Q9H6I2 (SOX17_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transcription factor SOX-17

Gene names

Name:

SOX17

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

General annotation (Comments)

Function	Acts as transcription regulator that binds target promoter DNA and bends the DNA. Binds to the sequences 5'-AACAAT-'3 or 5'-AACAAAG-3'. Modulates transcriptional regulation via WNT3A. Inhibits Wnt signaling. Promotes degradation of activated CTNNB1. Plays a key role in the regulation of embryonic development. Required for normal looping of the embryonic heart tube. Required for normal development of the definitive gut endoderm. Probable transcriptional activator in the premeiotic germ cells By similarity.
Subunit structure	Interacts with CTNNB1, LEF1 and TCF4 By similarity.
Subcellular location	Nucleus By similarity.
Tissue specificity	Expressed in adult heart, lung, spleen, testis, ovary, placenta, fetal lung, and kidney. In normal gastrointestinal tract, it is preferentially expressed in esophagus, stomach and small intestine than in colon and rectum. Ref.1
Involvement in disease	Vesicoureteral reflux 3 (VUR3) [MIM:613674]: A disease belonging to the group of congenital anomalies of the kidney and urinary tract. It is characterized by the reflux of urine from the bladder into the ureters and sometimes into the kidneys, and is a risk factor for urinary tract infections. Primary disease results from a developmental defect of the ureterovesical junction. In combination with intrarenal reflux, the resulting inflammatory reaction may result in renal injury or scarring, also called reflux nephropathy. Extensive renal scarring impairs renal function and may predispose patients to hypertension, proteinuria, renal insufficiency and end-stage renal disease. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4
Sequence similarities	Contains 1 HMG box DNA-binding domain. Contains 1 Sox C-terminal domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation Wnt signaling pathway
Cellular component	Nucleus
Disease	Disease mutation
Ligand	DNA-binding
Molecular function	Activator
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from sequence or structural similarity. Source: BHF-UCL canonical Wnt receptor signaling pathway Inferred from electronic annotation. Source: Compara cardiac cell fate determination Inferred from mutant phenotype PubMed 19736317. Source: BHF-UCL cardiogenic plate morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL cell migration involved in gastrulation Inferred from electronic annotation. Source: Compara common bile duct development Inferred from electronic annotation. Source: Compara embryonic foregut morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL embryonic organ development Inferred from electronic annotation. Source: Compara endocardial cell differentiation Inferred from sequence or structural similarity. Source: BHF-UCL endocardium formation Inferred from sequence or structural similarity. Source: BHF-UCL endodermal cell fate determination Inferred from electronic annotation. Source: Compara endodermal digestive tract morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL gall bladder development Inferred from electronic annotation. Source: Compara heart formation Traceable author statement PubMed 19736317. Source: BHF-UCL heart looping Inferred from sequence or structural similarity. Source: UniProtKB inner cell mass cellular morphogenesis Inferred from electronic annotation. Source: Compara mRNA transcription from RNA polymerase II promoter Inferred from direct assay PubMed 22292085. Source: BHF-UCL negative regulation of Wnt receptor signaling pathway involved in heart development Inferred from electronic annotation. Source: Compara negative regulation of canonical Wnt receptor signaling pathway Inferred from mutant phenotype PubMed 18413743Ref.4. Source: BHF-UCL negative regulation of cell growth Inferred from mutant phenotype PubMed 18413743. Source: BHF-UCL negative regulation of mesodermal cell fate specification Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara outflow tract morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of protein catabolic process Inferred from electronic annotation. Source: Compara positive regulation of skeletal muscle tissue development Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 22292085. Source: BHF-UCL protein destabilization Inferred from mutant phenotype PubMed 17875931. Source: BHF-UCL protein stabilization Inferred from mutant phenotype PubMed 17875931. Source: BHF-UCL regulation of cardiac cell fate specification Inferred from electronic annotation. Source: Compara regulation of embryonic development Inferred from sequence or structural similarity. Source: UniProtKB regulation of stem cell division Inferred from electronic annotation. Source: Compara regulation of stem cell proliferation Inferred from electronic annotation. Source: Compara regulation of transcription from RNA polymerase II promoter involved in definitive endodermal cell fate specification Inferred from sequence or structural similarity. Source: BHF-UCL renal system development Inferred from mutant phenotype Ref.4. Source: BHF-UCL rostrocaudal neural tube patterning Inferred from electronic annotation. Source: Compara signal transduction involved in regulation of gene expression Inferred from electronic annotation. Source: Compara spermatogenesis Inferred from electronic annotation. Source: Compara stem cell fate specification Inferred from electronic annotation. Source: Compara vasculogenesis Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular_component	transcription factor complex Inferred from direct assay PubMed 19736317. Source: BHF-UCL
Molecular_function	RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Inferred from sequence or structural similarity. Source: BHF-UCL sequence-specific DNA binding Inferred from electronic annotation. Source: Compara transcription coactivator activity Inferred from electronic annotation. Source: Compara transcription regulatory region DNA binding Inferred from sequence or structural similarity. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 414

414

Transcription factor SOX-17

PRO_0000048765

Regions

Domain

280 – 413

134

Sox C-terminal

DNA binding

68 – 136

69

HMG box

Compositional bias

312 – 351

40

Gln/Pro-rich

Natural variations

Natural variant

17

1

Q → QTQ in VUR3.

VAR_065168

Natural variant

178

1

G → C in VUR3. Ref.4

VAR_065169

Natural variant

259

1

Y → N in VUR3; increased levels of the mutant protein that is associated with increased suppression of CTNNB1 signaling of the Wnt pathway compared to wild-type. Ref.4

VAR_065170

Secondary structure

1

.

.

.

.

.

.

.

414

Helix Strand Turn

Details...

Helix

74 – 87

14

Helix

95 – 108

14

Helix

111 – 129

19

Sequences

	Sequence		Length	Mass (Da)
	Q9H6I2 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: C78D1F24BA00ECD1	FASTA	414	44,117
	10 20 30 40 50 60 MSSPDAGYAS DDQSQTQSAL PAVMAGLGPC PWAESLSPIG DMKVKGEAPA NSGAPAGAAG 70 80 90 100 110 120 RAKGESRIRR PMNAFMVWAK DERKRLAQQN PDLHNAELSK MLGKSWKALT LAEKRPFVEE 130 140 150 160 170 180 AERLRVQHMQ DHPNYKYRPR RRKQVKRLKR VEGGFLHGLA EPQAAALGPE GGRVAMDGLG 190 200 210 220 230 240 LQFPEQGFPA GPPLLPPHMG GHYRDCQSLG APPLDGYPLP TPDTSPLDGV DPDPAFFAAP 250 260 270 280 290 300 MPGDCPAAGT YSYAQVSDYA GPPEPPAGPM HPRLGPEPAG PSIPGLLAPP SALHVYYGAM 310 320 330 340 350 360 GSPGAGGGRG FQMQPQHQHQ HQHQHHPPGP GQPSPPPEAL PCRDGTDPSQ PAELLGEVDR 370 380 390 400 410 TEFEQYLHFV CKPEMGLPYQ GHDSGVNLPD SHGAISSVVS DASSAVYYCN YPDV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and characterization of human SOX17." Katoh M. Int. J. Mol. Med. 9:153-157(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"Solution structure of the HMG box of human transcription factor SOX-17." RIKEN structural genomics initiative (RSGI) Submitted (APR-2008) to the PDB data bank Cited for: STRUCTURE BY NMR OF 62-139.
[4]	"Mutations in SOX17 are associated with congenital anomalies of the kidney and the urinary tract." Gimelli S., Caridi G., Beri S., McCracken K., Bocciardi R., Zordan P., Dagnino M., Fiorio P., Murer L., Benetti E., Zuffardi O., Giorda R., Wells J.M., Gimelli G., Ghiggeri G.M. Hum. Mutat. 31:1352-1359(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS VUR3 17-GLN--GLN-19 INS; CYS-178 AND ASN-259.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB073988 mRNA. Translation: BAB83867.1.
AK025905 mRNA. Translation: BAB15277.1.

IPI

IPI00007874.

RefSeq

NP_071899.1. NM_022454.3.

UniGene

Hs.98367.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2YUL	NMR	-	A	68-136	[»]
4A3N	X-ray	2.40	A	68-136	[»]

ProteinModelPortal

Q9H6I2.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000297316.

PTM databases

PhosphoSite

Q9H6I2.

Polymorphism databases

DMDM

23822216.

Proteomic databases

PaxDb

Q9H6I2.

PRIDE

Q9H6I2.

Protocols and materials databases

DNASU

64321.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000297316; ENSP00000297316; ENSG00000164736.

GeneID

64321.

KEGG

hsa:64321.

UCSC

uc003xsb.4. human.

Organism-specific databases

CTD

64321.

GeneCards

GC08P055370.

H-InvDB

HIX0034521.

HGNC

HGNC:18122. SOX17.

HPA

CAB025594.

MIM

610928. gene.
613674. phenotype.

neXtProt

NX_Q9H6I2.

Orphanet

289365. Familial vesicoureteral reflux.

PharmGKB

PA38296.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG242943.

HOGENOM

HOG000069999.

HOVERGEN

HBG000517.

InParanoid

Q9H6I2.

KO

K04495.

OMA

ALPCRDG.

OrthoDB

EOG4KD6M5.

PhylomeDB

Q9H6I2.

Gene expression databases

ArrayExpress

Q9H6I2.

Bgee

Q9H6I2.

CleanEx

HS_SOX17.

Genevestigator

Q9H6I2.

GermOnline

ENSG00000164736. Homo sapiens.

Family and domain databases

Gene3D

1.10.30.10. 1 hit.

InterPro

IPR009071. HMG_box_dom.
IPR021934. Sox_C_TAD.
[Graphical view]

Pfam

PF00505. HMG_box. 1 hit.
PF12067. Sox_C_TAD. 2 hits.
[Graphical view]

SMART

SM00398. HMG. 1 hit.
[Graphical view]

SUPFAM

SSF47095. HMG-box. 1 hit.

PROSITE

PS50118. HMG_BOX_2. 1 hit.
PS51516. SOX_C. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9H6I2.

GenomeRNAi

64321.

NextBio

66237.

SOURCE

Search...

Entry information

Entry name

SOX17_HUMAN

Accession

Primary (citable) accession number: Q9H6I2

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 10, 2002
Last sequence update:	March 1, 2001
Last modified:	May 1, 2013
This is version 102 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.