Tubby-related protein 1 - Homo sapiens (Human)

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

Alternative products

Sequence annotation (Features)

Sequences

References

Web resources

Cross-references

Entry information

Relevant documents

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

Alternative products

Sequence annotation (Features)

Sequences

References

Web resources

Cross-references

Entry information

Relevant documents

Preferred order of sections

Molecule processing

Regions

Natural variations

Secondary structure

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Preferred order of sections

With

Entry

#Exp.

IntAct

Notes

Molecule processing

Regions

Natural variations

Secondary structure

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Protein names

Recommended name:
Tubby-related protein 1

Alternative name(s):
Tubby-like protein 1

Gene names

Name:	TULP1
Synonyms:	TUBL1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Sequence length	542 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

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. Ref.5
Subcellular location	Cytoplasm. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Secreted By similarity. Cell junction › synapse 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	Defects in TULP1 are the cause of retinitis pigmentosa type 14 (RP14) [MIM:600132]. 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. RP14 inheritance is autosomal recessive. Ref.6 Ref.8 Ref.9 Ref.11 Ref.12 Defects in TULP1 are the cause of Leber congenital amaurosis type 15 (LCA15) [MIM:613843]. LCA15 is 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. 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.

Keywords
Biological process	Phagocytosis Sensory transduction Vision
Cellular component	Cell junction Cell membrane Cytoplasm Membrane Secreted Synapse
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Leber congenital amaurosis Retinitis pigmentosa
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	dendrite development Inferred from sequence or structural similarity. Source: UniProtKB 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 positive regulation of phagocytosis Inferred from direct assay Ref.6. Source: UniProtKB
Cellular component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW 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 function	actin filament binding Inferred from direct assay Ref.5. Source: UniProtKB phosphatidylinositol-4,5-bisphosphate binding Inferred from direct assay Ref.5. Source: UniProtKB
Complete GO annotation...

With	Entry	#Exp.	IntAct	Notes
NCK1	P16333	2	EBI-1756778,EBI-389883

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Chain

1 – 542

542

Tubby-related protein 1

PRO_0000186466

Compositional bias

115 – 131

17

Poly-Glu

Compositional bias

248 – 254

7

Poly-Glu

Alternative sequence

64 – 116

53

Missing in isoform 2.

VSP_023031

Natural variant

67

1

T → R. Ref.1 Ref.2
Corresponds to variant rs7764472 [ dbSNP | Ensembl ].

VAR_008274

Natural variant

120 – 127

8

Missing in RP14.

VAR_013310

Natural variant

245

1

A → V in RP14.

VAR_008275

Natural variant

259

1

I → T. Ref.13
Corresponds to variant rs2064317 [ dbSNP | Ensembl ].

VAR_008276

Natural variant

261

1

K → N. Ref.1 Ref.2 Ref.4 Ref.13
Corresponds to variant rs2064318 [ dbSNP | Ensembl ].

VAR_034575

Natural variant

261

1

K → T in RP14.

VAR_008277

Natural variant

368

1

G → W in LCA15. Ref.10

VAR_065500

Natural variant

378

1

R → H in RP14.

VAR_008278

Natural variant

382

1

F → S in RP14. Ref.11

VAR_037584

Natural variant

400

1

R → W in LCA15. Ref.10

VAR_065501

Natural variant

420

1

R → P in RP14; no effect on RPE phagocytosis. Ref.6 Ref.9

VAR_007941

Natural variant

454

1

T → M in RP14.

VAR_008279

Natural variant

459

1

I → K in RP14; no effect on RPE phagocytosis. Ref.6 Ref.9

VAR_007942

Natural variant

482

1

R → W in RP14. Ref.12

VAR_065502

Natural variant

489

1

K → R in RP14; abolishes RPE phagocytosis. Ref.6 Ref.8

VAR_008280

Natural variant

491

1

F → L in RP14; abolishes RPE phagocytosis. Ref.6 Ref.9

VAR_007943

Natural variant

496

1

A → T in RP14; uncertain pathogenicity. Ref.8 Ref.13

VAR_008281

Natural variant

529

1

A → AFA in LCA15.

VAR_065503

1

.

542

Helix Strand Turn

Details...

Sequence		Length	Mass (Da)
Isoform 1 [UniParc]. Last modified September 23, 2008. Version 3. Checksum: 65320103E2674B60 Show »	FASTA	542	60,609
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 »	FASTA	489	54,667
10 20 30 40 50 60 MPLRDETLRE VWASDSGHEE ESLSPEAPRR PKQRPAPAQR LRKKRTEAPE SPCPTGSKPR 70 80 90 100 110 120 KPGEEEEEEE DEEDEEEEAE EKKEKILLPP KKPLREKSSA DLKERRAKAQ GPRGDLGSPD 130 140 150 160 170 180 PPPKPLRVRN KEAPAGEGTK MRKTKKKGSG EADKDPSGSP ASARKSPAAM FLVGEGSPDK 190 200 210 220 230 240 KALKKKGTPK GARKEEEEEE EAATVIKKSN QKGKAKGKGK KKAKEERAPS PPVEVDEPRE 250 260 270 280 290 300 FVLRPAPQGR TVRCRLTRDK KGMDRGMYPS YFLHLDTEKK VFLLAGRKRK RSKTANYLIS 310 320 330 340 350 360 IDPTNLSRGG ENFIGKLRSN LLGNRFTVFD NGQNPQRGYS TNVASLRQEL AAVIYETNVL 370 380 390 400 410 420 GFRGPRRMTV IIPGMSAENE RVPIRPRNAS DGLLVRWQNK TLESLIELHN KPPVWNDDSG 430 440 450 460 470 480 SYTLNFQGRV TQASVKNFQI VHADDPDYIV LQFGRVAEDA FTLDYRYPLC ALQAFAIALS SFDGKLACE « Hide

	« Hide 'large scale' referencesShow '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: 9096357] [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: 9462751] [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. Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [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: 15489334] [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: 16303976] [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: 19837063] [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: 9660588] [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: 9462750] [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: 15024725] [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: 15557452] [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: 17620573] [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: 17962469] [Abstract] Cited for: VARIANT LCA15 PHE-ALA-529 INS, VARIANTS THR-259; ASN-261 AND THR-496.
+	Additional computationally mapped references.

Mutations of the TULP1 gene

Retina International's Scientific Newsletter

GeneReviews

EMBL
GenBank
DDBJ

U82468 mRNA. Translation: AAB53700.1.
AF034923

AF034922 Genomic DNA. Translation: AAB97966.1.
AL033519 Genomic DNA. Translation: CAI20251.1. Sequence problems.
BC032714 mRNA. Translation: AAH32714.1.
BC065261 mRNA. Translation: AAH65261.1.

IPI

IPI00010894.
IPI00827823.

RefSeq

NP_003313.3. NM_003322.3.

UniGene

Hs.485208.

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2FIM	X-ray	1.90	A/B	290-542	[»]
3C5N	X-ray	1.80	A/B	291-536	[»]

ProteinModelPortal

O00294.

SMR

O00294. Positions 291-536.

ModBase

Search...

IntAct

O00294. 3 interactions.

MINT

MINT-7001899.

STRING

O00294.

PhosphoSite

O00294.

PRIDE

O00294.

DNASU

7287.

StructuralBiologyKnowledgebase

Search...

Ensembl

ENST00000229771; ENSP00000229771; ENSG00000112041.

GeneID

7287.

KEGG

hsa:7287.

UCSC

uc003okv.4. human.
uc003okw.4. human.

CTD

7287.

GeneCards

GC06M035512.

H-InvDB

HIX0005807.

HGNC

HGNC:12423. TULP1.

MIM

600132. phenotype.
602280. gene.
613843. phenotype.

neXtProt

NX_O00294.

Orphanet

65. Leber congenital amaurosis.
791. Retinitis pigmentosa.

PharmGKB

PA37085.

GenAtlas

Search...

eggNOG

NOG286778.

GeneTree

ENSGT00610000085970.

HOGENOM

HOG000016044.

HOVERGEN

HBG018010.

InParanoid

O00294.

OMA

EAPESPC.

OrthoDB

EOG42821K.

PhylomeDB

O00294.

ArrayExpress

O00294.

Bgee

O00294.

CleanEx

HS_TULP1.

Genevestigator

O00294.

GermOnline

ENSG00000112041. Homo sapiens.

Gene3D

G3DSA:3.20.90.10. Tubby_C. 1 hit.

InterPro

IPR000007. Tubby_C.
IPR025659. Tubby_C-like.
IPR018066. Tubby_C_CS.
[Graphical view]

Pfam

PF01167. Tub. 1 hit.
[Graphical view]

PRINTS

PR01573. SUPERTUBBY.

SUPFAM

SSF54518. Tubby_C. 1 hit.

PROSITE

PS01200. TUB_1. 1 hit.
PS01201. TUB_2. 1 hit.
[Graphical view]

ProtoNet

Search...

EvolutionaryTrace

O00294.

NextBio

28491.

SOURCE

Search...

Entry name

TULP1_HUMAN

Accession

Primary (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:	May 16, 2012
This is version 107 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.

Human chromosome 6

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

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.