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Protein

Neural retina-specific leucine zipper protein

Gene

NRL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Acts as a transcriptional activator which regulates the expression of several rod-specific genes, including RHO and PDE6B (PubMed:21981118). Functions also as a transcriptional coactivator, stimulating transcription mediated by the transcription factor CRX and NR2E3 (PubMed:17335001). Binds in a sequence-specific manner to the rhodopsin promoter (PubMed:17335001).2 Publications

GO - Molecular functioni

  • DNA binding Source: ProtInc
  • DNA-binding transcription factor activity Source: GO_Central
  • DNA-binding transcription factor activity, RNA polymerase II-specific Source: NTNU_SB
  • leucine zipper domain binding Source: UniProtKB
  • promoter-specific chromatin binding Source: Ensembl
  • proximal promoter DNA-binding transcription activator activity, RNA polymerase II-specific Source: NTNU_SB
  • RNA polymerase II proximal promoter sequence-specific DNA binding Source: NTNU_SB
  • sequence-specific DNA binding Source: UniProtKB
  • transcription coactivator activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionActivator, Developmental protein, DNA-binding
Biological processSensory transduction, Transcription, Transcription regulation, Vision

Enzyme and pathway databases

SignaLinkiP54845
SIGNORiP54845

Names & Taxonomyi

Protein namesi
Recommended name:
Neural retina-specific leucine zipper protein
Short name:
NRL
Gene namesi
Name:NRL
Synonyms:D14S46E
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000129535.12
HGNCiHGNC:8002 NRL
MIMi162080 gene
neXtProtiNX_P54845

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Retinitis pigmentosa 27 (RP27)8 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:613750
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07938250S → L in RP27; decreases phosphorylation; no effect on subcellular localization; increased transcriptional coactivator activity. 2 Publications1
Natural variantiVAR_07938350S → P in RP27; decreases phosphorylation; no effect on subcellular localization; increased transcriptional coactivator activity. 2 Publications1
Natural variantiVAR_00926850S → T in RP27; decreases phosphorylation; no effect on subcellular localization; increased transactivational activity; increased transcriptional coactivator activity. 3 PublicationsCorresponds to variant dbSNP:rs104894459EnsemblClinVar.1
Natural variantiVAR_07938451P → L in RP27; decreases phosphorylation; no effect on subcellular localization; increased transcriptional coactivator activity. 4 Publications1
Natural variantiVAR_07938551P → S in RP27; decreases phosphorylation; no effect on subcellular localization; increased transcriptional coactivator activity. 2 PublicationsCorresponds to variant dbSNP:rs794727281EnsemblClinVar.1
Natural variantiVAR_07938651P → T in RP27; autosomal dominant; decreases phosphorylation; no effect on subcellular localization; increased transcriptional coactivator activity. 2 Publications1
Natural variantiVAR_07938767P → S in RP27; no effect on phosphorylation; no effect on subcellular localization; no effect on transcriptional coactivator activity. 2 PublicationsCorresponds to variant dbSNP:rs199691910EnsemblClinVar.1
Natural variantiVAR_07938996M → T in RP27; increased transactivational activity. 1 PublicationCorresponds to variant dbSNP:rs397514516EnsemblClinVar.1
Natural variantiVAR_079390122G → E in RP27; unknown pathological significance; alters phosphorylation; no effect on subcellular localization; no effect on transcriptional coactivator activity. 2 PublicationsCorresponds to variant dbSNP:rs757038765Ensembl.1
Natural variantiVAR_068364170R → S in RP27. 1 Publication1
Retinal degeneration autosomal recessive clumped pigment type (RDCP)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:613750
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07938876A → V in RDCP; unknown pathological significance; alters phosphorylation; no effect on subcellular localization; no effect on transcriptional coactivator activity. 2 PublicationsCorresponds to variant dbSNP:rs149921817Ensembl.1
Natural variantiVAR_064977160L → P in RDCP; alters phosphorylation; no effect on subcellular localization; loss of transcriptional coactivator activity. 2 PublicationsCorresponds to variant dbSNP:rs104894463EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Retinitis pigmentosa

Organism-specific databases

DisGeNETi4901
GeneReviewsiNRL
MalaCardsiNRL
MIMi613750 phenotype
OpenTargetsiENSG00000129535
Orphaneti791 Retinitis pigmentosa
PharmGKBiPA31781

Polymorphism and mutation databases

BioMutaiNRL

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000766331 – 237Neural retina-specific leucine zipper proteinAdd BLAST237

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki20Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Cross-linki24Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

Post-translational modificationi

Phosphorylated (PubMed:11477108, PubMed:17335001).2 Publications
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).By similarity

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Proteomic databases

PaxDbiP54845
PeptideAtlasiP54845
PRIDEiP54845
ProteomicsDBi56738

PTM databases

iPTMnetiP54845
PhosphoSitePlusiP54845

Expressioni

Tissue specificityi

Expressed in the brain and the retina (PubMed:11477108). Expressed strongly in rod and cone cells (at protein level) (PubMed:11477108).1 Publication

Gene expression databases

BgeeiENSG00000129535 Expressed in 102 organ(s), highest expression level in pigmented layer of retina
CleanExiHS_NRL
ExpressionAtlasiP54845 baseline and differential
GenevisibleiP54845 HS

Organism-specific databases

HPAiCAB026066
HPA064599

Interactioni

Subunit structurei

Interacts with FIZ1; this interaction represses transactivation (By similarity). Interacts (via the leucine-zipper domain) with CRX (PubMed:10887186).By similarity1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi110957, 8 interactors
ELMiP54845
IntActiP54845, 3 interactors
STRINGi9606.ENSP00000380193

Structurei

3D structure databases

ProteinModelPortaliP54845
SMRiP54845
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini159 – 222bZIPPROSITE-ProRule annotationAdd BLAST64

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni30 – 93Minimal transactivation domain (MTD)1 PublicationAdd BLAST64
Regioni159 – 185Basic motifPROSITE-ProRule annotationAdd BLAST27
Regioni187 – 208Leucine-zipperPROSITE-ProRule annotationAdd BLAST22

Domaini

The minimal transactivation domain (MTD) is conserved across the MAF family, it may activate transcription by recruiting TBP and associated factors at the promoters of target genes.1 Publication

Sequence similaritiesi

Belongs to the bZIP family.Curated

Phylogenomic databases

eggNOGiKOG4196 Eukaryota
ENOG41102C7 LUCA
GeneTreeiENSGT00550000074549
HOGENOMiHOG000261683
HOVERGENiHBG000313
InParanoidiP54845
KOiK09038
OMAiEGPHGYY
OrthoDBiEOG091G0H46
PhylomeDBiP54845
TreeFamiTF325689

Family and domain databases

InterProiView protein in InterPro
IPR004827 bZIP
IPR004826 bZIP_Maf
IPR013592 Maf_TF_N
IPR028575 Nrl
IPR008917 TF_DNA-bd_sf
IPR024874 Transciption_factor_Maf_fam
PANTHERiPTHR10129 PTHR10129, 1 hit
PTHR10129:SF24 PTHR10129:SF24, 1 hit
PfamiView protein in Pfam
PF03131 bZIP_Maf, 1 hit
PF08383 Maf_N, 1 hit
SMARTiView protein in SMART
SM00338 BRLZ, 1 hit
SUPFAMiSSF47454 SSF47454, 1 hit
PROSITEiView protein in PROSITE
PS50217 BZIP, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: P54845-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MALPPSPLAM EYVNDFDLMK FEVKREPSEG RPGPPTASLG STPYSSVPPS
60 70 80 90 100
PTFSEPGMVG ATEGTRPGLE ELYWLATLQQ QLGAGEALGL SPEEAMELLQ
110 120 130 140 150
GQGPVPVDGP HGYYPGSPEE TGAQHVQLAE RFSDAALVSM SVRELNRQLR
160 170 180 190 200
GCGRDEALRL KQRRRTLKNR GYAQACRSKR LQQRRGLEAE RARLAAQLDA
210 220 230
LRAEVARLAR ERDLYKARCD RLTSSGPGSG DPSHLFL
Length:237
Mass (Da):25,940
Last modified:October 1, 1996 - v1
Checksum:iCCABEDC1C1123614
GO
Isoform 2 (identifier: P54845-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-139: Missing.

Note: No experimental confirmation available.
Show »
Length:98
Mass (Da):11,276
Checksum:i1553BA64DAED254C
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YNW2H0YNW2_HUMAN
Neural retina-specific leucine zipp...
NRL
65Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07938250S → L in RP27; decreases phosphorylation; no effect on subcellular localization; increased transcriptional coactivator activity. 2 Publications1
Natural variantiVAR_07938350S → P in RP27; decreases phosphorylation; no effect on subcellular localization; increased transcriptional coactivator activity. 2 Publications1
Natural variantiVAR_00926850S → T in RP27; decreases phosphorylation; no effect on subcellular localization; increased transactivational activity; increased transcriptional coactivator activity. 3 PublicationsCorresponds to variant dbSNP:rs104894459EnsemblClinVar.1
Natural variantiVAR_07938451P → L in RP27; decreases phosphorylation; no effect on subcellular localization; increased transcriptional coactivator activity. 4 Publications1
Natural variantiVAR_07938551P → S in RP27; decreases phosphorylation; no effect on subcellular localization; increased transcriptional coactivator activity. 2 PublicationsCorresponds to variant dbSNP:rs794727281EnsemblClinVar.1
Natural variantiVAR_07938651P → T in RP27; autosomal dominant; decreases phosphorylation; no effect on subcellular localization; increased transcriptional coactivator activity. 2 Publications1
Natural variantiVAR_07938767P → S in RP27; no effect on phosphorylation; no effect on subcellular localization; no effect on transcriptional coactivator activity. 2 PublicationsCorresponds to variant dbSNP:rs199691910EnsemblClinVar.1
Natural variantiVAR_07938876A → V in RDCP; unknown pathological significance; alters phosphorylation; no effect on subcellular localization; no effect on transcriptional coactivator activity. 2 PublicationsCorresponds to variant dbSNP:rs149921817Ensembl.1
Natural variantiVAR_07938996M → T in RP27; increased transactivational activity. 1 PublicationCorresponds to variant dbSNP:rs397514516EnsemblClinVar.1
Natural variantiVAR_079390122G → E in RP27; unknown pathological significance; alters phosphorylation; no effect on subcellular localization; no effect on transcriptional coactivator activity. 2 PublicationsCorresponds to variant dbSNP:rs757038765Ensembl.1
Natural variantiVAR_079391125H → Q Found in a patient with atypical retinitis pigmentosa and a patient with cone dysfunction; unknown pathological significance; no effect on phosphorylation; no effect on subcellular localization. 2 PublicationsCorresponds to variant dbSNP:rs201970559Ensembl.1
Natural variantiVAR_064977160L → P in RDCP; alters phosphorylation; no effect on subcellular localization; loss of transcriptional coactivator activity. 2 PublicationsCorresponds to variant dbSNP:rs104894463EnsemblClinVar.1
Natural variantiVAR_068364170R → S in RP27. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0555671 – 139Missing in isoform 2. 1 PublicationAdd BLAST139

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
AB593101 mRNA Translation: BAJ84041.1
AB593102 mRNA Translation: BAJ84042.1
AB593103 mRNA Translation: BAJ84043.1
AB593104 mRNA Translation: BAJ84044.1
AB593105 mRNA Translation: BAJ84045.1
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
CCDSiCCDS9608.1 [P54845-1]
PIRiA41796
RefSeqiNP_006168.1, NM_006177.3 [P54845-1]
XP_005267765.1, XM_005267708.4
XP_005267766.1, XM_005267709.3 [P54845-1]
XP_005267767.1, XM_005267710.3
XP_011535104.1, XM_011536802.1 [P54845-1]
XP_011535106.1, XM_011536804.2 [P54845-1]
XP_011535107.1, XM_011536805.2 [P54845-1]
UniGeneiHs.652297

Genome annotation databases

EnsembliENST00000396995; ENSP00000380191; ENSG00000129535 [P54845-2]
ENST00000396997; ENSP00000380193; ENSG00000129535 [P54845-1]
ENST00000397002; ENSP00000380197; ENSG00000129535 [P54845-1]
ENST00000560550; ENSP00000452966; ENSG00000129535 [P54845-2]
ENST00000561028; ENSP00000454062; ENSG00000129535 [P54845-1]
ENST00000642485; ENSP00000494928; ENSG00000285493 [P54845-2]
ENST00000643394; ENSP00000495627; ENSG00000285493 [P54845-1]
ENST00000645740; ENSP00000495155; ENSG00000285493 [P54845-2]
ENST00000646526; ENSP00000496316; ENSG00000285493 [P54845-1]
ENST00000647376; ENSP00000496275; ENSG00000285493 [P54845-1]
GeneIDi4901
KEGGihsa:4901
UCSCiuc001wlo.4 human [P54845-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Web resourcesi

Mutations of the NRL gene

Retina International's Scientific Newsletter

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
AB593101 mRNA Translation: BAJ84041.1
AB593102 mRNA Translation: BAJ84042.1
AB593103 mRNA Translation: BAJ84043.1
AB593104 mRNA Translation: BAJ84044.1
AB593105 mRNA Translation: BAJ84045.1
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
CCDSiCCDS9608.1 [P54845-1]
PIRiA41796
RefSeqiNP_006168.1, NM_006177.3 [P54845-1]
XP_005267765.1, XM_005267708.4
XP_005267766.1, XM_005267709.3 [P54845-1]
XP_005267767.1, XM_005267710.3
XP_011535104.1, XM_011536802.1 [P54845-1]
XP_011535106.1, XM_011536804.2 [P54845-1]
XP_011535107.1, XM_011536805.2 [P54845-1]
UniGeneiHs.652297

3D structure databases

ProteinModelPortaliP54845
SMRiP54845
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110957, 8 interactors
ELMiP54845
IntActiP54845, 3 interactors
STRINGi9606.ENSP00000380193

PTM databases

iPTMnetiP54845
PhosphoSitePlusiP54845

Polymorphism and mutation databases

BioMutaiNRL

Proteomic databases

PaxDbiP54845
PeptideAtlasiP54845
PRIDEiP54845
ProteomicsDBi56738

Protocols and materials databases

DNASUi4901
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000396995; ENSP00000380191; ENSG00000129535 [P54845-2]
ENST00000396997; ENSP00000380193; ENSG00000129535 [P54845-1]
ENST00000397002; ENSP00000380197; ENSG00000129535 [P54845-1]
ENST00000560550; ENSP00000452966; ENSG00000129535 [P54845-2]
ENST00000561028; ENSP00000454062; ENSG00000129535 [P54845-1]
ENST00000642485; ENSP00000494928; ENSG00000285493 [P54845-2]
ENST00000643394; ENSP00000495627; ENSG00000285493 [P54845-1]
ENST00000645740; ENSP00000495155; ENSG00000285493 [P54845-2]
ENST00000646526; ENSP00000496316; ENSG00000285493 [P54845-1]
ENST00000647376; ENSP00000496275; ENSG00000285493 [P54845-1]
GeneIDi4901
KEGGihsa:4901
UCSCiuc001wlo.4 human [P54845-1]

Organism-specific databases

CTDi4901
DisGeNETi4901
EuPathDBiHostDB:ENSG00000129535.12
GeneCardsiNRL
GeneReviewsiNRL
HGNCiHGNC:8002 NRL
HPAiCAB026066
HPA064599
MalaCardsiNRL
MIMi162080 gene
613750 phenotype
neXtProtiNX_P54845
OpenTargetsiENSG00000129535
Orphaneti791 Retinitis pigmentosa
PharmGKBiPA31781
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4196 Eukaryota
ENOG41102C7 LUCA
GeneTreeiENSGT00550000074549
HOGENOMiHOG000261683
HOVERGENiHBG000313
InParanoidiP54845
KOiK09038
OMAiEGPHGYY
OrthoDBiEOG091G0H46
PhylomeDBiP54845
TreeFamiTF325689

Enzyme and pathway databases

SignaLinkiP54845
SIGNORiP54845

Miscellaneous databases

ChiTaRSiNRL human
GeneWikiiNRL_(gene)
GenomeRNAii4901
PROiPR:P54845
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000129535 Expressed in 102 organ(s), highest expression level in pigmented layer of retina
CleanExiHS_NRL
ExpressionAtlasiP54845 baseline and differential
GenevisibleiP54845 HS

Family and domain databases

InterProiView protein in InterPro
IPR004827 bZIP
IPR004826 bZIP_Maf
IPR013592 Maf_TF_N
IPR028575 Nrl
IPR008917 TF_DNA-bd_sf
IPR024874 Transciption_factor_Maf_fam
PANTHERiPTHR10129 PTHR10129, 1 hit
PTHR10129:SF24 PTHR10129:SF24, 1 hit
PfamiView protein in Pfam
PF03131 bZIP_Maf, 1 hit
PF08383 Maf_N, 1 hit
SMARTiView protein in SMART
SM00338 BRLZ, 1 hit
SUPFAMiSSF47454 SSF47454, 1 hit
PROSITEiView protein in PROSITE
PS50217 BZIP, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNRL_HUMAN
AccessioniPrimary (citable) accession number: P54845
Secondary accession number(s): A8MX14, Q53XD0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 7, 2018
This is version 166 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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