TASP1

Treonin-aspartaza 1 je enzim koji je kod ljudi kodiran genom TASP1.^[5][6]

TASP1
Dostupne strukture PDB Pretraga ortologa: PDBe RCSB Spisak PDB ID kodova 2A8I, 2A8J, 2A8L, 2A8M
Identifikatori
Aliasi	TASP1
Vanjski ID-jevi	OMIM: 608270 MGI: 1923062 HomoloGene: 9795 GeneCards: TASP1
Lokacija gena (čovjek) Hrom. Hromosom 20 (čovjek)[1] Bend 20p12.1 Početak 13,389,392 bp[1] Kraj 13,638,932 bp[1]
Lokacija gena (miš) Hrom. Hromosom 2 (miš)[2] Bend 2|2 F3 Početak 139,675,400 bp[2] Kraj 139,908,725 bp[2]
Obrazac RNK ekspresije Više referentnih podataka o ekspresiji
Ontologija gena Molekularna funkcija • GO:0070122 peptidase activity • hydrolase activity • threonine-type endopeptidase activity • vezivanje identičnih proteina Ćelijska komponenta • citoplazma Biološki proces • GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated • Proteoliza • protein maturation Izvori:Amigo / QuickGO
Ortolozi
Vrste	Čovjek	Miš
Entrez	55617	75812
Ensembl	ENSG00000089123	ENSMUSG00000039033
UniProt	Q9H6P5	Q8R1G1
RefSeq (mRNK)	NM_017714 NM_001323602 NM_001323603 NM_001323604	NM_001159640 NM_001159641 NM_001289611 NM_175225
RefSeq (bjelančevina)	NP_001310531 NP_001310532 NP_001310533 NP_060184	NP_001153112 NP_001153113 NP_001276540 NP_780434
Lokacija (UCSC)	Chr 20: 13.39 – 13.64 Mb	Chr 2: 139.68 – 139.91 Mb
PubMed pretraga	[3]	[4]
Wikipodaci
Pogledaj/uredi – čovjek Pogledaj/uredi – miš

Funkcija

Ovaj gen kodira endopeptidazu koja cijepa specifične supstrate slijedeći aspartatne ostatke Kodirani protein prolazi posttranslacijsku autoproteolitsku obradu da bi se generirale alfa i beta podjedinice, koje se ponovno okupljaju u aktivni alfa2-beta2 heterotetramer. Potrebno je cijepati MLL, protein potreban za održavanje ekspresije gena HOX i TFIIA, bazni faktor transkripcije. Utvrđeno je da cijepanje transkripcijskog faktora II A pokreće spermatogenezu.^[7]

Opisane su alternativno prerađene varijante transkripta, ali njihova biološka valjanost nije utvrđena.^[6]

Aminokiselinska sekvenca

Simboli

C: Cistein
D: Asparaginska kiselina
E: Glutaminska kiselina
F: Fenilalanin
G: Glicin
H: Histidin
I: Izoleucin
K: Lizin
L: Leucin
M: Metionin
N: Asparagin
P: Prolin
Q: Glutamin
R: Arginin
S: Serin
T: Treonin
V: Valin
W: Triptofan
Y: Tirozin

10		20		30		40		50
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

Klinički značaj

Taspaza1 je prekomjerno izražena u primarnim ljudskim karcinomima i funkcionira kao neonkogen ovisna proteaza, koja koordinira karcinomsku proliferaciju ćelija i apoptozu. Zato taspaza 1 može poslužiti kao nova terapijska meta protiv raka.^[8]

Reference

1. GRCh38: Ensembl release 89: ENSG00000089123 - Ensembl, maj 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000039033 - Ensembl, maj 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Hsieh JJ, Cheng EH, Korsmeyer SJ (Nov 2003). "Taspase1: a threonine aspartase required for cleavage of MLL and proper HOX gene expression". Cell. 115 (3): 293–303. doi:10.1016/S0092-8674(03)00816-X. PMID 14636557. S2CID 18952302.
6. "Entrez Gene: TASP1 taspase, threonine aspartase, 1".
7. Oyama, T; Sasagawa, S; Takeda, S; Hess, R. A.; Lieberman, P. M.; Cheng, E. H.; Hsieh, J. J. (2013). "Cleavage of TFIIA by Taspase1 activates TRF2-specified mammalian male germ cell programs". Developmental Cell. 27 (2): 188–200. doi:10.1016/j.devcel.2013.09.025. PMC 3947863. PMID 24176642.
8. Chen DY, Liu H, Takeda S, Tu HC, Sasagawa S, Van Tine BA, Lu D, Cheng EH, Hsieh JJ (juli 2010). "Taspase1 functions as a non-oncogene addiction protease that coordinates cancer cell proliferation and apoptosis". Cancer Res. 70 (13): 5358–67. doi:10.1158/0008-5472.CAN-10-0027. PMC 2909739. PMID 20516119.

Dopunska literatura

• Zhou H, Spicuglia S, Hsieh JJ, et al. (2006). "Uncleaved TFIIA is a substrate for taspase 1 and active in transcription". Mol. Cell. Biol. 26 (7): 2728–35. doi:10.1128/MCB.26.7.2728-2735.2006. PMC 1430320. PMID 16537915.
• Khan JA, Dunn BM, Tong L (2006). "Crystal structure of human Taspase1, a crucial protease regulating the function of MLL". Structure. 13 (10): 1443–52. doi:10.1016/j.str.2005.07.006. PMID 16216576.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Hsieh JJ, Ernst P, Erdjument-Bromage H, et al. (2003). "Proteolytic cleavage of MLL generates a complex of N- and C-terminal fragments that confers protein stability and subnuclear localization". Mol. Cell. Biol. 23 (1): 186–94. doi:10.1128/MCB.23.1.186-194.2003. PMC 140678. PMID 12482972.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Deloukas P, Matthews LH, Ashurst J, et al. (2002). "The DNA sequence and comparative analysis of human chromosome 20". Nature. 414 (6866): 865–71. doi:10.1038/414865a. PMID 11780052.