HMBOX1

Protein sa homeoboksom 1, znan i kao protein 1 sa homeoboksnim vezanjem telomere (HOT1), je protein koji je kod ljudi kodiran genom HMBOX1.^[5] HMBOX1 directly binds to the double-stranded repeat sequence of telomeres.^[6][7]

HMBOX1
Dostupne strukture PDB Pretraga ortologa: PDBe RCSB Spisak PDB ID kodova 2CUF, 4J19
Identifikatori
Aliasi	HMBOX1
Vanjski ID-jevi	MGI: 2445066 HomoloGene: 11589 GeneCards: HMBOX1
Lokacija gena (čovjek) Hrom. Hromosom 8 (čovjek)[1] Bend 8p21.1-p12 Početak 28,890,395 bp[1] Kraj 29,064,764 bp[1]
Lokacija gena (miš) Hrom. Hromosom 14 (miš)[2] Bend 14|14 D1 Početak 65,049,049 bp[2] Kraj 65,187,320 bp[2]
Ontologija gena Molekularna funkcija • vezivanje sa DNK • telomerase activity • double-stranded telomeric DNA binding • GO:0001948, GO:0016582 vezivanje za proteine • vezivanje identičnih proteina • telomeric DNA binding • GO:0001078, GO:0001214, GO:0001206 DNA-binding transcription repressor activity, RNA polymerase II-specific • sequence-specific DNA binding • GO:0032403 protein-containing complex binding • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific Ćelijska komponenta • citoplazma • jedro • telomerase holoenzyme complex • nukleoplazma • citosol • nuclear body • Telomera • hromosom • Cajal body • PML body Biološki proces • GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated • positive regulation of telomere maintenance via telomerase • GO:0045996 negative regulation of transcription, DNA-templated • GO:0009373 regulation of transcription, DNA-templated • positive regulation of telomerase activity • transcription, DNA-templated • RNA-dependent DNA biosynthetic process • positive regulation of chromatin binding • GO:1901227 negative regulation of transcription by RNA polymerase II • regulation of telomerase activity Izvori:Amigo / QuickGO
Ortolozi
Vrste	Čovjek	Miš
Entrez	79618	219150
Ensembl	ENSG00000147421	ENSMUSG00000021972
UniProt	Q6NT76	Q8BJA3
RefSeq (mRNK)	NM_001135726 NM_024567 NM_001324382 NM_001324383 NM_001324384 NM_001324385 NM_001324386 NM_001324387 NM_001324388 NM_001324389 NM_001324390 NM_001324391 NM_001324392 NM_001324393 NM_001324394 NM_001324395 NM_001330498	NM_177338 NM_001347626 NM_001347627
RefSeq (bjelančevina)	NP_001129198 NP_001311311 NP_001311312 NP_001311313 NP_001311314 NP_001311315 NP_001311316 NP_001311317 NP_001311318 NP_001311319 NP_001311320 NP_001311321 NP_001311322 NP_001311323 NP_001311324 NP_001317427 NP_078843	NP_001334555 NP_001334556 NP_796312
Lokacija (UCSC)	Chr 8: 28.89 – 29.06 Mb	Chr 14: 65.05 – 65.19 Mb
PubMed pretraga	[3]	[4]
Wikipodaci
Pogledaj/uredi – čovjek Pogledaj/uredi – miš

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 420 aminokiselina, а molekulska težina 47.278 Da.^[8]

• 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
MLSSFPVVLL		ETMSHYTDEP		RFTIEQIDLL		QRLRRTGMTK		HEILHALETL
DRLDQEHSDK		FGRRSSYGGS		SYGNSTNNVP		ASSSTATAST		QTQHSGMSPS
PSNSYDTSPQ		PCTTNQNGRE		NNERLSTSNG		KMSPTRYHAN		SMGQRSYSFE
ASEEDLDVDD		KVEELMRRDS		SVIKEEIKAF		LANRRISQAV		VAQVTGISQS
RISHWLLQQG		SDLSEQKKRA		FYRWYQLEKT		NPGATLSMRP		APIPIEDPEW
RQTPPPVSAT		SGTFRLRRGS		RFTWRKECLA		VMESYFNENQ		YPDEAKREEI
ANACNAVIQK		PGKKLSDLER		VTSLKVYNWF		ANRRKEIKRR		ANIEAAILES
HGIDVQSPGG		HSNSDDVDGN		DYSEQDDSTS		HSDHQDPISL		AVEMAAVNHT
ILALARQGAN		EIKTEALDDD

Funkcija

HMBOX1 je prvobitno identificiran da se povezuje s telomernim hromatinom u ćelijama raka pozitivnim na telomerazu i ćelijama raka koje održavaju svoje telomere na osnovu alternativnog produženje telomera (ALT) pomoću obrnutog ChIP tehnika PICh (eng. skr. od proteomika izoliranih segmenata hromatina).^[6] Nakon toga je demonstrirano direktno vezivanje za telomernu DNK, preko kokristalnih struktura domen koji veže DNK HMBOX1 sa telomernom DNK.^[7] Eksperimenti s gubitkom i pojačanjem funkcije, klasificiraju HMBOX1 kao pozitivnog regulatora dužine telomera.^[7][9] HMBOX1 je prvobitno bio opisivan kao transkripcijski represor, na temelju testova reporteskih gena,^[10] ali pristupi cijelom genomu koji koriste RNK-seq i ChIP-seq ne vide takav učinak ili ga uopće nemaju, barem u nekoliko ćelijskih linija raka.^[11]

Reference

1. GRCh38: Ensembl release 89: ENSG00000147421 - Ensembl, maj 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000021972 - 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. "Entrez Gene: Homeobox containing 1".
6. Déjardin J, Kingston RE (januar 2009). "Purification of proteins associated with specific genomic Loci". Cell. 136 (1): 175–86. doi:10.1016/j.cell.2008.11.045. PMC 3395431. PMID 19135898.
7. Kappei D, Butter F, Benda C, Scheibe M, Draškovič I, Stevense M, Novo CL, Basquin C, Araki M, Araki K, Krastev DB, Kittler R, Jessberger R, Londoño-Vallejo JA, Mann M, Buchholz F (juni 2013). "HOT1 is a mammalian direct telomere repeat-binding protein contributing to telomerase recruitment". The EMBO Journal. 32 (12): 1681–701. doi:10.1038/emboj.2013.105. PMC 3680732. PMID 23685356.
8. "UniProt, Q6NT76" (jezik: engleski). Pristupljeno 19. 9. 2021.
9. Zhou S, Xiao Y, Zhuang Y, Liu Y, Zhao H, Yang H, Xie C, Zhou F, Zhou Y (juli 2017). "Knockdown of homeobox containing 1 increases the radiosensitivity of cervical cancer cells through telomere shortening". Oncology Reports. 38 (1): 515–521. doi:10.3892/or.2017.5707. PMID 28628186.
10. Chen S, Saiyin H, Zeng X, Xi J, Liu X, Li X, Yu L (2006). "Isolation and functional analysis of human HMBOX1, a homeobox containing protein with transcriptional repressor activity". Cytogenetic and Genome Research. 114 (2): 131–6. doi:10.1159/000093328. PMID 16825764. S2CID 21067536.
11. Jahn A, Rane G, Paszkowski-Rogacz M, Sayols S, Bluhm A, Han CT, Draškovič I, Londoño-Vallejo JA, Kumar AP, Buchholz F, Butter F, Kappei D (juni 2017). "ZBTB48 is both a vertebrate telomere-binding protein and a transcriptional activator". EMBO Reports. 18 (6): 929–946. doi:10.15252/embr.201744095. PMC 5452029. PMID 28500257.