UniProtKB - O75386 (TULP3_HUMAN)
Protein
Tubby-related protein 3
Gene
TULP3
Organism
Homo sapiens (Human)
Status
Functioni
Negative regulator of the Shh signaling transduction pathway: recruited to primary cilia via association with the IFT complex A (IFT-A) and is required for recruitment of G protein-coupled receptor GPR161 to cilia, a promoter of PKA-dependent basal repression machinery in Shh signaling. Binds to phosphorylated inositide (phosphoinositide) lipids. Both IFT-A- and phosphoinositide-binding properties are required to regulate ciliary G protein-coupled receptor trafficking. Not involved in ciliogenesis. During adipogenesis, regulates ciliary trafficking of FFAR4 in preadipocytes.3 Publications
GO - Molecular functioni
- enzyme binding Source: UniProtKB
- G protein-coupled receptor binding Source: MGI
- intraciliary transport particle A binding Source: UniProtKB
- phosphatidylinositol-4,5-bisphosphate binding Source: UniProtKB
- phosphatidylinositol binding Source: UniProtKB
- protein-containing complex binding Source: MGI
GO - Biological processi
- anterior/posterior pattern specification Source: Ensembl
- bone development Source: Ensembl
- brain development Source: Ensembl
- bronchus morphogenesis Source: Ensembl
- central nervous system neuron differentiation Source: Ensembl
- embryonic camera-type eye development Source: Ensembl
- embryonic digit morphogenesis Source: Ensembl
- embryonic neurocranium morphogenesis Source: Ensembl
- ganglion development Source: Ensembl
- G protein-coupled receptor signaling pathway Source: UniProtKB
- negative regulation of smoothened signaling pathway Source: UniProtKB
- negative regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning Source: Ensembl
- negative regulation of smoothened signaling pathway involved in ventral spinal cord patterning Source: Ensembl
- neural tube closure Source: Ensembl
- protein localization to cilium Source: MGI
- regulation of G protein-coupled receptor signaling pathway Source: UniProtKB
- regulation of transcription, DNA-templated Source: UniProtKB
- smoothened signaling pathway involved in dorsal/ventral neural tube patterning Source: Ensembl
Keywordsi
Molecular function | Developmental protein |
Enzyme and pathway databases
PathwayCommonsi | O75386 |
Reactomei | R-HSA-5610787, Hedgehog 'off' state |
SIGNORi | O75386 |
Names & Taxonomyi
Protein namesi | Recommended name: Tubby-related protein 3CuratedAlternative name(s): Tubby-like protein 3 |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:12425, TULP3 |
MIMi | 604730, gene |
neXtProti | NX_O75386 |
VEuPathDBi | HostDB:ENSG00000078246.15 |
Subcellular locationi
Nucleus
Plasma membrane
Extracellular region or secreted
- Secreted By similarity
Other locations
Note: Does not have a cleavable signal peptide and is secreted by a non-conventional pathway (By similarity). Translocates from the plasma membrane to the nucleus upon activation of guanine nucleotide-binding protein G(q) subunit alpha.By similarity
Cytoskeleton
- axoneme Source: Ensembl
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Nucleus
- nucleolus Source: HPA
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Plasma Membrane
- plasma membrane Source: HPA
Other locations
- 9+0 non-motile cilium Source: MGI
- ciliary base Source: MGI
- cilium Source: UniProtKB
Keywords - Cellular componenti
Cell membrane, Cell projection, Cilium, Cytoplasm, Membrane, Nucleus, SecretedPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 24 – 34 | RQAKLDYQRLL → AQAAADYAALA in mut12; abolishes association with the IFT complex A (IFT-A) without affecting phosphoinositide binding. Impaired localization to cilia. 1 PublicationAdd BLAST | 11 | |
Mutagenesisi | 268 – 270 | KLR → ALA in TULP3KR; abolishes phosphoinositide binding and impairs localization to cilia. Still associates with the IFT complex A (IFT-A). 1 Publication | 3 |
Organism-specific databases
DisGeNETi | 7289 |
OpenTargetsi | ENSG00000078246 |
PharmGKBi | PA37087 |
Miscellaneous databases
Pharosi | O75386, Tbio |
Genetic variation databases
BioMutai | TULP3 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000186470 | 1 – 442 | Tubby-related protein 3Add BLAST | 442 |
Proteomic databases
EPDi | O75386 |
jPOSTi | O75386 |
MassIVEi | O75386 |
MaxQBi | O75386 |
PaxDbi | O75386 |
PeptideAtlasi | O75386 |
PRIDEi | O75386 |
ProteomicsDBi | 30981 49959 [O75386-1] 6762 |
PTM databases
iPTMneti | O75386 |
PhosphoSitePlusi | O75386 |
Expressioni
Tissue specificityi
Expressed at high levels in testis, ovaries, thyroid, and spinal chord.1 Publication
Gene expression databases
Bgeei | ENSG00000078246, Expressed in secondary oocyte and 243 other tissues |
ExpressionAtlasi | O75386, baseline and differential |
Genevisiblei | O75386, HS |
Organism-specific databases
HPAi | ENSG00000078246, Low tissue specificity |
Interactioni
Subunit structurei
Associates with the IFT complex A (IFT-A).
2 PublicationsBinary interactionsi
Hide detailsO75386
GO - Molecular functioni
- enzyme binding Source: UniProtKB
- G protein-coupled receptor binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 113140, 72 interactors |
IntActi | O75386, 108 interactors |
STRINGi | 9606.ENSP00000380321 |
Miscellaneous databases
RNActi | O75386, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 23 – 68 | Required for association with the IFT complex A (IFT-A)Add BLAST | 46 |
Sequence similaritiesi
Belongs to the TUB family.Curated
Phylogenomic databases
eggNOGi | KOG2502, Eukaryota |
GeneTreei | ENSGT00940000158155 |
HOGENOMi | CLU_1570112_0_0_1 |
InParanoidi | O75386 |
OMAi | HNDVILH |
OrthoDBi | 1445357at2759 |
PhylomeDBi | O75386 |
TreeFami | TF314076 |
Family and domain databases
Gene3Di | 3.20.90.10, 1 hit |
InterProi | View protein in InterPro IPR025659, Tubby-like_C IPR000007, Tubby_C IPR018066, Tubby_C_CS IPR005398, Tubby_N |
Pfami | View protein in Pfam PF01167, Tub, 1 hit PF16322, Tub_N, 1 hit |
PRINTSi | PR01573, SUPERTUBBY PR01574, TUBBYPROTEIN |
SUPFAMi | SSF54518, SSF54518, 1 hit |
PROSITEi | View protein in PROSITE PS01200, TUB_1, 1 hit PS01201, TUB_2, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: O75386-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MEASRCRLSP SGDSVFHEEM MKMRQAKLDY QRLLLEKRQR KKRLEPFMVQ
60 70 80 90 100
PNPEARLRRA KPRASDEQTP LVNCHTPHSN VILHGIDGPA AVLKPDEVHA
110 120 130 140 150
PSVSSSVVEE DAENTVDTAS KPGLQERLQK HDISESVNFD EETDGISQSA
160 170 180 190 200
CLERPNSASS QNSTDTGTSG SATAAQPADN LLGDIDDLED FVYSPAPQGV
210 220 230 240 250
TVRCRIIRDK RGMDRGLFPT YYMYLEKEEN QKIFLLAARK RKKSKTANYL
260 270 280 290 300
ISIDPVDLSR EGESYVGKLR SNLMGTKFTV YDRGICPMKG RGLVGAAHTR
310 320 330 340 350
QELAAISYET NVLGFKGPRK MSVIIPGMTL NHKQIPYQPQ NNHDSLLSRW
360 370 380 390 400
QNRTMENLVE LHNKAPVWNS DTQSYVLNFR GRVTQASVKN FQIVHKNDPD
410 420 430 440
YIVMQFGRVA DDVFTLDYNY PLCAVQAFGI GLSSFDSKLA CE
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketF5H7B9 | F5H7B9_HUMAN | Tubby-related protein 3 | TULP3 | 137 | Annotation score: | ||
H0YFU8 | H0YFU8_HUMAN | Tubby-related protein 3 | TULP3 | 109 | Annotation score: | ||
H0YG12 | H0YG12_HUMAN | Tubby-related protein 3 | TULP3 | 133 | Annotation score: | ||
F5GWL5 | F5GWL5_HUMAN | Tubby-related protein 3 | TULP3 | 39 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 168 – 181 | TSGSA…PADNL → IPVLLLPPNQLITF in AAC95431 (PubMed:9828123).CuratedAdd BLAST | 14 | |
Sequence conflicti | 187 | D → Y in AAH32587 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 193 – 194 | YS → LV in AAC95431 (PubMed:9828123).Curated | 2 | |
Sequence conflicti | 219 – 226 | PTYYMYLE → SHLLYVLG in AAC95431 (PubMed:9828123).Curated | 8 | |
Sequence conflicti | 393 | I → L in AAC95431 (PubMed:9828123).Curated | 1 | |
Sequence conflicti | 429 – 431 | GIG → AIS in AAC95431 (PubMed:9828123).Curated | 3 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_055761 | 1 – 19 | Missing in isoform 3. 1 PublicationAdd BLAST | 19 | |
Alternative sequenceiVSP_055762 | 165 – 189 | DTGTS…IDDLE → FSSFCQKTEDTGYRHFRFCY CRPTS in isoform 3. 1 PublicationAdd BLAST | 25 | |
Alternative sequenceiVSP_055763 | 190 – 442 | Missing in isoform 3. 1 PublicationAdd BLAST | 253 | |
Alternative sequenceiVSP_054752 | 437 – 442 | SKLACE → KCIQTLRMQELCELHRQHHS AASLVHRTVCQRWVGHPWRL LPQTSLLWTDLSPPPVVPAP HQISM in isoform 2. Curated | 6 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF045583 mRNA Translation: AAC95431.1 AK024246 mRNA Translation: BAG51279.1 AK299990 mRNA Translation: BAH13188.1 AC005911 Genomic DNA No translation available. CH471116 Genomic DNA Translation: EAW88876.1 CH471116 Genomic DNA Translation: EAW88877.1 CH471116 Genomic DNA Translation: EAW88878.1 BC032587 mRNA Translation: AAH32587.1 |
CCDSi | CCDS53737.1 [O75386-2] CCDS8519.1 [O75386-1] |
RefSeqi | NP_001153880.1, NM_001160408.1 [O75386-2] NP_003315.2, NM_003324.4 [O75386-1] |
Genome annotation databases
Ensembli | ENST00000397132; ENSP00000380321; ENSG00000078246 [O75386-2] ENST00000448120; ENSP00000410051; ENSG00000078246 [O75386-1] ENST00000540184; ENSP00000444110; ENSG00000078246 [O75386-3] |
GeneIDi | 7289 |
KEGGi | hsa:7289 |
UCSCi | uc001qlj.3, human [O75386-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF045583 mRNA Translation: AAC95431.1 AK024246 mRNA Translation: BAG51279.1 AK299990 mRNA Translation: BAH13188.1 AC005911 Genomic DNA No translation available. CH471116 Genomic DNA Translation: EAW88876.1 CH471116 Genomic DNA Translation: EAW88877.1 CH471116 Genomic DNA Translation: EAW88878.1 BC032587 mRNA Translation: AAH32587.1 |
CCDSi | CCDS53737.1 [O75386-2] CCDS8519.1 [O75386-1] |
RefSeqi | NP_001153880.1, NM_001160408.1 [O75386-2] NP_003315.2, NM_003324.4 [O75386-1] |
3D structure databases
SMRi | O75386 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 113140, 72 interactors |
IntActi | O75386, 108 interactors |
STRINGi | 9606.ENSP00000380321 |
PTM databases
iPTMneti | O75386 |
PhosphoSitePlusi | O75386 |
Genetic variation databases
BioMutai | TULP3 |
Proteomic databases
EPDi | O75386 |
jPOSTi | O75386 |
MassIVEi | O75386 |
MaxQBi | O75386 |
PaxDbi | O75386 |
PeptideAtlasi | O75386 |
PRIDEi | O75386 |
ProteomicsDBi | 30981 49959 [O75386-1] 6762 |
Protocols and materials databases
Antibodypediai | 10458, 246 antibodies |
DNASUi | 7289 |
Genome annotation databases
Ensembli | ENST00000397132; ENSP00000380321; ENSG00000078246 [O75386-2] ENST00000448120; ENSP00000410051; ENSG00000078246 [O75386-1] ENST00000540184; ENSP00000444110; ENSG00000078246 [O75386-3] |
GeneIDi | 7289 |
KEGGi | hsa:7289 |
UCSCi | uc001qlj.3, human [O75386-1] |
Organism-specific databases
CTDi | 7289 |
DisGeNETi | 7289 |
GeneCardsi | TULP3 |
HGNCi | HGNC:12425, TULP3 |
HPAi | ENSG00000078246, Low tissue specificity |
MIMi | 604730, gene |
neXtProti | NX_O75386 |
OpenTargetsi | ENSG00000078246 |
PharmGKBi | PA37087 |
VEuPathDBi | HostDB:ENSG00000078246.15 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2502, Eukaryota |
GeneTreei | ENSGT00940000158155 |
HOGENOMi | CLU_1570112_0_0_1 |
InParanoidi | O75386 |
OMAi | HNDVILH |
OrthoDBi | 1445357at2759 |
PhylomeDBi | O75386 |
TreeFami | TF314076 |
Enzyme and pathway databases
PathwayCommonsi | O75386 |
Reactomei | R-HSA-5610787, Hedgehog 'off' state |
SIGNORi | O75386 |
Miscellaneous databases
BioGRID-ORCSi | 7289, 5 hits in 901 CRISPR screens |
ChiTaRSi | TULP3, human |
GenomeRNAii | 7289 |
Pharosi | O75386, Tbio |
PROi | PR:O75386 |
RNActi | O75386, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000078246, Expressed in secondary oocyte and 243 other tissues |
ExpressionAtlasi | O75386, baseline and differential |
Genevisiblei | O75386, HS |
Family and domain databases
Gene3Di | 3.20.90.10, 1 hit |
InterProi | View protein in InterPro IPR025659, Tubby-like_C IPR000007, Tubby_C IPR018066, Tubby_C_CS IPR005398, Tubby_N |
Pfami | View protein in Pfam PF01167, Tub, 1 hit PF16322, Tub_N, 1 hit |
PRINTSi | PR01573, SUPERTUBBY PR01574, TUBBYPROTEIN |
SUPFAMi | SSF54518, SSF54518, 1 hit |
PROSITEi | View protein in PROSITE PS01200, TUB_1, 1 hit PS01201, TUB_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | TULP3_HUMAN | |
Accessioni | O75386Primary (citable) accession number: O75386 Secondary accession number(s): B3KNB7 Q8N5B0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 30, 2000 |
Last sequence update: | February 6, 2007 | |
Last modified: | February 10, 2021 | |
This is version 163 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 12
Human chromosome 12: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families