P12755 (SKI_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ski oncogene

Alternative name(s):
Proto-oncogene c-Ski

Gene names

Name:

SKI

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	728 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May play a role in terminal differentiation of skeletal muscle cells but not in the determination of cells to the myogenic lineage. Functions as a repressor of TGF-beta signaling. Ref.4
Subunit structure	Interacts with SMAD2, SMAD3 and SMAD4. Interacts with HIPK2. Part of a complex with HIPK2 and SMAD1/2/3. Interacts with PRDM16 and SMAD3; the interaction with PRDM16 promotes the recruitment SMAD3-HDAC1 complex on the promoter of TGF-beta target genes. Ref.3 Ref.4
Subcellular location	Nucleus.
Sequence similarities	Belongs to the SKI family.

Ontologies

Keywords
Cellular component	Nucleus
Disease	Proto-oncogene
Domain	Coiled coil Repeat
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	BMP signaling pathway Traceable author statement. Source: Reactome SMAD protein signal transduction Inferred from direct assay Ref.3. Source: UniProtKB anterior/posterior axis specification Inferred from sequence or structural similarity. Source: BHF-UCL bone morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL cell motility Non-traceable author statement PubMed 14583455. Source: BHF-UCL cell proliferation Non-traceable author statement PubMed 14583455. Source: BHF-UCL embryonic limb morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL face morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL lens morphogenesis in camera-type eye Inferred from sequence or structural similarity. Source: BHF-UCL myelination in peripheral nervous system Inferred from sequence or structural similarity. Source: BHF-UCL myotube differentiation Inferred from direct assay PubMed 19008232. Source: UniProtKB negative regulation of BMP signaling pathway Inferred from direct assay PubMed 14699069. Source: UniProtKB negative regulation of Schwann cell proliferation Inferred from genetic interaction PubMed 15312649. Source: MGI negative regulation of activin receptor signaling pathway Inferred from direct assay PubMed 14699069. Source: UniProtKB negative regulation of fibroblast proliferation Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of osteoblast differentiation Inferred from direct assay PubMed 14699069. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 17469184. Source: UniProtKB negative regulation of transforming growth factor beta receptor signaling pathway Inferred from direct assay PubMed 17469184. Source: UniProtKB neural tube closure Inferred from sequence or structural similarity. Source: BHF-UCL nose morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL olfactory bulb development Inferred from sequence or structural similarity. Source: BHF-UCL palate development Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of DNA binding Inferred from direct assay PubMed 15107821. Source: UniProtKB positive regulation of Wnt receptor signaling pathway Non-traceable author statement PubMed 14583455. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: BHF-UCL protein homotrimerization Inferred from direct assay PubMed 8514802. Source: UniProtKB regulation of apoptotic process Inferred from sequence or structural similarity. Source: BHF-UCL retina development in camera-type eye Inferred from sequence or structural similarity. Source: BHF-UCL skeletal muscle fiber development Inferred from sequence or structural similarity. Source: BHF-UCL somatic stem cell maintenance Inferred from sequence or structural similarity. Source: BHF-UCL transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome transforming growth factor beta receptor signaling pathway Non-traceable author statement PubMed 14583455. Source: BHF-UCL
Cellular_component	PML body Inferred from direct assay PubMed 11430826. Source: UniProtKB cytoplasm Inferred from sequence or structural similarity. Source: BHF-UCL transcription factor complex Inferred from sequence or structural similarity. Source: BHF-UCL transcriptional repressor complex Inferred from sequence or structural similarity. Source: BHF-UCL
Molecular_function	chromatin binding Inferred from electronic annotation. Source: Compara histone deacetylase inhibitor activity Inferred from sequence or structural similarity. Source: BHF-UCL nucleotide binding Inferred from electronic annotation. Source: InterPro transcription corepressor activity Inferred from direct assay PubMed 17469184. Source: UniProtKB zinc ion binding Inferred from direct assay PubMed 12419246. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Fam89b	Q9QUI1	6	EBI-347281,EBI-6503100	From a different organism.
NCOR1	O75376	2	EBI-347281,EBI-347233
Ncor1	Q60974	5	EBI-347281,EBI-349004	From a different organism.
SIN3A	Q96ST3	3	EBI-347281,EBI-347218
SMAD4	Q13485	3	EBI-347281,EBI-347263

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 728

728

Ski oncogene

PRO_0000129382

Regions

Coiled coil

536 – 710

175

Potential

Amino acid modifications

Modified residue

480

1

Phosphoserine Ref.5

Secondary structure

1

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728

Helix Strand Turn

Details...

Beta strand

101 – 105

5

Beta strand

108 – 115

8

Beta strand

118 – 122

5

Helix

123 – 127

5

Turn

128 – 133

6

Helix

136 – 145

10

Helix

155 – 163

9

Beta strand

175 – 178

4

Helix

179 – 190

12

Beta strand

219 – 222

4

Beta strand

228 – 232

5

Helix

234 – 236

3

Beta strand

245 – 247

3

Turn

248 – 250

3

Helix

256 – 259

4

Beta strand

269 – 275

7

Helix

278 – 280

3

Helix

281 – 284

4

Helix

296 – 310

15

Sequences

	Sequence		Length	Mass (Da)
	P12755 [UniParc]. Last modified October 1, 1989. Version 1. Checksum: 9B78C4840A28C2DA	FASTA	728	80,005
	10 20 30 40 50 60 MEAAAGGRGC FQPHPGLQKT LEQFHLSSMS SLGGPAAFSA RWAQEAYKKE SAKEAGAAAV 70 80 90 100 110 120 PAPVPAATEP PPVLHLPAIQ PPPPVLPGPF FMPSDRSTER CETVLEGETI SCFVVGGEKR 130 140 150 160 170 180 LCLPQILNSV LRDFSLQQIN AVCDELHIYC SRCTADQLEI LKVMGILPFS APSCGLITKT 190 200 210 220 230 240 DAERLCNALL YGGAYPPPCK KELAASLALG LELSERSVRV YHECFGKCKG LLVPELYSSP 250 260 270 280 290 300 SAACIQCLDC RLMYPPHKFV VHSHKALENR TCHWGFDSAN WRAYILLSQD YTGKEEQARL 310 320 330 340 350 360 GRCLDDVKEK FDYGNKYKRR VPRVSSEPPA SIRPKTDDTS SQSPAPSEKD KPSSWLRTLA 370 380 390 400 410 420 GSSNKSLGCV HPRQRLSAFR PWSPAVSASE KELSPHLPAL IRDSFYSYKS FETAVAPNVA 430 440 450 460 470 480 LAPPAQQKVV SSPPCAAAVS RAPEPLATCT QPRKRKLTVD TPGAPETLAP VAAPEEDKDS 490 500 510 520 530 540 EAEVEVESRE EFTSSLSSLS SPSFTSSSSA KDLGSPGARA LPSAVPDAAA PADAPSGLEA 550 560 570 580 590 600 ELEHLRQALE GGLDTKEAKE KFLHEVVKMR VKQEEKLSAA LQAKRSLHQE LEFLRVAKKE 610 620 630 640 650 660 KLREATEAKR NLRKEIERLR AENEKKMKEA NESRLRLKRE LEQARQARVC DKGCEAGRLR 670 680 690 700 710 720 AKYSAQIEDL QVKLQHAEAD REQLRADLLR EREAREHLEK VVKELQEQLW PRARPEAAGS EGAAELEP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation of human cDNA clones of ski and the ski-related gene, sno." Nomura N., Sasamoto S., Ishii S., Date T., Matsui M., Ishizaki R. Nucleic Acids Res. 17:5489-5500(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"Requirement of the co-repressor homeodomain-interacting protein kinase 2 for ski-mediated inhibition of bone morphogenetic protein-induced transcriptional activation." Harada J., Kokura K., Kanei-Ishii C., Nomura T., Khan M.M., Kim Y., Ishii S. J. Biol. Chem. 278:38998-39005(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HIPK2; SMAD2; SMAD3 AND SMAD4.
[4]	"SKI and MEL1 cooperate to inhibit transforming growth factor-beta signal in gastric cancer cells." Takahata M., Inoue Y., Tsuda H., Imoto I., Koinuma D., Hayashi M., Ichikura T., Yamori T., Nagasaki K., Yoshida M., Matsuoka M., Morishita K., Yuki K., Hanyu A., Miyazawa K., Inazawa J., Miyazono K., Imamura T. J. Biol. Chem. 284:3334-3344(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PRDM16 AND SMAD3.
[5]	"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-480, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X15218 mRNA. Translation: CAA33288.1.
AL590822 Genomic DNA. No translation available.

IPI

IPI00220921.

PIR

TVHUSK. S06053.

RefSeq

NP_003027.1. NM_003036.3.

UniGene

Hs.656507.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1MR1	X-ray	2.85	C/D	219-313	[»]
1SBX	X-ray	1.65	A	91-192	[»]

ProteinModelPortal

P12755.

ModBase

Search...

Protein-protein interaction databases

IntAct

P12755. 9 interactions.

MINT

MINT-269973.

STRING

9606.ENSP00000367797.

PTM databases

PhosphoSite

P12755.

Polymorphism databases

DMDM

134517.

Proteomic databases

PaxDb

P12755.

PRIDE

P12755.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000378536; ENSP00000367797; ENSG00000157933.

GeneID

6497.

KEGG

hsa:6497.

UCSC

uc001aja.4. human.

Organism-specific databases

CTD

6497.

GeneCards

GC01P002173.

HGNC

HGNC:10896. SKI.

HPA

CAB010449.

MIM

164780. gene.

neXtProt

NX_P12755.

PharmGKB

PA35796.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG82850.

HOGENOM

HOG000039989.

HOVERGEN

HBG006599.

InParanoid

P12755.

OMA

TERCETI.

OrthoDB

EOG44QT1K.

PhylomeDB

P12755.

Enzyme and pathway databases

Pathway_Interaction_DB

bmppathway. BMP receptor signaling.
smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling.

Reactome

REACT_111102. Signal Transduction.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

P12755.

Bgee

P12755.

CleanEx

HS_SKI.

Genevestigator

P12755.

GermOnline

ENSG00000157933. Homo sapiens.

Family and domain databases

Gene3D

3.10.260.20. 1 hit.
3.10.390.10. 1 hit.

InterPro

IPR014890. c-SKI_SMAD4-bd_dom.
IPR009061. DNA-bd_dom_put.
IPR010919. SAND_dom-like.
IPR003380. Transform_Ski.
IPR023216. Tscrpt_reg_SKI_SnoN.
[Graphical view]

PANTHER

PTHR10005. PTHR10005. 1 hit.

Pfam

PF08782. c-SKI_SMAD_bind. 1 hit.
PF02437. Ski_Sno. 1 hit.
[Graphical view]

SMART

SM01046. c-SKI_SMAD_bind. 1 hit.
[Graphical view]

SUPFAM

SSF46955. Putativ_DNA_bind. 1 hit.
SSF63763. SAND_like. 1 hit.

ProtoNet

Search...

Other

ChiTaRS

SKI. human.

EvolutionaryTrace

P12755.

GenomeRNAi

6497.

NextBio

25255.

SOURCE

Search...

Entry information

Entry name

SKI_HUMAN

Accession

Primary (citable) accession number: P12755
Secondary accession number(s): Q5SYT7

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	October 1, 1989
Last modified:	May 1, 2013
This is version 129 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.