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Reviewed, UniProtKB/Swiss-Prot O75398 (DEAF1_HUMAN)

Last modified November 25, 2008. Version 84. Feed History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length565 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence 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.

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 565565Deformed epidermal autoregulatory factor 1 homolog
PRO_0000074084

Regions

Domain193 – 27381SAND
Zinc finger504 – 54037MYND-type
Motif301 – 31616Nuclear localization signal Potential
Compositional bias2 – 122121Ala-rich
Compositional bias383 – 43957Pro-rich

Amino acid modifications

Modified residue1761Phosphoserine

Natural variations

Alternative sequence1 – 6868Missing in isoform 4.
VSP_005966
Alternative sequence15 – 2915EAAAV…VAAAA → D in isoform 3.
VSP_005967
Natural variant1861E → V in a primary colorectal cancer.
VAR_013725
Natural variant1911K → I in a primary colorectal cancer.
VAR_013726
Natural variant1911K → N in a primary colorectal cancer.
VAR_013727
Natural variant199 – 2024YDSE → CDND in a primary colorectal cancer.
VAR_013728
Natural variant2021E → D in a primary colorectal cancer.
VAR_013729
Natural variant2181R → K in a primary colorectal cancer.
VAR_013730
Natural variant350 – 3523DRA → GQT in a primary colorectal cancer.
VAR_013731
Natural variant3561E → H in a primary colorectal cancer; requires 2 nucleotide substitutions.
VAR_013732
Natural variant3641S → N in a primary colorectal cancer.
VAR_013733
Natural variant3671Q → H in a primary colorectal cancer.
VAR_013734
Natural variant3701V → L in a primary colorectal cancer.
VAR_013735
Natural variant3971Y → F in a primary colorectal cancer.
VAR_013736
Natural variant4421V → A in a primary colorectal cancer.
VAR_013737
Natural variant4491E → K in a primary colorectal cancer.
VAR_013738
Natural variant451 – 4522RS → GI in a primary colorectal cancer.
VAR_013739
Natural variant4681Q → H in a primary colorectal cancer.
VAR_013740
Natural variant4791H → L in a primary colorectal cancer.
VAR_013741
Natural variant4981E → K in a primary colorectal cancer.
VAR_013742
Natural variant5261T → N in a primary colorectal cancer.
VAR_013743
Natural variant5301R → L in a primary colorectal cancer.
VAR_013744
Natural variant537 – 5382QH → HL in a primary colorectal cancer.
VAR_013745
Natural variant5421Q → H in a primary colorectal cancer.
VAR_013746
Natural variant5451A → G in a primary colorectal cancer.
VAR_013747
Natural variant5451A → V in a primary colorectal cancer.
VAR_013748

Experimental info

Mutagenesis2151Y → Q: Reduces transcription activation
Mutagenesis2261R → A: Reduces transcription activation
Mutagenesis2461R → A: Reduces transcription activation
Mutagenesis2501K → A: Abolishes DNA-binding
Mutagenesis2521W → Q: Abolishes DNA-binding
Mutagenesis2531K → A: Abolishes DNA-binding
Mutagenesis3021R → T: Abolishes nuclear localization
Mutagenesis3041K → T: Abolishes nuclear localization
Sequence conflict721E → D in AAB62704. Ref.3
Sequence conflict2471A → T in AAB62704. Ref.3
Sequence conflict2941V → L in AAB62704. Ref.3
Sequence conflict3801S → I in AAC25718. Ref.2
Sequence conflict4401A → E in AAC25718. Ref.2
Sequence conflict4571E → K in AAC25718. Ref.2
Sequence conflict4821T → S in AAC25718. Ref.2
Sequence conflict4871A → G in AAC25718. Ref.2
Sequence conflict496 – 4972DA → VS in AAC25718. Ref.2
Sequence conflict5021Q → H in AAC25718. Ref.2
Sequence conflict5221N → K in AAB62704. Ref.3

Secondary structure

............. 565
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1998. Version 1.
Checksum: 3BDFEDBF6AD4BDDE

FASTA56559,327
        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 

« Hide

Isoform 3 (NUDR8) [UniParc].

Checksum: 9ABE2A02D3AA8DA1
Show »

55158,262
Isoform 4 (Suppressin) [UniParc].

Checksum: 4EC4279532D8A4DE
Show »

49752,717

References

« Hide '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

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.
RefSeqNP_066288.2.
UniGeneHs.243994
Hs.448664

3D structure databases