Reviewed, UniProtKB/Swiss-Prot O75398 (DEAF1_HUMAN)

Names and origin

Protein names

Recommended name:
    Deformed epidermal autoregulatory factor 1 homolog
Alternative name(s):
    Nuclear DEAF-1-related transcriptional regulator
      Short name=NUDR
    Suppressin
    Zinc finger MYND domain-containing protein 5

Gene names

Name:	DEAF1
Synonyms:	SPN, ZMYND5

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

General annotation (Comments)

Function	Transcription factor that binds to sequence with multiple copies of TTC[CG]G present in its own promoter and that of the HNRPA2B1 gene. Down-regulates transcription of these genes. Binds to the retinoic acid response element (RARE) AGGGTTCACCGAAAGTTCA. Activates the proenkephalin gene independently of promoter binding, probably through protein-protein interaction. When secreted, behaves as an inhibitor of cell proliferation, by arresting cells in the G0 or G1 phase.
Subunit structure	Homodimer Probable. Binds to LMO4 (via its C-terminus), LMO2 and CLIM2 By similarity. May interact with the corepressor NCOR.
Subcellular location	Nucleus. Note= Cytoplasmic in non-mucinous colorectal carcinoma. Isoform 3: Secreted. Note= Secreted in some cell types. Isoform 4: Secreted. Note= Secreted in some cell types.
Tissue specificity	Expressed in various tissues and cells such as in peripheral mononuclear cells and hormone-secreting pituitary cells.
Involvement in disease	Defects in DEAF1 could confer a growth advantage to the mutated cell that may have implications for the development and progression of neoplasia, e.g. in the case of colorectal adenocarcinomas (CRC).
Miscellaneous	Subcellular location in CRC (cytoplasmic or nuclear) is a prognostic factor that identifies a subgroup of patients with reduced survival. In addition, changes in the subcellular location correlates with the proliferative status of the cells.
Sequence similarities	Contains 1 MYND-type zinc finger. Contains 1 SAND domain.
Caution	This protein was first known as suppressin (characterized in bovine neuroendocrine and immune cells). However, according to Ref.1, it is uncertain whether it corresponds really to the suppressin also described in Ref.3. DEAF1 has been described as a nuclear dimeric protein and suppressin as a secreted monomeric protein.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus Secreted
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	anatomical structure morphogenesis Ref.1 Traceable author statement. Source: ProtInc germ cell development Ref.1 Traceable author statement. Source: ProtInc regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription from RNA polymerase II promoter Ref.1 Traceable author statement. Source: ProtInc
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	DNA binding Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Notes: Experimental confirmation may be lacking for some isoforms.

Isoform 1 (identifier: O75398-1)

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 3 (identifier: O75398-3)

Also known as: NUDR8;

The sequence of this isoform differs from the canonical sequence as follows:
     15-29: EAAAVAAAAAVAAAA → D

Notes: Secreted in some cell types.

Isoform 4 (identifier: O75398-4)

Also known as: Suppressin;

The sequence of this isoform differs from the canonical sequence as follows:
     1-68: Missing.

Notes: Secreted in some cell types. Have no predictable signal peptide. Ref.2 (AAC25718/AAC25719) sequences differ from that shown due to frameshifts in positions 222 and 236.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 565

565

Deformed epidermal autoregulatory factor 1 homolog

PRO_0000074084

Regions

Domain

193 – 273

81

SAND

Zinc finger

504 – 540

37

MYND-type

Motif

301 – 316

16

Nuclear localization signal Potential

Compositional bias

2 – 122

121

Ala-rich

Compositional bias

383 – 439

57

Pro-rich

Amino acid modifications

Modified residue

176

1

Phosphoserine

Natural variations

Alternative sequence

1 – 68

68

Missing in isoform 4.

VSP_005966

Alternative sequence

15 – 29

15

EAAAV…VAAAA → D in isoform 3.

VSP_005967

Natural variant

186

1

E → V in a primary colorectal cancer.

VAR_013725

Natural variant

191

1

K → I in a primary colorectal cancer.

VAR_013726

Natural variant

191

1

K → N in a primary colorectal cancer.

VAR_013727

Natural variant

199 – 202

4

YDSE → CDND in a primary colorectal cancer.

VAR_013728

Natural variant

202

1

E → D in a primary colorectal cancer.

VAR_013729

Natural variant

218

1

R → K in a primary colorectal cancer.

VAR_013730

Natural variant

350 – 352

3

DRA → GQT in a primary colorectal cancer.

VAR_013731

Natural variant

356

1

E → H in a primary colorectal cancer; requires 2 nucleotide substitutions.

VAR_013732

Natural variant

364

1

S → N in a primary colorectal cancer.

VAR_013733

Natural variant

367

1

Q → H in a primary colorectal cancer.

VAR_013734

Natural variant

370

1

V → L in a primary colorectal cancer.

VAR_013735

Natural variant

397

1

Y → F in a primary colorectal cancer.

VAR_013736

Natural variant

442

1

V → A in a primary colorectal cancer.

VAR_013737

Natural variant

449

1

E → K in a primary colorectal cancer.

VAR_013738

Natural variant

451 – 452

2

RS → GI in a primary colorectal cancer.

VAR_013739

Natural variant

468

1

Q → H in a primary colorectal cancer.

VAR_013740

Natural variant

479

1

H → L in a primary colorectal cancer.

VAR_013741

Natural variant

498

1

E → K in a primary colorectal cancer.

VAR_013742

Natural variant

526

1

T → N in a primary colorectal cancer.

VAR_013743

Natural variant

530

1

R → L in a primary colorectal cancer.

VAR_013744

Natural variant

537 – 538

2

QH → HL in a primary colorectal cancer.

VAR_013745

Natural variant

542

1

Q → H in a primary colorectal cancer.

VAR_013746

Natural variant

545

1

A → G in a primary colorectal cancer.

VAR_013747

Natural variant

545

1

A → V in a primary colorectal cancer.

VAR_013748

Experimental info

Mutagenesis

215

1

Y → Q: Reduces transcription activation

Mutagenesis

226

1

R → A: Reduces transcription activation

Mutagenesis

246

1

R → A: Reduces transcription activation

Mutagenesis

250

1

K → A: Abolishes DNA-binding

Mutagenesis

252

1

W → Q: Abolishes DNA-binding

Mutagenesis

253

1

K → A: Abolishes DNA-binding

Mutagenesis

302

1

R → T: Abolishes nuclear localization

Mutagenesis

304

1

K → T: Abolishes nuclear localization

Sequence conflict

72

1

E → D in AAB62704. Ref.3

Sequence conflict

247

1

A → T in AAB62704. Ref.3

Sequence conflict

294

1

V → L in AAB62704. Ref.3

Sequence conflict

380

1

S → I in AAC25718. Ref.2

Sequence conflict

440

1

A → E in AAC25718. Ref.2

Sequence conflict

457

1

E → K in AAC25718. Ref.2

Sequence conflict

482

1

T → S in AAC25718. Ref.2

Sequence conflict

487

1

A → G in AAC25718. Ref.2

Sequence conflict

496 – 497

2

DA → VS in AAC25718. Ref.2

Sequence conflict

502

1

Q → H in AAC25718. Ref.2

Sequence conflict

522

1

N → K in AAB62704. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

565

Helix Strand Turn

Details...

Beta strand

505 – 510

6

Beta strand

512 – 514

3

Turn

516 – 518

3

Beta strand

520 – 525

6

Helix

526 – 532

7

Turn

533 – 535

3

Helix

536 – 538

3

Turn

539 – 541

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 3BDFEDBF6AD4BDDE	FASTA	565	59,327
	10 20 30 40 50 60 MEDSDSAAKQ LGLAEAAAVA AAAAVAAAAA AAAGGEAEEP VLSRDEDSEE DADSEAERET 70 80 90 100 110 120 PRVTAVAVMA AEPGHMDMGA EALPGPDEAA AAAAFAEVTT VTVANVGAAA DNVFTTSVAN 130 140 150 160 170 180 AASISGHVLS GRTALQIGDS LNTEKATLIV VHTDGSIVET TGLKGPAAPL TPGPQSPPTP 190 200 210 220 230 240 LAPGQEKGGT KYNWDPSVYD SELPVRCRNI SGTLYKNRLG SGGRGRCIKQ GENWYSPTEF 250 260 270 280 290 300 EAMAGRASSK DWKRSIRYAG RPLQCLIQDG ILNPHAASCT CAACCDDMTL SGPVRLFVPY 310 320 330 340 350 360 KRRKKENELP TTPVKKDSPK NITLLPATAA TTFTVTPSGQ ITTSGALTFD RASTVEATAV 370 380 390 400 410 420 ISESPAQGDV FAGATVQEAS VQPPCRASHP EPHYPGYQDS CQIAPFPEAA LPTSHPKIVL 430 440 450 460 470 480 TSLPALAVPP PTPTKAAPPA LVNGLELSEP RSWLYLEEMV NSLLNTAQQL KTLFEQAKHA 490 500 510 520 530 540 STYREAATNQ AKIHADAERK EQSCVNCGRE AMSECTGCHK VNYCSTFCQR KDWKDHQHIC 550 560 GQSAAVTVQA DEVHVAESVM EKVTV
	Isoform 3 (NUDR8) [UniParc]. Checksum: 9ABE2A02D3AA8DA1		551	58,262
	10 20 30 40 50 60 MEDSDSAAKQ LGLADAAAAG GEAEEPVLSR DEDSEEDADS EAERETPRVT AVAVMAAEPG 70 80 90 100 110 120 HMDMGAEALP GPDEAAAAAA FAEVTTVTVA NVGAAADNVF TTSVANAASI SGHVLSGRTA 130 140 150 160 170 180 LQIGDSLNTE KATLIVVHTD GSIVETTGLK GPAAPLTPGP QSPPTPLAPG QEKGGTKYNW 190 200 210 220 230 240 DPSVYDSELP VRCRNISGTL YKNRLGSGGR GRCIKQGENW YSPTEFEAMA GRASSKDWKR 250 260 270 280 290 300 SIRYAGRPLQ CLIQDGILNP HAASCTCAAC CDDMTLSGPV RLFVPYKRRK KENELPTTPV 310 320 330 340 350 360 KKDSPKNITL LPATAATTFT VTPSGQITTS GALTFDRAST VEATAVISES PAQGDVFAGA 370 380 390 400 410 420 TVQEASVQPP CRASHPEPHY PGYQDSCQIA PFPEAALPTS HPKIVLTSLP ALAVPPPTPT 430 440 450 460 470 480 KAAPPALVNG LELSEPRSWL YLEEMVNSLL NTAQQLKTLF EQAKHASTYR EAATNQAKIH 490 500 510 520 530 540 ADAERKEQSC VNCGREAMSE CTGCHKVNYC STFCQRKDWK DHQHICGQSA AVTVQADEVH 550 VAESVMEKVT V
	Isoform 4 (Suppressin) [UniParc]. Checksum: 4EC4279532D8A4DE		497	52,717
	10 20 30 40 50 60 MAAEPGHMDM GAEALPGPDE AAAAAAFAEV TTVTVANVGA AADNVFTTSV ANAASISGHV 70 80 90 100 110 120 LSGRTALQIG DSLNTEKATL IVVHTDGSIV ETTGLKGPAA PLTPGPQSPP TPLAPGQEKG 130 140 150 160 170 180 GTKYNWDPSV YDSELPVRCR NISGTLYKNR LGSGGRGRCI KQGENWYSPT EFEAMAGRAS 190 200 210 220 230 240 SKDWKRSIRY AGRPLQCLIQ DGILNPHAAS CTCAACCDDM TLSGPVRLFV PYKRRKKENE 250 260 270 280 290 300 LPTTPVKKDS PKNITLLPAT AATTFTVTPS GQITTSGALT FDRASTVEAT AVISESPAQG 310 320 330 340 350 360 DVFAGATVQE ASVQPPCRAS HPEPHYPGYQ DSCQIAPFPE AALPTSHPKI VLTSLPALAV 370 380 390 400 410 420 PPPTPTKAAP PALVNGLELS EPRSWLYLEE MVNSLLNTAQ QLKTLFEQAK HASTYREAAT 430 440 450 460 470 480 NQAKIHADAE RKEQSCVNCG REAMSECTGC HKVNYCSTFC QRKDWKDHQH ICGQSAAVTV 490 QADEVHVAES VMEKVTV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of a nuclear deformed epidermal autoregulatory factor-1 (DEAF-1)-related (NUDR) transcriptional regulator protein." Huggenvik J.I., Michelson R.J., Collard M.W., Ziemba A.J., Gurley P., Mowen K.A. Mol. Endocrinol. 12:1619-1639(1998) [PubMed: 9773984] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), MUTAGENESIS OF ARG-302 AND LYS-304. Tissue: Choriocarcinoma.
[2]	"Altered subcellular localization of suppressin, a novel inhibitor of cell-cycle entry, is an independent prognostic factor in colorectal adenocarcinomas." Manne U., Gary B.D., Oelschlager D.K., Weiss H.L., Frost A.R., Grizzle W.E. Clin. Cancer Res. 7:3495-3503(2001) [PubMed: 11705868] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), VARIANTS CRC VAL-186; ASN-191; ILE-191; 199-CYS-ASP-ASN-ASP-202; ASP-202; LYS-218; 350-GLY-GLN-THR-352; HIS-356; ASN-364; HIS-367; LEU-370; PHE-397; ALA-442; LYS-449; 451-GLY-ILE-452; HIS-468; LEU-479; LYS-498; ASN-526; LEU-530; 537-HIS-LEU-538; HIS-542; GLY-545 AND VAL-545. Tissue: Colon and Colon adenocarcinoma.
[3]	"Cloning and sequence analysis of the cDNA for human suppressin (spn)." LeBoeuf R.D., Blalock J.E., Tauber J.D. Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4). Tissue: Mammary gland.
[4]	"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] (ISOFORM 1). Tissue: Ovary.
[5]	"Nuclear DEAF-1-related (NUDR) protein contains a novel DNA binding domain and represses transcription of the heterogeneous nuclear ribonucleoprotein A2/B1 promoter." Michelson R.J., Collard M.W., Ziemba A.J., Persinger J., Bartholomew B., Huggenvik J.I. J. Biol. Chem. 274:30510-30519(1999) [PubMed: 10521432] [Abstract] Cited for: FUNCTION.
[6]	"The SAND domain structure defines a novel DNA-binding fold in transcriptional regulation." Bottomley M.J., Collard M.W., Huggenvik J.I., Liu Z., Gibson T.J., Sattler M. Nat. Struct. Biol. 8:626-633(2001) [PubMed: 11427895] [Abstract] Cited for: FUNCTION OF SAND DOMAIN, MUTAGENESIS OF TYR-215; ARG-226; ARG-246; LYS-250; TRP-252 AND LYS-253.
[7]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-176, MASS SPECTROMETRY. Tissue: Epithelium.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF049459 mRNA. Translation: AAC79676.1. AF049460 mRNA. Translation: AAC79677.1. AF068893 mRNA. Translation: AAC25715.1. AF068894 mRNA. Translation: AAC25716.1. AF068895 mRNA. Translation: AAC25717.1. AF068896 mRNA. Translation: AAC25718.1. Frameshift. AF068897 mRNA. Translation: AAC25719.1. Frameshift. AF007165 mRNA. Translation: AAB62704.1. BC053322 mRNA. Translation: AAH53322.1.
RefSeq	NP_066288.2.
UniGene	Hs.243994 Hs.448664
3D structure databases