TASP1_HUMAN
ID TASP1_HUMAN Reviewed; 420 AA.
AC Q9H6P5; B7Z690; B7Z963; Q5TDU9; Q9BQN0; Q9NQ08; Q9NTS6; Q9NXJ2;
DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Threonine aspartase 1;
DE Short=Taspase-1;
DE EC=3.4.25.-;
DE Contains:
DE RecName: Full=Threonine aspartase subunit alpha;
DE Contains:
DE RecName: Full=Threonine aspartase subunit beta;
GN Name=TASP1; Synonyms=C20orf13;
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] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Brain, Colon mucosa, Hepatoma, and Uterus;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Ovary;
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 [4]
RP PROTEIN SEQUENCE OF 124-145, FUNCTION, AND MUTAGENESIS OF ASP-233 AND
RP THR-234.
RX PubMed=14636557; DOI=10.1016/s0092-8674(03)00816-x;
RA Hsieh J.J.-D., Cheng E.H.-Y., Korsmeyer S.J.;
RT "Taspase1: a threonine aspartase required for cleavage of MLL and proper
RT HOX gene expression.";
RL Cell 115:293-303(2003).
RN [5]
RP INVOLVEMENT IN SULEHS, AND VARIANTS SULEHS 67-ARG--ASN-420 DEL AND MET-234.
RX PubMed=31209944; DOI=10.1002/humu.23844;
RA Suleiman J., Riedhammer K.M., Jicinsky T., Mundt M., Werner L., Gusic M.,
RA Burgemeister A.L., Alsaif H.S., Abdulrahim M., Moghrabi N.N.,
RA Nicolas-Jilwan M., Alsayed M., Bi W., Sampath S., Alkuraya F.S.,
RA El-Hattab A.W.;
RT "Homozygous loss-of-function variants of TASP1, a gene encoding an
RT activator of the histone methyltransferases KMT2A and KMT2D, cause a
RT syndrome of developmental delay, happy demeanor, distinctive facial
RT features, and congenital anomalies.";
RL Hum. Mutat. 40:1985-1992(2019).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS), ACTIVE SITE, SUBUNIT, AND
RP MUTAGENESIS OF THR-234.
RX PubMed=16216576; DOI=10.1016/j.str.2005.07.006;
RA Khan J.A., Dunn B.M., Tong L.;
RT "Crystal structure of human Taspase1, a crucial protease regulating the
RT function of MLL.";
RL Structure 13:1443-1452(2005).
CC -!- FUNCTION: Protease responsible for KMT2A/MLL1 processing and activation
CC (PubMed:14636557). It also activates KMT2D/MLL2 (By similarity).
CC Through substrate activation, it controls the expression of HOXA genes,
CC and the expression of key cell cycle regulators including CCNA1, CCNB1,
CC CCNE1 and CDKN2A (By similarity) (PubMed:14636557).
CC {ECO:0000250|UniProtKB:Q8R1G1, ECO:0000269|PubMed:14636557}.
CC -!- SUBUNIT: Intramolecular proteolysis generates 2 subunits, alpha and
CC beta, which reassemble through a non-covalent association to form the
CC fully active enzyme. {ECO:0000305|PubMed:16216576}.
CC -!- INTERACTION:
CC Q9H6P5; Q9H6P5: TASP1; NbExp=6; IntAct=EBI-15557979, EBI-15557979;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9H6P5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H6P5-2; Sequence=VSP_056327, VSP_056328;
CC Name=3;
CC IsoId=Q9H6P5-3; Sequence=VSP_056533, VSP_056534;
CC -!- DISEASE: Suleiman-El-Hattab syndrome (SULEHS) [MIM:618950]: An
CC autosomal recessive syndrome characterized by global developmental
CC delay with poor expressive language, poor fine motor skills and
CC hypotonia, microcephaly, feeding difficulties with failure to thrive,
CC recurrent respiratory infections, cardiovascular malformations,
CC cryptorchidism, happy demeanor, and facial dysmorphism. Distinctive
CC facial features are excessive forehead hair, arched and thick eyebrows
CC with synophrys, epicanthus, hypertelorism, thick eyelids with
CC periorbital fullness, broad nasal bridge, long and smooth philtrum,
CC thin upper lip, and low set prominent ears.
CC {ECO:0000269|PubMed:31209944}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the Ntn-hydrolase family. {ECO:0000305}.
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DR EMBL; AK000219; BAA91018.1; -; mRNA.
DR EMBL; AK025671; BAB15209.1; -; mRNA.
DR EMBL; AK299940; BAH13176.1; -; mRNA.
DR EMBL; AK304488; BAH14199.1; -; mRNA.
DR EMBL; AK316311; BAH14682.1; -; mRNA.
DR EMBL; AL050320; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL121754; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL121782; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL133463; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL158089; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC025266; AAH25266.1; -; mRNA.
DR CCDS; CCDS13116.1; -. [Q9H6P5-1]
DR RefSeq; NP_060184.2; NM_017714.2. [Q9H6P5-1]
DR PDB; 2A8I; X-ray; 2.00 A; A/B=1-420.
DR PDB; 2A8J; X-ray; 1.90 A; A/B=1-420.
DR PDB; 2A8L; X-ray; 2.00 A; A/B=1-420.
DR PDB; 2A8M; X-ray; 2.60 A; A/B=1-420.
DR PDB; 6UGK; X-ray; 2.15 A; A/B=41-183, A/B=234-416.
DR PDB; 6VIN; X-ray; 3.04 A; A/B=41-416.
DR PDBsum; 2A8I; -.
DR PDBsum; 2A8J; -.
DR PDBsum; 2A8L; -.
DR PDBsum; 2A8M; -.
DR PDBsum; 6UGK; -.
DR PDBsum; 6VIN; -.
DR AlphaFoldDB; Q9H6P5; -.
DR SMR; Q9H6P5; -.
DR BioGRID; 120757; 8.
DR DIP; DIP-48456N; -.
DR IntAct; Q9H6P5; 1.
DR STRING; 9606.ENSP00000338624; -.
DR BindingDB; Q9H6P5; -.
DR ChEMBL; CHEMBL6153; -.
DR GuidetoPHARMACOLOGY; 2419; -.
DR MEROPS; T02.004; -.
DR iPTMnet; Q9H6P5; -.
DR MetOSite; Q9H6P5; -.
DR PhosphoSitePlus; Q9H6P5; -.
DR BioMuta; TASP1; -.
DR DMDM; 29839766; -.
DR EPD; Q9H6P5; -.
DR jPOST; Q9H6P5; -.
DR MassIVE; Q9H6P5; -.
DR MaxQB; Q9H6P5; -.
DR PaxDb; Q9H6P5; -.
DR PeptideAtlas; Q9H6P5; -.
DR PRIDE; Q9H6P5; -.
DR ProteomicsDB; 6759; -.
DR ProteomicsDB; 7008; -.
DR ProteomicsDB; 81004; -. [Q9H6P5-1]
DR Antibodypedia; 24250; 197 antibodies from 26 providers.
DR DNASU; 55617; -.
DR Ensembl; ENST00000337743.9; ENSP00000338624.4; ENSG00000089123.16. [Q9H6P5-1]
DR GeneID; 55617; -.
DR KEGG; hsa:55617; -.
DR MANE-Select; ENST00000337743.9; ENSP00000338624.4; NM_017714.3; NP_060184.2.
DR UCSC; uc002woi.4; human. [Q9H6P5-1]
DR CTD; 55617; -.
DR DisGeNET; 55617; -.
DR GeneCards; TASP1; -.
DR HGNC; HGNC:15859; TASP1.
DR HPA; ENSG00000089123; Low tissue specificity.
DR MalaCards; TASP1; -.
DR MIM; 608270; gene.
DR MIM; 618950; phenotype.
DR neXtProt; NX_Q9H6P5; -.
DR OpenTargets; ENSG00000089123; -.
DR PharmGKB; PA25671; -.
DR VEuPathDB; HostDB:ENSG00000089123; -.
DR eggNOG; KOG1592; Eukaryota.
DR GeneTree; ENSGT00950000183045; -.
DR HOGENOM; CLU_021603_5_0_1; -.
DR InParanoid; Q9H6P5; -.
DR OMA; RLWCAFT; -.
DR OrthoDB; 1450528at2759; -.
DR PhylomeDB; Q9H6P5; -.
DR TreeFam; TF106358; -.
DR PathwayCommons; Q9H6P5; -.
DR SignaLink; Q9H6P5; -.
DR BioGRID-ORCS; 55617; 11 hits in 1083 CRISPR screens.
DR ChiTaRS; TASP1; human.
DR EvolutionaryTrace; Q9H6P5; -.
DR GeneWiki; TASP1; -.
DR GenomeRNAi; 55617; -.
DR Pharos; Q9H6P5; Tchem.
DR PRO; PR:Q9H6P5; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9H6P5; protein.
DR Bgee; ENSG00000089123; Expressed in popliteal artery and 190 other tissues.
DR ExpressionAtlas; Q9H6P5; baseline and differential.
DR Genevisible; Q9H6P5; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004298; F:threonine-type endopeptidase activity; IMP:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0051604; P:protein maturation; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IMP:CACAO.
DR CDD; cd04514; Taspase1_like; 1.
DR InterPro; IPR029055; Ntn_hydrolases_N.
DR InterPro; IPR000246; Peptidase_T2.
DR InterPro; IPR037464; Taspase1.
DR PANTHER; PTHR10188; PTHR10188; 1.
DR Pfam; PF01112; Asparaginase_2; 1.
DR SUPFAM; SSF56235; SSF56235; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Autocatalytic cleavage;
KW Direct protein sequencing; Disease variant; Hydrolase; Protease;
KW Reference proteome; Threonine protease; Zymogen.
FT CHAIN 1..233
FT /note="Threonine aspartase subunit alpha"
FT /id="PRO_0000002350"
FT CHAIN 234..420
FT /note="Threonine aspartase subunit beta"
FT /id="PRO_0000002351"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 234
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:16216576"
FT VAR_SEQ 95..129
FT /note="DSPFTNAGMGSNLNLLGEIECDASIMDGKSLNFGA -> VYTHSYTSWSCIQ
FT PSIHVLLVKRQRKSPLPRISTF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056327"
FT VAR_SEQ 96..145
FT /note="SPFTNAGMGSNLNLLGEIECDASIMDGKSLNFGAVGALSGIKNPVSVANR
FT -> VESILCAPYWLENVHMLYKLRMLTKPCWRLCKTSLSVHLSLPVKMACLAE (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056533"
FT VAR_SEQ 130..420
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056328"
FT VAR_SEQ 146..420
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056534"
FT VARIANT 67..420
FT /note="Missing (in SULEHS)"
FT /evidence="ECO:0000269|PubMed:31209944"
FT /id="VAR_084461"
FT VARIANT 234
FT /note="T -> M (in SULEHS; dbSNP:rs904200599)"
FT /evidence="ECO:0000269|PubMed:31209944"
FT /id="VAR_084462"
FT MUTAGEN 233
FT /note="D->A: 0.1% enzymatic activity; no intramolecular
FT processing."
FT /evidence="ECO:0000269|PubMed:14636557,
FT ECO:0000269|PubMed:16216576"
FT MUTAGEN 234
FT /note="T->A: Complete loss of enzymatic activity; no
FT intramolecular processing."
FT /evidence="ECO:0000269|PubMed:14636557"
FT CONFLICT 357
FT /note="S -> F (in Ref. 1; BAA91018)"
FT /evidence="ECO:0000305"
FT STRAND 42..52
FT /evidence="ECO:0007829|PDB:2A8J"
FT HELIX 57..77
FT /evidence="ECO:0007829|PDB:2A8J"
FT HELIX 82..95
FT /evidence="ECO:0007829|PDB:2A8J"
FT STRAND 99..102
FT /evidence="ECO:0007829|PDB:2A8J"
FT STRAND 115..121
FT /evidence="ECO:0007829|PDB:2A8J"
FT TURN 122..124
FT /evidence="ECO:0007829|PDB:2A8J"
FT STRAND 127..133
FT /evidence="ECO:0007829|PDB:2A8J"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:2A8J"
FT HELIX 139..151
FT /evidence="ECO:0007829|PDB:2A8J"
FT TURN 152..154
FT /evidence="ECO:0007829|PDB:2A8J"
FT STRAND 157..160
FT /evidence="ECO:0007829|PDB:6VIN"
FT STRAND 163..166
FT /evidence="ECO:0007829|PDB:2A8J"
FT HELIX 167..176
FT /evidence="ECO:0007829|PDB:2A8J"
FT HELIX 184..187
FT /evidence="ECO:0007829|PDB:2A8I"
FT HELIX 190..204
FT /evidence="ECO:0007829|PDB:2A8I"
FT TURN 221..225
FT /evidence="ECO:0007829|PDB:6VIN"
FT STRAND 235..241
FT /evidence="ECO:0007829|PDB:2A8J"
FT STRAND 246..252
FT /evidence="ECO:0007829|PDB:2A8J"
FT HELIX 265..267
FT /evidence="ECO:0007829|PDB:2A8J"
FT TURN 269..271
FT /evidence="ECO:0007829|PDB:2A8J"
FT STRAND 272..276
FT /evidence="ECO:0007829|PDB:2A8J"
FT STRAND 282..292
FT /evidence="ECO:0007829|PDB:2A8J"
FT HELIX 294..299
FT /evidence="ECO:0007829|PDB:2A8J"
FT HELIX 302..309
FT /evidence="ECO:0007829|PDB:2A8J"
FT HELIX 315..325
FT /evidence="ECO:0007829|PDB:2A8J"
FT TURN 326..329
FT /evidence="ECO:0007829|PDB:2A8J"
FT HELIX 331..333
FT /evidence="ECO:0007829|PDB:2A8J"
FT STRAND 341..348
FT /evidence="ECO:0007829|PDB:2A8J"
FT STRAND 365..383
FT /evidence="ECO:0007829|PDB:2A8J"
FT TURN 384..386
FT /evidence="ECO:0007829|PDB:2A8J"
FT STRAND 390..395
FT /evidence="ECO:0007829|PDB:2A8J"
FT TURN 402..404
FT /evidence="ECO:0007829|PDB:2A8J"
FT STRAND 407..414
FT /evidence="ECO:0007829|PDB:2A8J"
SQ SEQUENCE 420 AA; 44455 MW; D0C1020E708B0FCF CRC64;
MTMEKGMSSG EGLPSRSSQV SAGKITAKEL ETKQSYKEKR GGFVLVHAGA GYHSESKAKE
YKHVCKRACQ KAIEKLQAGA LATDAVTAAL VELEDSPFTN AGMGSNLNLL GEIECDASIM
DGKSLNFGAV GALSGIKNPV SVANRLLCEG QKGKLSAGRI PPCFLVGEGA YRWAVDHGIP
SCPPNIMTTR FSLAAFKRNK RKLELAERVD TDFMQLKKRR QSSEKENDSG TLDTVGAVVV
DHEGNVAAAV SSGGLALKHP GRVGQAALYG CGCWAENTGA HNPYSTAVST SGCGEHLVRT
ILARECSHAL QAEDAHQALL ETMQNKFISS PFLASEDGVL GGVIVLRSCR CSAEPDSSQN
KQTLLVEFLW SHTTESMCVG YMSAQDGKAK THISRLPPGA VAGQSVAIEG GVCRLESPVN
