ID   TXND2_HUMAN             Reviewed;         553 AA.
AC   Q86VQ3; A5YM73; Q8N7U4; Q96RX3; Q9H0L8;
DT   05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT   30-NOV-2010, sequence version 4.
DT   24-JAN-2024, entry version 177.
DE   RecName: Full=Thioredoxin domain-containing protein 2;
DE   AltName: Full=Spermatid-specific thioredoxin-1;
DE            Short=Sptrx-1;
GN   Name=TXNDC2; Synonyms=SPTRX, SPTRX1;
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] (ISOFORM 2), SUBCELLULAR LOCATION, TISSUE
RP   SPECIFICITY, AND ENZYME ACTIVITY IN VITRO.
RX   PubMed=11399755; DOI=10.1074/jbc.m101760200;
RA   Miranda-Vizuete A., Ljung J., Damdimopoulos A.E., Gustafsson J.-A., Oko R.,
RA   Pelto-Huikko M., Spyrou G.;
RT   "Characterization of Sptrx, a novel member of the thioredoxin family
RT   specifically expressed in human spermatozoa.";
RL   J. Biol. Chem. 276:31567-31574(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND VARIANT LYS-341.
RA   Schupp I.;
RL   Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS LYS-341;
RP   ASP-357 AND THR-487.
RC   TISSUE=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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16177791; DOI=10.1038/nature03983;
RA   Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA   Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA   Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA   Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA   Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA   Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA   Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA   Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA   Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT   "DNA sequence and analysis of human chromosome 18.";
RL   Nature 437:551-555(2005).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS LYS-341
RP   AND ASP-357.
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   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 393-553, AND VARIANT THR-461.
RC   TISSUE=Testis;
RX   PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA   Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA   Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA   Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA   Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA   Klein M., Poustka A.;
RT   "Towards a catalog of human genes and proteins: sequencing and analysis of
RT   500 novel complete protein coding human cDNAs.";
RL   Genome Res. 11:422-435(2001).
RN   [7]
RP   ENZYME ACTIVITY IN VITRO.
RX   PubMed=12387870; DOI=10.1016/s0014-5793(02)03417-8;
RA   Jimenez A., Johansson C., Ljung J., Sagemark J., Berndt K.D., Ren B.,
RA   Tibbelin G., Ladenstein R., Kieselbach T., Holmgren A., Gustafsson J.-A.,
RA   Miranda-Vizuete A.;
RT   "Human spermatid-specific thioredoxin-1 (Sptrx-1) is a two-domain protein
RT   with oxidizing activity.";
RL   FEBS Lett. 530:79-84(2002).
CC   -!- FUNCTION: Probably plays a regulatory role in sperm development. May
CC       participate in regulation of fibrous sheath (FS) assembly by supporting
CC       the formation of disulfide bonds during sperm tail morphogenesis. May
CC       also be required to rectify incorrect disulfide pairing and generate
CC       suitable pairs between the FS constituents. Can reduce disulfide bonds
CC       in vitro in the presence of NADP and thioredoxin reductase.
CC   -!- INTERACTION:
CC       Q86VQ3; P35638: DDIT3; NbExp=3; IntAct=EBI-1220595, EBI-742651;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11399755}. Note=In
CC       ejaculated spermatozoa, it localizes in the caudal region of the head
CC       to the end of the principal piece.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q86VQ3-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q86VQ3-2; Sequence=VSP_014328;
CC       Name=3;
CC         IsoId=Q86VQ3-3; Sequence=VSP_053684;
CC   -!- TISSUE SPECIFICITY: Testis-specific. Only expressed during
CC       spermiogenesis, prominently in round and elongating spermatids.
CC       {ECO:0000269|PubMed:11399755}.
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DR   EMBL; AF080095; AAK94950.1; -; mRNA.
DR   EMBL; EF560747; ABQ59057.1; -; mRNA.
DR   EMBL; AK097656; BAC05133.1; -; mRNA.
DR   EMBL; AC006238; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC050132; AAH50132.1; -; mRNA.
DR   EMBL; AL136742; CAB66676.2; -; mRNA.
DR   CCDS; CCDS11846.1; -. [Q86VQ3-2]
DR   CCDS; CCDS42414.1; -. [Q86VQ3-1]
DR   RefSeq; NP_001091999.1; NM_001098529.1. [Q86VQ3-1]
DR   RefSeq; NP_115619.4; NM_032243.5. [Q86VQ3-2]
DR   RefSeq; XP_016881530.1; XM_017026041.1.
DR   AlphaFoldDB; Q86VQ3; -.
DR   SMR; Q86VQ3; -.
DR   BioGRID; 123944; 16.
DR   IntAct; Q86VQ3; 2.
DR   STRING; 9606.ENSP00000304908; -.
DR   iPTMnet; Q86VQ3; -.
DR   PhosphoSitePlus; Q86VQ3; -.
DR   BioMuta; TXNDC2; -.
DR   DMDM; 313104290; -.
DR   jPOST; Q86VQ3; -.
DR   MassIVE; Q86VQ3; -.
DR   MaxQB; Q86VQ3; -.
DR   PaxDb; 9606-ENSP00000304908; -.
DR   PeptideAtlas; Q86VQ3; -.
DR   ProteomicsDB; 70057; -. [Q86VQ3-1]
DR   ProteomicsDB; 70058; -. [Q86VQ3-2]
DR   Antibodypedia; 6577; 28 antibodies from 16 providers.
DR   DNASU; 84203; -.
DR   Ensembl; ENST00000306084.6; ENSP00000304908.6; ENSG00000168454.13. [Q86VQ3-1]
DR   Ensembl; ENST00000357775.6; ENSP00000350419.4; ENSG00000168454.13. [Q86VQ3-2]
DR   GeneID; 84203; -.
DR   KEGG; hsa:84203; -.
DR   MANE-Select; ENST00000357775.6; ENSP00000350419.4; NM_032243.6; NP_115619.4. [Q86VQ3-2]
DR   UCSC; uc002koh.5; human. [Q86VQ3-1]
DR   AGR; HGNC:16470; -.
DR   CTD; 84203; -.
DR   DisGeNET; 84203; -.
DR   GeneCards; TXNDC2; -.
DR   HGNC; HGNC:16470; TXNDC2.
DR   HPA; ENSG00000168454; Tissue enriched (testis).
DR   MIM; 617790; gene.
DR   neXtProt; NX_Q86VQ3; -.
DR   OpenTargets; ENSG00000168454; -.
DR   PharmGKB; PA38147; -.
DR   VEuPathDB; HostDB:ENSG00000168454; -.
DR   eggNOG; KOG0907; Eukaryota.
DR   GeneTree; ENSGT00940000163147; -.
DR   HOGENOM; CLU_045129_0_0_1; -.
DR   InParanoid; Q86VQ3; -.
DR   OrthoDB; 5263941at2759; -.
DR   PhylomeDB; Q86VQ3; -.
DR   TreeFam; TF106377; -.
DR   PathwayCommons; Q86VQ3; -.
DR   SignaLink; Q86VQ3; -.
DR   BioGRID-ORCS; 84203; 10 hits in 1143 CRISPR screens.
DR   GeneWiki; TXNDC2; -.
DR   GenomeRNAi; 84203; -.
DR   Pharos; Q86VQ3; Tbio.
DR   PRO; PR:Q86VQ3; -.
DR   Proteomes; UP000005640; Chromosome 18.
DR   RNAct; Q86VQ3; Protein.
DR   Bgee; ENSG00000168454; Expressed in left testis and 89 other cell types or tissues.
DR   ExpressionAtlas; Q86VQ3; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0004791; F:thioredoxin-disulfide reductase (NADP) activity; IDA:UniProtKB.
DR   GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR   GO; GO:0045454; P:cell redox homeostasis; NAS:UniProtKB.
DR   GO; GO:0007283; P:spermatogenesis; NAS:UniProtKB.
DR   CDD; cd02947; TRX_family; 1.
DR   Gene3D; 3.40.30.10; Glutaredoxin; 1.
DR   InterPro; IPR036249; Thioredoxin-like_sf.
DR   InterPro; IPR013766; Thioredoxin_domain.
DR   PANTHER; PTHR10438; THIOREDOXIN; 1.
DR   PANTHER; PTHR10438:SF107; THIOREDOXIN DOMAIN-CONTAINING PROTEIN 2; 1.
DR   Pfam; PF00085; Thioredoxin; 1.
DR   SUPFAM; SSF52833; Thioredoxin-like; 1.
DR   PROSITE; PS51352; THIOREDOXIN_2; 1.
DR   Genevisible; Q86VQ3; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cytoplasm; Developmental protein; Differentiation;
KW   Disulfide bond; Phosphoprotein; Redox-active center; Reference proteome;
KW   Repeat; Spermatogenesis.
FT   CHAIN           1..553
FT                   /note="Thioredoxin domain-containing protein 2"
FT                   /id="PRO_0000120153"
FT   REPEAT          113..127
FT                   /note="1"
FT   REPEAT          128..142
FT                   /note="2"
FT   REPEAT          143..157
FT                   /note="3"
FT   REPEAT          158..172
FT                   /note="4"
FT   REPEAT          173..187
FT                   /note="5"
FT   REPEAT          188..202
FT                   /note="6"
FT   REPEAT          203..217
FT                   /note="7"
FT   REPEAT          218..232
FT                   /note="8"
FT   REPEAT          233..247
FT                   /note="9"
FT   REPEAT          248..262
FT                   /note="10"
FT   REPEAT          263..277
FT                   /note="11"
FT   REPEAT          278..292
FT                   /note="12"
FT   REPEAT          293..307
FT                   /note="13"
FT   REPEAT          308..322
FT                   /note="14"
FT   REPEAT          323..337
FT                   /note="15"
FT   REPEAT          338..352
FT                   /note="16"
FT   REPEAT          353..367
FT                   /note="17"
FT   REPEAT          368..382
FT                   /note="18"
FT   REPEAT          383..397
FT                   /note="19"
FT   REPEAT          398..412
FT                   /note="20"
FT   REPEAT          413..427
FT                   /note="21"
FT   REPEAT          428..442
FT                   /note="22"
FT   DOMAIN          429..553
FT                   /note="Thioredoxin"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   REGION          1..37
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          77..442
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          113..442
FT                   /note="22 X 15 AA approximate tandem repeat of Q-P-K-X-G-D-
FT                   I-P-K-S-[PS]-E-[KE]-X-I"
FT   COMPBIAS        87..101
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        102..140
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        177..206
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        237..251
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        282..372
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        388..442
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         362
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q5XHX6"
FT   MOD_RES         392
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q5XHX6"
FT   DISULFID        480..483
FT                   /note="Redox-active"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   VAR_SEQ         1..67
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:11399755,
FT                   ECO:0000303|PubMed:15489334"
FT                   /id="VSP_014328"
FT   VAR_SEQ         304..318
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|Ref.2"
FT                   /id="VSP_053684"
FT   VARIANT         225
FT                   /note="A -> P (in dbSNP:rs11662946)"
FT                   /id="VAR_057351"
FT   VARIANT         314
FT                   /note="I -> L (in dbSNP:rs2240909)"
FT                   /id="VAR_057352"
FT   VARIANT         341
FT                   /note="E -> K (in dbSNP:rs11081510)"
FT                   /evidence="ECO:0000269|PubMed:14702039,
FT                   ECO:0000269|PubMed:15489334, ECO:0000269|Ref.2"
FT                   /id="VAR_022762"
FT   VARIANT         357
FT                   /note="G -> D (in dbSNP:rs2240906)"
FT                   /evidence="ECO:0000269|PubMed:14702039,
FT                   ECO:0000269|PubMed:15489334"
FT                   /id="VAR_022763"
FT   VARIANT         461
FT                   /note="A -> T (in dbSNP:rs17732496)"
FT                   /evidence="ECO:0000269|PubMed:11230166"
FT                   /id="VAR_022764"
FT   VARIANT         487
FT                   /note="R -> T (in dbSNP:rs17805544)"
FT                   /evidence="ECO:0000269|PubMed:14702039"
FT                   /id="VAR_022765"
SQ   SEQUENCE   553 AA;  60404 MW;  74EE3210BA5EBCF1 CRC64;
     MDVDKELGME SVKAGASGKP EMRLGTQEET SEGDANESSL LVLSSNVPLL ALEFLEIAQA
     KEKAFLPMVS HTFHMRTEES DASQEGDDLP KSSANTSHPK QDDSPKSSEE TIQPKEGDIP
     KAPEETIQSK KEDLPKSSEK AIQPKESNIP KSSAKPIQPK LGNIPKASVK PSQPKEGDIP
     KAPEETIQSK KEDLPKSSEE AIQPKEGDIP KSSAKPIQPK LGNIAKTSVK PSQPKESDIP
     KSPEETIQPK EGDIPKSSAK PIQPKLGNIP KASVKPSQPK EGDISKSPEE AIQPKEGDLP
     KSLEEAIQPK EGDIPKSPEE AIQPKEGDIP KSLEEAIQPK EGDIPKSPEE TIQPKKGDIP
     KSPEEAIQPK EGDIPKSPKQ AIQPKEGDIP KSLEEAIPPK EIDIPKSPEE TIQPKEDDSP
     KSLEEATPSK EGDILKPEEE TMEFPEGDKV KVILSKEDFE ASLKEAGERL VAVDFSATWC
     GPCRTIRPFF HALSVKHEDV VFLEVDADNC EEVVRECAIM CVPTFQFYKK EEKVDELCGA
     LKEKLEAVIA ELK
//