Q8N427 (TXND3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Thioredoxin domain-containing protein 3

Alternative name(s):
NM23-H8
NME/NM23 family member 8
Spermatid-specific thioredoxin-2
Short name=Sptrx-2

Gene names

Name:	NME8
Synonyms:	SPTRX2, TXNDC3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	588 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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 structure	Monomer.
Subcellular location	Cytoplasm Ref.2.
Tissue specificity	Testis-specific. Expressed only in primary spermatocytes and round spermatids. Ref.2
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.
Involvement in disease	Primary ciliary dyskinesia 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5
Sequence similarities	In the C-terminal section; belongs to the NDK family. Contains 1 thioredoxin domain.

Ontologies

Keywords
Biological process	Differentiation Spermatogenesis
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Ciliopathy Primary ciliary dyskinesia
Domain	Redox-active center Repeat
Molecular function	Developmental protein
PTM	Disulfide bond
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	CTP biosynthetic process Inferred from electronic annotation. Source: InterPro GTP biosynthetic process Inferred from electronic annotation. Source: InterPro UTP biosynthetic process Inferred from electronic annotation. Source: InterPro cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW cell redox homeostasis Inferred from electronic annotation. Source: InterPro multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW spermatogenesis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell microtubule cytoskeleton Inferred from direct assay. Source: HPA
Molecular_function	ATP binding Inferred from electronic annotation. Source: InterPro nucleoside diphosphate kinase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 588	588	Thioredoxin domain-containing protein 3		PRO_0000120156
Regions
	Domain	2 – 119	118	Thioredoxin
	Region	157 – 257	101	NDK 1
	Region	315 – 455	141	NDK 2
	Region	456 – 588	133	NDK 3
Amino acid modifications
	Disulfide bond	39 ↔ 42		Redox-active By similarity
Natural variations
	Natural variant	43	1	R → K. Corresponds to variant rs2722372 [ dbSNP | Ensembl ].		VAR_032948
	Natural variant	208	1	C → R. Ref.4 Corresponds to variant rs10250905 [ dbSNP | Ensembl ].		VAR_022766
	Natural variant	289	1	I → T in a breast cancer sample; somatic mutation. Ref.6		VAR_036171
	Natural variant	493	1	I → T. Ref.4 Corresponds to variant rs56128139 [ dbSNP | Ensembl ].		VAR_061898

Sequences

	Sequence		Length	Mass (Da)
	Q8N427 [UniParc]. Last modified July 5, 2005. Version 2. Checksum: 161A5101E06EE5A7	FASTA	588	67,270
	10 20 30 40 50 60 MASKKREVQL QTVINNQSLW DEMLQNKGLT VIDVYQAWCG PCRAMQPLFR KLKNELNEDE 70 80 90 100 110 120 ILHFAVAEAD NIVTLQPFRD KCEPVFLFSV NGKIIEKIQG ANAPLVNKKV INLIDEERKI 130 140 150 160 170 180 AAGEMARPQY PEIPLVDSDS EVSEESPCES VQELYSIAII KPDAVISKKV LEIKRKITKA 190 200 210 220 230 240 GFIIEAEHKT VLTEEQVVNF YSRIADQCDF EEFVSFMTSG LSYILVVSQG SKHNPPSEET 250 260 270 280 290 300 EPQTDTEPNE RSEDQPEVEA QVTPGMMKNK QDSLQEYLER QHLAQLCDIE EDAANVAKFM 310 320 330 340 350 360 DAFFPDFKKM KSMKLEKTLA LLRPNLFHER KDDVLRIIKD EDFKILEQRQ VVLSEKEAQA 370 380 390 400 410 420 LCKEYENEDY FNKLIENMTS GPSLALVLLR DNGLQYWKQL LGPRTVEEAI EYFPESLCAQ 430 440 450 460 470 480 FAMDSLPVNQ LYGSDSLETA EREIQHFFPL QSTLGLIKPH ATSEQREQIL KIVKEAGFDL 490 500 510 520 530 540 TQVKKMFLTP EQIEKIYPKV TGKDFYKDLL EMLSVGPSMV MILTKWNAVA EWRRLMGPTD 550 560 570 580 PEEAKLLSPD SIRAQFGISK LKNIVHGASN AYEAKEVVNR LFEDPEEN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The human Nm23/nucleoside diphosphate kinases." Lacombe M.-L.L., Milon L., Munier A., Mehus J.G., Lambeth D.O. J. Bioenerg. Biomembr. 32:247-258(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Sptrx-2, a fusion protein composed of one thioredoxin and three tandemly repeated NDP-kinase domains is expressed in human testis germ cells." Sadek C.M., Damdimopoulos A.E., Pelto-Huikko M., Gustafsson J.-A., Spyrou G., Miranda-Vizuete A. Genes Cells 6:1077-1090(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[3]	"The DNA sequence of human chromosome 7." 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. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ARG-208 AND THR-493. Tissue: Brain.
[5]	"A common variant in combination with a nonsense mutation in a member of the thioredoxin family causes primary ciliary dyskinesia." Duriez B., Duquesnoy P., Escudier E., Bridoux A.-M., Escalier D., Rayet I., Marcos E., Vojtek A.-M., Bercher J.-F., Amselem S. Proc. Natl. Acad. Sci. U.S.A. 104:3336-3341(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN CILD6.
[6]	"The consensus coding sequences of human breast and colorectal cancers." 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. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] THR-289.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF202051 mRNA. Translation: AAF20909.2. AF305596 mRNA. Translation: AAN04258.1. AC018634 Genomic DNA. No translation available. BC036816 mRNA. Translation: AAH36816.1.
IPI	IPI00296545.
RefSeq	NP_057700.3. NM_016616.4.
UniGene	Hs.723454.
3D structure databases
ProteinModelPortal	Q8N427.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000199447.
PTM databases
PhosphoSite	Q8N427.
Polymorphism databases
DMDM	68566210.
Proteomic databases
PaxDb	Q8N427.
PRIDE	Q8N427.
Protocols and materials databases
DNASU	51314.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000199447; ENSP00000199447; ENSG00000086288. ENST00000440017; ENSP00000397063; ENSG00000086288.
GeneID	51314.
KEGG	hsa:51314.
UCSC	uc003tfn.3. human.
Organism-specific databases
CTD	51314.
GeneCards	GC07P037889.
HGNC	HGNC:16473. NME8.
HPA	CAB016416. HPA019259.
MIM	607421. gene. 610852. phenotype.
neXtProt	NX_Q8N427.
Orphanet	244. Primary ciliary dyskinesia.
PharmGKB	PA134925065.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0105.
HOGENOM	HOG000111057.
HOVERGEN	HBG061844.
InParanoid	Q8N427.
OMA	SLCAQFA.
OrthoDB	EOG434W5W.
PhylomeDB	Q8N427.
Gene expression databases
ArrayExpress	Q8N427.
Bgee	Q8N427.
CleanEx	HS_TXNDC3.
Genevestigator	Q8N427.
GermOnline	ENSG00000086288. Homo sapiens.
Family and domain databases
Gene3D	3.30.70.141. 3 hits. 3.40.30.10. 1 hit.
InterPro	IPR001564. Nucleoside_diP_kinase. IPR012336. Thioredoxin-like_fold. IPR017937. Thioredoxin_CS. IPR013766. Thioredoxin_domain. [Graphical view]
PANTHER	PTHR11349. PTHR11349. 1 hit.
Pfam	PF00334. NDK. 3 hits. PF00085. Thioredoxin. 1 hit. [Graphical view]
SMART	SM00562. NDK. 2 hits. [Graphical view]
SUPFAM	SSF54919. NDK. 3 hits. SSF52833. Thiordxn-like_fd. 1 hit.
PROSITE	PS00469. NDP_KINASES. False negative. PS00194. THIOREDOXIN_1. 1 hit. PS51352. THIOREDOXIN_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	51314.
NextBio	54669.
SOURCE	Search...

Entry information

Entry name

TXND3_HUMAN

Accession

Primary (citable) accession number: Q8N427
Secondary accession number(s): Q9NZH1

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 5, 2005
Last sequence update:	July 5, 2005
Last modified:	May 1, 2013
This is version 105 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.