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P08923 (LTK_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Leukocyte tyrosine kinase receptor

EC=2.7.10.1
Gene names
Name:Ltk
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length888 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Orphan receptor with a tyrosine-protein kinase activity. The exact function of this protein is not known. Studies with chimeric proteins (replacing its extracellular region with that of several known growth factor receptors, such as EGFR and CSFIR) demonstrate its ability to promote growth and specifically neurite outgrowth, and cell survival. Signaling appears to involve the PI3 kinase pathway. Involved in regulation of the secretory pathway involving endoplasmic reticulum (ER) export sites (ERESs) and ER to Golgi transport By similarity.

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Subunit structure

Homodimer when bound to ligand Probable. Part of a complex including LTK, TNK2 and GRB2, in which GRB2 promotes LTK recruitment by TNK2 By similarity. Isoform A binds calnexin.

Subcellular location

Cell membrane; Single-pass type I membrane protein Ref.6.

Isoform A: Endoplasmic reticulum. Note: Retained in the endoplasmic reticulum. Ref.6

Isoform B: Endoplasmic reticulum. Note: Retained in the endoplasmic reticulum. Ref.6

Tissue specificity

Subsets of lymphoid and neuronal cells.

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.

Contains 1 protein kinase domain.

Sequence caution

The sequence CAA30793.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Cellular componentCell membrane
Endoplasmic reticulum
Membrane
   Coding sequence diversityAlternative promoter usage
Alternative splicing
Polymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMGlycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to retinoic acid

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

phosphatidylinositol 3-kinase signaling

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cardiac muscle cell apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of neuron projection development

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

transmembrane receptor protein tyrosine kinase signaling pathway

Inferred from electronic annotation. Source: InterPro

   Cellular_componentendoplasmic reticulum

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

transmembrane receptor protein tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative promoter usage and alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform D (identifier: P08923-1)

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.
Note: May be produced by alternative promoter usage.
Isoform A (identifier: P08923-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-251: Missing.
     252-252: L → M
     271-331: Missing.
Note: May be produced by alternative promoter usage. Starts at a CUG codon.
Isoform B (identifier: P08923-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-251: Missing.
     252-252: L → M
Note: May be produced by alternative promoter usage. Starts at a CUG codon.
Isoform C (identifier: P08923-4)

The sequence of this isoform differs from the canonical sequence as follows:
     271-331: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1616 Potential
Chain17 – 888872Leukocyte tyrosine kinase receptor
PRO_0000016739

Regions

Topological domain17 – 421405Extracellular Potential
Transmembrane422 – 44625Helical; Potential
Topological domain447 – 888442Cytoplasmic Potential
Domain506 – 782277Protein kinase
Nucleotide binding512 – 5209ATP By similarity

Sites

Active site6391Proton acceptor By similarity
Binding site5401ATP By similarity

Amino acid modifications

Modified residue6721Phosphotyrosine; by autocatalysis By similarity
Glycosylation3771N-linked (GlcNAc...) Potential
Glycosylation4091N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 251251Missing in isoform A and isoform B.
VSP_002950
Alternative sequence2521L → M in isoform A and isoform B.
VSP_002951
Alternative sequence271 – 33161Missing in isoform A and isoform C.
VSP_002952
Natural variant7461G → E. Ref.7

Experimental info

Sequence conflict261T → A in AAA39451. Ref.3
Sequence conflict1131V → A in AAA39451. Ref.3
Sequence conflict7891V → M in CAA36848. Ref.2
Sequence conflict7891V → M in AAA39451. Ref.3
Sequence conflict8751H → Q in CAA36848. Ref.2
Sequence conflict8751H → Q in AAA39451. Ref.3

Sequences

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

Last modified July 27, 2011. Version 3.
Checksum: 7D204A474DEF0AC6

FASTA88894,471
        10         20         30         40         50         60 
MGCSHRLLLW LGAAGTILCS NSEFQTPFLT PSLLPVLVLN SQEQKVTPTP SKLEPASLPN 

        70         80         90        100        110        120 
PLGTRGPWVF NTCGASGRSG PTQTQCDGAY TGSSVMVTVG AAGPLKGVQL WRVPDTGQYL 

       130        140        150        160        170        180 
ISAYGAAGGK GAQNHLSRAH GIFLSAVFFL RRGEPVYILV GQQGQDACPG GSPESQLVCL 

       190        200        210        220        230        240 
GESGEHATTY GTERIPGWRR WAGGGGGGGG ATSIFRLRAG EPEPLLVAAG GGGRSYRRRP 

       250        260        270        280        290        300 
DRGRTQAVPE RLETRAAAPG SGGRGGAAGG GSGWTSRAHS PQAGRSPREG AEGGEGCAEA 

       310        320        330        340        350        360 
WAALRWAAAG GFGGGGGACA AGGGGGGYRG GDTSESDLLW ADGEDGTSFV HPSGELYLQP 

       370        380        390        400        410        420 
LAVTEGHGEV EIRKHPNCSH CPFKDCQWQA ELWTAECTCP EGTELAVDNV TCMDLPTTAS 

       430        440        450        460        470        480 
PLILMGAVVA ALALSLLMMC AVLILVNQKC QGLWGTRLPG PELELSKLRS SAIRTAPNPY 

       490        500        510        520        530        540 
YCQVGLSPAQ PWPLPPGLTE VSPANVTLLR ALGHGAFGEV YEGLVTGLPG DSSPLPVAIK 

       550        560        570        580        590        600 
TLPELCSHQD ELDFLMEALI ISKFSHQNIV RCVGLSFRSA PRLILLELMS GGDMKSFLRH 

       610        620        630        640        650        660 
SRPHPGQLAP LTMQDLLQLA QDIAQGCHYL EENHFIHRDI AARNCLLSCS GASRVAKIGD 

       670        680        690        700        710        720 
FGMARDIYQA SYYRKGGRTL LPVKWMPPEA LLEGLFTSKT DSWSFGVLLW EIFSLGYMPY 

       730        740        750        760        770        780 
PGHTNQEVLD FIATGNRMDP PRNCPGPVYR IMTQCWQHQP ELRPDFGSIL ERIQYCTQDP 

       790        800        810        820        830        840 
DVLNSPLPVE PGPILEEEEA SRLGNRSLEG LRSPKPLELS SQNLKSWGGG LLGSWLPSGL 

       850        860        870        880 
KTLKPRCLQP QNIWNPTYGS WTPRGPQGED TGIEHCNGSS SSSIPGIQ 

« Hide

Isoform A [UniParc].

Checksum: 3598526F13E50B4E
Show »

FASTA57662,749
Isoform B [UniParc].

Checksum: 72225A1464E47365
Show »

FASTA63768,323
Isoform C [UniParc].

Checksum: 906AFE379E266FD6
Show »

FASTA82788,897

References

« Hide 'large scale' references
[1]"The ltk receptor tyrosine kinase is expressed in pre-B lymphocytes and cerebral neurons and uses a non-AUG translational initiator."
Bernards A., de la Monte S.
EMBO J. 9:2279-2287(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
Strain: BALB/c.
[2]"Alternatively spliced ltk mRNA in neurons predicts a receptor with a larger putative extracellular domain."
Haase V.H., Snijders A.J., Cooke S.M., Teng M.N., Kaul D., le Beau M.M., Bruns G.A., Bernards A.
Oncogene 6:2319-2325(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
Strain: BALB/c.
[3]"Four tissue-specific mouse ltk mRNAs predict tyrosine kinases that differ upstream of their transmembrane segment."
Snijders A.J., Haase V.H., Bernards A.
Oncogene 8:27-35(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B; C AND D).
[4]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[5]"Leukocytes express a novel gene encoding a putative transmembrane protein-kinase devoid of an extracellular domain."
Ben-Neriah Y., Bauskin A.R.
Nature 333:672-676(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 260-888 (ISOFORM A).
[6]"A lymphocyte-specific Ltk tyrosine kinase isoform is retained in the endoplasmic reticulum in association with calnexin."
Snijders A.J., Ho S.C., Haase V.H., Pillai S., Bernards A.
J. Biol. Chem. 272:1297-1301(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH CALNEXIN (ISOFORM A).
[7]"Gain-of-function polymorphism in mouse and human Ltk: implications for the pathogenesis of systemic lupus erythematosus."
Li N., Nakamura K., Jiang Y., Tsurui H., Matsuoka S., Abe M., Ohtsuji M., Nishimura H., Kato K., Kawai T., Atsumi T., Koike T., Shirai T., Ueno H., Hirose S.
Hum. Mol. Genet. 13:171-179(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLU-746.
Strain: NZB.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X52621 mRNA. Translation: CAA36848.1.
M90470 mRNA. Translation: AAA39451.1.
AL844536 Genomic DNA. Translation: CAM18081.1.
X07984 mRNA. Translation: CAA30793.1. Different initiation.
PIRI58378.
S12792.
RefSeqNP_976220.2. NM_203345.2.
NP_996824.1. NM_206941.1.
NP_996825.2. NM_206942.2.
UniGeneMm.1740.

3D structure databases

ProteinModelPortalP08923.
SMRP08923. Positions 498-789.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteP08923.

Proteomic databases

PaxDbP08923.
PRIDEP08923.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000028759; ENSMUSP00000028759; ENSMUSG00000027297. [P08923-1]
ENSMUST00000082130; ENSMUSP00000080774; ENSMUSG00000027297. [P08923-4]
ENSMUST00000182203; ENSMUSP00000138201; ENSMUSG00000027297. [P08923-2]
GeneID17005.
KEGGmmu:17005.
UCSCuc008lug.1. mouse. [P08923-3]
uc008lui.1. mouse. [P08923-1]

Organism-specific databases

CTD4058.
MGIMGI:96840. Ltk.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00750000117362.
HOGENOMHOG000231766.
HOVERGENHBG052371.
InParanoidA2AQ22.
KOK05118.
OMAAEGGQGC.
OrthoDBEOG7GN2KT.
TreeFamTF351636.

Enzyme and pathway databases

BRENDA2.7.10.1. 3474.

Gene expression databases

ArrayExpressP08923.
BgeeP08923.
CleanExMM_LTK.
GenevestigatorP08923.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR026984. LTK.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR002011. Tyr_kinase_rcpt_2_CS.
[Graphical view]
PANTHERPTHR24416:SF138. PTHR24416:SF138. 1 hit.
PfamPF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSPR00109. TYRKINASE.
SMARTSM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00239. RECEPTOR_TYR_KIN_II. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio291120.
PROP08923.
SOURCESearch...

Entry information

Entry nameLTK_MOUSE
AccessionPrimary (citable) accession number: P08923
Secondary accession number(s): A2AQ22
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: July 27, 2011
Last modified: April 16, 2014
This is version 144 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot