of motile cilia. Respiratory
CC infections leading to chronic inflammation and bronchiectasis are
CC recurrent, due to defects in the respiratory cilia; reduced fertility
CC is often observed in male patients due to abnormalities of sperm tails.
CC Half of the patients exhibit randomization of left-right body asymmetry
CC and situs inversus, due to dysfunction of monocilia at the embryonic
CC node. Primary ciliary dyskinesia associated with situs inversus is
CC referred to as Kartagener syndrome. {ECO:0000269|PubMed:17360648}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: In the C-terminal section; belongs to the NDK family.
CC {ECO:0000305}.
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DR EMBL; AF202051; AAF20909.2; -; mRNA.
DR EMBL; AF305596; AAN04258.1; -; mRNA.
DR EMBL; AC018634; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC036816; AAH36816.1; -; mRNA.
DR CCDS; CCDS5452.1; -.
DR RefSeq; NP_057700.3; NM_016616.4.
DR AlphaFoldDB; Q8N427; -.
DR SMR; Q8N427; -.
DR BioGRID; 119465; 10.
DR IntAct; Q8N427; 4.
DR STRING; 9606.ENSP00000199447; -.
DR iPTMnet; Q8N427; -.
DR PhosphoSitePlus; Q8N427; -.
DR BioMuta; NME8; -.
DR DMDM; 68566210; -.
DR EPD; Q8N427; -.
DR MassIVE; Q8N427; -.
DR PaxDb; Q8N427; -.
DR PeptideAtlas; Q8N427; -.
DR PRIDE; Q8N427; -.
DR ProteomicsDB; 71868; -.
DR Antibodypedia; 12974; 108 antibodies from 26 providers.
DR DNASU; 51314; -.
DR Ensembl; ENST00000199447.9; ENSP00000199447.4; ENSG00000086288.12.
DR Ensembl; ENST00000440017.5; ENSP00000397063.1; ENSG00000086288.12.
DR GeneID; 51314; -.
DR KEGG; hsa:51314; -.
DR MANE-Select; ENST00000199447.9; ENSP00000199447.4; NM_016616.5; NP_057700.3.
DR UCSC; uc003tfn.4; human.
DR CTD; 51314; -.
DR DisGeNET; 51314; -.
DR GeneCards; NME8; -.
DR GeneReviews; NME8; -.
DR HGNC; HGNC:16473; NME8.
DR HPA; ENSG00000086288; Group enriched (bone marrow, testis).
DR MalaCards; NME8; -.
DR MIM; 607421; gene.
DR MIM; 610852; phenotype.
DR neXtProt; NX_Q8N427; -.
DR OpenTargets; ENSG00000086288; -.
DR Orphanet; 244; Primary ciliary dyskinesia.
DR PharmGKB; PA134925065; -.
DR VEuPathDB; HostDB:ENSG00000086288; -.
DR eggNOG; KOG0888; Eukaryota.
DR eggNOG; KOG0907; Eukaryota.
DR GeneTree; ENSGT00940000161182; -.
DR HOGENOM; CLU_016708_0_0_1; -.
DR InParanoid; Q8N427; -.
DR OMA; REIQYFF; -.
DR OrthoDB; 971216at2759; -.
DR PhylomeDB; Q8N427; -.
DR TreeFam; TF106374; -.
DR PathwayCommons; Q8N427; -.
DR SignaLink; Q8N427; -.
DR BioGRID-ORCS; 51314; 13 hits in 1059 CRISPR screens.
DR GeneWiki; TXNDC3; -.
DR GenomeRNAi; 51314; -.
DR Pharos; Q8N427; Tbio.
DR PRO; PR:Q8N427; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q8N427; protein.
DR Bgee; ENSG00000086288; Expressed in granulocyte and 100 other tissues.
DR ExpressionAtlas; Q8N427; baseline and differential.
DR Genevisible; Q8N427; HS.
DR GO; GO:0005930; C:axoneme; ISS:ARUK-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:ARUK-UCL.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:ARUK-UCL.
DR GO; GO:0036157; C:outer dynein arm; IMP:SYSCILIA_CCNET.
DR GO; GO:0097598; C:sperm cytoplasmic droplet; IEA:Ensembl.
DR GO; GO:0097225; C:sperm midpiece; IDA:ARUK-UCL.
DR GO; GO:0097228; C:sperm principal piece; IDA:ARUK-UCL.
DR GO; GO:0008017; F:microtubule binding; IDA:SYSCILIA_CCNET.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; IEA:Ensembl.
DR GO; GO:0060271; P:cilium assembly; IMP:SYSCILIA_CCNET.
DR GO; GO:0030317; P:flagellated sperm motility; IBA:GO_Central.
DR GO; GO:0007283; P:spermatogenesis; IEA:UniProtKB-KW.
DR Gene3D; 3.30.70.141; -; 3.
DR InterPro; IPR034907; NDK-like_dom.
DR InterPro; IPR036850; NDK-like_dom_sf.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR InterPro; IPR017937; Thioredoxin_CS.
DR InterPro; IPR013766; Thioredoxin_domain.
DR Pfam; PF00334; NDK; 3.
DR Pfam; PF00085; Thioredoxin; 1.
DR SMART; SM00562; NDK; 2.
DR SUPFAM; SSF52833; SSF52833; 1.
DR SUPFAM; SSF54919; SSF54919; 3.
DR PROSITE; PS00194; THIOREDOXIN_1; 1.
DR PROSITE; PS51352; THIOREDOXIN_2; 1.
PE 2: Evidence at transcript level;
KW Ciliopathy; Cytoplasm; Developmental protein; Differentiation;
KW Disulfide bond; Primary ciliary dyskinesia; Redox-active center;
KW Reference proteome; Repeat; Spermatogenesis.
FT CHAIN 1..588
FT /note="Thioredoxin domain-containing protein 3"
FT /id="PRO_0000120156"
FT DOMAIN 2..119
FT /note="Thioredoxin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT REGION 157..257
FT /note="NDK 1"
FT REGION 230..261
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 315..455
FT /note="NDK 2"
FT REGION 456..588
FT /note="NDK 3"
FT COMPBIAS 238..257
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 39..42
FT /note="Redox-active"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT VARIANT 43
FT /note="R -> K (in dbSNP:rs2722372)"
FT /id="VAR_032948"
FT VARIANT 208
FT /note="C -> R (in dbSNP:rs10250905)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_022766"
FT VARIANT 289
FT /note="I -> T (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036171"
FT VARIANT 493
FT /note="I -> T (in dbSNP:rs56128139)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_061898"
SQ SEQUENCE 588 AA; 67270 MW; 161A5101E06EE5A7 CRC64;
MASKKREVQL QTVINNQSLW DEMLQNKGLT VIDVYQAWCG PCRAMQPLFR KLKNELNEDE
ILHFAVAEAD NIVTLQPFRD KCEPVFLFSV NGKIIEKIQG ANAPLVNKKV INLIDEERKI
AAGEMARPQY PEIPLVDSDS EVSEESPCES VQELYSIAII KPDAVISKKV LEIKRKITKA
GFIIEAEHKT VLTEEQVVNF YSRIADQCDF EEFVSFMTSG LSYILVVSQG SKHNPPSEET
EPQTDTEPNE RSEDQPEVEA QVTPGMMKNK QDSLQEYLER QHLAQLCDIE EDAANVAKFM
DAFFPDFKKM KSMKLEKTLA LLRPNLFHER KDDVLRIIKD EDFKILEQRQ VVLSEKEAQA
LCKEYENEDY FNKLIENMTS GPSLALVLLR DNGLQYWKQL LGPRTVEEAI EYFPESLCAQ
FAMDSLPVNQ LYGSDSLETA EREIQHFFPL QSTLGLIKPH ATSEQREQIL KIVKEAGFDL
TQVKKMFLTP EQIEKIYPKV TGKDFYKDLL EMLSVGPSMV MILTKWNAVA EWRRLMGPTD
PEEAKLLSPD SIRAQFGISK LKNIVHGASN AYEAKEVVNR LFEDPEEN
