Reviewed, UniProtKB/Swiss-Prot P48436 (SOX9_HUMAN)

Names and origin

Protein names

Recommended name:
    Transcription factor SOX-9

Gene names

Name:

SOX9

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

General annotation (Comments)

Function	Plays an important role in the normal skeletal development. May regulate the expression of other genes involved in chondrogenesis by acting as a transcription factor for these genes.
Subcellular location	Nucleus Potential.
Involvement in disease	Defects in SOX9 are the cause of campomelic dysplasia (CMD1) [MIM:114290]. CMD1 is a rare, often lethal, dominantly inherited, congenital osteochondrodysplasia, associated with male-to-female autosomal sex reversal in two-thirds of the affected karyotypic males. A disease of the newborn characterized by congenital bowing and angulation of long bones, unusually small scapulae, deformed pelvis and spine and a missing pair of ribs. Craniofacial defects such as cleft palate, micrognatia, flat face and hypertelorism are common. Various defects of the ear are often evident, affecting the cochlea, malleus incus, stapes and tympanum. Most patients die soon after birth due to respiratory distress which has been attributed to hypoplasia of the tracheobronchial cartilage and small thoracic cage. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9
Sequence similarities	Contains 1 HMG box DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Disease	Disease mutation
Ligand	DNA-binding
Technical term	3D-structure
Gene Ontology (GO)
Biological process	transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from direct assay. Source: HPA
Molecular function	specific RNA polymerase II transcription factor activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 509

509

Transcription factor SOX-9

PRO_0000048739

Regions

DNA binding

105 – 173

69

HMG box

Compositional bias

339 – 378

40

Gln/Pro-rich

Compositional bias

342 – 346

5

Poly-Pro

Natural variations

Natural variant

108

1

P → L in CMD1. Ref.6

VAR_003735

Natural variant

112

1

F → L in CMD1; loss of DNA binding. Ref.5 Ref.7 Ref.8

VAR_003736

Natural variant

112

1

F → S in CMD1. Ref.5 Ref.7 Ref.8

VAR_003737

Natural variant

119

1

A → V in CMD1; almost no loss of DNA binding. Ref.5 Ref.8

VAR_003738

Natural variant

143

1

W → R in CMD1. Ref.6

VAR_003739

Natural variant

152

1

R → P in CMD1. Ref.6

VAR_003740

Natural variant

154

1

F → L in CMD1; 19-fold reduction in DNA binding. Ref.9

VAR_008529

Natural variant

158

1

A → T in CMD1; 6-fold reduction in DNA binding. Ref.9

VAR_008530

Natural variant

165

1

H → Y in CMD1; loss of DNA binding. Ref.8

VAR_008531

Natural variant

170

1

P → R in CMD1. Ref.6 Ref.8

VAR_003741

Natural variant

354 – 356

3

Missing in CMD1.

VAR_003742

Secondary structure

1

.

.

.

.

.

.

.

.

509

Helix Strand Turn

Details...

Helix

111 – 126

16

Beta strand

131 – 133

3

Helix

134 – 144

11

Helix

148 – 169

22

Sequences

	Sequence		Length	Mass (Da)
	P48436-1 [UniParc]. Last modified February 1, 1996. Version 1. Checksum: 9289CFBB8D6631A2	FASTA	509	56,137
	10 20 30 40 50 60 MNLLDPFMKM TDEQEKGLSG APSPTMSEDS AGSPCPSGSG SDTENTRPQE NTFPKGEPDL 70 80 90 100 110 120 KKESEEDKFP VCIREAVSQV LKGYDWTLVP MPVRVNGSSK NKPHVKRPMN AFMVWAQAAR 130 140 150 160 170 180 RKLADQYPHL HNAELSKTLG KLWRLLNESE KRPFVEEAER LRVQHKKDHP DYKYQPRRRK 190 200 210 220 230 240 SVKNGQAEAE EATEQTHISP NAIFKALQAD SPHSSSGMSE VHSPGEHSGQ SQGPPTPPTT 250 260 270 280 290 300 PKTDVQPGKA DLKREGRPLP EGGRQPPIDF RDVDIGELSS DVISNIETFD VNEFDQYLPP 310 320 330 340 350 360 NGHPGVPATH GQVTYTGSYG ISSTAATPAS AGHVWMSKQQ APPPPPQQPP QAPPAPQAPP 370 380 390 400 410 420 QPQAAPPQQP AAPPQQPQAH TLTTLSSEPG QSQRTHIKTE QLSPSHYSEQ QQHSPQQIAY 430 440 450 460 470 480 SPFNLPHYSP SYPPITRSQY DYTDHQNSSS YYSHAAGQGT GLYSTFTYMN PAQRPMYTPI 490 500 ADTSGVPSIP QTHSPQHWEQ PVYTQLTRP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene." Foster J.W., Dominguez-Steglich M.A., Guioli S., Kowk G., Weller P.A., Stevanovic M., Weissenbach J., Mansour S., Young I.D., Goodfellow P.N., Schafer A.J. Nature 372:525-530(1994) [PubMed: 7990924] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Testis.
[2]	"Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9." Wagner T., Wirth J., Meyer J., Zabel B., Held M., Zimmer J., Pasantes J., Bricarelli F.D., Keutel J., Hustert E., Wolf U., Tommerup N., Schempp W., Scherer G. Cell 79:1111-1120(1994) [PubMed: 8001137] [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: Eye and PNS.
[4]	"Mutations in SRY and SOX9: testis-determining genes." Cameron F.J., Sinclair A.H. Hum. Mutat. 9:388-395(1997) [PubMed: 9143916] [Abstract] Cited for: REVIEW ON VARIANTS.
[5]	"Mutations in SOX9, the gene responsible for Campomelic dysplasia and autosomal sex reversal." Kwok C., Weller P.A., Guioli S., Foster J.W., Mansour S., Zuffardi O., Punnett H.H., Dominguez-Steglich M.A., Brook J.D., Young I.D., Goodfellow P.N., Schafer A.J. Am. J. Hum. Genet. 57:1028-1036(1995) [PubMed: 7485151] [Abstract] Cited for: VARIANTS CMD1 LEU-112 AND VAL-119.
[6]	"Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations." Meyer J., Suedbeck P., Held M., Wagner T., Schmitz M.L., Bricarelli F.D., Eggermont E., Friedrich U., Haas O.A., Kobelt A., Leroy J.G., van Maldergem L., Michel E., Mitulla B., Pfeiffer R.A., Schinzel A., Schmidt H., Scherer G. Hum. Mol. Genet. 6:91-98(1997) [PubMed: 9002675] [Abstract] Cited for: VARIANTS CMD1 LEU-108; ARG-143; PRO-152 AND ARG-170.
[7]	"Novel missense mutation in the HMG box of SOX9 gene in a Japanese XY male resulted in campomelic dysplasia and severe defect in masculinization." Goji K., Nishijima E., Tsugawa C., Nishio H., Pokharel R.K., Matsuo M. Hum. Mutat. Suppl. 1:S114-S116(1998) [PubMed: 9452059] [Abstract] Cited for: VARIANT CMD1 SER-112.
[8]	"Functional and structural studies of wild type SOX9 and mutations causing campomelic dysplasia." McDowall S., Argentaro A., Ranganathan S., Weller P., Mertin S., Mansour S., Tolmie J., Harley V. J. Biol. Chem. 274:24023-24030(1999) [PubMed: 10446171] [Abstract] Cited for: VARIANTS CMD1 LEU-112; VAL-119; TYR-165 AND ARG-170, 3D-STRUCTURE MODELING.
[9]	"Functional analysis of two novel SOX9 mutations causing campomelic dysplasia." Preiss A., Argentaro A., Barroso I., Schafer A.J., Clayton A.H., Ogata T., Harley V.R. Unpublished observations (JAN-2000) Cited for: VARIANTS CMD1 LEU-154 AND THR-158.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

Z46629 mRNA. Translation: CAA86598.1.
S74506, S74504, S74505 Genomic DNA. Translation: AAB32870.1.
BC007951 mRNA. Translation: AAH07951.1.
BC056420 mRNA. Translation: AAH56420.1.

IPI

IPI00009713.

PIR

A55204.

RefSeq

NP_000337.1.

UniGene

Hs.707993

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1S9M	model	-	A	101-177	[»]
1SX9	model	-	A	101-177	[»]

ModBase

Search...

PTM databases

PhosphoSite

P48436.

Proteomic databases

PRIDE

P48436.

Genome annotation databases

Ensembl

ENSG00000125398. Homo sapiens. [Contig view]

GeneID

6662.

KEGG

hsa:6662.

Organism-specific databases

GeneCards

GC17P067628.

H-InvDB

HIX0014127.

HGNC

HGNC:11204. SOX9.

HPA

HPA001758.

MIM

114290. phenotype.
608160. gene.

Orphanet

140. Campomelic dysplasia.

PharmGKB

PA36041.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P48436.

HOVERGEN

P48436.

OMA

P48436. GAGHVWM.

Gene expression databases

ArrayExpress

P48436.

Bgee

P48436.

CleanEx

HS_SOX9.

GermOnline

ENSG00000125398. Homo sapiens.

Family and domain databases

InterPro

IPR000910. HMG_HMG1/HMG2.
[Graphical view]

Gene3D

G3DSA:1.10.30.10. HMG-box. 1 hit.

Pfam

PF00505. HMG_box. 1 hit.
[Graphical view]

SMART

SM00398. HMG. 1 hit.
[Graphical view]

PROSITE

PS50118. HMG_BOX_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

25973.

SOURCE

Search...

Entry information

Entry name

SOX9_HUMAN

Accession

Primary (citable) accession number: P48436

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	June 16, 2009
This is version 96 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)