Q9UKY1 (ZHX1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Zinc fingers and homeoboxes protein 1

Gene names

Name:

ZHX1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	873 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Acts as a transcriptional repressor. Increases DNMT3B-mediated repressive transcriptional activity when DNMT3B is tethered to DNA. May link molecule between DNMT3B and other co-repressor proteins. Ref.5
Subunit structure	Forms homodimers. Heterodimer (via HD1 domain) with ZHX2 (via HD1 domain). Also forms a heterodimer with ZHX3 which is a prerequisite for repressor activity. Interacts with ATF7IP and NFYA. Interacts (via homeobox domains) with DNMT3B (via PWWP domain). Ref.1 Ref.4 Ref.5 Ref.6 Ref.7 Ref.10
Subcellular location	Nucleus. Note: Colocalized in the nucleus with DNMT3B. Ref.5 Ref.8
Tissue specificity	Ubiquitously expressed. Expressed in podocytes. Ref.1 Ref.8
Sequence similarities	Belongs to the ZHX family. Contains 2 C2H2-type zinc fingers. Contains 5 homeobox DNA-binding domains.

Ontologies

Keywords
Biological process	Differentiation Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Homeobox Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Repressor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.10. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleus Inferred from direct assay Ref.5Ref.8Ref.10. Source: UniProtKB
Molecular_function	protein heterodimerization activity Inferred from direct assay Ref.6Ref.7. Source: UniProtKB sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding transcription factor activity Inferred from direct assay Ref.5. Source: UniProtKB transcription corepressor activity Inferred from direct assay Ref.10. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ATXN1	P54253	5	EBI-347767,EBI-930964
DNMT3B	Q9UBC3-1	4	EBI-347767,EBI-6083193

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9UKY1-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q96EF9-1)

Also known as: ZHX1-C8orf76;

The sequence of this isoform can be found in the external entry Q96EF9.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Note: Based on a readthrough transcript which may produce a ZHX1-C8orf76 fusion protein. No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 873

873

Zinc fingers and homeoboxes protein 1

PRO_0000049388

Regions

Zinc finger

70 – 93

24

C2H2-type 1

Zinc finger

102 – 125

24

C2H2-type 2

DNA binding

284 – 346

63

Homeobox 1

DNA binding

464 – 526

63

Homeobox 2

DNA binding

569 – 630

62

Homeobox 3

DNA binding

660 – 722

63

Homeobox 4

DNA binding

777 – 832

56

Homeobox 5

Region

272 – 564

293

Required for interaction with NFYA Ref.4

Region

272 – 432

161

Required for dimerization Ref.5

Region

734 – 768

35

Required for nuclear localization Ref.5

Region

831 – 873

43

Required for repressor activity Ref.5

Amino acid modifications

Modified residue

45

1

Phosphoserine Ref.11

Modified residue

47

1

Phosphoserine Ref.11 Ref.12

Modified residue

48

1

Phosphoserine Ref.11 Ref.12

Modified residue

648

1

Phosphoserine Ref.12

Experimental info

Sequence conflict

263

1

V → M in AAH40481. Ref.3

Sequence conflict

792

1

H → R in AAH40481. Ref.3

Secondary structure

1

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873

Helix Strand Turn

Details...

Turn

60 – 62

3

Beta strand

68 – 71

4

Beta strand

78 – 80

3

Helix

82 – 92

11

Beta strand

102 – 104

3

Turn

105 – 108

4

Beta strand

109 – 113

5

Helix

115 – 118

4

Helix

120 – 123

4

Beta strand

131 – 135

5

Beta strand

144 – 150

7

Helix

473 – 485

13

Helix

491 – 501

11

Helix

505 – 518

14

Turn

519 – 523

5

Helix

577 – 589

13

Helix

595 – 604

10

Helix

609 – 624

16

Beta strand

664 – 667

4

Helix

669 – 681

13

Helix

687 – 697

11

Helix

701 – 715

15

Turn

716 – 718

3

Helix

721 – 730

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 66CF1CEC5EF824E5	FASTA	873	98,098
	10 20 30 40 50 60 MASRRKSTTP CMVLASEQDP DLELISDLDE GPPVLTPVEN TRAESISSDE EVHESVDSDN 70 80 90 100 110 120 QQNKKVEGGY ECKYCTFQTP DLNMFTFHVD SEHPNVVLNS SYVCVECNFL TKRYDALSEH 130 140 150 160 170 180 NLKYHPGEEN FKLTMVKRNN QTIFEQTIND LTFDGSFVKE ENAEQAESTE VSSSGISISK 190 200 210 220 230 240 TPIMKMMKNK VENKRIAVHH NSVEDVPEEK ENEIKPDREE IVENPSSSAS ESNTSTSIVN 250 260 270 280 290 300 RIHPSTASTV VTPAAVLPGL AQVITAVSAQ QNSNLIPKVL IPVNSIPTYN AALDNNPLLL 310 320 330 340 350 360 NTYNKFPYPT MSEITVLSAQ AKYTEEQIKI WFSAQRLKHG VSWTPEEVEE ARRKQFNGTV 370 380 390 400 410 420 HTVPQTITVI PTHISTGSNG LPSILQTCQI VGQPGLVLTQ VAGTNTLPVT APIALTVAGV 430 440 450 460 470 480 PSQNNIQKSQ VPAAQPTAET KPATAAVPTS QSVKHETALV NPDSFGIRAK KTKEQLAELK 490 500 510 520 530 540 VSYLKNQFPH DSEIIRLMKI TGLTKGEIKK WFSDTRYNQR NSKSNQCLHL NNDSSTTIII 550 560 570 580 590 600 DSSDETTESP TVGTAQPKQS WNPFPDFTPQ KFKEKTAEQL RVLQASFLNS SVLTDEELNR 610 620 630 640 650 660 LRAQTKLTRR EIDAWFTEKK KSKALKEEKM EIDESNAGSS KEEAGETSPA DESGAPKSGS 670 680 690 700 710 720 TGKICKKTPE QLHMLKSAFV RTQWPSPEEY DKLAKESGLA RTDIVSWFGD TRYAWKNGNL 730 740 750 760 770 780 KWYYYYQSAN SSSMNGLSSL RKRGRGRPKG RGRGRPRGRP RGSKRINNWD RGPSLIKFKT 790 800 810 820 830 840 GTAILKDYYL KHKFLNEQDL DELVNKSHMG YEQVREWFAE RQRRSELGIE LFEENEEEDE 850 860 870 VIDDQEEDEE ETDDSDTWEP PRHVKRKLSK SDD
	Isoform 2 (ZHX1-C8orf76) [UniParc]. See Q96EF9.		–	–

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human ZHX1: cloning, chromosomal location, and interaction with transcription factor NF-Y." Yamada K., Printz R.L., Osawa H., Granner D.K. Biochem. Biophys. Res. Commun. 261:614-621(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INTERACTION WITH NFYA. Tissue: Liver.
[2]	"Identification and cloning of the human ZHX1 gene." Mueller R., Ziegler B.L. Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Testis.
[4]	"Identification of proteins that interact with NF-YA." Yamada K., Osawa H., Granner D.K. FEBS Lett. 460:41-45(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NFYA.
[5]	"Functional analysis and the molecular dissection of zinc-fingers and homeoboxes 1 (ZHX1)." Yamada K., Kawata H., Matsuura K., Shou Z., Hirano S., Mizutani T., Yazawa T., Yoshino M., Sekiguchi T., Kajitani T., Miyamoto K. Biochem. Biophys. Res. Commun. 297:368-374(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, HOMODIMERIZATION, SUBCELLULAR LOCATION.
[6]	"Analysis of zinc-fingers and homeoboxes (ZHX)-1-interacting proteins: molecular cloning and characterization of a member of the ZHX family, ZHX3." Yamada K., Kawata H., Shou Z., Hirano S., Mizutani T., Yazawa T., Sekiguchi T., Yoshino M., Kajitani T., Miyamoto K. Biochem. J. 373:167-178(2003) [PubMed] [Europe PMC] [Abstract] Cited for: HETERODIMERIZATION WITH ZHX3, INTERACTION WITH ATF7IP.
[7]	"Zinc-fingers and homeoboxes (ZHX) 2, a novel member of the ZHX family, functions as a transcriptional repressor." Kawata H., Yamada K., Shou Z., Mizutani T., Yazawa T., Yoshino M., Sekiguchi T., Kajitani T., Miyamoto K. Biochem. J. 373:747-757(2003) [PubMed] [Europe PMC] [Abstract] Cited for: HETERODIMERIZATION WITH ZHX2.
[8]	"ZHX proteins regulate podocyte gene expression during the development of nephrotic syndrome." Liu G., Clement L.C., Kanwar Y.S., Avila-Casado C., Chugh S.S. J. Biol. Chem. 281:39681-39692(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Kidney.
[9]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[10]	"Zinc-fingers and homeoboxes 1 (ZHX1) binds DNA methyltransferase (DNMT) 3B to enhance DNMT3B-mediated transcriptional repression." Kim S.H., Park J., Choi M.C., Kim H.P., Park J.H., Jung Y., Lee J.H., Oh D.Y., Im S.A., Bang Y.J., Kim T.Y. Biochem. Biophys. Res. Commun. 355:318-323(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DNMT3B.
[11]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-45; SER-47 AND SER-48, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47; SER-48 AND SER-648, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[13]	"Solution structure of the zinc-finger region of human zinc-fingers and homeoboxes 1 (ZHX1)." Structural proteomics in Europe (SPINE) Submitted (APR-2006) to the PDB data bank Cited for: STRUCTURE BY NMR OF 60-153.
[14]	"The solution structure of the third homeobox domain of human zinc fingers and homeoboxes protein." RIKEN structural genomics initiative (RSGI) Submitted (FEB-2007) to the PDB data bank Cited for: STRUCTURE BY NMR OF 565-640.
[15]	"The tandem zinc-finger region of human ZHX adopts a novel C2H2 zinc finger structure with a C-terminal extension." Wienk H., Lammers I., Hotze A., Wu J., Wechselberger R.W., Owens R., Stammers D.K., Stuart D., Kaptein R., Folkers G.E. Biochemistry 48:4431-4439(2009) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 60-153.
[16]	"Novel structural features in two ZHX homeodomains derived from a systematic study of single and multiple domains." Bird L.E., Ren J., Nettleship J.E., Folkers G.E., Owens R.J., Stammers D.K. BMC Struct. Biol. 10:13-13(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 655-731.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF106862 mRNA. Translation: AAD50624.1.
AF195766 mRNA. Translation: AAF35183.1.
BC040481 mRNA. Translation: AAH40481.1.

IPI

IPI00293086.

PIR

JC7079.

RefSeq

NP_001017926.1. NM_001017926.2.
NP_009153.3. NM_007222.4.

UniGene

Hs.521800.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2ECB	NMR	-	A	565-640	[»]
2GHF	NMR	-	A	60-153	[»]
2LY9	NMR	-	A	462-532	[»]
3NAR	X-ray	2.60	A/B	655-731	[»]

ProteinModelPortal

Q9UKY1.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UKY1. 51 interactions.

MINT

MINT-1424551.

STRING

9606.ENSP00000297857.

PTM databases

PhosphoSite

Q9UKY1.

Polymorphism databases

DMDM

44888551.

Proteomic databases

PaxDb

Q9UKY1.

PRIDE

Q9UKY1.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000297857; ENSP00000297857; ENSG00000165156.
ENST00000395571; ENSP00000378938; ENSG00000165156.
ENST00000522655; ENSP00000428821; ENSG00000165156.

GeneID

11244.

KEGG

hsa:11244.

UCSC

uc003yqe.3. human.

Organism-specific databases

CTD

11244.

GeneCards

GC08M124260.

HGNC

HGNC:12871. ZHX1.

MIM

604764. gene.

neXtProt

NX_Q9UKY1.

PharmGKB

PA37460.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG39488.

HOGENOM

HOG000013231.

HOVERGEN

HBG007920.

InParanoid

Q9UKY1.

OMA

KHKFLNE.

OrthoDB

EOG4KWJS7.

PhylomeDB

Q9UKY1.

Gene expression databases

ArrayExpress

Q9UKY1.

Bgee

Q9UKY1.

CleanEx

HS_ZHX1.

Genevestigator

Q9UKY1.

GermOnline

ENSG00000165156. Homo sapiens.

Family and domain databases

Gene3D

1.10.10.60. 5 hits.

InterPro

IPR001356. Homeodomain.
IPR009057. Homeodomain-like.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
[Graphical view]

Pfam

PF00046. Homeobox. 4 hits.
[Graphical view]

SMART

SM00389. HOX. 5 hits.
SM00355. ZnF_C2H2. 2 hits.
[Graphical view]

SUPFAM

SSF46689. Homeodomain_like. 5 hits.

PROSITE

PS00027. HOMEOBOX_1. False negative.
PS50071. HOMEOBOX_2. 4 hits.
PS00028. ZINC_FINGER_C2H2_1. False negative.
PS50157. ZINC_FINGER_C2H2_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9UKY1.

GenomeRNAi

11244.

NextBio

42786.

SOURCE

Search...

Entry information

Entry name

ZHX1_HUMAN

Accession

Primary (citable) accession number: Q9UKY1
Secondary accession number(s): Q8IWD8

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 2004
Last sequence update:	May 1, 2000
Last modified:	May 1, 2013
This is version 114 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.