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Thioredoxin domain-containing protein 3 (NM23-H8) (NME/NM23 family member 8) (Spermatid-specific thioredoxin-2) (Sptrx-2)

 TXND3_HUMAN             Reviewed;         588 AA.
Q8N427; Q9NZH1;
05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
05-JUL-2005, sequence version 2.
28-MAR-2018, entry version 148.
RecName: Full=Thioredoxin domain-containing protein 3;
AltName: Full=NM23-H8;
AltName: Full=NME/NM23 family member 8;
AltName: Full=Spermatid-specific thioredoxin-2;
Short=Sptrx-2;
Name=NME8; Synonyms=SPTRX2, TXNDC3;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=11768308; DOI=10.1023/A:1005584929050;
Lacombe M.-L.L., Milon L., Munier A., Mehus J.G., Lambeth D.O.;
"The human Nm23/nucleoside diphosphate kinases.";
J. Bioenerg. Biomembr. 32:247-258(2000).
[2]
NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE
SPECIFICITY.
PubMed=11737268; DOI=10.1046/j.1365-2443.2001.00484.x;
Sadek C.M., Damdimopoulos A.E., Pelto-Huikko M., Gustafsson J.-A.,
Spyrou G., Miranda-Vizuete A.;
"Sptrx-2, a fusion protein composed of one thioredoxin and three
tandemly repeated NDP-kinase domains is expressed in human testis germ
cells.";
Genes Cells 6:1077-1090(2001).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=12853948; DOI=10.1038/nature01782;
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R.,
Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K.,
Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
Waterston R.H., Wilson R.K.;
"The DNA sequence of human chromosome 7.";
Nature 424:157-164(2003).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ARG-208 AND
THR-493.
TISSUE=Brain;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
INVOLVEMENT IN CILD6.
PubMed=17360648; DOI=10.1073/pnas.0611405104;
Duriez B., Duquesnoy P., Escudier E., Bridoux A.-M., Escalier D.,
Rayet I., Marcos E., Vojtek A.-M., Bercher J.-F., Amselem S.;
"A common variant in combination with a nonsense mutation in a member
of the thioredoxin family causes primary ciliary dyskinesia.";
Proc. Natl. Acad. Sci. U.S.A. 104:3336-3341(2007).
[6]
VARIANT [LARGE SCALE ANALYSIS] THR-289.
PubMed=16959974; DOI=10.1126/science.1133427;
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
Vogelstein B., Kinzler K.W., Velculescu V.E.;
"The consensus coding sequences of human breast and colorectal
cancers.";
Science 314:268-274(2006).
-!- FUNCTION: Probably required during the final stages of sperm tail
maturation in the testis and/or epididymis, where extensive
disulfide bonding of fibrous sheath (FS) proteins occurs. May be
involved in the reduction of disulfide bonds within the sperm FS
components. In vitro, it has neither NDP kinase nor reducing
activity on disulfide bonds.
-!- SUBUNIT: Monomer.
-!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11737268}.
-!- TISSUE SPECIFICITY: Testis-specific. Expressed only in primary
spermatocytes and round spermatids. {ECO:0000269|PubMed:11737268}.
-!- DEVELOPMENTAL STAGE: Restricted to spermiogenesis, starting at the
pachytene spermatocyte level and peaking at the round and
elongating spermatid stage.
-!- DOMAIN: Contains 3 inactive NDK domains that each lack the active
His residue, suggesting that they have no NDP kinase activity.
-!- DISEASE: Ciliary dyskinesia, primary, 6 (CILD6) [MIM:610852]: A
disorder characterized by abnormalities of motile cilia.
Respiratory infections leading to chronic inflammation and
bronchiectasis are recurrent, due to defects in the respiratory
cilia; reduced fertility is often observed in male patients due to
abnormalities of sperm tails. Half of the patients exhibit
randomization of left-right body asymmetry and situs inversus, due
to dysfunction of monocilia at the embryonic node. Primary ciliary
dyskinesia associated with situs inversus is referred to as
Kartagener syndrome. {ECO:0000269|PubMed:17360648}. Note=The
disease is caused by mutations affecting the gene represented in
this entry.
-!- SIMILARITY: In the C-terminal section; belongs to the NDK family.
{ECO:0000305}.
-----------------------------------------------------------------------
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EMBL; AF202051; AAF20909.2; -; mRNA.
EMBL; AF305596; AAN04258.1; -; mRNA.
EMBL; AC018634; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; BC036816; AAH36816.1; -; mRNA.
CCDS; CCDS5452.1; -.
RefSeq; NP_057700.3; NM_016616.4.
UniGene; Hs.723454; -.
ProteinModelPortal; Q8N427; -.
SMR; Q8N427; -.
BioGrid; 119465; 7.
IntAct; Q8N427; 4.
STRING; 9606.ENSP00000199447; -.
iPTMnet; Q8N427; -.
PhosphoSitePlus; Q8N427; -.
BioMuta; NME8; -.
DMDM; 68566210; -.
EPD; Q8N427; -.
PaxDb; Q8N427; -.
PeptideAtlas; Q8N427; -.
PRIDE; Q8N427; -.
DNASU; 51314; -.
Ensembl; ENST00000199447; ENSP00000199447; ENSG00000086288.
Ensembl; ENST00000440017; ENSP00000397063; ENSG00000086288.
GeneID; 51314; -.
KEGG; hsa:51314; -.
UCSC; uc003tfn.4; human.
CTD; 51314; -.
DisGeNET; 51314; -.
EuPathDB; HostDB:ENSG00000086288.11; -.
GeneCards; NME8; -.
GeneReviews; NME8; -.
HGNC; HGNC:16473; NME8.
HPA; CAB016416; -.
HPA; HPA019259; -.
MalaCards; NME8; -.
MIM; 607421; gene.
MIM; 610852; phenotype.
neXtProt; NX_Q8N427; -.
OpenTargets; ENSG00000086288; -.
Orphanet; 244; Primary ciliary dyskinesia.
PharmGKB; PA134925065; -.
eggNOG; KOG0888; Eukaryota.
eggNOG; KOG0907; Eukaryota.
eggNOG; COG0105; LUCA.
GeneTree; ENSGT00760000119146; -.
HOGENOM; HOG000111057; -.
HOVERGEN; HBG061844; -.
InParanoid; Q8N427; -.
KO; K19868; -.
OMA; SLCAQFA; -.
OrthoDB; EOG091G03O2; -.
PhylomeDB; Q8N427; -.
TreeFam; TF106374; -.
ChiTaRS; NME8; human.
GeneWiki; TXNDC3; -.
GenomeRNAi; 51314; -.
PRO; PR:Q8N427; -.
Proteomes; UP000005640; Chromosome 7.
Bgee; ENSG00000086288; -.
CleanEx; HS_TXNDC3; -.
ExpressionAtlas; Q8N427; baseline and differential.
Genevisible; Q8N427; HS.
GO; GO:0036157; C:outer dynein arm; IMP:SYSCILIA_CCNET.
GO; GO:0097598; C:sperm cytoplasmic droplet; IEA:Ensembl.
GO; GO:0097228; C:sperm principal piece; IEA:Ensembl.
GO; GO:0008017; F:microtubule binding; IDA:SYSCILIA_CCNET.
GO; GO:0004550; F:nucleoside diphosphate kinase activity; IBA:GO_Central.
GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
GO; GO:0045454; P:cell redox homeostasis; IEA:InterPro.
GO; GO:0034614; P:cellular response to reactive oxygen species; IEA:Ensembl.
GO; GO:0060271; P:cilium assembly; IMP:SYSCILIA_CCNET.
GO; GO:0030317; P:flagellated sperm motility; IEA:Ensembl.
GO; GO:0007275; P:multicellular organism development; IEA:UniProtKB-KW.
GO; GO:0007283; P:spermatogenesis; IEA:UniProtKB-KW.
Gene3D; 3.30.70.141; -; 3.
InterPro; IPR034907; NDK-like_dom.
InterPro; IPR036850; NDK-like_dom_sf.
InterPro; IPR036249; Thioredoxin-like_sf.
InterPro; IPR017937; Thioredoxin_CS.
InterPro; IPR013766; Thioredoxin_domain.
Pfam; PF00334; NDK; 3.
Pfam; PF00085; Thioredoxin; 1.
SMART; SM00562; NDK; 2.
SUPFAM; SSF52833; SSF52833; 1.
SUPFAM; SSF54919; SSF54919; 3.
PROSITE; PS00194; THIOREDOXIN_1; 1.
PROSITE; PS51352; THIOREDOXIN_2; 1.
2: Evidence at transcript level;
Ciliopathy; Complete proteome; Cytoplasm; Developmental protein;
Differentiation; Disulfide bond; Polymorphism;
Primary ciliary dyskinesia; Redox-active center; Reference proteome;
Repeat; Spermatogenesis.
CHAIN 1 588 Thioredoxin domain-containing protein 3.
/FTId=PRO_0000120156.
DOMAIN 2 119 Thioredoxin. {ECO:0000255|PROSITE-
ProRule:PRU00691}.
REGION 157 257 NDK 1.
REGION 315 455 NDK 2.
REGION 456 588 NDK 3.
DISULFID 39 42 Redox-active. {ECO:0000255|PROSITE-
ProRule:PRU00691}.
VARIANT 43 43 R -> K (in dbSNP:rs2722372).
/FTId=VAR_032948.
VARIANT 208 208 C -> R (in dbSNP:rs10250905).
{ECO:0000269|PubMed:15489334}.
/FTId=VAR_022766.
VARIANT 289 289 I -> T (in a breast cancer sample;
somatic mutation).
{ECO:0000269|PubMed:16959974}.
/FTId=VAR_036171.
VARIANT 493 493 I -> T (in dbSNP:rs56128139).
{ECO:0000269|PubMed:15489334}.
/FTId=VAR_061898.
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


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