Reviewed, UniProtKB/Swiss-Prot Q06418 (TYRO3_HUMAN)

Names and origin

Protein names

Recommended name:
    Tyrosine-protein kinase receptor TYRO3
    EC=2.7.10.1
Alternative name(s):
    Tyrosine-protein kinase RSE
    Tyrosine-protein kinase SKY
    Tyrosine-protein kinase DTK
    Tyrosine-protein kinase byk

Gene names

Name:	TYRO3
Synonyms:	BYK, DTK, RSE, SKY

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	890 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	May be involved in cell adhesion processes, particularly in the central nervous system. In case of filovirus infection, seems to function as a cell entry factor.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Monomer and homodimer. Interacts with GAS6.
Subcellular location	Cell membrane; Single-pass type I membrane protein.
Tissue specificity	Abundant in the brain and lower levels in other tissues.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. AXL/UFO subfamily. Contains 2 fibronectin type-III domains. Contains 2 Ig-like C2-type (immunoglobulin-like) domains. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Immunoglobulin domain Repeat Signal Transmembrane
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cell adhesion Ref.2 Traceable author statement. Source: ProtInc protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro signal transduction Ref.1 Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from direct assay. Source: HPA integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc nucleus Inferred from direct assay. Source: HPA
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro protein binding Inferred from electronic annotation. Source: UniProtKB-KW receptor signaling protein tyrosine kinase activity Ref.1 Traceable author statement. Source: ProtInc transmembrane receptor protein tyrosine kinase activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 40

40

Potential

Chain

41 – 890

850

Tyrosine-protein kinase receptor TYRO3

PRO_0000024478

Regions

Topological domain

41 – 429

389

Extracellular Potential

Transmembrane

430 – 450

21

Potential

Topological domain

451 – 890

440

Cytoplasmic Potential

Domain

41 – 128

88

Ig-like C2-type 1

Domain

139 – 220

82

Ig-like C2-type 2

Domain

225 – 317

93

Fibronectin type-III 1

Domain

322 – 413

92

Fibronectin type-III 2

Domain

518 – 790

273

Protein kinase

Nucleotide binding

524 – 532

9

ATP By similarity

Sites

Active site

655

1

Proton acceptor By similarity

Binding site

550

1

ATP By similarity

Amino acid modifications

Modified residue

685

1

Phosphotyrosine By similarity

Modified residue

686

1

Phosphotyrosine; by autocatalysis By similarity

Glycosylation

63

1

N-linked (GlcNAc...) Potential

Glycosylation

191

1

N-linked (GlcNAc...) Potential

Glycosylation

230

1

N-linked (GlcNAc...) Potential

Glycosylation

240

1

N-linked (GlcNAc...) Potential

Glycosylation

293

1

N-linked (GlcNAc...) Potential

Glycosylation

366

1

N-linked (GlcNAc...) Potential

Glycosylation

380

1

N-linked (GlcNAc...) Potential

Disulfide bond

64 ↔ 117

Disulfide bond

160 ↔ 203

Natural variations

Natural variant

21

1

P → L: dbSNP rs17854578.

VAR_045886

Natural variant

346

1

I → N: dbSNP rs12148316.

VAR_045887

Natural variant

542

1

G → S: dbSNP rs17857363.

VAR_045888

Natural variant

815

1

A → V: dbSNP rs1042057.

VAR_045889

Natural variant

819

1

L → M: dbSNP rs17854579.

VAR_045890

Natural variant

824

1

R → G: dbSNP rs17857364.

VAR_045891

Natural variant

831

1

A → T

VAR_041876

Experimental info

Mutagenesis

99

1

I → R: Abolishes dimerization

Sequence conflict

29 – 36

8

Missing in AAC50070. Ref.3

Sequence conflict

285

1

L → F in BAA21781. Ref.4

Sequence conflict

293

1

N → I in BAA21781. Ref.4

Sequence conflict

341

1

E → V in BAA21781. Ref.4

Sequence conflict

812

1

E → D in BAA21781. Ref.4

Secondary structure

1

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890

Helix Strand Turn

Details...

Beta strand

50 – 55

6

Beta strand

60 – 68

9

Beta strand

74 – 78

5

Beta strand

85 – 94

10

Beta strand

97 – 106

10

Helix

109 – 111

3

Beta strand

113 – 121

9

Beta strand

131 – 136

6

Beta strand

140 – 143

4

Beta strand

148 – 150

3

Beta strand

156 – 163

8

Beta strand

165 – 167

3

Beta strand

170 – 175

6

Beta strand

183 – 192

10

Beta strand

199 – 207

9

Beta strand

210 – 213

4

Beta strand

217 – 221

5

Sequences

	Sequence		Length	Mass (Da)
	Q06418-1 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: F9EC675077C4E8F1	FASTA	890	96,905
	10 20 30 40 50 60 MALRRSMGRP GLPPLPLPPP PRLGLLLAAL ASLLLPESAA AGLKLMGAPV KLTVSQGQPV 70 80 90 100 110 120 KLNCSVEGME EPDIQWVKDG AVVQNLDQLY IPVSEQHWIG FLSLKSVERS DAGRYWCQVE 130 140 150 160 170 180 DGGETEISQP VWLTVEGVPF FTVEPKDLAV PPNAPFQLSC EAVGPPEPVT IVWWRGTTKI 190 200 210 220 230 240 GGPAPSPSVL NVTGVTQSTM FSCEAHNLKG LASSRTATVH LQALPAAPFN ITVTKLSSSN 250 260 270 280 290 300 ASVAWMPGAD GRALLQSCTV QVTQAPGGWE VLAVVVPVPP FTCLLRDLVP ATNYSLRVRC 310 320 330 340 350 360 ANALGPSPYA DWVPFQTKGL APASAPQNLH AIRTDSGLIL EWEEVIPEAP LEGPLGPYKL 370 380 390 400 410 420 SWVQDNGTQD ELTVEGTRAN LTGWDPQKDL IVRVCVSNAV GCGPWSQPLV VSSHDRAGQQ 430 440 450 460 470 480 GPPHSRTSWV PVVLGVLTAL VTAAALALIL LRKRRKETRF GQAFDSVMAR GEPAVHFRAA 490 500 510 520 530 540 RSFNRERPER IEATLDSLGI SDELKEKLED VLIPEQQFTL GRMLGKGEFG SVREAQLKQE 550 560 570 580 590 600 DGSFVKVAVK MLKADIIASS DIEEFLREAA CMKEFDHPHV AKLVGVSLRS RAKGRLPIPM 610 620 630 640 650 660 VILPFMKHGD LHAFLLASRI GENPFNLPLQ TLIRFMVDIA CGMEYLSSRN FIHRDLAARN 670 680 690 700 710 720 CMLAEDMTVC VADFGLSRKI YSGDYYRQGC ASKLPVKWLA LESLADNLYT VQSDVWAFGV 730 740 750 760 770 780 TMWEIMTRGQ TPYAGIENAE IYNYLIGGNR LKQPPECMED VYDLMYQCWS ADPKQRPSFT 790 800 810 820 830 840 CLRMELENIL GQLSVLSASQ DPLYINIERA EEPTAGGSLE LPGRDQPYSG AGDGSGMGAV 850 860 870 880 890 GGTPSDCRYI LTPGGLAEQP GQAEHQPESP LNETQRLLLL QQGLLPHSSC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"RSE, a novel receptor-type tyrosine kinase with homology to Axl/Ufo, is expressed at high levels in the brain." Mark M.R., Scadden D.T., Wang Z., Gu Q., Goddard A., Godowski P.J. J. Biol. Chem. 269:10720-10728(1994) [PubMed: 7511603] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cloning of the cDNA for a novel receptor tyrosine kinase, Sky, predominantly expressed in brain." Ohashi K., Mizuno K., Kuma K., Miyata T., Nakamura T. Oncogene 9:699-705(1994) [PubMed: 8108112] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Isolation and characterization of the human DTK receptor tyrosine kinase." Crosier K.E., Hall L.R., Lewis P.M., Morris C.M., Wood C.R., Morris J.C., Crosier P.S. Growth Factors 11:137-144(1994) [PubMed: 7857658] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-815. Tissue: Brain.
[4]	"A tyrosine kinase-like molecule is localized in the nuclear membrane of neurons: hippocampal behavior under stress." Kajii Y., Ninomiya D., Kato M., Mizuguchi M., Saji M., Katsumoto T., Ohno K., Takashima S., Onodera K. Biol. Cell 88:45-54(1996) [PubMed: 9175267] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[5]	"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], VARIANTS LEU-21; SER-542; MET-819 AND GLY-824. Tissue: Skin and Testis.
[6]	"The human TYRO3 gene and pseudogene are located in chromosome 15q14-q25." Polvi A., Armstrong E., Lai C., Lemke G., Huebner K., Spritz R.A., Giuda L.C., Nicholls R.D., Alitalo K. Gene 134:289-293(1993) [PubMed: 8262388] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 519-720.
[7]	"Tyro3 family-mediated cell entry of Ebola and Marburg viruses." Shimojima M., Takada A., Ebihara H., Neumann G., Fujioka K., Irimura T., Jones S., Feldmann H., Kawaoka Y. J. Virol. 80:10109-10116(2006) [PubMed: 17005688] [Abstract] Cited for: FUNCTION AS CELL ENTRY FACTOR IN FILOVIRUS INFECTION.
[8]	"Ligand recognition and homophilic interactions in Tyro3: structural insights into the Axl/Tyro3 receptor tyrosine kinase family." Heiring C., Dahlbaeck B., Muller Y.A. J. Biol. Chem. 279:6952-6958(2004) [PubMed: 14623883] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) OF 41-222, SUBUNIT, INTERACTION WITH GAS6, MUTAGENESIS OF ILE-99, DISULFIDE BONDS.
[9]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] THR-831.

Cross-references

Sequence databases

EMBLGenBankDDBJ

U05682 mRNA. Translation: AAA19236.1.
D17517 mRNA. Translation: BAA04467.1.
U18934 mRNA. Translation: AAC50070.1.
D50479 mRNA. Translation: BAA21781.1. Different initiation.
BC049368 mRNA. Translation: AAH49368.1.
BC051756 mRNA. Translation: AAH51756.1.
X72886 mRNA. Translation: CAA51396.1.

PIR

A53743.
I38912.

RefSeq

NP_006284.2.

UniGene

Hs.381282

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1RHF	X-ray	1.96	A/B	41-222	[»]

ModBase

Search...

PTM databases

PhosphoSite

Q06418.

Genome annotation databases

Ensembl

ENSG00000092445. Homo sapiens. [Contig view]

GeneID

7301.

KEGG

hsa:7301.

Organism-specific databases

H-InvDB

HIX0012156.

HGNC

HGNC:12446. TYRO3.

HPA

HPA007654.

MIM

600341. gene.

PharmGKB

PA37097.

GenAtlas

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GeneCards

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