Q96NR8 (RDH12_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Retinol dehydrogenase 12
EC=1.1.1.-

Alternative name(s):
All-trans and 9-cis retinol dehydrogenase

Gene names

Name:

RDH12

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

General annotation (Comments)

Function	Exhibits an oxidoreductive catalytic activity towards retinoids. Most efficient as an NADPH-dependent retinal reductase. Displays high activity toward 9-cis and all-trans-retinol. Also involved in the metabolism of short-chain aldehydes. No steroid dehydrogenase activity detected. Might be the key enzyme in the formation of 11-cis-retinal from 11-cis-retinol during regeneration of the cone visual pigments. Ref.5
Tissue specificity	Widely expressed, mostly in eye, kidney, brain, skeletal muscle and stomach.
Involvement in disease	Leber congenital amaurosis 13 (LCA13) [MIM:612712]: A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.7 Retinitis pigmentosa 53 (RP53) [MIM:612712]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.10
Sequence similarities	Belongs to the short-chain dehydrogenases/reductases (SDR) family.

Ontologies

Keywords
Biological process	Sensory transduction Vision
Coding sequence diversity	Polymorphism
Disease	Disease mutation Leber congenital amaurosis Retinitis pigmentosa
Ligand	NADP
Molecular function	Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	photoreceptor cell maintenance Traceable author statement Ref.5. Source: UniProtKB response to stimulus Inferred from electronic annotation. Source: UniProtKB-KW retinol metabolic process Inferred from direct assay Ref.5. Source: UniProtKB
Cellular_component	intracellular Inferred from direct assay Ref.5. Source: UniProtKB
Molecular_function	nucleotide binding Inferred from electronic annotation. Source: InterPro retinol dehydrogenase activity Inferred from direct assay Ref.5. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 316	316	Retinol dehydrogenase 12		PRO_0000054766
Regions
	Nucleotide binding	46 – 52	7	NADP By similarity
Sites
	Active site	200	1	Proton acceptor By similarity
	Binding site	175	1	Substrate By similarity
Natural variations
	Natural variant	47	1	A → T in retinal dystrophy; exhibits a profound loss of catalytic activity. Ref.8		VAR_064163
	Natural variant	49	1	T → M in LCA13; aberrant activity in interconverting isomers of retinol and retinal; there is differing activity profiles associated with each of the alleles of the R-161-Q polymorphism; genetic background may act as a modifier of mutation effect. Ref.7 Corresponds to variant rs28940314 [ dbSNP | Ensembl ].		VAR_020858
	Natural variant	51	1	I → N in LCA13. Ref.6		VAR_020859
	Natural variant	55	1	T → M in retinal dystrophy; exhibits a profound loss of catalytic activity. Ref.8		VAR_064164
	Natural variant	65	1	R → Q. Ref.8		VAR_064165
	Natural variant	76	1	G → R in RP53. Ref.10		VAR_064166
	Natural variant	79	1	A → V Found in a patient with LCA13. Ref.11		VAR_067193
	Natural variant	99	1	L → I in LCA13; exhibits a profound loss of catalytic activity. Ref.6 Ref.8 Corresponds to variant rs28940315 [ dbSNP | Ensembl ].		VAR_020860
	Natural variant	101	1	D → N. Ref.8		VAR_064167
	Natural variant	125	1	N → K in retinal dystrophy; exhibits a profound loss of catalytic activity. Ref.8		VAR_064168
	Natural variant	126	1	A → V in RP53. Ref.9		VAR_064169
	Natural variant	145	1	G → E in retinal dystrophy; exhibits a profound loss of catalytic activity. Ref.8		VAR_064170
	Natural variant	151	1	H → D in LCA13; exhibits a profound loss of catalytic activity. Ref.6 Ref.8		VAR_020861
	Natural variant	151	1	H → N in LCA13. Ref.6		VAR_020862
	Natural variant	155	1	T → I in retinal dystrophy; exhibits a profound loss of catalytic activity. Ref.8		VAR_064171
	Natural variant	161	1	R → Q. Ref.1 Ref.8 Ref.11 Corresponds to variant rs17852293 [ dbSNP | Ensembl ].		VAR_028281
	Natural variant	175	1	S → P in LCA13. Ref.6		VAR_020863
	Natural variant	193	1	R → C in retinal dystrophy; uncertain pathogenicity. Ref.8		VAR_064172
	Natural variant	206	1	A → D in retinal dystrophy; exhibits a profound loss of catalytic activity. Ref.8		VAR_064173
	Natural variant	206	1	A → V in retinal dystrophy; uncertain pathogenicity. Ref.8		VAR_064174
	Natural variant	226	1	Y → C in LCA13; diminished activity in interconverting isomers of retinol and retinal. Ref.7 Corresponds to variant rs28940313 [ dbSNP | Ensembl ].		VAR_020864
	Natural variant	230	1	P → A in LCA13. Ref.6		VAR_020865
	Natural variant	230	1	P → L in retinal dystrophy; uncertain pathogenicity. Ref.8		VAR_064175
	Natural variant	234	1	R → H in retinal dystrophy; uncertain pathogenicity; exhibits a loss of catalytic activity. Ref.8		VAR_064176
	Natural variant	239	1	R → W in retinal dystrophy; exhibits a profound loss of catalytic activity. Ref.8		VAR_064177
	Natural variant	274	1	L → P in retinal dystrophy; exhibits a profound loss of catalytic activity. Ref.8		VAR_064178
	Natural variant	285	1	C → Y in retinal dystrophy; exhibits a profound loss of catalytic activity. Ref.8		VAR_064179

Sequences

	Sequence		Length	Mass (Da)
	Q96NR8 [UniParc]. Last modified October 17, 2006. Version 3. Checksum: EA0915E1E484879B	FASTA	316	35,094
	10 20 30 40 50 60 MLVTLGLLTS FFSFLYMVAP SIRKFFAGGV CRTNVQLPGK VVVITGANTG IGKETARELA 70 80 90 100 110 120 SRGARVYIAC RDVLKGESAA SEIRVDTKNS QVLVRKLDLS DTKSIRAFAE GFLAEEKQLH 130 140 150 160 170 180 ILINNAGVMM CPYSKTADGF ETHLGVNHLG HFLLTYLLLE RLKVSAPARV VNVSSVAHHI 190 200 210 220 230 240 GKIPFHDLQS EKRYSRGFAY CHSKLANVLF TRELAKRLQG TGVTTYAVHP GVVRSELVRH 250 260 270 280 290 300 SSLLCLLWRL FSPFVKTARE GAQTSLHCAL AEGLEPLSGK YFSDCKRTWV SPRARNNKTA 310 ERLWNVSCEL LGIRWE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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 GLN-161. Tissue: Cerebellum and Kidney.
[2]	"The DNA sequence and analysis of human chromosome 14." Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J. Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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]. Tissue: Brain.
[5]	"Dual-substrate specificity short chain retinol dehydrogenases from the vertebrate retina." Haeseleer F., Jang G.-F., Imanishi Y., Driessen C.A.G.G., Matsumura M., Nelson P.S., Palczewski K. J. Biol. Chem. 277:45537-45546(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[6]	"Retinal dehydrogenase 12 (RDH12) mutations in Leber congenital amaurosis." Perrault I., Hanein S., Gerber S., Barbet F., Ducroq D., Dollfus H., Hamel C., Dufier J.-L., Munnich A., Kaplan J., Rozet J.-M. Am. J. Hum. Genet. 75:639-646(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LCA13 ASN-51; ILE-99; ASN-151; ASP-151; PRO-175 AND ALA-230.
[7]	"Mutations in RDH12 encoding a photoreceptor cell retinol dehydrogenase cause childhood-onset severe retinal dystrophy." Janecke A.R., Thompson D.A., Utermann G., Becker C., Huebner C.A., Schmid E., McHenry C.L., Nair A.R., Rueschendorf F., Heckenlively J., Wissinger B., Nuernberg P., Gal A. Nat. Genet. 36:850-854(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LCA13 MET-49 AND CYS-226.
[8]	"Retinal degeneration associated with RDH12 mutations results from decreased 11-cis retinal synthesis due to disruption of the visual cycle." Thompson D.A., Janecke A.R., Lange J., Feathers K.L., Hubner C.A., McHenry C.L., Stockton D.W., Rammesmayer G., Lupski J.R., Antinolo G., Ayuso C., Baiget M., Gouras P., Heckenlively J.R., den Hollander A., Jacobson S.G., Lewis R.A., Sieving P.A. , Wissinger B., Yzer S., Zrenner E., Utermann G., Gal A. Hum. Mol. Genet. 14:3865-3875(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS RETINAL DYSTROPHY THR-47; MET-55; ILE-99; LYS-125; GLU-145; ASP-151; ILE-155; CYS-193; ASP-206; VAL-206; LEU-230; HIS-234; TRP-239; PRO-274 AND TYR-285, VARIANTS GLN-65; ASN-101; GLN-161 AND CYS-193, CHARACTERIZATION OF VARIANTS RETINAL DYSTROPHY THR-47; MET-55; ILE-99; LYS-125; GLU-145; ASP-151; ILE-155; CYS-193; ASP-206; VAL-206; LEU-230; HIS-234; TRP-239; PRO-274 AND TYR-285, CHARACTERIZATION OF VARIANT GLN-161.
[9]	"Genetic heterogeneity in two consanguineous families segregating early onset retinal degeneration: the pitfalls of homozygosity mapping." Benayoun L., Spiegel R., Auslender N., Abbasi A.H., Rizel L., Hujeirat Y., Salama I., Garzozi H.J., Allon-Shalev S., Ben-Yosef T. Am. J. Med. Genet. A 149:650-656(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT RP53 VAL-126.
[10]	"Molecular characterization of retinitis pigmentosa in Saudi Arabia." Aldahmesh M.A., Safieh L.A., Alkuraya H., Al-Rajhi A., Shamseldin H., Hashem M., Alzahrani F., Khan A.O., Alqahtani F., Rahbeeni Z., Alowain M., Khalak H., Al-Hazzaa S., Meyer B.F., Alkuraya F.S. Mol. Vis. 15:2464-2469(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT RP53 ARG-76.
[11]	"Detection of variants in 15 genes in 87 unrelated Chinese patients with Leber congenital amaurosis." Li L., Xiao X., Li S., Jia X., Wang P., Guo X., Jiao X., Zhang Q., Hejtmancik J.F. PLoS ONE 6:E19458-E19458(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS VAL-79 AND GLN-161.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK054835 mRNA. Translation: BAB70811.1. AK315462 mRNA. Translation: BAG37849.1. AL049779 Genomic DNA. No translation available. CH471061 Genomic DNA. Translation: EAW80951.1. BC025724 mRNA. Translation: AAH25724.1.
IPI	IPI00163384.
RefSeq	NP_689656.2. NM_152443.2.
UniGene	Hs.415322.
3D structure databases
ProteinModelPortal	Q96NR8.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96NR8. 3 interactions.
STRING	9606.ENSP00000267502.
PTM databases
PhosphoSite	Q96NR8.
Polymorphism databases
DMDM	116242750.
Proteomic databases
PaxDb	Q96NR8.
PRIDE	Q96NR8.
Protocols and materials databases
DNASU	145226.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000267502; ENSP00000267502; ENSG00000139988. ENST00000539142; ENSP00000438715; ENSG00000139988. ENST00000551171; ENSP00000449079; ENSG00000139988.
GeneID	145226.
KEGG	hsa:145226.
UCSC	uc001xjz.4. human.
Organism-specific databases
CTD	145226.
GeneCards	GC14P068168.
HGNC	HGNC:19977. RDH12.
MIM	608830. gene. 612712. phenotype.
neXtProt	NX_Q96NR8.
Orphanet	65. Leber congenital amaurosis. 791. Retinitis pigmentosa.
PharmGKB	PA134864793.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1028.
HOVERGEN	HBG078800.
InParanoid	Q96NR8.
KO	K11153.
OMA	PGARVYI.
OrthoDB	EOG4640CK.
PhylomeDB	Q96NR8.
Enzyme and pathway databases
BioCyc	MetaCyc:ENSG00000139988-MONOMER.
BRENDA	1.1.1.105. 2681.
Pathway_Interaction_DB	cone_pathway. Visual signal transduction: Cones. rhodopsin_pathway. Visual signal transduction: Rods.
Gene expression databases
Bgee	Q96NR8.
CleanEx	HS_RDH12.
Genevestigator	Q96NR8.
GermOnline	ENSG00000139988. Homo sapiens.
Family and domain databases
Gene3D	3.40.50.720. 1 hit.
InterPro	IPR002198. DH_sc/Rdtase_SDR. IPR002347. Glc/ribitol_DH. IPR016040. NAD(P)-bd_dom. [Graphical view]
Pfam	PF00106. adh_short. 1 hit. [Graphical view]
PRINTS	PR00081. GDHRDH. PR00080. SDRFAMILY.
PROSITE	PS00061. ADH_SHORT. False negative. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00162. Vitamin A.
GenomeRNAi	145226.
NextBio	85049.
SOURCE	Search...

Entry information

Entry name

RDH12_HUMAN

Accession

Primary (citable) accession number: Q96NR8
Secondary accession number(s): B2RDA2, Q8TAW6

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 29, 2003
Last sequence update:	October 17, 2006
Last modified:	May 1, 2013
This is version 105 of the entry and version 3 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.