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P08923

- LTK_MOUSE

UniProt

P08923 - LTK_MOUSE

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Protein

Leukocyte tyrosine kinase receptor

Gene

Ltk

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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).By similarity

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei540 – 5401ATPPROSITE-ProRule annotation
Active sitei639 – 6391Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi512 – 5209ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. protein kinase activity Source: UniProtKB
  3. transmembrane receptor protein tyrosine kinase activity Source: UniProtKB-EC

GO - Biological processi

  1. cell proliferation Source: UniProtKB
  2. cellular response to retinoic acid Source: Ensembl
  3. negative regulation of apoptotic process Source: UniProtKB
  4. phosphatidylinositol 3-kinase signaling Source: UniProtKB
  5. positive regulation of cardiac muscle cell apoptotic process Source: Ensembl
  6. positive regulation of neuron projection development Source: Ensembl
  7. protein phosphorylation Source: UniProtKB
  8. transmembrane receptor protein tyrosine kinase signaling pathway Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1. 3474.

Names & Taxonomyi

Protein namesi
Recommended name:
Leukocyte tyrosine kinase receptor (EC:2.7.10.1)
Gene namesi
Name:Ltk
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 2

Organism-specific databases

MGIiMGI:96840. Ltk.

Subcellular locationi

Cell membrane 1 Publication; Single-pass type I membrane protein 1 Publication
Isoform A : Endoplasmic reticulum
Note: Retained in the endoplasmic reticulum.
Isoform B : Endoplasmic reticulum
Note: Retained in the endoplasmic reticulum.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini17 – 421405ExtracellularSequence AnalysisAdd
BLAST
Transmembranei422 – 44625HelicalSequence AnalysisAdd
BLAST
Topological domaini447 – 888442CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. endoplasmic reticulum Source: UniProtKB-KW
  2. integral component of membrane Source: UniProtKB-KW
  3. membrane Source: UniProtKB
  4. plasma membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1616Sequence AnalysisAdd
BLAST
Chaini17 – 888872Leukocyte tyrosine kinase receptorPRO_0000016739Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi377 – 3771N-linked (GlcNAc...)Sequence Analysis
Glycosylationi409 – 4091N-linked (GlcNAc...)Sequence Analysis
Modified residuei672 – 6721Phosphotyrosine; by autocatalysisBy similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP08923.
PaxDbiP08923.
PRIDEiP08923.

PTM databases

PhosphoSiteiP08923.

Expressioni

Tissue specificityi

Subsets of lymphoid and neuronal cells.

Gene expression databases

BgeeiP08923.
CleanExiMM_LTK.
ExpressionAtlasiP08923. baseline and differential.
GenevestigatoriP08923.

Interactioni

Subunit structurei

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.By similarityCurated

Structurei

3D structure databases

ProteinModelPortaliP08923.
SMRiP08923. Positions 498-789.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini506 – 782277Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118818.
HOGENOMiHOG000231766.
HOVERGENiHBG052371.
InParanoidiP08923.
KOiK05118.
OMAiAEGGQGC.
OrthoDBiEOG7GN2KT.
TreeFamiTF351636.

Family and domain databases

InterProiIPR011009. 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]
PANTHERiPTHR24416:SF138. PTHR24416:SF138. 1 hit.
PfamiPF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSiPR00109. TYRKINASE.
SMARTiSM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. 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]

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative promoter usage and alternative splicing. Align

Note: Additional isoforms seem to exist.

Isoform D (identifier: P08923-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MGCSHRLLLW LGAAGTILCS NSEFQTPFLT PSLLPVLVLN SQEQKVTPTP
60 70 80 90 100
SKLEPASLPN PLGTRGPWVF NTCGASGRSG PTQTQCDGAY TGSSVMVTVG
110 120 130 140 150
AAGPLKGVQL WRVPDTGQYL ISAYGAAGGK GAQNHLSRAH GIFLSAVFFL
160 170 180 190 200
RRGEPVYILV GQQGQDACPG GSPESQLVCL GESGEHATTY GTERIPGWRR
210 220 230 240 250
WAGGGGGGGG ATSIFRLRAG EPEPLLVAAG GGGRSYRRRP DRGRTQAVPE
260 270 280 290 300
RLETRAAAPG SGGRGGAAGG GSGWTSRAHS PQAGRSPREG AEGGEGCAEA
310 320 330 340 350
WAALRWAAAG GFGGGGGACA AGGGGGGYRG GDTSESDLLW ADGEDGTSFV
360 370 380 390 400
HPSGELYLQP LAVTEGHGEV EIRKHPNCSH CPFKDCQWQA ELWTAECTCP
410 420 430 440 450
EGTELAVDNV TCMDLPTTAS PLILMGAVVA ALALSLLMMC AVLILVNQKC
460 470 480 490 500
QGLWGTRLPG PELELSKLRS SAIRTAPNPY YCQVGLSPAQ PWPLPPGLTE
510 520 530 540 550
VSPANVTLLR ALGHGAFGEV YEGLVTGLPG DSSPLPVAIK TLPELCSHQD
560 570 580 590 600
ELDFLMEALI ISKFSHQNIV RCVGLSFRSA PRLILLELMS GGDMKSFLRH
610 620 630 640 650
SRPHPGQLAP LTMQDLLQLA QDIAQGCHYL EENHFIHRDI AARNCLLSCS
660 670 680 690 700
GASRVAKIGD FGMARDIYQA SYYRKGGRTL LPVKWMPPEA LLEGLFTSKT
710 720 730 740 750
DSWSFGVLLW EIFSLGYMPY PGHTNQEVLD FIATGNRMDP PRNCPGPVYR
760 770 780 790 800
IMTQCWQHQP ELRPDFGSIL ERIQYCTQDP DVLNSPLPVE PGPILEEEEA
810 820 830 840 850
SRLGNRSLEG LRSPKPLELS SQNLKSWGGG LLGSWLPSGL KTLKPRCLQP
860 870 880
QNIWNPTYGS WTPRGPQGED TGIEHCNGSS SSSIPGIQ

Note: May be produced by alternative promoter usage.

Length:888
Mass (Da):94,471
Last modified:July 27, 2011 - v3
Checksum:i7D204A474DEF0AC6
GO
Isoform A (identifier: P08923-2) [UniParc]FASTAAdd to Basket

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.

Show »
Length:576
Mass (Da):62,749
Checksum:i3598526F13E50B4E
GO
Isoform B (identifier: P08923-3) [UniParc]FASTAAdd to Basket

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.

Show »
Length:637
Mass (Da):68,323
Checksum:i72225A1464E47365
GO
Isoform C (identifier: P08923-4) [UniParc]FASTAAdd to Basket

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

Show »
Length:827
Mass (Da):88,897
Checksum:i906AFE379E266FD6
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti26 – 261T → A in AAA39451. (PubMed:8380920)Curated
Sequence conflicti113 – 1131V → A in AAA39451. (PubMed:8380920)Curated
Sequence conflicti789 – 7891V → M in CAA36848. (PubMed:1662793)Curated
Sequence conflicti789 – 7891V → M in AAA39451. (PubMed:8380920)Curated
Sequence conflicti875 – 8751H → Q in CAA36848. (PubMed:1662793)Curated
Sequence conflicti875 – 8751H → Q in AAA39451. (PubMed:8380920)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti746 – 7461G → E.1 Publication

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 251251Missing in isoform A and isoform B. 4 PublicationsVSP_002950Add
BLAST
Alternative sequencei252 – 2521L → M in isoform A and isoform B. 4 PublicationsVSP_002951
Alternative sequencei271 – 33161Missing in isoform A and isoform C. 4 PublicationsVSP_002952Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X52621 mRNA. Translation: CAA36848.1.
M90470 mRNA. Translation: AAA39451.1.
AL844536 Genomic DNA. Translation: CAM18081.1.
X07984 mRNA. Translation: CAA30793.1. Different initiation.
CCDSiCCDS16608.1. [P08923-1]
CCDS16609.1. [P08923-4]
CCDS50674.1. [P08923-2]
PIRiI58378.
S12792.
RefSeqiNP_976220.2. NM_203345.2. [P08923-1]
NP_996824.1. NM_206941.1. [P08923-3]
NP_996825.2. NM_206942.2. [P08923-4]
UniGeneiMm.1740.

Genome annotation databases

EnsembliENSMUST00000028759; ENSMUSP00000028759; ENSMUSG00000027297. [P08923-1]
ENSMUST00000082130; ENSMUSP00000080774; ENSMUSG00000027297. [P08923-4]
ENSMUST00000182203; ENSMUSP00000138201; ENSMUSG00000027297. [P08923-2]
GeneIDi17005.
KEGGimmu:17005.
UCSCiuc008lug.1. mouse. [P08923-3]
uc008lui.1. mouse. [P08923-1]

Keywords - Coding sequence diversityi

Alternative promoter usage, Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X52621 mRNA. Translation: CAA36848.1 .
M90470 mRNA. Translation: AAA39451.1 .
AL844536 Genomic DNA. Translation: CAM18081.1 .
X07984 mRNA. Translation: CAA30793.1 . Different initiation.
CCDSi CCDS16608.1. [P08923-1 ]
CCDS16609.1. [P08923-4 ]
CCDS50674.1. [P08923-2 ]
PIRi I58378.
S12792.
RefSeqi NP_976220.2. NM_203345.2. [P08923-1 ]
NP_996824.1. NM_206941.1. [P08923-3 ]
NP_996825.2. NM_206942.2. [P08923-4 ]
UniGenei Mm.1740.

3D structure databases

ProteinModelPortali P08923.
SMRi P08923. Positions 498-789.
ModBasei Search...
MobiDBi Search...

PTM databases

PhosphoSitei P08923.

Proteomic databases

MaxQBi P08923.
PaxDbi P08923.
PRIDEi P08923.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000028759 ; ENSMUSP00000028759 ; ENSMUSG00000027297 . [P08923-1 ]
ENSMUST00000082130 ; ENSMUSP00000080774 ; ENSMUSG00000027297 . [P08923-4 ]
ENSMUST00000182203 ; ENSMUSP00000138201 ; ENSMUSG00000027297 . [P08923-2 ]
GeneIDi 17005.
KEGGi mmu:17005.
UCSCi uc008lug.1. mouse. [P08923-3 ]
uc008lui.1. mouse. [P08923-1 ]

Organism-specific databases

CTDi 4058.
MGIi MGI:96840. Ltk.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00760000118818.
HOGENOMi HOG000231766.
HOVERGENi HBG052371.
InParanoidi P08923.
KOi K05118.
OMAi AEGGQGC.
OrthoDBi EOG7GN2KT.
TreeFami TF351636.

Enzyme and pathway databases

BRENDAi 2.7.10.1. 3474.

Miscellaneous databases

NextBioi 291120.
PROi P08923.
SOURCEi Search...

Gene expression databases

Bgeei P08923.
CleanExi MM_LTK.
ExpressionAtlasi P08923. baseline and differential.
Genevestigatori P08923.

Family and domain databases

InterProi IPR011009. 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 ]
PANTHERi PTHR24416:SF138. PTHR24416:SF138. 1 hit.
Pfami PF07714. Pkinase_Tyr. 1 hit.
[Graphical view ]
PRINTSi PR00109. TYRKINASE.
SMARTi SM00219. TyrKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS00107. 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 ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.

Entry informationi

Entry nameiLTK_MOUSE
AccessioniPrimary (citable) accession number: P08923
Secondary accession number(s): A2AQ22
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: July 27, 2011
Last modified: October 29, 2014
This is version 148 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3