P54845 (NRL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Neural retina-specific leucine zipper protein
Short name=NRL

Gene names

Name:	NRL
Synonyms:	D14S46E

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

General annotation (Comments)

Function	Transcription factor which regulates the expression of several rod-specific genes, in cluding RHO and PDE6B By similarity.
Subunit structure	Interacts with FIZ1. This interaction represses transactivation By similarity. Interacts (via the leucine-zipper domain) with CRX. Ref.10
Subcellular location	Nucleus.
Tissue specificity	Neural retina.
Domain	The minimal transactivation domain (MTD) is conserved across the MAF family, it may activate trancription by recruiting TBP and associated factors at the promoters of target genes. Ref.11
Post-translational modification	Disumoylated at Lys-20. Sumoylation modulates the transcriptional activity of NRL on RHO and NR2E3 promoters, and is required for normal rod differentiation By similarity.
Involvement in disease	Defects in NRL are the cause of retinitis pigmentosa type 27 (RP27) [MIM:613750]. RP leads to degeneration of retinal photoreceptor cells. 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. RP27 inheritance is autosomal dominant. Ref.12 Defects in NRL are a cause of retinal degeneration autosomal recessive clumped pigment type (RDCP) [MIM:162080]. A retinopathy characterized by night blindness since early childhood, consistent with a severe reduction in rod function. Color vision is normal although there is a relatively enhanced function of short-wavelength-sensitive cones in the macula. Signs of retinal degeneration and clusters of clumped pigment deposits in the peripheral fundus at the level of the retinal pigment epithelium are present (clumped pigmentary retinal degeneration). Ref.13
Sequence similarities	Belongs to the bZIP family. Contains 1 bZIP domain.

Ontologies

Keywords
Biological process	Sensory transduction Transcription Transcription regulation Vision
Cellular component	Nucleus
Disease	Disease mutation Retinitis pigmentosa
Ligand	DNA-binding
Molecular function	Developmental protein
PTM	Isopeptide bond Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	response to stimulus Inferred from electronic annotation. Source: UniProtKB-KW transcription from RNA polymerase II promoter Traceable author statement. Source: ProtInc visual perception Traceable author statement. Source: ProtInc
Cellular component	nucleus Traceable author statement. Source: ProtInc
Molecular function	leucine zipper domain binding Inferred from physical interaction Ref.10. Source: UniProtKB sequence-specific DNA binding 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 – 237	237	Neural retina-specific leucine zipper protein		PRO_0000076633
Regions
	Domain	187 – 208	22	Leucine-zipper
	DNA binding	159 – 185	27	Basic motif
	Region	30 – 93	64	Minimal transactivation domain (MTD)
Amino acid modifications
	Cross-link	20		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
	Cross-link	24		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Natural variations
	Natural variant	50	1	S → T in RP27; increased transactivation activity. Ref.12		VAR_009268
	Natural variant	160	1	L → P in RDCP; severely reduced transcriptional activity. Ref.13		VAR_064977

Sequences

	Sequence		Length	Mass (Da)
	P54845 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: CCABEDC1C1123614	FASTA	237	25,940
	10 20 30 40 50 60 MALPPSPLAM EYVNDFDLMK FEVKREPSEG RPGPPTASLG STPYSSVPPS PTFSEPGMVG 70 80 90 100 110 120 ATEGTRPGLE ELYWLATLQQ QLGAGEALGL SPEEAMELLQ GQGPVPVDGP HGYYPGSPEE 130 140 150 160 170 180 TGAQHVQLAE RFSDAALVSM SVRELNRQLR GCGRDEALRL KQRRRTLKNR GYAQACRSKR 190 200 210 220 230 LQQRRGLEAE RARLAAQLDA LRAEVARLAR ERDLYKARCD RLTSSGPGSG DPSHLFL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A conserved retina-specific gene encodes a basic motif/leucine zipper domain." Swaroop A., Xu J.Z., Pawar H., Jackson A.U., Skolnick C., Agarwal N. Proc. Natl. Acad. Sci. U.S.A. 89:266-270(1992) [PubMed: 1729696] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Retina.
[2]	Jackson A.U., Skolnick C., Swaroop A. Submitted (OCT-1993) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Retina.
[3]	"Human bZIP transcription factor gene NRL: structure, genomic sequence, and fine linkage mapping at 14q11.2 and negative mutation analysis in patients with retinal degeneration." Farjo Q., Jackson A.U., Pieke-Dahl S., Scott K., Kimberling W.J., Sieving P.A., Richards J.E., Swaroop A. Genomics 45:395-401(1997) [PubMed: 9344665] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Full-length cDNA libraries and normalization." Li W.B., Gruber C., Jessee J., Polayes D. Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: B-cell and Neuroblastoma.
[5]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"Full-length transcriptome analysis of human retina-derived cell lines ARPE-19 and Y79 using the vector-capping method." Oshikawa M., Tsutsui C., Ikegami T., Fuchida Y., Matsubara M., Toyama S., Usami R., Ohtoko K., Kato S. Invest. Ophthalmol. Vis. Sci. 52:6662-6670(2011) [PubMed: 21697133] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Retinoblastoma.
[7]	"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: 12508121] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	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].
[9]	"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.
[10]	"The leucine zipper of NRL interacts with the CRX homeodomain. A possible mechanism of transcriptional synergy in rhodopsin regulation." Mitton K.P., Swain P.K., Chen S., Xu S., Zack D.J., Swaroop A. J. Biol. Chem. 275:29794-29799(2000) [PubMed: 10887186] [Abstract] Cited for: INTERACTION WITH CRX.
[11]	"The minimal transactivation domain of the basic motif-leucine zipper transcription factor NRL interacts with TATA-binding protein." Friedman J.S., Khanna H., Swain P.K., Denicola R., Cheng H., Mitton K.P., Weber C.H., Hicks D., Swaroop A. J. Biol. Chem. 279:47233-47241(2004) [PubMed: 15328344] [Abstract] Cited for: DOMAIN MINIMAL TRANSACTIVATION DOMAIN.
[12]	"A mutation in NRL is associated with autosomal dominant retinitis pigmentosa." Bessant D.A.R., Payne A.M., Mitton K.P., Wang Q.-L., Swain P.K., Plant C., Bird A.C., Zack D.J., Swaroop A., Bhattacharya S.S. Nat. Genet. 21:355-356(1999) [PubMed: 10192380] [Abstract] Cited for: VARIANT RP27 THR-50.
[13]	"Recessive NRL mutations in patients with clumped pigmentary retinal degeneration and relative preservation of blue cone function." Nishiguchi K.M., Friedman J.S., Sandberg M.A., Swaroop A., Berson E.L., Dryja T.P. Proc. Natl. Acad. Sci. U.S.A. 101:17819-17824(2004) [PubMed: 15591106] [Abstract] Cited for: VARIANT RDCP PRO-160, CHARACTERIZATION OF VARIANT RDCP PRO-160.
+	Additional computationally mapped references.

Web resources

Mutations of the NRL gene

Retina International's Scientific Newsletter

Cross-references

Sequence databases
EMBL GenBank DDBJ	M95925 mRNA. Translation: AAA96828.1. M81840 mRNA. Translation: AAA59948.1. U95012 Genomic DNA. Translation: AAB82768.1. BX161381 mRNA. Translation: CAD61873.1. BX161522 mRNA. Translation: CAD61954.1. AB593102 mRNA. Translation: BAJ84042.1. AB593104 mRNA. Translation: BAJ84044.1. AB593106 mRNA. Translation: BAJ84046.1. BT006942 mRNA. Translation: AAP35588.1. AL136295 Genomic DNA. No translation available. CH471078 Genomic DNA. Translation: EAW66116.1. BC012395 mRNA. Translation: AAH12395.1.
IPI	IPI00008875.
PIR	A41796.
RefSeq	NP_006168.1. NM_006177.3.
UniGene	Hs.652297.
3D structure databases
ProteinModelPortal	P54845.
SMR	P54845. Positions 132-226.
ModBase	Search...
Protein-protein interaction databases
STRING	P54845.
PTM databases
PhosphoSite	P54845.
Polymorphism databases
DMDM	1709348.
Proteomic databases
PRIDE	P54845.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000337947; ENSP00000337023; ENSG00000129535. ENST00000396997; ENSP00000380193; ENSG00000129535. ENST00000397002; ENSP00000380197; ENSG00000129535.
GeneID	4901.
KEGG	hsa:4901.
UCSC	uc001wlo.1. human.
Organism-specific databases
CTD	4901.
GeneCards	GC14M024549.
H-InvDB	HIX0011551.
HGNC	HGNC:8002. NRL.
MIM	162080. gene+phenotype. 613750. phenotype.
neXtProt	NX_P54845.
Orphanet	791. Retinitis pigmentosa.
PharmGKB	PA31781.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG12194.
HOGENOM	HBG714605.
HOVERGEN	HBG000313.
InParanoid	P54845.
OMA	GDHAHFF.
OrthoDB	EOG4F1X44.
PhylomeDB	P54845.
Gene expression databases
ArrayExpress	P54845.
Bgee	P54845.
CleanEx	HS_NRL.
Genevestigator	P54845.
GermOnline	ENSG00000129535. Homo sapiens.
Family and domain databases
InterPro	IPR004827. bZIP. IPR004826. bZIP_Maf. IPR008917. Euk_TF_DNA-bd. IPR013592. Maf_TF_N. IPR024874. Transciption_factor_Maf. [Graphical view]
Gene3D	G3DSA:1.10.880.10. G3DSA:1.10.880.10. 1 hit.
KO	K09038.
PANTHER	PTHR10129. PTHR10129. 1 hit.
Pfam	PF03131. bZIP_Maf. 1 hit. PF08383. Maf_N. 1 hit. [Graphical view]
SMART	SM00338. BRLZ. 1 hit. [Graphical view]
SUPFAM	SSF47454. Euk_transcr_DNA. 1 hit.
PROSITE	PS50217. BZIP. 1 hit. PS00036. BZIP_BASIC. False negative. [Graphical view]
ProtoNet	Search...
Other
NextBio	18863.
SOURCE	Search...

Entry information

Entry name

NRL_HUMAN

Accession

Primary (citable) accession number: P54845
Secondary accession number(s): Q53XD0

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	January 25, 2012
This is version 104 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.