P50443 (S26A2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sulfate transporter

Alternative name(s):
Diastrophic dysplasia protein
Solute carrier family 26 member 2

Gene names

Name:	SLC26A2
Synonyms:	DTD, DTDST

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

General annotation (Comments)

Function	Sulfate transporter. May play a role in endochondral bone formation.
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Ubiquitously expressed.
Involvement in disease	Defects in SLC26A2 are the cause of diastrophic dysplasia (DTD) [MIM:222600]. DTD is an autosomal recessive disease characterized by osteochondrodysplasia with clinical features including dwarfism, spinal deformation, and specific joint abnormalities. Defects in SLC26A2 are the cause of achondrogenesis type 1B (ACG1B) [MIM:600972]. ACG1B is a recessively inherited chondrodysplasia characterized by extremely poor skeletal development and perinatal death. Ref.9 Defects in SLC26A2 are the cause of atelosteogenesis type 2 (AO2) [MIM:256050]; also known as neonatal osseous dysplasia 1. AO2 is characterized by severely shortened limbs, small chest, scoliosis, club foot of the equinovarus type (talipes equinovarus), abducted thumbs and great toes, and cleft palate. Patients die of respiratory insufficiency shortly after birth because of the collapse of the airways and pulmonary hypoplasia due to the small rib cage. Ref.10 Defects in SLC26A2 are the cause of multiple epiphyseal dysplasia type 4 (EDM4) [MIM:226900]. EDM is a generalized skeletal dysplasia associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. EDM is broadly categorized into the more severe Fairbank and the milder Ribbing types. EDM4 is a recessively inherited form, characterized by early childhood-onset hip dysplasia and recurrent patella dislocation. Short stature in EDM4 patients is not frequent. Ref.12 Ref.13
Sequence similarities	Belongs to the SLC26A/SulP transporter (TC 2.A.53) family. [View classification] Contains 1 STAS domain.

Ontologies

Keywords
Biological process	Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Dwarfism
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular component	integral to plasma membrane Traceable author statement. Source: ProtInc membrane fraction Traceable author statement. Source: ProtInc
Molecular function	secondary active sulfate transmembrane transporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 739	739	Sulfate transporter		PRO_0000080158
Regions
	Topological domain	1 – 111	111	Cytoplasmic Potential
	Transmembrane	112 – 132	21	Helical; Potential
	Topological domain	133 – 136	4	Extracellular Potential
	Transmembrane	137 – 157	21	Helical; Potential
	Topological domain	158 – 159	2	Cytoplasmic Potential
	Transmembrane	160 – 180	21	Helical; Potential
	Topological domain	181 – 218	38	Extracellular Potential
	Transmembrane	219 – 239	21	Helical; Potential
	Topological domain	240 – 241	2	Cytoplasmic Potential
	Transmembrane	242 – 262	21	Helical; Potential
	Topological domain	263 – 296	34	Extracellular Potential
	Transmembrane	297 – 317	21	Helical; Potential
	Topological domain	318 – 328	11	Cytoplasmic Potential
	Transmembrane	329 – 349	21	Helical; Potential
	Topological domain	350 – 377	28	Extracellular Potential
	Transmembrane	378 – 398	21	Helical; Potential
	Topological domain	399 – 420	22	Cytoplasmic Potential
	Transmembrane	421 – 441	21	Helical; Potential
	Topological domain	442 – 454	13	Extracellular Potential
	Transmembrane	455 – 475	21	Helical; Potential
	Topological domain	476 – 523	48	Cytoplasmic Potential
	Transmembrane	524 – 544	21	Helical; Potential
	Topological domain	545 – 643	99	Extracellular Potential
	Transmembrane	644 – 664	21	Helical; Potential
	Topological domain	665 – 739	75	Cytoplasmic Potential
	Domain	568 – 719	152	STAS
Amino acid modifications
	Modified residue	12	1	Phosphoserine Ref.8
	Modified residue	16	1	Phosphoserine Ref.7 Ref.8
	Glycosylation	199	1	N-linked (GlcNAc...) Potential
	Glycosylation	205	1	N-linked (GlcNAc...) Potential
	Glycosylation	357	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	255	1	G → E in AO2. Ref.10		VAR_007434
	Natural variant	256	1	F → S in EDM4. Ref.13		VAR_066835
	Natural variant	279	1	R → W in AO2 and EDM4. Ref.10 Ref.13		VAR_007435
	Natural variant	340	1	Missing in ACG1B.		VAR_007436
	Natural variant	425	1	N → D in ACG1B. Ref.9		VAR_007437
	Natural variant	454	1	Q → P in diatrophic dysplasia; broad bone-platyspondylic variant. Ref.11		VAR_018654
	Natural variant	574	1	I → T. Ref.1 Ref.2 Ref.5 Corresponds to variant rs30832 [ dbSNP | Ensembl ].		VAR_058415
	Natural variant	653	1	C → S in EDM4. Ref.12 Ref.13		VAR_018655
	Natural variant	678	1	G → V in ACG1B. Ref.9		VAR_007438
	Natural variant	689	1	T → S. Corresponds to variant rs3776070 [ dbSNP | Ensembl ].		VAR_020402
	Natural variant	715	1	A → V in AO2 and EDM4. Ref.10 Ref.13		VAR_007439
Experimental info
	Sequence conflict	619	1	R → G in CAE45819. Ref.6
	Sequence conflict	622	1	K → R in BAG35488. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P50443 [UniParc]. Last modified July 28, 2009. Version 2. Checksum: 577984D0E973087F	FASTA	739	81,662
	10 20 30 40 50 60 MSSESKEQHN VSPRDSAEGN DSYPSGIHLE LQRESSTDFK QFETNDQCRP YHRILIERQE 70 80 90 100 110 120 KSDTNFKEFV IKKLQKNCQC SPAKAKNMIL GFLPVLQWLP KYDLKKNILG DVMSGLIVGI 130 140 150 160 170 180 LLVPQSIAYS LLAGQEPVYG LYTSFFASII YFLLGTSRHI SVGIFGVLCL MIGETVDREL 190 200 210 220 230 240 QKAGYDNAHS APSLGMVSNG STLLNHTSDR ICDKSCYAIM VGSTVTFIAG VYQVAMGFFQ 250 260 270 280 290 300 VGFVSVYLSD ALLSGFVTGA SFTILTSQAK YLLGLNLPRT NGVGSLITTW IHVFRNIHKT 310 320 330 340 350 360 NLCDLITSLL CLLVLLPTKE LNEHFKSKLK APIPIELVVV VAATLASHFG KLHENYNSSI 370 380 390 400 410 420 AGHIPTGFMP PKVPEWNLIP SVAVDAIAIS IIGFAITVSL SEMFAKKHGY TVKANQEMYA 430 440 450 460 470 480 IGFCNIIPSF FHCFTTSAAL AKTLVKESTG CHTQLSGVVT ALVLLLVLLV IAPLFYSLQK 490 500 510 520 530 540 SVLGVITIVN LRGALRKFRD LPKMWSISRM DTVIWFVTML SSALLSTEIG LLVGVCFSIF 550 560 570 580 590 600 CVILRTQKPK SSLLGLVEES EVFESVSAYK NLQIKPGIKI FRFVAPLYYI NKECFKSALY 610 620 630 640 650 660 KQTVNPILIK VAWKKAAKRK IKEKVVTLGG IQDEMSVQLS HDPLELHTIV IDCSAIQFLD 670 680 690 700 710 720 TAGIHTLKEV RRDYEAIGIQ VLLAQCNPTV RDSLTNGEYC KKEEENLLFY SVYEAMAFAE 730 VSKNQKGVCV PNGLSLSSD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The diastrophic dysplasia gene encodes a novel sulfate transporter: positional cloning by fine-structure linkage disequilibrium mapping." Haestbacka J., de la Chapelle A., Mahtani M.M., Clines G., Reeve-Daly M.P., Daly M., Hamilton B.A., Kusumi K., Trivedi B., Weaver A., Coloma A., Lovett M., Buckler A., Kaitila I., Lander E.S. Cell 78:1073-1087(1994) [PubMed: 7923357] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT THR-574. Tissue: Brain.
[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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT THR-574. Tissue: Tongue.
[3]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed: 15372022] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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], VARIANT THR-574. Tissue: Placenta.
[6]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 614-739. Tissue: Prostate.
[7]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12 AND SER-16, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"Achondrogenesis type IB is caused by mutations in the diastrophic dysplasia sulphate transporter gene." Superti-Furga A., Haestbacka J., Wilcox W.R., Cohn D.H., van der Harten H.J., Rossi A., Blau N., Rimoin D.L., Steinmann B., Lander E.S., Gitzelmann R. Nat. Genet. 12:100-102(1996) [PubMed: 8528239] [Abstract] Cited for: VARIANTS ACG1B VAL-340 DEL; ASP-425 AND VAL-678.
[10]	"Atelosteogenesis type II is caused by mutations in the diastrophic dysplasia sulfate-transporter gene (DTDST): evidence for a phenotypic series involving three chondrodysplasias." Haestbacka J., Superti-Furga A., Wilcox W.R., Rimoin D.L., Cohn D.H., Lander E.S. Am. J. Hum. Genet. 58:255-262(1996) [PubMed: 8571951] [Abstract] Cited for: VARIANTS AO2 GLU-255; TRP-279 AND VAL-715.
[11]	"Homozygosity for a novel DTDST mutation in a child with a 'broad bone-platyspondylic' variant of diastrophic dysplasia." Megarbane A., Haddad F.A., Haddad-Zebouni S., Achram M., Eich G., Le Merrer M., Superti-Furga A. Clin. Genet. 56:71-76(1999) [PubMed: 10466420] [Abstract] Cited for: VARIANT DIATROPHIC DYSPLASIA PRO-454.
[12]	"Autosomal recessive multiple epiphyseal dysplasia with homozygosity for C653S in the DTDST gene: double-layer patella as a reliable sign." Maekitie O., Savarirayan R., Bonafe L., Robertson S., Susic M., Superti-Furga A., Cole W.G. Am. J. Med. Genet. A 122:187-192(2003) [PubMed: 12966518] [Abstract] Cited for: VARIANT EDM4 SER-653.
[13]	"Pseudoachondroplasia and multiple epiphyseal dysplasia: A 7-year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution." Jackson G.C., Mittaz-Crettol L., Taylor J.A., Mortier G.R., Spranger J., Zabel B., Le Merrer M., Cormier-Daire V., Hall C.M., Offiah A., Wright M.J., Savarirayan R., Nishimura G., Ramsden S.C., Elles R., Bonafe L., Superti-Furga A., Unger S., Zankl A., Briggs M.D. Hum. Mutat. 0:0-0(2011) [PubMed: 21922596] [Abstract] Cited for: VARIANTS EDM4 SER-256; TRP-279; SER-653 AND VAL-715.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	U14528 mRNA. Translation: AAA70081.1. AK290358 mRNA. Translation: BAF83047.1. AK312596 mRNA. Translation: BAG35488.1. AC008427 Genomic DNA. No translation available. CH471062 Genomic DNA. Translation: EAW61755.1. BC059390 mRNA. Translation: AAH59390.1. BX640696 mRNA. Translation: CAE45819.1.
IPI	IPI00032107.
PIR	A54808.
RefSeq	NP_000103.2. NM_000112.3.
UniGene	Hs.302738.
3D structure databases
ProteinModelPortal	P50443.
SMR	P50443. Positions 548-723.
ModBase	Search...
Protein-protein interaction databases
STRING	P50443.
Protein family/group databases
TCDB	2.A.53.2.1. sulfate permease (SulP) family.
PTM databases
PhosphoSite	P50443.
Polymorphism databases
DMDM	254763328.
Proteomic databases
PRIDE	P50443.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000286298; ENSP00000286298; ENSG00000155850.
GeneID	1836.
KEGG	hsa:1836.
Organism-specific databases
CTD	1836.
GeneCards	GC05P149320.
H-InvDB	HIX0005307.
HGNC	HGNC:10994. SLC26A2.
HPA	HPA041957.
MIM	222600. phenotype. 226900. phenotype. 256050. phenotype. 600972. phenotype. 606718. gene.
neXtProt	NX_P50443.
Orphanet	93298. Achondrogenesis type 1B. 56304. Atelosteogenesis type II. 628. Diastrophic dwarfism. 93307. Multiple epiphyseal dysplasia type 4.
PharmGKB	PA149.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG14800.
GeneTree	ENSGT00570000078891.
HOGENOM	HBG446299.
HOVERGEN	HBG000639.
InParanoid	P50443.
OMA	TSDRICD.
OrthoDB	EOG4BZN22.
PhylomeDB	P50443.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	P50443.
Bgee	P50443.
CleanEx	HS_SLC26A2.
Genevestigator	P50443.
GermOnline	ENSG00000155850. Homo sapiens.
Family and domain databases
InterPro	IPR018045. S04_transporter_CS. IPR002645. SO4_transptr/STAS. IPR001902. SulP_transpt. IPR011547. Sulph_transpt. [Graphical view]
Gene3D	G3DSA:3.30.750.24. STAS. 2 hits.
KO	K14701.
Pfam	PF01740. STAS. 1 hit. PF00916. Sulfate_transp. 1 hit. [Graphical view]
SUPFAM	SSF52091. STAS. 1 hit.
TIGRFAMs	TIGR00815. SulP. 1 hit.
PROSITE	PS01130. SLC26A. 1 hit. PS50801. STAS. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	7495.
SOURCE	Search...

Entry information

Entry name

S26A2_HUMAN

Accession

Primary (citable) accession number: P50443
Secondary accession number(s): A8K2U3, B2R6J1, Q6N051

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	July 28, 2009
Last modified:	January 25, 2012
This is version 119 of the entry and version 2 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.