O75386 (TULP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tubby-related protein 3

Alternative name(s):
Tubby-like protein 3

Gene names

Name:	TULP3
Synonyms:	TUBL3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	442 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.5 Ref.6
Subunit structure	Associates with the IFT complex A (IFT-A).
Subcellular location	Nucleus. Cell membrane. Cell projection › cilium. Cytoplasm By similarity. Secreted By similarity. 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. Ref.5 Ref.6
Tissue specificity	Expressed at high levels in testis, ovaries, thyroid, and spinal chord. Ref.1
Sequence similarities	Belongs to the TUB family.

Ontologies

Keywords
Cellular component	Cell membrane Cell projection Cilium Cytoplasm Membrane Nucleus Secreted
Molecular function	Developmental protein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor signaling pathway Non-traceable author statement Ref.5. Source: UniProtKB multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of smoothened signaling pathway Inferred from direct assay Ref.6. Source: UniProtKB regulation of G-protein coupled receptor protein signaling pathway Inferred from direct assay Ref.6. Source: UniProtKB regulation of transcription, DNA-dependent Non-traceable author statement Ref.5. Source: UniProtKB
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay Ref.6. Source: UniProtKB plasma membrane Non-traceable author statement Ref.5. Source: UniProtKB primary cilium Inferred from direct assay Ref.6. Source: UniProtKB
Molecular_function	phosphatidylinositol-4,5-bisphosphate binding Non-traceable author statement Ref.5. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NEB	P20929	2	EBI-5357290,EBI-1049657
vpr	P12520	2	EBI-5357290,EBI-6164519	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 442	442	Tubby-related protein 3		PRO_0000186470
Regions
	Region	23 – 68	46	Required for association with the IFT complex A (IFT-A)
Experimental info
	Mutagenesis	24 – 34	11	RQAKLDYQRLL → AQAAADYAALA in mut12; abolishes association with the IFT complex A (IFT-A) without affecting phosphoinositide binding. Impaired localization to cilia. Ref.6
	Mutagenesis	268 – 270	3	KLR → ALA in TULP3KR; abolishes phosphoinositide binding and impairs localization to cilia. Still associates with the IFT complex A (IFT-A). Ref.6
	Sequence conflict	168 – 181	14	TSGSA…PADNL → IPVLLLPPNQLITF in AAC95431. Ref.1
	Sequence conflict	187	1	D → Y in AAH32587. Ref.4
	Sequence conflict	193 – 194	2	YS → LV in AAC95431. Ref.1
	Sequence conflict	219 – 226	8	PTYYMYLE → SHLLYVLG in AAC95431. Ref.1
	Sequence conflict	393	1	I → L in AAC95431. Ref.1
	Sequence conflict	429 – 431	3	GIG → AIS in AAC95431. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O75386 [UniParc]. Last modified February 6, 2007. Version 2. Checksum: 13DBC83305BFAC1D	FASTA	442	49,642
	10 20 30 40 50 60 MEASRCRLSP SGDSVFHEEM MKMRQAKLDY QRLLLEKRQR KKRLEPFMVQ PNPEARLRRA 70 80 90 100 110 120 KPRASDEQTP LVNCHTPHSN VILHGIDGPA AVLKPDEVHA PSVSSSVVEE DAENTVDTAS 130 140 150 160 170 180 KPGLQERLQK HDISESVNFD EETDGISQSA CLERPNSASS QNSTDTGTSG SATAAQPADN 190 200 210 220 230 240 LLGDIDDLED FVYSPAPQGV TVRCRIIRDK RGMDRGLFPT YYMYLEKEEN QKIFLLAARK 250 260 270 280 290 300 RKKSKTANYL ISIDPVDLSR EGESYVGKLR SNLMGTKFTV YDRGICPMKG RGLVGAAHTR 310 320 330 340 350 360 QELAAISYET NVLGFKGPRK MSVIIPGMTL NHKQIPYQPQ NNHDSLLSRW QNRTMENLVE 370 380 390 400 410 420 LHNKAPVWNS DTQSYVLNFR GRVTQASVKN FQIVHKNDPD YIVMQFGRVA DDVFTLDYNY 430 440 PLCAVQAFGI GLSSFDSKLA CE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular characterization of a novel tubby gene family member, TULP3, in mouse and humans." Nishina P.M., North M.A., Ikeda A., Yan Y., Naggert J.K. Genomics 54:215-220(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	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].
[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]. Tissue: Eye.
[5]	"G-protein signaling through tubby proteins." Santagata S., Boggon T.J., Baird C.L., Gomez C.A., Zhao J., Shan W.S., Myszka D.G., Shapiro L. Science 292:2041-2050(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN G-PROTEIN SIGNALING, SUBCELLULAR LOCATION.
[6]	"TULP3 bridges the IFT-A complex and membrane phosphoinositides to promote trafficking of G protein-coupled receptors into primary cilia." Mukhopadhyay S., Wen X., Chih B., Nelson C.D., Lane W.S., Scales S.J., Jackson P.K. Genes Dev. 24:2180-2193(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, ASSOCIATION WITH THE IFT-A COMPLEX, MUTAGENESIS OF 24-ARG--LEU-34 AND 268-LYS--ARG-270.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF045583 mRNA. Translation: AAC95431.1. AK024246 mRNA. Translation: BAG51279.1. CH471116 Genomic DNA. Translation: EAW88876.1. CH471116 Genomic DNA. Translation: EAW88877.1. CH471116 Genomic DNA. Translation: EAW88878.1. BC032587 mRNA. Translation: AAH32587.1.
IPI	IPI00025353.
RefSeq	NP_001153880.1. NM_001160408.1. NP_003315.2. NM_003324.4.
UniGene	Hs.655333.
3D structure databases
ProteinModelPortal	O75386.
ModBase	Search...
Protein-protein interaction databases
IntAct	O75386. 56 interactions.
STRING	9606.ENSP00000228245.
PTM databases
PhosphoSite	O75386.
Proteomic databases
PaxDb	O75386.
PRIDE	O75386.
Protocols and materials databases
DNASU	7289.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000228245; ENSP00000228245; ENSG00000078246. ENST00000448120; ENSP00000410051; ENSG00000078246.
GeneID	7289.
KEGG	hsa:7289.
UCSC	uc010seh.1. human.
Organism-specific databases
CTD	7289.
GeneCards	GC12P002987.
HGNC	HGNC:12425. TULP3.
HPA	HPA015285.
MIM	604730. gene.
neXtProt	NX_O75386.
PharmGKB	PA37087.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG286778.
HOGENOM	HOG000016044.
HOVERGEN	HBG018010.
InParanoid	O75386.
OrthoDB	EOG42BX8M.
PhylomeDB	O75386.
Gene expression databases
ArrayExpress	O75386.
Bgee	O75386.
CleanEx	HS_TULP3.
Genevestigator	O75386.
GermOnline	ENSG00000078246. Homo sapiens.
Family and domain databases
Gene3D	3.20.90.10. 1 hit.
InterPro	IPR000007. Tubby_C. IPR025659. Tubby_C-like. IPR018066. Tubby_C_CS. IPR005398. Tubby_N. [Graphical view]
Pfam	PF01167. Tub. 1 hit. [Graphical view]
PRINTS	PR01573. SUPERTUBBY. PR01574. TUBBYPROTEIN.
SUPFAM	SSF54518. Tubby_C. 1 hit.
PROSITE	PS01200. TUB_1. 1 hit. PS01201. TUB_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	7289.
NextBio	28499.
SOURCE	Search...

Entry information

Entry name

TULP3_HUMAN

Accession

Primary (citable) accession number: O75386
Secondary accession number(s): B3KNB7, D3DUQ4, Q8N5B0

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	February 6, 2007
Last modified:	May 1, 2013
This is version 97 of the entry and version 2 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.