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Protein

Leukocyte tyrosine kinase receptor

Gene

LTK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei544ATPPROSITE-ProRule annotation1
Active sitei643Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi516 – 524ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • protein kinase activity Source: UniProtKB
  • protein tyrosine kinase activity Source: ProtInc
  • transmembrane receptor protein tyrosine kinase activity Source: ProtInc

GO - Biological processi

  • cell proliferation Source: UniProtKB
  • cellular response to retinoic acid Source: BHF-UCL
  • negative regulation of apoptotic process Source: UniProtKB
  • phosphatidylinositol 3-kinase signaling Source: UniProtKB
  • positive regulation of cardiac muscle cell apoptotic process Source: UniProtKB
  • positive regulation of neuron projection development Source: BHF-UCL
  • protein phosphorylation Source: UniProtKB
  • signal transduction Source: ProtInc
  • 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

BioCyciZFISH:HS00769-MONOMER.
BRENDAi2.7.10.1. 2681.
SignaLinkiP29376.
SIGNORiP29376.

Names & Taxonomyi

Protein namesi
Recommended name:
Leukocyte tyrosine kinase receptor (EC:2.7.10.1)
Alternative name(s):
Protein tyrosine kinase 1
Gene namesi
Name:LTK
Synonyms:TYK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:6721. LTK.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini17 – 424ExtracellularSequence analysisAdd BLAST408
Transmembranei425 – 449HelicalSequence analysisAdd BLAST25
Topological domaini450 – 864CytoplasmicSequence analysisAdd BLAST415

GO - Cellular componenti

  • integral component of plasma membrane Source: ProtInc
  • intracellular Source: GOC
  • membrane Source: UniProtKB
  • plasma membrane Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Genetic variations in LTK that cause up-regulation of the PI3K pathway may possibly contribute to susceptibility to abnormal proliferation of self-reactive B-cells and, therefore, to systemic lupus erythematosus (SLE). SLE is a chronic, inflammatory and often febrile multisystemic disorder of connective tissue, thought to represent a failure of the regulatory mechanisms of the autoimmune system.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi544K → M: Loss of interaction with PLCG1, PI3-kinase subunit p85, Ras GTPase-activating protein and RAF1. 1 Publication1
Mutagenesisi750G → E: Increases autophosphorylation and interaction with PI3-kinase subunit p85 (demonstrated with chimeric EGFR-LTK). 1 Publication1
Mutagenesisi753Y → F: Abolishes interaction with PI3-kinase subunit p85, impairs PI3 kinase activity and leads to apoptosis (demonstrated with chimeric EGFR-LTK). 1 Publication1
Mutagenesisi862Y → F: Impairs phosphorylation of CBLC (demonstrated with chimeric EGFR-LTK). 1 Publication1

Keywords - Diseasei

Systemic lupus erythematosus

Organism-specific databases

DisGeNETi4058.
OpenTargetsiENSG00000062524.
PharmGKBiPA30483.

Chemistry databases

ChEMBLiCHEMBL5627.
GuidetoPHARMACOLOGYi1838.

Polymorphism and mutation databases

BioMutaiLTK.
DMDMi143811416.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 16Sequence analysisAdd BLAST16
ChainiPRO_000001673817 – 864Leukocyte tyrosine kinase receptorAdd BLAST848

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi257N-linked (GlcNAc...)Sequence analysis1
Glycosylationi380N-linked (GlcNAc...)Sequence analysis1
Glycosylationi412N-linked (GlcNAc...)Sequence analysis1
Modified residuei676Phosphotyrosine; by autocatalysisBy similarity1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP29376.
PeptideAtlasiP29376.
PRIDEiP29376.

PTM databases

iPTMnetiP29376.
PhosphoSitePlusiP29376.

Expressioni

Tissue specificityi

Expressed in non-hematopoietic cell lines and T- and B-cell lines.1 Publication

Gene expression databases

BgeeiENSG00000062524.
CleanExiHS_LTK.
ExpressionAtlasiP29376. baseline and differential.
GenevisibleiP29376. HS.

Organism-specific databases

HPAiHPA059545.

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.Curated

Binary interactionsi

WithEntry#Exp.IntActNotes
FAM150AQ6UXT83EBI-6596163,EBI-11691642

Protein-protein interaction databases

BioGridi110236. 8 interactors.
IntActiP29376. 5 interactors.
MINTiMINT-6744900.
STRINGi9606.ENSP00000263800.

Chemistry databases

BindingDBiP29376.

Structurei

3D structure databases

ProteinModelPortaliP29376.
SMRiP29376.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini510 – 786Protein kinasePROSITE-ProRule annotationAdd BLAST277

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

eggNOGiKOG1095. Eukaryota.
ENOG410XPVX. LUCA.
GeneTreeiENSGT00760000118818.
HOGENOMiHOG000231766.
HOVERGENiHBG052371.
InParanoidiP29376.
KOiK05118.
OMAiAEGGQGC.
OrthoDBiEOG091G003T.
PhylomeDBiP29376.
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:SF294. PTHR24416:SF294. 3 hits.
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 (5)i

Sequence statusi: Complete.

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

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform Lambda P2 (identifier: P29376-1) [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
MGCWGQLLVW FGAAGAILCS SPGSQETFLR SSPLPLASPS PRDPKVSAPP
60 70 80 90 100
SILEPASPLN SPGTEGSWLF STCGASGRHG PTQTQCDGAY AGTSVVVTVG
110 120 130 140 150
AAGQLRGVQL WRVPGPGQYL ISAYGAAGGK GAKNHLSRAH GVFVSAIFSL
160 170 180 190 200
GLGESLYILV GQQGEDACPG GSPESQLVCL GESRAVEEHA AMDGSEGVPG
210 220 230 240 250
SRRWAGGGGG GGGATYVFRV RAGELEPLLV AAGGGGRAYL RPRDRGRTQA
260 270 280 290 300
SPEKLENRSE APGSGGRGGA AGGGGGWTSR APSPQAGRSL QEGAEGGQGC
310 320 330 340 350
SEAWATLGWA AAGGFGGGGG ACTAGGGGGG YRGGDASETD NLWADGEDGV
360 370 380 390 400
SFIHPSSELF LQPLAVTENH GEVEIRRHLN CSHCPLRDCQ WQAELQLAEC
410 420 430 440 450
LCPEGMELAV DNVTCMDLHK PPGPLVLMVA VVATSTLSLL MVCGVLILVK
460 470 480 490 500
QKKWQGLQEM RLPSPELELS KLRTSAIRTA PNPYYCQVGL GPAQSWPLPP
510 520 530 540 550
GVTEVSPANV TLLRALGHGA FGEVYEGLVI GLPGDSSPLQ VAIKTLPELC
560 570 580 590 600
SPQDELDFLM EALIISKFRH QNIVRCVGLS LRATPRLILL ELMSGGDMKS
610 620 630 640 650
FLRHSRPHLG QPSPLVMRDL LQLAQDIAQG CHYLEENHFI HRDIAARNCL
660 670 680 690 700
LSCAGPSRVA KIGDFGMARD IYRASYYRRG DRALLPVKWM PPEAFLEGIF
710 720 730 740 750
TSKTDSWSFG VLLWEIFSLG YMPYPGRTNQ EVLDFVVGGG RMDPPRGCPG
760 770 780 790 800
PVYRIMTQCW QHEPELRPSF ASILERLQYC TQDPDVLNSL LPMELGPTPE
810 820 830 840 850
EEGTSGLGNR SLECLRPPQP QELSPEKLKS WGGSPLGPWL SSGLKPLKSR
860
GLQPQNLWNP TYRS
Length:864
Mass (Da):91,681
Last modified:April 3, 2007 - v3
Checksum:i0617F378AA04298E
GO
Isoform Lambda P1 (identifier: P29376-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     170-170: G → VAAASGDGAAPAPGARAAWGPGERAFLGAGSPAQRGEAPGPRRFPPPLPAG
     171-864: Missing.

Show »
Length:220
Mass (Da):21,952
Checksum:iEC71C9296310B1AA
GO
Isoform Lambda P3 (identifier: P29376-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     448-448: L → GTKRLAGTVDSRLLLSSELGWVSAAGSRRQ
     449-864: Missing.

Show »
Length:477
Mass (Da):48,354
Checksum:i55867ECA5C4A4CF4
GO
Isoform 2 (identifier: P29376-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     274-334: Missing.

Show »
Length:803
Mass (Da):86,213
Checksum:i3877888B402CE78A
GO
Isoform 5 (identifier: P29376-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     274-334: Missing.
     449-544: VKQKKWQGLQ...DSSPLQVAIK → GGAWPGPVLASATRCHRGFPSQCYSAQ

Show »
Length:734
Mass (Da):78,714
Checksum:iAAB41D3555D6DF93
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti106R → G in BAG59451 (PubMed:14702039).Curated1
Sequence conflicti220V → L in CAA43113 (PubMed:1655406).Curated1
Sequence conflicti449V → GTKRLAGTVDSRLLLSM in CAA36460 (PubMed:2320375).Curated1
Sequence conflicti652 – 654SCA → MR in CAA36460 (PubMed:2320375).Curated3

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03156942R → Q.2 PublicationsCorresponds to variant rs2305030dbSNPEnsembl.1
Natural variantiVAR_046106384C → R.1 PublicationCorresponds to variant rs55683312dbSNPEnsembl.1
Natural variantiVAR_046107535D → N.1 PublicationCorresponds to variant rs35932273dbSNPEnsembl.1
Natural variantiVAR_046108569R → S.1 PublicationCorresponds to variant rs148513655dbSNPEnsembl.1
Natural variantiVAR_046109673R → Q.1 PublicationCorresponds to variant rs55876255dbSNPEnsembl.1
Natural variantiVAR_046110745P → S.1 PublicationCorresponds to variant rs55900837dbSNPEnsembl.1
Natural variantiVAR_065465763E → K May possibly contribute to susceptibility to systemic lupus erythematosus; increases autophosphorylation and interaction with PI3-kinase subunit p85. 1 PublicationCorresponds to variant rs76282169dbSNPEnsembl.1
Natural variantiVAR_046111838P → S.1 PublicationCorresponds to variant rs56367146dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_002946170G → VAAASGDGAAPAPGARAAWG PGERAFLGAGSPAQRGEAPG PRRFPPPLPAG in isoform Lambda P1. Curated1
Alternative sequenceiVSP_002947171 – 864Missing in isoform Lambda P1. CuratedAdd BLAST694
Alternative sequenceiVSP_035109274 – 334Missing in isoform 2 and isoform 5. 2 PublicationsAdd BLAST61
Alternative sequenceiVSP_002948448L → GTKRLAGTVDSRLLLSSELG WVSAAGSRRQ in isoform Lambda P3. Curated1
Alternative sequenceiVSP_002949449 – 864Missing in isoform Lambda P3. CuratedAdd BLAST416
Alternative sequenceiVSP_044521449 – 544VKQKK…QVAIK → GGAWPGPVLASATRCHRGFP SQCYSAQ in isoform 5. 1 PublicationAdd BLAST96

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D16105 mRNA. Translation: BAA03679.1.
X60702 mRNA. Translation: CAA43113.1.
AK296892 mRNA. Translation: BAG59451.1.
AC016134 Genomic DNA. No translation available.
AC087721 Genomic DNA. No translation available.
CH471125 Genomic DNA. Translation: EAW92496.1.
X52213 mRNA. Translation: CAA36460.1.
CCDSiCCDS10077.1. [P29376-1]
CCDS10078.1. [P29376-4]
CCDS45237.1. [P29376-5]
PIRiA48266.
RefSeqiNP_001129157.1. NM_001135685.1. [P29376-5]
NP_002335.2. NM_002344.5. [P29376-1]
NP_996844.1. NM_206961.3. [P29376-4]
UniGeneiHs.434481.

Genome annotation databases

EnsembliENST00000263800; ENSP00000263800; ENSG00000062524. [P29376-1]
ENST00000355166; ENSP00000347293; ENSG00000062524. [P29376-4]
ENST00000453182; ENSP00000392196; ENSG00000062524. [P29376-5]
GeneIDi4058.
KEGGihsa:4058.
UCSCiuc001zoa.4. human. [P29376-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D16105 mRNA. Translation: BAA03679.1.
X60702 mRNA. Translation: CAA43113.1.
AK296892 mRNA. Translation: BAG59451.1.
AC016134 Genomic DNA. No translation available.
AC087721 Genomic DNA. No translation available.
CH471125 Genomic DNA. Translation: EAW92496.1.
X52213 mRNA. Translation: CAA36460.1.
CCDSiCCDS10077.1. [P29376-1]
CCDS10078.1. [P29376-4]
CCDS45237.1. [P29376-5]
PIRiA48266.
RefSeqiNP_001129157.1. NM_001135685.1. [P29376-5]
NP_002335.2. NM_002344.5. [P29376-1]
NP_996844.1. NM_206961.3. [P29376-4]
UniGeneiHs.434481.

3D structure databases

ProteinModelPortaliP29376.
SMRiP29376.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110236. 8 interactors.
IntActiP29376. 5 interactors.
MINTiMINT-6744900.
STRINGi9606.ENSP00000263800.

Chemistry databases

BindingDBiP29376.
ChEMBLiCHEMBL5627.
GuidetoPHARMACOLOGYi1838.

PTM databases

iPTMnetiP29376.
PhosphoSitePlusiP29376.

Polymorphism and mutation databases

BioMutaiLTK.
DMDMi143811416.

Proteomic databases

PaxDbiP29376.
PeptideAtlasiP29376.
PRIDEiP29376.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000263800; ENSP00000263800; ENSG00000062524. [P29376-1]
ENST00000355166; ENSP00000347293; ENSG00000062524. [P29376-4]
ENST00000453182; ENSP00000392196; ENSG00000062524. [P29376-5]
GeneIDi4058.
KEGGihsa:4058.
UCSCiuc001zoa.4. human. [P29376-1]

Organism-specific databases

CTDi4058.
DisGeNETi4058.
GeneCardsiLTK.
H-InvDBHIX0038138.
HGNCiHGNC:6721. LTK.
HPAiHPA059545.
MIMi151520. gene.
neXtProtiNX_P29376.
OpenTargetsiENSG00000062524.
PharmGKBiPA30483.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1095. Eukaryota.
ENOG410XPVX. LUCA.
GeneTreeiENSGT00760000118818.
HOGENOMiHOG000231766.
HOVERGENiHBG052371.
InParanoidiP29376.
KOiK05118.
OMAiAEGGQGC.
OrthoDBiEOG091G003T.
PhylomeDBiP29376.
TreeFamiTF351636.

Enzyme and pathway databases

BioCyciZFISH:HS00769-MONOMER.
BRENDAi2.7.10.1. 2681.
SignaLinkiP29376.
SIGNORiP29376.

Miscellaneous databases

GeneWikiiLeukocyte_receptor_tyrosine_kinase.
GenomeRNAii4058.
PROiP29376.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000062524.
CleanExiHS_LTK.
ExpressionAtlasiP29376. baseline and differential.
GenevisibleiP29376. HS.

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:SF294. PTHR24416:SF294. 3 hits.
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]
ProtoNetiSearch...

Entry informationi

Entry nameiLTK_HUMAN
AccessioniPrimary (citable) accession number: P29376
Secondary accession number(s): A6NNJ8, B4DL89, E9PFX4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: April 3, 2007
Last modified: November 2, 2016
This is version 170 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Miscellaneous

Transgenic mice expressing human LTK show specific activation (tyrosine phosphorylation, kinase activity, membrane localization and homooligomerization) in heart combined with cardiac hypertrophy, cardiomyocyte degeneration.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.