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Protein

Leukocyte tyrosine kinase receptor

Gene

LTK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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.

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: GO_Central
  • transmembrane signaling receptor activity Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionKinase, Receptor, Transferase, Tyrosine-protein kinase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000062524.15
HGNCiHGNC:6721 LTK
MIMi151520 gene
neXtProtiNX_P29376

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

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...) asparagineSequence analysis1
Glycosylationi380N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi412N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei676Phosphotyrosine; by autocatalysisBy similarity1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP29376
PeptideAtlasiP29376
PRIDEiP29376
ProteomicsDBi54561
54562 [P29376-2]
54563 [P29376-3]
54564 [P29376-4]

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 Expressed in 98 organ(s), highest expression level in mucosa of transverse colon
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
ALKAL1Q6UXT83EBI-6596163,EBI-11691642

Protein-protein interaction databases

BioGridi110236, 13 interactors
IntActiP29376, 5 interactors
MINTiP29376
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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
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
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00219 TyrKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
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

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.

This entry has 5 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H3BVG6H3BVG6_HUMAN
Tyrosine-protein kinase receptor
LTK
562Annotation score:

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 → Q2 PublicationsCorresponds to variant dbSNP:rs2305030Ensembl.1
Natural variantiVAR_046106384C → R1 PublicationCorresponds to variant dbSNP:rs55683312Ensembl.1
Natural variantiVAR_046107535D → N1 PublicationCorresponds to variant dbSNP:rs35932273Ensembl.1
Natural variantiVAR_046108569R → S1 PublicationCorresponds to variant dbSNP:rs148513655Ensembl.1
Natural variantiVAR_046109673R → Q1 PublicationCorresponds to variant dbSNP:rs55876255Ensembl.1
Natural variantiVAR_046110745P → S1 PublicationCorresponds to variant dbSNP:rs55900837Ensembl.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 dbSNP:rs76282169Ensembl.1
Natural variantiVAR_046111838P → S1 PublicationCorresponds to variant dbSNP:rs56367146Ensembl.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

Similar proteinsi

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, 13 interactors
IntActiP29376, 5 interactors
MINTiP29376
STRINGi9606.ENSP00000263800

Chemistry databases

BindingDBiP29376
ChEMBLiCHEMBL5627
GuidetoPHARMACOLOGYi1838

PTM databases

iPTMnetiP29376
PhosphoSitePlusiP29376

Polymorphism and mutation databases

BioMutaiLTK
DMDMi143811416

Proteomic databases

PaxDbiP29376
PeptideAtlasiP29376
PRIDEiP29376
ProteomicsDBi54561
54562 [P29376-2]
54563 [P29376-3]
54564 [P29376-4]

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
EuPathDBiHostDB:ENSG00000062524.15
GeneCardsiLTK
H-InvDBiHIX0038138
HGNCiHGNC:6721 LTK
HPAiHPA059545
MIMi151520 gene
neXtProtiNX_P29376
OpenTargetsiENSG00000062524
PharmGKBiPA30483
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BRENDAi2.7.10.1 2681
SignaLinkiP29376
SIGNORiP29376

Miscellaneous databases

GeneWikiiLeukocyte_receptor_tyrosine_kinase
GenomeRNAii4058
PROiPR:P29376
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000062524 Expressed in 98 organ(s), highest expression level in mucosa of transverse colon
CleanExiHS_LTK
ExpressionAtlasiP29376 baseline and differential
GenevisibleiP29376 HS

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
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
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00219 TyrKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
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
ProtoNetiSearch...

Entry informationi

Entry nameiLTK_HUMAN
AccessioniPrimary (citable) accession number: P29376
Secondary accession number(s): A6NNJ8, B4DL89, E9PFX4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: April 3, 2007
Last modified: November 7, 2018
This is version 180 of the entry and version 3 of the sequence. See 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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 chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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Main funding by: National Institutes of Health

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