ZMYND8

ZMYND8
Dostupne strukture
PDB	Pretraga Human UniProta: PDBe RCSB
Spisak PDB ID kodova
	4COS
Identifikatori
Aliasi	ZMYND8
Vanjski ID-jevi	OMIM: 615713 MGI: 1918025 HomoloGene: 32679 GeneCards: ZMYND8
Lokacija gena (čovjek)
Hrom.	Hromosom 20 (čovjek)
Kraj	47,356,889 bp
Lokacija gena (miš)
Hrom.	Hromosom 2 (miš)
Kraj	165,740,936 bp
Obrazac RNK ekspresije
	; ; ; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• GO:0001106 transcription corepressor activity; • RNA polymerase II transcription regulatory region sequence-specific DNA binding; • chromatin binding; • GO:0001104 transcription coregulator activity; • GO:0001948, GO:0016582 vezivanje za proteine; • vezivanje iona metala; • methylated histone binding; • lysine-acetylated histone binding; • protein N-terminus binding; • vezivanje iona cinka; • protein domain specific binding;
Ćelijska komponenta	• citoplazma; • dendritic shaft; • dendritična kičma; • jedro;
Biološki proces	• regulation of postsynaptic density protein 95 clustering; • positive regulation of filopodium assembly; • positive regulation of dendritic spine development; • positive regulation of dendritic spine maintenance; • modulation of excitatory postsynaptic potential; • transcription, DNA-templated; • GO:0009373 regulation of transcription, DNA-templated; • negative regulation of cell migration; • negative regulation of nucleic acid-templated transcription;
	Izvori:Amigo / QuickGO
Ortolozi
	23613
	228880
	ENSG00000101040
	ENSMUSG00000039671
	Q9ULU4
	n/a
NM_001281769; NM_001281771; NM_001281772; NM_001281773; NM_001281774;
	NM_001281775; NM_001281776; NM_001281777; NM_001281778; NM_001281779; NM_001281780; NM_001281781; NM_001281782; NM_001281783; NM_001281784; NM_012408; NM_183047; NM_183048; NM_001363714; NM_001363741
NM_001252584; NM_001252585; NM_001252587; NM_001281926; NM_001291158;
	NM_027230; NM_172270; NM_001363018; NM_001363019; NM_001363020; NM_001363021
NP_001268698; NP_001268700; NP_001268701; NP_001268702; NP_001268703;
	NP_001268704; NP_001268705; NP_001268706; NP_001268707; NP_001268708; NP_001268709; NP_001268710; NP_001268711; NP_001268712; NP_001268713; NP_036540; NP_898868; NP_898869; NP_001350643; NP_001350670
	n/a
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Protein-kinazni C-vezujuči protein 1 je enzim koji je kod ljudi kodiran genom ZMYND8.^[5]

Protein koji je kodiran ovim genom je receptor za aktivirani protein C-kinaze (RACK). Dokazano je da se kodirani protein in vitro veže na aktiviranu protein kinazu C beta I. Pored toga, ovaj protein je antigen povezan s kožnim limfomom T-ćelija. Napokon, protein sadrži bromodomen i dva cinkova prsta, a smatra se da je regulator transkripcije. Za ovaj gen pronađeno je više varijanti transkripta koji kodiraju nekoliko različitih izoformi.^[5]

Kloniranje i ekspresija[uredi | uredi izvor]

Upotreba monoklonskog antitijela usmjerenog protiv RACK1 (GNB2L1; 176981) za scrining biblioteke ljudske hipokampusne cDNK, praćeno EST pomjeranjem sa pet primjeraka i RACE u pet glavnih grupa, Fossey et al. (2000) klonirali su ZMYND8, koji su nazvali PRKCBP1. Izvedeni protein s 615 aminokiselina ima N-terminalni osnovni domen konzerviran u proteinima neurofilamenta i citoskeleta, navodni motiv C4 cinkovog prsta i C-terminalnu sekvencu WD40. Northern blot analizom otkriven je transkript od 3.1 kb u svim ispitivanim ljudskim tkivima, s najvećom ekspresijom u mozgu, plućima, pankreasu i posteljici. Analiza baze podataka RT-PCR i EST predložila je sveprisutnu ekspresiju ZMYND8.^[6]

Funkcija gena[uredi | uredi izvor]

Koristeći imunoprecipitaciju i testove pada proteina, Fossey et al. (2000) pokazali su da je C-terminalni WD40 domen PRKCBP1 specifično u interakciji s PKC-beta-1 (PRKCB1; 176970). FHOD1 (606881) regulira transkripciju gena, strukturu aktin-citoskeleta i migraciju ćelija. Koristeći 2-hibridni zaslon kvasca s bibliotekom ekspresije cDNK ljudske koštane srži, Westendorf i Koka (2004) otkrili su da je FHOD1 u interakciji sa središnjim dijelom PRKCBP1, kao i sa ciklofilinom B (PPIB; 123841) i izoformom B WISH (NCKIPSD; 606671).

Utvrđivanjem hromatinskog okruženja genomskih lokacija vezanih za RACK7 u ćelijama ljudskogog raka dojke, Shen et al. (2016) otkrili su da su RACK7 i KDM5C (314690) zauzeli mnoga aktivna mjesta za poboljšanje, uključujući gotovo sve super-pojačivače. Gubitak RACK7 ili KDM5C rezultirao je preaktivacijom pojačivača, koje karakterizira taloženje histone H3 (vidi 602810) trimetilacije lys4 (H3K4me3) i acetilacije H3K27 (H3K27Ac) i gubitka H3K4me1, kao i povećana transkripcija pojačivača RNK i obližnjih gena. Gubitak RACK7 značajno je oslabio uključivanje KDM5C za pojačivače. Ljudske ćelije karcinoma dojke kojima nedostaje RACK7 ili KDM5C pokazale su poboljšani rast, migraciju i invaziju, neovisno o sidrenju in vitro, kao i pojačani rast tumora u modelu ksentransplanta na mišu. Shen et al. (2016) zaključili su da aktivni pojačivači podliježu negativnoj regulaciji i da RACK7 i KDM5C djeluju zajedno kao 'kočnica' za aktivne pojačivaće kontrolirajući dinamičku izmjenu između H3K4me1 i H3K4me3.^[7]^[8]^[9]

Aminokiselinska sekvenca[uredi | uredi izvor]

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
MDISTRSKDP	GSAERTAQKR	KFPSPPHSSN	GHSPQDTSTS	PIKKKKKPGL
LNSNNKEQSE	LRHGPFYYMK	QPLTTDPVDV	VPQDGRNDFY	CWVCHREGQV
LCCELCPRVY	HAKCLRLTSE	PEGDWFCPEC	EKITVAECIE	TQSKAMTMLT
IEQLSYLLKF	AIQKMKQPGT	DAFQKPVPLE	QHPDYAEYIF	HPMDLCTLEK
NAKKKMYGCT	EAFLADAKWI	LHNCIIYNGG	NHKLTQIAKV	VIKICEHEMN
EIEVCPECYL	AACQKRDNWF	CEPCSNPHPL	VWAKLKGFPF	WPAKALRDKD
GQVDARFFGQ	HDRAWVPINN	CYLMSKEIPF	SVKKTKSIFN	SAMQEMEVYV
ENIRRKFGVF	NYSPFRTPYT	PNSQYQMLLD	PTNPSAGTAK	IDKQEKVKLN
FDMTASPKIL	MSKPVLSGGT	GRRISLSDMP	RSPMSTNSSV	HTGSDVEQDA
EKKATSSHFS	ASEESMDFLD	KSTASPASTK	TGQAGSLSGS	PKPFSPQLSA
PITTKTDKTS	TTGSILNLNL	DRSKAEMDLK	ELSESVQQQS	TPVPLISPKR
QIRSRFQLNL	DKTIESCKAQ	LGINEISEDV	YTAVEHSDSE	DSEKSDSSDS
EYISDDEQKS	KNEPEDTEDK	EGCQMDKEPS	AVKKKPKPTN	PVEIKEELKS
TSPASEKADP	GAVKDKASPE	PEKDFSEKAK	PSPHPIKDKL	KGKDETDSPT
VHLGLDSDSE	SELVIDLGED	HSGREGRKNK	KEPKEPSPKQ	DVVGKTPPST
TVGSHSPPET	PVLTRSSAQT	SAAGATATTS	TSSTVTVTAP	APAATGSPVK
KQRPLLPKET	APAVQRVVWN	SSSKFQTSSQ	KWHMQKMQRQ	QQQQQQQNQQ
QQPQSSQGTR	YQTRQAVKAV	QQKEITQSPS	TSTITLVTST	QSSPLVTSSG
SMSTLVSSVN	ADLPIATASA	DVAADIAKYT	SKMMDAIKGT	MTEIYNDLSK
NTTGSTIAEI	RRLRIEIEKL	QWLHQQELSE	MKHNLELTMA	EMRQSLEQER
DRLIAEVKKQ	LELEKQQAVD	ETKKKQWCAN	CKKEAIFYCC	WNTSYCDYPC
QQAHWPEHMK	SCTQSATAPQ	QEADAEVNTE	TLNKSSQGSS	SSTQSAPSET
ASASKEKETS	AEKSKESGST	LDLSGSRETP	SSILLGSNQG	SDHSRSNKSS
WSSSDEKRGS	TRSDHNTSTS	TKSLLPKESR	LDTFWD

Model organizmi[uredi | uredi izvor]

Fenotip *Zmynd8* nokaut miša
Svojstvo	Fenotip
Vijabilmost homozigota	Nenormalna
Studija letalne recesivnosti	Nenormalna
Tjelesna težina	Normalna
Anksioznost u test otvorenog polja	Normalna
Neurološka procjena	Normalna
Snaga stiska	Normalna
Vruća ploča test	Normalan
Dismorfologija	Normalna
Indirektna kalorimetrija	Normalna
Test tolerancije glukoze	Normalan
Slušni odgovor moždanog stabla	Normalan
DEXA	Normalna
Radiografija	Normalna
Tjelesna temperatura	Normalna
Morfologija oka	Normalna
Klinička hemija	Normalna
Hematologija	Normalna
Limfociti periferne krvi	Normalni
Mikronukleus test	Normalan
Težina srca	Normalna
Histopatologija kože	Normalna
Svi podaci nsu prema linku^[10]^[11]

U studiji funkcije gena ZMYND8 upotrebljavani su i modelni organizmi. Linija uvjetnog nokaut miša, zvanog Zmynd8^{tm1a(EUCOMM)Wtsi}^[12]^[13] generiran je kao dio programa Međunarodnog konzorcija za miševe – visokopropusnog projekta mutageneze za generisanje i distribuciju životinjskih modela bolesti zainteresiranim naučnicima.^[14]^[15]^[16]

Muške i ženske životinje prolazile su standardizirani fenotipski pregled, kako bi se utvrdili efekti delecije.^[10]^[17] Izvršen je dvadeset jedan test na mutantnim miševima i uočene su dvije značajne abnormalnosti.^[10] Nekoliko homozigotnih mutanata embriona je identifikovano tokom gestacije, a nijedan nije preživio do odvikavanja. Preostali testovi izvedeni su na heterozigotnim mutiranim odraslim miševima; kod ovih životinja nisu opažene nikakve dodatne značajne abnormalnosti.^[10]

Reference[uredi | uredi izvor]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000101040 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000039671 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b "Entrez Gene: ZMYND8 zinc finger, MYND-type containing 8".
^ Fossey, S. C., Kuroda, S., Price, J. A., Pendleton, J. K., Freedman, B. I., Bowden, D. W. Identification and characterization of PRKCBP1, a candidate RACK-like protein. Mammalian Genome 11: 919-925, 2000. [PubMed]: 11003709
^ Gross, M. B. Personal Communication. Baltimore, Md. 3/28/2014.
^ Shen, H., Xu, W., Guo, R., Rong, B., Gu, L., Wang, Z., He, C., Zheng, L., Hu, X., Hu, Z., Shao, Z.-M., Yang, P., Wu, F., Shi, Y. G., Shi, Y., Lan, F. Suppression of enhancer overactivation by a RACK7-histone demethylase complex. Cell 165: 331-342, 2016. [PubMed]: 27058665
^ Westendorf, J. J., Koka, S. Identification of FHOD1-binding proteins and mechanisms of FHOD1-regulated actin dynamics. J. Cell. Biochem. 92: 29-41, 2004. [PubMed[: 15095401
^ ^a ^b ^c ^d Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
^ "International Knockout Mouse Consortium".^{[mrtav link]}
^ "Mouse Genome Informatics".
^ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
^ Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
^ Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Dopunska literatura[uredi | uredi izvor]

Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
Suzuki Y; Yoshitomo-Nakagawa K; Maruyama K; et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
Mahony D, Kalionis B, Antalis TM (1999). "Plasminogen activator inhibitor type-2 (PAI-2) gene transcription requires a novel NF-kappaB-like transcriptional regulatory motif". Eur. J. Biochem. 263 (3): 765–72. doi:10.1046/j.1432-1327.1999.00552.x. PMID 10469140.
Hirosawa M; Nagase T; Ishikawa K; et al. (2000). "Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain". DNA Res. 6 (5): 329–36. doi:10.1093/dnares/6.5.329. PMID 10574461.
Fossey SC; Kuroda S; Price JA; et al. (2000). "Identification and characterization of PRKCBP1, a candidate RACK-like protein". Mamm. Genome. 11 (10): 919–25. doi:10.1007/s003350010174. PMID 11003709. S2CID 646555.
Eichmuller S; Usener D; Dummer R; et al. (2001). "Serological detection of cutaneous T-cell lymphoma-associated antigens". Proc. Natl. Acad. Sci. U.S.A. 98 (2): 629–34. doi:10.1073/pnas.021386498. PMC 14639. PMID 11149944.
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.
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.
Galey D; Becker K; Haughey N; et al. (2003). "Differential transcriptional regulation by human immunodeficiency virus type 1 and gp120 in human astrocytes". J. Neurovirol. 9 (3): 358–71. doi:10.1080/13550280390201119. PMID 12775419. S2CID 22016092.
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.
Westendorf JJ, Koka S (2004). "Identification of FHOD1-binding proteins and mechanisms of FHOD1-regulated actin dynamics". J. Cell. Biochem. 92 (1): 29–41. doi:10.1002/jcb.20031. PMID 15095401. S2CID 40202935.
Colland F; Jacq X; Trouplin V; et al. (2004). "Functional Proteomics Mapping of a Human Signaling Pathway". Genome Res. 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC 442148. PMID 15231748.
Beausoleil SA; Jedrychowski M; Schwartz D; et al. (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. Bibcode:2004PNAS..10112130B. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
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.
Miles RR, Crockett DK, Lim MS, Elenitoba-Johnson KS (2006). "Analysis of BCL6-interacting proteins by tandem mass spectrometry". Mol. Cell. Proteomics. 4 (12): 1898–909. doi:10.1074/mcp.M500112-MCP200. PMID 16147992.
Lim J; Hao T; Shaw C; et al. (2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID 16713569. S2CID 13709685.
Olsen JV; Blagoev B; Gnad F; et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983. S2CID 7827573.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000101040 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000039671 - 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.

[entrez-5] "Entrez Gene: ZMYND8 zinc finger, MYND-type containing 8".

[6] Fossey, S. C., Kuroda, S., Price, J. A., Pendleton, J. K., Freedman, B. I., Bowden, D. W. Identification and characterization of PRKCBP1, a candidate RACK-like protein. Mammalian Genome 11: 919-925, 2000. [PubMed]: 11003709

[7] Gross, M. B. Personal Communication. Baltimore, Md. 3/28/2014.

[8] Shen, H., Xu, W., Guo, R., Rong, B., Gu, L., Wang, Z., He, C., Zheng, L., Hu, X., Hu, Z., Shao, Z.-M., Yang, P., Wu, F., Shi, Y. G., Shi, Y., Lan, F. Suppression of enhancer overactivation by a RACK7-histone demethylase complex. Cell 165: 331-342, 2016. [PubMed]: 27058665

[9] Westendorf, J. J., Koka, S. Identification of FHOD1-binding proteins and mechanisms of FHOD1-regulated actin dynamics. J. Cell. Biochem. 92: 29-41, 2004. [PubMed[: 15095401

[mgp_reference-10] Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.

[11] Mouse Resources Portal, Wellcome Trust Sanger Institute.

[allele_ref-12] "International Knockout Mouse Consortium".^{[mrtav link]}

[mgi_allele_ref-13] "Mouse Genome Informatics".

[pmid21677750-14] Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.

[mouse_library-15] Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.

[mouse_for_all_reasons-16] Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.

[pmid21722353-17] van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

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