Reviewed, UniProtKB/Swiss-Prot Q05516 (ZBT16_HUMAN)

Names and origin

Protein names

Recommended name:
    Zinc finger and BTB domain-containing protein 16
Alternative name(s):
    Zinc finger protein PLZF
    Promyelocytic leukemia zinc finger protein
    Zinc finger protein 145

Gene names

Name:	ZBTB16
Synonyms:	PLZF, ZNF145

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	673 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Probable transcription factor. May play a role in myeloid maturation and in the development and/or maintenance of other differentiated tissues. Probable substrate-recognition component of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Binds EPN1. Interacts with ZBTB32 and CUL3.
Subcellular location	Nucleus.
Tissue specificity	Within the hematopoietic system, PLZF is expressed in bone marrow, early myeloid cell lines and peripheral blood mononuclear cells. Also expressed in the ovary, and at lower levels, in the kidney and lung.
Induction	By retinoic acid.
Involvement in disease	A chromosomal aberration involving ZBTB16 may be a cause of acute promyelocytic leukemia (APL). Translocation t(11;17)(q32;q21) with RARA.
Sequence similarities	Belongs to the krueppel C2H2-type zinc-finger protein family. Contains 1 BTB (POZ) domain. Contains 9 C2H2-type zinc fingers.

Ontologies

Keywords
Biological process	Transcription Transcription regulation Ubl conjugation pathway
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Chromosomal rearrangement
Disease	Proto-oncogene
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	apoptosis Non-traceable author statement. Source: UniProtKB central nervous system development Inferred from sequence or structural similarity. Source: UniProtKB mesonephros development Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of myeloid cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of transcription, DNA-dependent Inferred from direct assay. Source: MGI ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	PML body Inferred from direct assay. Source: UniProtKB nuclear speck Inferred from direct assay. Source: UniProtKB nucleolus Inferred from direct assay. Source: HPA transcriptional repressor complex Inferred from direct assay. Source: MGI
Molecular function	DNA binding Non-traceable author statement. Source: UniProtKB protein homodimerization activity Inferred from direct assay. Source: UniProtKB specific transcriptional repressor activity Inferred from direct assay. Source: MGI zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		1	EBI-711925,EBI-711925
	Q8IUB0	4	EBI-711925,EBI-1189421
PML	P29590-5	1	EBI-711925,EBI-304008
PML	Q15959	2	EBI-711925,EBI-779712

Alternative products

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

Isoform PLZFB (identifier: Q05516-1)

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 PLZFA (identifier: Q05516-2)

The sequence of this isoform differs from the canonical sequence as follows:
     255-377: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 673

673

Zinc finger and BTB domain-containing protein 16

PRO_0000047729

Regions

Domain

34 – 96

63

BTB

Zinc finger

404 – 426

23

C2H2-type 1

Zinc finger

432 – 454

23

C2H2-type 2

Zinc finger

461 – 483

23

C2H2-type 3

Zinc finger

490 – 512

23

C2H2-type 4

Zinc finger

518 – 540

23

C2H2-type 5

Zinc finger

546 – 568

23

C2H2-type 6

Zinc finger

574 – 596

23

C2H2-type 7

Zinc finger

602 – 624

23

C2H2-type 8

Zinc finger

630 – 652

23

C2H2-type 9

Sites

Site

394 – 395

2

Breakpoint for translocation to form PLZF-RAR-alpha oncogene

Amino acid modifications

Modified residue

76

1

Phosphoserine; by PDPK Potential

Modified residue

184

1

Phosphoserine; by PDPK Potential

Modified residue

197

1

Phosphoserine; by PDPK Potential

Modified residue

256

1

Phosphoserine; by PDPK Potential

Modified residue

282

1

Phosphothreonine; by PDPK Potential

Modified residue

628

1

Phosphoserine; by PDPK Potential

Natural variations

Alternative sequence

255 – 377

123

Missing in isoform PLZFA.

VSP_006896

Experimental info

Sequence conflict

580

1

G → D in CAA79489. Ref.1

Secondary structure

1

.

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.

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673

Helix Strand Turn

Details...

Beta strand

9 – 12

4

Helix

16 – 30

15

Turn

31 – 33

3

Beta strand

36 – 42

7

Beta strand

44 – 47

4

Helix

49 – 55

7

Helix

57 – 62

6

Beta strand

68 – 72

5

Helix

77 – 89

13

Beta strand

90 – 94

5

Helix

96 – 98

3

Helix

99 – 109

11

Helix

112 – 125

14

Sequences

	Sequence		Length	Mass (Da)
	Isoform PLZFB [UniParc]. Last modified March 7, 2006. Version 2. Checksum: 51F8E361FA31239E	FASTA	673	74,274
	10 20 30 40 50 60 MDLTKMGMIQ LQNPSHPTGL LCKANQMRLA GTLCDVVIMV DSQEFHAHRT VLACTSKMFE 70 80 90 100 110 120 ILFHRNSQHY TLDFLSPKTF QQILEYAYTA TLQAKAEDLD DLLYAAEILE IEYLEEQCLK 130 140 150 160 170 180 MLETIQASDD NDTEATMADG GAEEEEDRKA RYLKNIFISK HSSEESGYAS VAGQSLPGPM 190 200 210 220 230 240 VDQSPSVSTS FGLSAMSPTK AAVDSLMTIG QSLLQGTLQP PAGPEEPTLA GGGRHPGVAE 250 260 270 280 290 300 VKTEMMQVDE VPSQDSPGAA ESSISGGMGD KVEERGKEGP GTPTRSSVIT SARELHYGRE 310 320 330 340 350 360 ESAEQVPPPA EAGQAPTGRP EHPAPPPEKH LGIYSVLPNH KADAVLSMPS SVTSGLHVQP 370 380 390 400 410 420 ALAVSMDFST YGGLLPQGFI QRELFSKLGE LAVGMKSESR TIGEQCSVCG VELPDNEAVE 430 440 450 460 470 480 QHRKLHSGMK TYGCELCGKR FLDSLRLRMH LLAHSAGAKA FVCDQCGAQF SKEDALETHR 490 500 510 520 530 540 QTHTGTDMAV FCLLCGKRFQ AQSALQQHME VHAGVRSYIC SECNRTFPSH TALKRHLRSH 550 560 570 580 590 600 TGDHPYECEF CGSCFRDEST LKSHKRIHTG EKPYECNGCG KKFSLKHQLE THYRVHTGEK 610 620 630 640 650 660 PFECKLCHQR SRDYSAMIKH LRTHNGASPY QCTICTEYCP SLSSMQKHMK GHKPEEIPPD 670 WRIEKTYLYL CYV
	Isoform PLZFA [UniParc]. Checksum: 1051E16C91FDC089		550	61,601
	10 20 30 40 50 60 MDLTKMGMIQ LQNPSHPTGL LCKANQMRLA GTLCDVVIMV DSQEFHAHRT VLACTSKMFE 70 80 90 100 110 120 ILFHRNSQHY TLDFLSPKTF QQILEYAYTA TLQAKAEDLD DLLYAAEILE IEYLEEQCLK 130 140 150 160 170 180 MLETIQASDD NDTEATMADG GAEEEEDRKA RYLKNIFISK HSSEESGYAS VAGQSLPGPM 190 200 210 220 230 240 VDQSPSVSTS FGLSAMSPTK AAVDSLMTIG QSLLQGTLQP PAGPEEPTLA GGGRHPGVAE 250 260 270 280 290 300 VKTEMMQVDE VPSQGFIQRE LFSKLGELAV GMKSESRTIG EQCSVCGVEL PDNEAVEQHR 310 320 330 340 350 360 KLHSGMKTYG CELCGKRFLD SLRLRMHLLA HSAGAKAFVC DQCGAQFSKE DALETHRQTH 370 380 390 400 410 420 TGTDMAVFCL LCGKRFQAQS ALQQHMEVHA GVRSYICSEC NRTFPSHTAL KRHLRSHTGD 430 440 450 460 470 480 HPYECEFCGS CFRDESTLKS HKRIHTGEKP YECNGCGKKF SLKHQLETHY RVHTGEKPFE 490 500 510 520 530 540 CKLCHQRSRD YSAMIKHLRT HNGASPYQCT ICTEYCPSLS SMQKHMKGHK PEEIPPDWRI 550 EKTYLYLCYV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Fusion between a novel Kruppel-like zinc finger gene and the retinoic acid receptor-alpha locus due to a variant t(11;17) translocation associated with acute promyelocytic leukaemia." Chen Z., Brand N.J., Chen A., Chen S.-J., Tong J.-H., Wang Z.-Y., Waxman S., Zelent A. EMBO J. 12:1161-1167(1993) [PubMed: 8384553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Heart ventricle.
[2]	"Genomic sequence, structural organization, molecular evolution, and aberrant rearrangement of promyelocytic leukemia zinc finger gene." Zhang T., Xiong H., Kan L.-X., Zhang C.-K., Jiao X.-F., Fu G., Zhang Q.-H., Lu L., Tong J.-H., Gu B.-W., Yu M., Liu J.-X., Licht J., Waxman S., Zelent A., Chen E., Chen S.-J. Proc. Natl. Acad. Sci. U.S.A. 96:11422-11427(1999) [PubMed: 10500192] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	"Rearrangements of the retinoic acid receptor alpha and promyelocytic leukemia zinc finger genes resulting from t(11;17)(q23;q21) in a patient with acute promyelocytic leukemia." Chen S.-J., Zelent A., Tong J.-H., Yu H.-Q., Wang Z.-Y., Derre J., Berger R., Waxman S., Chen Z. J. Clin. Invest. 91:2260-2267(1993) [PubMed: 8387545] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 424-455.
[5]	"A novel BTB/POZ transcriptional repressor protein interacts with the Fanconi anemia group C protein and PLZF." Hoatlin M.E., Zhi Y., Ball H., Silvey K., Melnick A., Stone S., Arai S., Hawe N., Owen G., Zelent A., Licht J.D. Blood 94:3737-3747(1999) [PubMed: 10572087] [Abstract] Cited for: INTERACTION WITH ZBTB32.
[6]	"Role of the ENTH domain in phosphatidylinositol-4,5-bisphosphate binding and endocytosis." Itoh T., Koshiba S., Kigawa T., Kikuchi A., Yokoyama S., Takenawa T. Science 291:1047-1051(2001) [PubMed: 11161217] [Abstract] Cited for: INTERACTION WITH EPN1.
[7]	"Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases." Furukawa M., He Y.J., Borchers C., Xiong Y. Nat. Cell Biol. 5:1001-1007(2003) [PubMed: 14528312] [Abstract] Cited for: FUNCTION AS A E3 UBIQUITIN-PROTEIN LIGASE, INTERACTION WITH CUL3.
[8]	"Crystal structure of the BTB domain from PLZF." Ahmad K.F., Engel C.K., Prive G.G. Proc. Natl. Acad. Sci. U.S.A. 95:12123-12128(1998) [PubMed: 9770450] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 6-126.
[9]	"Structure-function studies of the BTB/POZ transcriptional repression domain from the promyelocytic leukemia zinc finger oncoprotein." Li X., Peng H., Schultz D.C., Lopez-Guisa J.M., Rauscher F.J. III, Marmorstein R. Cancer Res. 59:5275-5282(1999) [PubMed: 10537309] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 7-122.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBLGenBankDDBJ

Z19002 mRNA. Translation: CAA79489.1.
AF060568 Genomic DNA. Translation: AAD03619.1.
BC026902 mRNA. Translation: AAH26902.1.
BC029812 mRNA. Translation: AAH29812.1.
S60093 Genomic DNA. Translation: AAC60590.2.

PIR

S36336.

RefSeq

NP_001018011.1.
NP_005997.2.

UniGene

Hs.591945
Hs.682144

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BUO	X-ray	1.90	A	6-126	[»]
1CS3	X-ray	2.00	A	7-122	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:2654N.

IntAct

Q05516.

PTM databases

PhosphoSite

Q05516.

Genome annotation databases

Ensembl

ENSG00000109906. Homo sapiens. [Contig view]

GeneID

7704.

KEGG

hsa:7704.

Organism-specific databases

HGNC

HGNC:12930. ZBTB16.

HPA

CAB004540.
HPA001499.

MIM

176797. gene.

Orphanet

520. Acute promyelocytic leukaemia.

PharmGKB

PA37517.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

Q05516.

HOVERGEN

Q05516.

Gene expression databases

ArrayExpress

Q05516.

CleanEx

HS_ZBTB16.

GermOnline

ENSG00000109906. Homo sapiens.

Family and domain databases

InterPro

IPR000210. BTB/POZ-like.
IPR011333. BTB/POZ_fold.
IPR013069. BTB_POZ.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]

Gene3D

G3DSA:3.30.710.10. BTB/POZ_fold. 1 hit.
G3DSA:3.30.160.60. Znf_C2H2/integrase_DNA-bd. 3 hits.

Pfam

PF00651. BTB. 1 hit.
PF00096. zf-C2H2. 8 hits.
[Graphical view]

ProDom

PD000003. Znf_C2H2. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00225. BTB. 1 hit.
SM00355. ZnF_C2H2. 9 hits.
[Graphical view]

PROSITE

PS50097. BTB. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 8 hits.
PS50157. ZINC_FINGER_C2H2_2. 9 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

29862.

SOURCE

Search...

Entry information

Entry name

ZBT16_HUMAN

Accession

Primary (citable) accession number: Q05516
Secondary accession number(s): Q8TAL4

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	March 7, 2006
Last modified:	November 25, 2008
This is version 95 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)