Q00796 (DHSO_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sorbitol dehydrogenase
EC=1.1.1.14

Alternative name(s):
L-iditol 2-dehydrogenase

Gene names

Name:

SORD

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	357 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Converts sorbitol to fructose. Part of the polyol pathway that plays an important role in sperm physiology. May play a role in the sperm motility by providing an energetic source for sperm By similarity. Ref.9
Catalytic activity	L-iditol + NAD+ = L-sorbose + NADH.
Cofactor	Binds 1 zinc ion per subunit.
Subunit structure	Homotetramer. Ref.13
Subcellular location	Mitochondrion membrane; Peripheral membrane protein. Cell projection › cilium › flagellum. Note: Associated with mitochondria of the midpiece and near the plasma membrane in the principal piece of the flagellum. Also found in the epididymosome, secreted by the epididymal epithelium and that transfers proteins from the epididymal fluid to the sperm surface By similarity.
Tissue specificity	Expressed in kidney and epithelial cells of both benign and malignant prostate tissue. Expressed in epididymis (at protein level). Ref.9 Ref.10 Ref.11
Induction	Up-regulated by androgens and down-regulated by castration. Ref.10
Miscellaneous	The polyol pathway is proposed to be involved the cellular toxicity of diabetic hyperglycemia.
Sequence similarities	Belongs to the zinc-containing alcohol dehydrogenase family.

Ontologies

Keywords
Cellular component	Cell projection Cilium Flagellum Membrane Mitochondrion
Coding sequence diversity	Polymorphism
Ligand	Metal-binding NAD Zinc
Molecular function	Oxidoreductase
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	L-xylitol catabolic process Inferred from direct assay PubMed 8487505. Source: UniProtKB fructose biosynthetic process Inferred from direct assay PubMed 3365415PubMed 6870831PubMed 8487505. Source: UniProtKB glucose metabolic process Traceable author statement PubMed 14965227. Source: UniProtKB sorbitol catabolic process Inferred from direct assay Ref.13PubMed 3365415PubMed 6870831PubMed 8487505. Source: UniProtKB sperm motility Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	extracellular space Traceable author statement PubMed 6177277. Source: UniProtKB membrane Inferred from direct assay PubMed 8487505. Source: UniProtKB mitochondrial membrane Inferred from electronic annotation. Source: UniProtKB-SubCell motile cilium Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	L-iditol 2-dehydrogenase activity Inferred from direct assay PubMed 3365415PubMed 6870831PubMed 8487505. Source: UniProtKB NAD binding Inferred from direct assay Ref.13. Source: UniProtKB carbohydrate binding Non-traceable author statement Ref.13. Source: UniProtKB zinc ion binding Inferred from direct assay Ref.13. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.7 Ref.8

Chain

2 – 357

356

Sorbitol dehydrogenase

PRO_0000160817

Sites

Metal binding

45

1

Zinc; catalytic

Metal binding

70

1

Zinc; catalytic

Metal binding

71

1

Zinc; catalytic

Binding site

51

1

Substrate By similarity

Binding site

156

1

Substrate By similarity

Binding site

299

1

Substrate By similarity

Binding site

300

1

Substrate By similarity

Natural variations

Natural variant

239

1

Q → L. Ref.2
Corresponds to variant rs55739437 [ dbSNP | Ensembl ].

VAR_000430

Natural variant

269

1

N → T. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6
Corresponds to variant rs2229659 [ dbSNP | Ensembl ].

VAR_060351

Experimental info

Sequence conflict

5

1

Missing AA sequence Ref.7

Sequence conflict

59

1

N → D AA sequence Ref.7

Sequence conflict

186

1

M → E AA sequence Ref.7

Sequence conflict

281

1

T → S AA sequence Ref.7

Sequence conflict

289

1

I → T AA sequence Ref.7

Secondary structure

1

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357

Helix Strand Turn

Details...

Beta strand

10 – 16

7

Beta strand

19 – 24

6

Beta strand

34 – 44

11

Helix

46 – 54

9

Beta strand

55 – 57

3

Beta strand

71 – 79

9

Beta strand

91 – 94

4

Beta strand

96 – 98

3

Helix

104 – 107

4

Helix

111 – 113

3

Beta strand

130 – 136

7

Helix

137 – 139

3

Beta strand

140 – 142

3

Helix

149 – 168

20

Beta strand

175 – 179

5

Helix

183 – 194

12

Beta strand

198 – 205

8

Helix

207 – 215

9

Beta strand

219 – 223

5

Helix

229 – 240

12

Beta strand

245 – 249

5

Helix

254 – 263

10

Beta strand

269 – 272

4

Helix

284 – 289

6

Beta strand

293 – 296

4

Helix

304 – 312

9

Helix

319 – 321

3

Beta strand

322 – 327

6

Helix

328 – 330

3

Helix

331 – 339

9

Beta strand

344 – 349

6

Sequences

	Sequence		Length	Mass (Da)
	Q00796 [UniParc]. Last modified March 23, 2010. Version 4. Checksum: FF13DDD5EBE47754	FASTA	357	38,325
	10 20 30 40 50 60 MAAAAKPNNL SLVVHGPGDL RLENYPIPEP GPNEVLLRMH SVGICGSDVH YWEYGRIGNF 70 80 90 100 110 120 IVKKPMVLGH EASGTVEKVG SSVKHLKPGD RVAIEPGAPR ENDEFCKMGR YNLSPSIFFC 130 140 150 160 170 180 ATPPDDGNLC RFYKHNAAFC YKLPDNVTFE EGALIEPLSV GIHACRRGGV TLGHKVLVCG 190 200 210 220 230 240 AGPIGMVTLL VAKAMGAAQV VVTDLSATRL SKAKEIGADL VLQISKESPQ EIARKVEGQL 250 260 270 280 290 300 GCKPEVTIEC TGAEASIQAG IYATRSGGNL VLVGLGSEMT TVPLLHAAIR EVDIKGVFRY 310 320 330 340 350 CNTWPVAISM LASKSVNVKP LVTHRFPLEK ALEAFETFKK GLGLKIMLKC DPSDQNP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The human sorbitol dehydrogenase gene: cDNA cloning, sequence determination, and mapping by fluorescence in situ hybridization." Lee F.K., Cheung M.C., Chung S. Genomics 21:354-358(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT THR-269. Tissue: Liver.
[2]	"Structural organization of the human sorbitol dehydrogenase gene (SORD)." Iwata T., Popescu N.C., Zimonjic D.B., Karlsson C., Hoeoeg J.-O., Vaca G., Rodriguez I.R., Carper D. Genomics 26:55-62(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANTS LEU-239 AND THR-269.
[3]	"Identification and characterisation of a sequence related to human sorbitol dehydrogenase." Carr I.M., Markham A.F., Coletta P.L. Eur. J. Biochem. 245:760-767(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-269.
[4]	"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], VARIANT THR-269. Tissue: Brain.
[5]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT THR-269. Tissue: Brain and Lymph.
[7]	"Variability within mammalian sorbitol dehydrogenases. The primary structure of the human liver enzyme." Karlsson C., Maret W., Auld D.S., Hoeoeg J.-O., Joernvall H. Eur. J. Biochem. 186:543-550(1989) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-357. Tissue: Liver.
[8]	"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-21. Tissue: Platelet.
[9]	"Polyol pathway in human epididymis and semen." Frenette G., Thabet M., Sullivan R. J. Androl. 27:233-239(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[10]	"Sorbitol dehydrogenase expression is regulated by androgens in the human prostate." Szabo Z., Hamalainen J., Loikkanen I., Moilanen A.M., Hirvikoski P., Vaisanen T., Paavonen T.K., Vaarala M.H. Oncol. Rep. 23:1233-1239(2010) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, INDUCTION.
[11]	"ZAC1 is up-regulated by hypertonicity and decreases sorbitol dehydrogenase expression, allowing accumulation of sorbitol in kidney cells." Lanaspa M.A., Andres-Hernando A., Rivard C.J., Dai Y., Li N., Berl T. J. Biol. Chem. 284:19974-19981(2009) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[12]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"X-ray crystallographic and kinetic studies of human sorbitol dehydrogenase." Pauly T.A., Ekstrom J.L., Beebe D.A., Chrunyk B., Cunningham D., Griffor M., Kamath A., Lee S.E., Madura R., Mcguire D., Subashi T., Wasilko D., Watts P., Mylari B.L., Oates P.J., Adams P.D., Rath V.L. Structure 11:1071-1085(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U07361 mRNA. Translation: AAA66064.1.
L29008 mRNA. Translation: AAA80565.1.
L29254 , L29249, L29250, L29251, L29252, L29253 Genomic DNA. Translation: AAA80566.1.
U67243 , U67236, U67237, U67238, U67239, U67240, U67241, U67242 Genomic DNA. Translation: AAB61898.1.
AK312444 mRNA. Translation: BAG35352.1.
AC090888 Genomic DNA. No translation available.
AC091117 Genomic DNA. No translation available.
BC021085 mRNA. Translation: AAH21085.1.
BC025295 mRNA. Translation: AAH25295.1.

IPI

IPI00216057.

PIR

A54674.

RefSeq

NP_003095.2. NM_003104.5.

UniGene

Hs.878.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1PL6	X-ray	2.00	A/B/C/D	2-357	[»]
1PL7	X-ray	2.20	A/B/C/D	2-357	[»]
1PL8	X-ray	1.90	A/B/C/D	2-357	[»]

ProteinModelPortal

Q00796.

SMR

Q00796. Positions 2-357.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q00796. 1 interaction.

MINT

MINT-5004436.

STRING

9606.ENSP00000267814.

PTM databases

PhosphoSite

Q00796.

Polymorphism databases

DMDM

292495088.

2D gel databases

REPRODUCTION-2DPAGE

IPI00216057.

Proteomic databases

PaxDb

Q00796.

PRIDE

Q00796.

Protocols and materials databases

DNASU

6652.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000267814; ENSP00000267814; ENSG00000140263.

GeneID

6652.

KEGG

hsa:6652.

UCSC

uc001zul.4. human.

Organism-specific databases

CTD

6652.

GeneCards

GC15P045315.

HGNC

HGNC:11184. SORD.

HPA

HPA040260.
HPA040621.

MIM

182500. gene.

neXtProt

NX_Q00796.

PharmGKB

PA36021.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1063.

HOGENOM

HOG000294670.

HOVERGEN

HBG005484.

InParanoid

Q00796.

KO

K00008.

OMA

GNLCRYY.

OrthoDB

EOG4WSW9S.

PhylomeDB

Q00796.

Enzyme and pathway databases

SABIO-RK

Q00796.

Gene expression databases

ArrayExpress

Q00796.

Bgee

Q00796.

CleanEx

HS_SORD.

Genevestigator

Q00796.

GermOnline

ENSG00000140263. Homo sapiens.

Family and domain databases

Gene3D

3.40.50.720. 1 hit.
3.90.180.10. 1 hit.

InterPro

IPR013149. ADH_C.
IPR013154. ADH_GroES-like.
IPR002085. ADH_SF_Zn-type.
IPR002328. ADH_Zn_CS.
IPR011032. GroES-like.
IPR016040. NAD(P)-bd_dom.
[Graphical view]

PANTHER

PTHR11695. PTHR11695. 1 hit.

Pfam

PF08240. ADH_N. 1 hit.
PF00107. ADH_zinc_N. 1 hit.
[Graphical view]

SUPFAM

SSF50129. GroES_like. 1 hit.

PROSITE

PS00059. ADH_ZINC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL2275.

DrugBank

DB00157. NADH.

EvolutionaryTrace

Q00796.

GenomeRNAi

6652.

NextBio

25929.

SOURCE

Search...

Entry information

Entry name

DHSO_HUMAN

Accession

Primary (citable) accession number: Q00796
Secondary accession number(s): B2R655 , J3JZZ5, Q16682, Q9UMD6

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	March 23, 2010
Last modified:	May 29, 2013
This is version 150 of the entry and version 4 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.