Q92781 (RDH1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
11-cis retinol dehydrogenase
Short name=11-cis RDH
Short name=11-cis RoDH
EC=1.1.1.315

Alternative name(s):
9-cis retinol dehydrogenase
Short name=9cRDH

Gene names

Name:	RDH5
Synonyms:	RDH1

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 › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	318 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	Stereospecific 11-cis retinol dehydrogenase, which catalyzes the final step in the biosynthesis of 11-cis retinaldehyde, the universal chromophore of visual pigments. Also able to oxidize 9-cis-retinol and 13-cis-retinol, but not all-trans-retinol. Active in the presence of NAD as cofactor but not in the presence of NADP. Ref.2 Ref.5
Catalytic activity	11-cis-retinol-[retinal-binding-protein] + NAD+ = 11-cis-retinal-[retinol-binding-protein] + NADH. Ref.2 Ref.5
Enzyme regulation	Inhibited by 9-cis-, 13-cis- and all-trans-retinoic acids, with the most potent inhibitor being 13-cis-retinoic acid. Weakly inhibited by oleic acid. Ref.5
Pathway	Cofactor metabolism; retinol metabolism. Ref.2
Subunit structure	Homodimer. Ref.6
Subcellular location	Membrane; Peripheral membrane protein. Endoplasmic reticulum lumen Ref.6.
Tissue specificity	Abundant in the retinal pigment epithelium. Expressed at high levels in mammary tissue, kidney and testis, and at lower levels in liver, heart, adrenal gland, lung, pancreas and skeletal muscle. Ref.2
Involvement in disease	Retinitis punctata albescens (RPA) [MIM:136880]: Rare form of stationary night blindness characterized by a delay in the regeneration of cone and rod photopigments. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13
Sequence similarities	Belongs to the short-chain dehydrogenases/reductases (SDR) family.
Biophysicochemical properties	pH dependence: Optimum pH is 7.5-8.0 for 9-cis retinol dehydrogenase activity. Ref.2

Ontologies

Keywords
Biological process	Sensory transduction Vision
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal
Ligand	NAD
Molecular function	Oxidoreductase
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	phototransduction, visible light Traceable author statement. Source: Reactome retinoid metabolic process Traceable author statement. Source: Reactome retinol metabolic process Inferred from electronic annotation. Source: UniProtKB-UniPathway visual perception Traceable author statement Ref.8. Source: ProtInc
Cellular_component	cell body Inferred from electronic annotation. Source: Ensembl endoplasmic reticulum lumen Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum membrane Traceable author statement. Source: Reactome
Molecular_function	retinol dehydrogenase activity Traceable author statement Ref.2. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Potential
	Chain	24 – 318	295	11-cis retinol dehydrogenase		PRO_0000054758
Regions
	Nucleotide binding	32 – 56	25	NADP By similarity
Sites
	Active site	175	1	Proton acceptor By similarity
	Binding site	163	1	Substrate By similarity
Amino acid modifications
	Glycosylation	160	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	21	1	R → Q. Corresponds to variant rs3138143 [ dbSNP | Ensembl ].		VAR_052321
	Natural variant	33	1	I → V. Ref.8 Corresponds to variant rs62638195 [ dbSNP | Ensembl ].		VAR_009272
	Natural variant	35	1	G → S in RPA; decreased stability. Ref.6 Ref.10		VAR_016814
	Natural variant	70	1	R → G. Ref.2 Corresponds to variant rs1058635 [ dbSNP | Ensembl ].		VAR_052322
	Natural variant	73	1	S → F in RPA; decreased stability; loss of enzymatic activity; accumulates in the perinuclear region. Ref.6 Ref.8		VAR_009273
	Natural variant	105	1	L → I in RPA; decreased stability. Ref.6		VAR_068716
	Natural variant	107	1	G → R in RPA; associated with macular dystrophy. Ref.10 Ref.12		VAR_016815
	Natural variant	128	1	D → N in RPA; decreased stability. Ref.6		VAR_068717
	Natural variant	132	1	V → M in RPA. Ref.10 Corresponds to variant rs62638187 [ dbSNP | Ensembl ].		VAR_016816
	Natural variant	157	1	R → W in RPA; decreased stability. Ref.6		VAR_068718
	Natural variant	164	1	V → F in RPA. Ref.13		VAR_016817
	Natural variant	177	1	V → G in RPA. Ref.9		VAR_016818
	Natural variant	238	1	G → W in RPA; decreased stability; loss of enzymatic activity; accumulates in the perinuclear region. Ref.6 Ref.7 Ref.8 Corresponds to variant rs62638191 [ dbSNP | Ensembl ].		VAR_009274
	Natural variant	264	1	V → G in RPA; decreased stability. Ref.6		VAR_068719
	Natural variant	267	1	C → W in RPA. Ref.11		VAR_016819
	Natural variant	280	1	R → H in RPA; decreased stability; loss of enzymatic activity. Ref.6 Ref.7 Ref.9 Ref.10		VAR_016820
	Natural variant	281	1	Y → H in RPA. Ref.10		VAR_016821
	Natural variant	294	1	A → P in RPA; associated with H-280; no effect on enzymatic activity; accumulates in the perinuclear region. Ref.6 Ref.7		VAR_016822
	Natural variant	310	1	L → EV in RPA; loss of enzymatic activity; accumulates in the perinuclear region.		VAR_016823
Experimental info
	Sequence conflict	30	1	F → L in AAH28298. Ref.4
	Sequence conflict	51 – 52	2	RG → KS in AAB93668. Ref.2
	Sequence conflict	75 – 77	3	RLH → GFN in AAB93668. Ref.2
	Sequence conflict	89	1	V → F in AAB93668. Ref.2
	Sequence conflict	200	1	V → E in AAB93668. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q92781 [UniParc]. Last modified February 1, 1997. Version 1. Checksum: 2CE24343F2EEA4B7	FASTA	318	34,979
	10 20 30 40 50 60 MWLPLLLGAL LWAVLWLLRD RQSLPASNAF VFITGCDSGF GRLLALQLDQ RGFRVLASCL 70 80 90 100 110 120 TPSGAEDLQR VASSRLHTTL LDITDPQSVQ QAAKWVEMHV KEAGLFGLVN NAGVAGIIGP 130 140 150 160 170 180 TPWLTRDDFQ RVLNVNTMGP IGVTLALLPL LQQARGRVIN ITSVLGRLAA NGGGYCVSKF 190 200 210 220 230 240 GLEAFSDSLR RDVAHFGIRV SIVEPGFFRT PVTNLESLEK TLQACWARLP PATQAHYGGA 250 260 270 280 290 300 FLTKYLKMQQ RIMNLICDPD LTKVSRCLEH ALTARHPRTR YSPGWDAKLL WLPASYLPAS 310 LVDAVLTWVL PKPAQAVY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure of human 11-cis retinol dehydrogenase and organization and chromosomal localization of the corresponding gene." Simon A., Lagercrantz J., Bajalica-Lagercrantz S., Eriksson U. Genomics 36:424-430(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Identification and characterization of a stereospecific human enzyme that catalyzes 9-cis-retinol oxidation. A possible role in 9-cis-retinoic acid formation." Mertz J.R., Shang E., Piantedosi R., Wei S., Wolgemuth D.J., Blaner W.S. J. Biol. Chem. 272:11744-11749(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, PATHWAY, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, VARIANT GLY-70. Tissue: Mammary gland.
[3]	"Retinol dehydrogenase: complete genomic sequence and its relationship to retinitis pigmentosa." Gu S., Jablonka S., Gal A. Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Blood.
[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]	"Biochemical properties, tissue expression, and gene structure of a short chain dehydrogenase/reductase able to catalyze cis-retinol oxidation." Gamble M.V., Shang E., Zott R.P., Mertz J.R., Wolgemuth D.J., Blaner W.S. J. Lipid Res. 40:2279-2292(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION.
[6]	"Biochemical defects in 11-cis-retinol dehydrogenase mutants associated with fundus albipunctatus." Liden M., Romert A., Tryggvason K., Persson B., Eriksson U. J. Biol. Chem. 276:49251-49257(2001) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS RPA SER-35; PHE-73; ILE-105; ASN-128; TRP-157; TRP-238; GLY-264; HIS-280; PRO-294 AND 309-GLU-VAL-310 DELINS.
[7]	"11-cis retinol dehydrogenase mutations as a major cause of the congenital night-blindness disorder known as fundus albipunctatus." Gonzalez-Fernandez F., Kurz D., Bao Y., Newman S., Conway B.P., Young J.E., Han D.P., Khani S.C. Mol. Vis. 5:41-41(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS RPA TRP-238; HIS-280 AND PRO-294.
[8]	"Mutations in the gene encoding 11-cis retinol dehydrogenase cause delayed dark adaptation and fundus albipunctatus." Yamamoto H., Simon A., Eriksson U., Harris E., Berson E.L., Dryja T.P. Nat. Genet. 22:188-191(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS RPA PHE-73 AND TRP-238, VARIANT VAL-33.
[9]	"A novel compound heterozygous mutation in the RDH5 gene in a patient with fundus albipunctatus." Kuroiwa S., Kikuchi T., Yoshimura N. Am. J. Ophthalmol. 130:672-675(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS RPA GLY-177 AND HIS-280.
[10]	"A high association with cone dystrophy in Fundus albipunctatus caused by mutations of the RDH5 gene." Nakamura M., Hotta Y., Tanikawa A., Terasaki H., Miyake Y. Invest. Ophthalmol. Vis. Sci. 41:3925-3932(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS RPA SER-35; ARG-107; MET-132; HIS-280; HIS-281 AND 309-GLU-VAL-310 DELINS.
[11]	"Null mutation in the human 11-cis retinol dehydrogenase gene associated with fundus albipunctatus." Driessen C.A., Janssen B.P., Winkens H.J., Kuhlmann L.D., Van Vugt A.H., Pinckers A.J., Deutman A.F., Janssen J.J. Ophthalmology 108:1479-1484(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT RPA TRP-267.
[12]	"Macular dystrophy in a Japanese family with fundus albipunctatus." Hotta K., Nakamura M., Kondo M., Ito S., Terasaki H., Miyake Y., Hida T. Am. J. Ophthalmol. 135:917-919(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT RPA ARG-107.
[13]	"A novel RDH5 gene mutation in a patient with fundus albipunctatus presenting with macular atrophy and fading white dots." Yamamoto H., Yakushijin K., Kusuhara S., Escano M.F., Nagai A., Negi A. Am. J. Ophthalmol. 136:572-574(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT RPA PHE-164.
+	Additional computationally mapped references.

Web resources

Mutations of the RDH5 gene

Retina International's Scientific Newsletter

Cross-references

Sequence databases
EMBL GenBank DDBJ	U43559 mRNA. Translation: AAC50725.1. U89717 mRNA. Translation: AAB93668.1. AF037062 Genomic DNA. Translation: AAC09250.1. BC028298 mRNA. Translation: AAH28298.1.
CCDS	CCDS31829.1.
RefSeq	NP_001186700.1. NM_001199771.1. NP_002896.2. NM_002905.3.
UniGene	Hs.600940.
3D structure databases
ProteinModelPortal	Q92781.
SMR	Q92781. Positions 25-273.
ModBase	Search...
MobiDB	Search...
Protein-protein interaction databases
BioGrid	111892. 2 interactions.
STRING	9606.ENSP00000257895.
Chemistry
DrugBank	DB00157. NADH. DB00162. Vitamin A.
PTM databases
PhosphoSite	Q92781.
Polymorphism databases
DMDM	2492753.
Proteomic databases
PaxDb	Q92781.
PRIDE	Q92781.
Protocols and materials databases
DNASU	5959.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000257895; ENSP00000257895; ENSG00000135437. ENST00000548082; ENSP00000447128; ENSG00000135437.
GeneID	5959.
KEGG	hsa:5959.
UCSC	uc001shk.3. human.
Organism-specific databases
CTD	5959.
GeneCards	GC12P056121.
HGNC	HGNC:9940. RDH5.
MIM	136880. phenotype. 601617. gene.
neXtProt	NX_Q92781.
Orphanet	227796. Fundus albipunctatus. 52427. Retinitis punctata albescens.
PharmGKB	PA34308.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1028.
HOVERGEN	HBG005482.
InParanoid	Q92781.
KO	K00061.
OMA	GPTPWLT.
PhylomeDB	Q92781.
TreeFam	TF325617.
Enzyme and pathway databases
BioCyc	MetaCyc:HS06003-MONOMER.
BRENDA	1.1.1.105. 2681.
Reactome	REACT_111102. Signal Transduction. REACT_116125. Disease.
UniPathway	UPA00912.
Gene expression databases
Bgee	Q92781.
CleanEx	HS_RDH5.
Genevestigator	Q92781.
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.
ProtoNet	Search...
Other
ChiTaRS	RDH5. human.
GeneWiki	RDH5.
GenomeRNAi	5959.
NextBio	23204.
PRO	Q92781.
SOURCE	Search...

Entry information

Entry name

RDH1_HUMAN

Accession

Primary (citable) accession number: Q92781
Secondary accession number(s): O00179, Q8TAI2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	February 1, 1997
Last modified:	July 9, 2014
This is version 129 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.