HMBOX1

Homeobox containing 1, also known as homeobox telomere-binding protein 1 (HOT1), is a protein that in humans is encoded by the HMBOX1 gene.[5] HMBOX1 directly binds to the double-stranded repeat sequence of telomeres.[6][7]

HMBOX1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2CUF, 4J19
Identifiers
Aliases	HMBOX1, HNF1LA, HOT1, PBHNF, homeobox containing 1, TAH1
External IDs	MGI: 2445066 HomoloGene: 11589 GeneCards: HMBOX1
Gene location (Human) Chr. Chromosome 8 (human)[1] Band 8p21.1-p12 Start 28,890,395 bp[1] End 29,064,764 bp[1]
Gene location (Mouse) Chr. Chromosome 14 (mouse)[2] Band 14|14 D1 Start 64,811,600 bp[2] End 64,949,871 bp[2]
Gene ontology Molecular function • DNA binding • telomerase activity • double-stranded telomeric DNA binding • GO:0001948 protein binding • identical protein binding • telomeric DNA binding • GO:0001078, GO:0001214, GO:0001206 DNA-binding transcription repressor activity, RNA polymerase II-specific • sequence-specific DNA binding • GO:0032403 macromolecular complex binding • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component • cytoplasm • cell nucleus • telomerase holoenzyme complex • nucleoplasm • cytosol • nuclear body • nuclear chromosome, telomeric region • chromosome, telomeric region • chromosome • Cajal body • PML body Biological process • positive regulation of transcription, DNA-templated • positive regulation of telomere maintenance via telomerase • negative regulation of transcription, DNA-templated • regulation of transcription, DNA-templated • positive regulation of telomerase activity • transcription, DNA-templated • RNA-dependent DNA biosynthetic process • positive regulation of chromatin binding • negative regulation of transcription from RNA polymerase II promoter • regulation of telomerase activity Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	79618	219150
Ensembl	ENSG00000147421	ENSMUSG00000021972
UniProt	Q6NT76	Q8BJA3
RefSeq (mRNA)	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 (protein)	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
Location (UCSC)	Chr 8: 28.89 – 29.06 Mb	Chr 14: 64.81 – 64.95 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

HMBOX1 has originally been identified to associate with telomeric chromatin in telomerase-positive cancer cells and cancer cells that maintain their telomeres based on the Alternative Lengthening of Telomeres (ALT) mechanism by the 'reverse ChIP' technique PICh (Proteomics of Isolated Chromatin segments).[6] Subsequently, direct binding to telomeric DNA was demonstrated through a co-crystal structure of the DNA-binding domain of HMBOX1 with telomeric DNA.[7] Loss-of-function and gain-of-function experiments classify HMBOX1 as a positive regulator of telomere length.[7][8] HMBOX1 had originally been described as a transcriptional repressor based on reporter gene assays,[9] but genome-wide approaches using RNA-seq and ChIP-seq see little to no such effect at least in several cancer cell lines.[10]

References

1. GRCh38: Ensembl release 89: ENSG00000147421 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000021972 - Ensembl, May 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 (January 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 (June 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. Zhou S, Xiao Y, Zhuang Y, Liu Y, Zhao H, Yang H, Xie C, Zhou F, Zhou Y (July 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.
9. 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.
10. 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 (June 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.

Further reading