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O00294 (TULP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tubby-related protein 1
Alternative name(s):
Tubby-like protein 1
Gene names
Name:TULP1
Synonyms:TUBL1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length542 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Required for normal development of photoreceptor synapses. Required for normal photoreceptor function and for long-term survival of photoreceptor cells. Interacts with cytoskeleton proteins and may play a role in protein transport in photoreceptor cells By similarity. Binds lipids, especially phosphatidylinositol 3-phosphate, phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, phosphatidylinositol 3,4-bisphosphate, phosphatidylinositol 4,5-bisphosphate, phosphatidylinositol 3,4,5-bisphosphate, phosphatidylserine and phosphatidic acid (in vitro). Contribute to stimulation of phagocytosis of apoptotic retinal pigment epithelium (RPE) cells and macrophages. Ref.5 Ref.6

Subunit structure

Homodimer Probable. May interact with ABCF1, PSIP1, ZEB1 and HMGB2 Potential. Interacts with DNM1 By similarity. Interacts with F-actin. Interacts with TUB By similarity. Interacts with TYRO3 By similarity. Ref.5

Subcellular location

Cytoplasm. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Secreted By similarity. Cell junctionsynapse By similarity. Note: Detected at synapses between photoreceptor cells and second-order neurons. Does not have a cleavable signal peptide and is secreted by an alternative pathway By similarity. Ref.5

Tissue specificity

Retina-specific.

Involvement in disease

Retinitis pigmentosa 14 (RP14) [MIM:600132]: 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.6 Ref.8 Ref.9 Ref.11 Ref.12

Leber congenital amaurosis 15 (LCA15) [MIM:613843]: 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.10 Ref.13

Sequence similarities

Belongs to the TUB family.

Sequence caution

The sequence CAI20251.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
   Biological processPhagocytosis
Sensory transduction
Vision
   Cellular componentCell junction
Cell membrane
Cytoplasm
Membrane
Secreted
Synapse
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Leber congenital amaurosis
Retinitis pigmentosa
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processdendrite development

Inferred from sequence or structural similarity. Source: UniProtKB

detection of light stimulus involved in visual perception

Inferred from mutant phenotype Ref.11. Source: UniProt

eye photoreceptor cell development

Inferred from sequence or structural similarity. Source: UniProtKB

phagocytosis

Inferred from electronic annotation. Source: UniProtKB-KW

photoreceptor cell maintenance

Inferred from sequence or structural similarity. Source: UniProtKB

phototransduction

Inferred from electronic annotation. Source: Ensembl

positive regulation of phagocytosis

Inferred from direct assay Ref.6. Source: UniProtKB

retina development in camera-type eye

Inferred from electronic annotation. Source: Ensembl

retina homeostasis

Inferred from mutant phenotype Ref.11. Source: UniProt

visual perception

Traceable author statement Ref.9. Source: ProtInc

   Cellular_componentcell junction

Inferred from electronic annotation. Source: UniProtKB-KW

cell projection

Inferred from direct assay Ref.5. Source: UniProtKB

cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular region

Inferred from electronic annotation. Source: UniProtKB-SubCell

photoreceptor inner segment

Inferred from sequence or structural similarity. Source: UniProtKB

photoreceptor outer segment

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from direct assay Ref.5. Source: UniProtKB

synapse

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionG-protein coupled photoreceptor activity

Inferred from electronic annotation. Source: Ensembl

actin filament binding

Inferred from direct assay Ref.5. Source: UniProtKB

phosphatidylinositol-4,5-bisphosphate binding

Inferred from direct assay Ref.5. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 17474147. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

NCK1P163332EBI-1756778,EBI-389883

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O00294-1)

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.
Isoform 2 (identifier: O00294-2)

The sequence of this isoform differs from the canonical sequence as follows:
     64-116: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 542542Tubby-related protein 1
PRO_0000186466

Regions

Compositional bias115 – 13117Poly-Glu
Compositional bias248 – 2547Poly-Glu

Natural variations

Alternative sequence64 – 11653Missing in isoform 2.
VSP_023031
Natural variant671T → R. Ref.1 Ref.2
Corresponds to variant rs7764472 [ dbSNP | Ensembl ].
VAR_008274
Natural variant120 – 1278Missing in RP14.
VAR_013310
Natural variant2451A → V in RP14.
VAR_008275
Natural variant2591I → T. Ref.13
Corresponds to variant rs2064317 [ dbSNP | Ensembl ].
VAR_008276
Natural variant2611K → N. Ref.1 Ref.2 Ref.4 Ref.13
Corresponds to variant rs2064318 [ dbSNP | Ensembl ].
VAR_034575
Natural variant2611K → T in RP14.
VAR_008277
Natural variant3681G → W in LCA15. Ref.10
VAR_065500
Natural variant3781R → H in RP14.
VAR_008278
Natural variant3821F → S in RP14. Ref.11
VAR_037584
Natural variant4001R → W in LCA15. Ref.10
VAR_065501
Natural variant4201R → P in RP14; no effect on RPE phagocytosis. Ref.6 Ref.9
VAR_007941
Natural variant4541T → M in RP14.
Corresponds to variant rs138200747 [ dbSNP | Ensembl ].
VAR_008279
Natural variant4591I → K in RP14; no effect on RPE phagocytosis. Ref.6 Ref.9
Corresponds to variant rs121909075 [ dbSNP | Ensembl ].
VAR_007942
Natural variant4821R → W in RP14. Ref.12
VAR_065502
Natural variant4891K → R in RP14; abolishes RPE phagocytosis. Ref.6 Ref.8
VAR_008280
Natural variant4911F → L in RP14; abolishes RPE phagocytosis. Ref.6 Ref.9
VAR_007943
Natural variant4961A → T in RP14; unknown pathological significance. Ref.8 Ref.13
Corresponds to variant rs141980901 [ dbSNP | Ensembl ].
VAR_008281
Natural variant5291A → AFA in LCA15.
VAR_065503

Secondary structure

......................................... 542
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified September 23, 2008. Version 3.
Checksum: 65320103E2674B60

FASTA54260,609
        10         20         30         40         50         60 
MPLRDETLRE VWASDSGHEE ESLSPEAPRR PKQRPAPAQR LRKKRTEAPE SPCPTGSKPR 

        70         80         90        100        110        120 
KPGAGRTGRP REEPSPDPAQ ARAPQTVYAR FLRDPEAKKR DPRETFLVAR APDAEDEEEE 

       130        140        150        160        170        180 
EEEDEEDEEE EAEEKKEKIL LPPKKPLREK SSADLKERRA KAQGPRGDLG SPDPPPKPLR 

       190        200        210        220        230        240 
VRNKEAPAGE GTKMRKTKKK GSGEADKDPS GSPASARKSP AAMFLVGEGS PDKKALKKKG 

       250        260        270        280        290        300 
TPKGARKEEE EEEEAATVIK KSNQKGKAKG KGKKKAKEER APSPPVEVDE PREFVLRPAP 

       310        320        330        340        350        360 
QGRTVRCRLT RDKKGMDRGM YPSYFLHLDT EKKVFLLAGR KRKRSKTANY LISIDPTNLS 

       370        380        390        400        410        420 
RGGENFIGKL RSNLLGNRFT VFDNGQNPQR GYSTNVASLR QELAAVIYET NVLGFRGPRR 

       430        440        450        460        470        480 
MTVIIPGMSA ENERVPIRPR NASDGLLVRW QNKTLESLIE LHNKPPVWND DSGSYTLNFQ 

       490        500        510        520        530        540 
GRVTQASVKN FQIVHADDPD YIVLQFGRVA EDAFTLDYRY PLCALQAFAI ALSSFDGKLA 


CE 

« Hide

Isoform 2 [UniParc].

Checksum: A687CD39AB3E8000
Show »

FASTA48954,667

References

« Hide 'large scale' references
[1]"Molecular characterization of TUB, TULP1, and TULP2, members of the novel tubby gene family and their possible relation to ocular diseases."
North M.A., Naggert J.K., Yan Y., Noben-Trauth K., Nishina P.M.
Proc. Natl. Acad. Sci. U.S.A. 94:3128-3133(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS ARG-67 AND ASN-261.
Tissue: Retina.
[2]"TULP1 mutation in two extended Dominican kindreds with autosomal recessive retinitis pigmentosa."
Banerjee P., Kleyn P.W., Knowles J.A., Lewis C.A., Ross B.M., Parano E., Kovats S.G., Lee J.J., Penchaszadeh G.K., Ott J., Jacobson S.G., Gilliam T.C.
Nat. Genet. 18:177-179(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-67 AND ASN-261.
[3]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
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] (ISOFORM 2), VARIANT ASN-261.
Tissue: Eye.
[5]"Tubby-like protein 1 (TULP1) interacts with F-actin in photoreceptor cells."
Xi Q., Pauer G.J.T., Marmorstein A.D., Crabb J.W., Hagstrom S.A.
Invest. Ophthalmol. Vis. Sci. 46:4754-4761(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PHOSPHATIDYLINOSITOL PHOSPHOLIPIDS, SUBCELLULAR LOCATION, INTERACTION WITH F-ACTIN.
[6]"Identification of tubby and tubby-like protein 1 as eat-me signals by phage display."
Caberoy N.B., Maiguel D., Kim Y., Li W.
Exp. Cell Res. 316:245-257(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS RP14 PRO-420; LYS-459; ARG-489 AND LEU-491.
[7]"Structure of human TULP1 in complex with IP3."
Structural genomics consortium (SGC)
Submitted (FEB-2009) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 291-536 IN COMPLEX WITH IP3.
[8]"Tubby-like protein-1 mutations in autosomal recessive retinitis pigmentosa."
Gu S., Lennon A., Li Y., Lorenz B., Fossarello M., North M., Gal A., Wright A.
Lancet 351:1103-1104(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS RP14 120-GLU--ASP-127 DEL; ARG-489 AND THR-496.
[9]"Recessive mutations in the gene encoding the tubby-like protein TULP1 in patients with retinitis pigmentosa."
Hagstrom S.A., North M.A., Nishina P.M., Berson E.L., Dryja T.P.
Nat. Genet. 18:174-176(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS RP14 PRO-420; LYS-459 AND LEU-491.
[10]"Leber congenital amaurosis: comprehensive survey of the genetic heterogeneity, refinement of the clinical definition, and genotype-phenotype correlations as a strategy for molecular diagnosis."
Hanein S., Perrault I., Gerber S., Tanguy G., Barbet F., Ducroq D., Calvas P., Dollfus H., Hamel C., Lopponen T., Munier F., Santos L., Shalev S., Zafeiriou D., Dufier J.-L., Munnich A., Rozet J.-M., Kaplan J.
Hum. Mutat. 23:306-317(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LCA15 TRP-368 AND TRP-400.
[11]"A homozygosity-based search for mutations in patients with autosomal recessive retinitis pigmentosa, using microsatellite markers."
Kondo H., Qin M., Mizota A., Kondo M., Hayashi H., Hayashi K., Oshima K., Tahira T., Hayashi K.
Invest. Ophthalmol. Vis. Sci. 45:4433-4439(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT RP14 SER-382.
[12]"Novel compound heterozygous TULP1 mutations in a family with severe early-onset retinitis pigmentosa."
den Hollander A.I., van Lith-Verhoeven J.J., Arends M.L., Strom T.M., Cremers F.P., Hoyng C.B.
Arch. Ophthalmol. 125:932-935(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT RP14 TRP-482.
[13]"Novel TULP1 mutation causing Leber congenital amaurosis or early onset retinal degeneration."
Mataftsi A., Schorderet D.F., Chachoua L., Boussalah M., Nouri M.T., Barthelmes D., Borruat F.X., Munier F.L.
Invest. Ophthalmol. Vis. Sci. 48:5160-5167(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LCA15 PHE-ALA-529 INS, VARIANTS THR-259; ASN-261 AND THR-496.
+Additional computationally mapped references.

Web resources

Mutations of the TULP1 gene

Retina International's Scientific Newsletter

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U82468 mRNA. Translation: AAB53700.1.
AF034923 expand/collapse EMBL AC list , AF034919, AF034920, AF034921, AF034922 Genomic DNA. Translation: AAB97966.1.
AL033519 Genomic DNA. Translation: CAI20251.1. Sequence problems.
BC032714 mRNA. Translation: AAH32714.1.
BC065261 mRNA. Translation: AAH65261.1.
CCDSCCDS4807.1. [O00294-1]
RefSeqNP_001276324.1. NM_001289395.1. [O00294-2]
NP_003313.3. NM_003322.4. [O00294-1]
UniGeneHs.485208.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2FIMX-ray1.90A/B290-542[»]
3C5NX-ray1.80A/B291-536[»]
ProteinModelPortalO00294.
SMRO00294. Positions 291-536.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActO00294. 3 interactions.
STRING9606.ENSP00000229771.

PTM databases

PhosphoSiteO00294.

Proteomic databases

PaxDbO00294.
PRIDEO00294.

Protocols and materials databases

DNASU7287.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000229771; ENSP00000229771; ENSG00000112041. [O00294-1]
ENST00000322263; ENSP00000319414; ENSG00000112041. [O00294-2]
GeneID7287.
KEGGhsa:7287.
UCSCuc003okv.4. human. [O00294-1]
uc003okw.4. human. [O00294-2]

Organism-specific databases

CTD7287.
GeneCardsGC06M035465.
GeneReviewsTULP1.
H-InvDBHIX0005807.
HGNCHGNC:12423. TULP1.
MIM600132. phenotype.
602280. gene.
613843. phenotype.
neXtProtNX_O00294.
Orphanet65. Leber congenital amaurosis.
791. Retinitis pigmentosa.
PharmGKBPA37085.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG286778.
HOGENOMHOG000016044.
HOVERGENHBG018010.
InParanoidO00294.
OMAEAPESPC.
OrthoDBEOG77HDDQ.
PhylomeDBO00294.
TreeFamTF314076.

Gene expression databases

ArrayExpressO00294.
BgeeO00294.
CleanExHS_TULP1.
GenevestigatorO00294.

Family and domain databases

Gene3D3.20.90.10. 1 hit.
InterProIPR000007. Tubby_C.
IPR025659. Tubby_C-like.
IPR018066. Tubby_C_CS.
[Graphical view]
PfamPF01167. Tub. 1 hit.
[Graphical view]
PRINTSPR01573. SUPERTUBBY.
SUPFAMSSF54518. SSF54518. 1 hit.
PROSITEPS01200. TUB_1. 1 hit.
PS01201. TUB_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO00294.
GeneWikiTULP1.
GenomeRNAi7287.
NextBio28491.
PROO00294.
SOURCESearch...

Entry information

Entry nameTULP1_HUMAN
AccessionPrimary (citable) accession number: O00294
Secondary accession number(s): O43536, Q5TGM5, Q8N571
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: September 23, 2008
Last modified: July 9, 2014
This is version 130 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM