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Protein

TYRO protein tyrosine kinase-binding protein

Gene

TYROBP

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

Functioni

Non-covalently associates with activating receptors of the CD300 family. Cross-linking of CD300-TYROBP complexes results in cellular activation. Involved for instance in neutrophil activation mediated by integrin.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei54Important for interaction with transmembrane receptors1

GO - Molecular functioni

  • receptor binding Source: UniProtKB
  • signal transducer activity, downstream of receptor Source: ProtInc

GO - Biological processi

Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:ENSG00000011600-MONOMER.
ReactomeiR-HSA-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
R-HSA-2172127. DAP12 interactions.
R-HSA-2424491. DAP12 signaling.
R-HSA-391160. Signal regulatory protein (SIRP) family interactions.
R-HSA-416700. Other semaphorin interactions.
R-HSA-6798695. Neutrophil degranulation.
SignaLinkiO43914.

Names & Taxonomyi

Protein namesi
Recommended name:
TYRO protein tyrosine kinase-binding protein
Alternative name(s):
DNAX-activation protein 12
Killer-activating receptor-associated protein
Short name:
KAR-associated protein
Gene namesi
Name:TYROBP
Synonyms:DAP12, KARAP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:12449. TYROBP.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini22 – 40ExtracellularSequence analysisAdd BLAST19
Transmembranei41 – 61HelicalSequence analysisAdd BLAST21
Topological domaini62 – 113CytoplasmicSequence analysisAdd BLAST52

GO - Cellular componenti

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

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionRecessively inherited disease characterized by a combination of psychotic symptoms rapidly progressing to presenile dementia and bone cysts restricted to wrists and ankles. PLOSL has a global distribution, although most of the patients have been diagnosed in Finland and Japan, with an estimated population prevalence of 2x10(-6) in the Finns.
See also OMIM:221770

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi54T → A: Reduced interaction with KLRC2 and KIR2DS3. 1 Publication1

Organism-specific databases

DisGeNETi7305.
MalaCardsiTYROBP.
MIMi221770. phenotype.
OpenTargetsiENSG00000011600.
Orphaneti2770. Nasu-Hakola disease.
PharmGKBiPA37100.

Polymorphism and mutation databases

BioMutaiTYROBP.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000002260322 – 113TYRO protein tyrosine kinase-binding proteinAdd BLAST92

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi35Interchain1 Publication
Modified residuei91PhosphotyrosineBy similarity1
Modified residuei102PhosphotyrosineBy similarity1

Post-translational modificationi

Tyrosine phosphorylated.

Keywords - PTMi

Disulfide bond, Phosphoprotein

Proteomic databases

EPDiO43914.
PaxDbiO43914.
PeptideAtlasiO43914.
PRIDEiO43914.

PTM databases

iPTMnetiO43914.
PhosphoSitePlusiO43914.

Expressioni

Tissue specificityi

Expressed at low levels in the early development of the hematopoietic system and in the promonocytic stage and at high levels in mature monocytes. Expressed in hematological cells and tissues such as peripheral blood leukocytes and spleen. Also found in bone marrow, lymph nodes, placenta, lung and liver. Expressed at lower levels in different parts of the brain especially in the basal ganglia and corpus callosum.1 Publication

Gene expression databases

BgeeiENSG00000011600.
CleanExiHS_TYROBP.
ExpressionAtlasiO43914. baseline and differential.
GenevisibleiO43914. HS.

Organism-specific databases

HPAiCAB009493.
HPA041899.

Interactioni

Subunit structurei

Homodimer; disulfide-linked. Interacts with SIRPB1 and TREM1. Interacts with CLECSF5. Interacts with SIGLEC14. Interacts with CD300LB and CD300E. Interacts with CD300D (By similarity). Interacts (via ITAM domain) with SYK (via SH2 domains); activates SYK mediating neutrophils and macrophages integrin-mediated activation (By similarity). Interacts with KLRC2 and KIR2DS3.By similarity7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself2EBI-2214794,EBI-2214794
KLRC2P267172EBI-2214794,EBI-3862171
SIRPB1O002414EBI-2214794,EBI-2615458

GO - Molecular functioni

  • receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi113155. 7 interactors.
IntActiO43914. 8 interactors.
STRINGi9606.ENSP00000262629.

Structurei

Secondary structure

1113
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi40 – 65Combined sources26

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2L34NMR-A/B35-67[»]
2L35NMR-A35-67[»]
B35-66[»]
4WO1X-ray2.14A/B/C/D35-67[»]
4WOLX-ray1.77A/B/C35-67[»]
ProteinModelPortaliO43914.
SMRiO43914.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO43914.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini80 – 108ITAMAdd BLAST29

Sequence similaritiesi

Belongs to the TYROBP family.Curated
Contains 1 ITAM domain.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410J1XS. Eukaryota.
ENOG410Z4TN. LUCA.
GeneTreeiENSGT00390000016786.
HOGENOMiHOG000056440.
HOVERGENiHBG061468.
InParanoidiO43914.
KOiK07992.
PhylomeDBiO43914.
TreeFamiTF336898.

Family and domain databases

InterProiIPR026200. Tyrobp.
[Graphical view]
PANTHERiPTHR17554. PTHR17554. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O43914-1) [UniParc]FASTAAdd to basket
Also known as: KARAP-a

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
MGGLEPCSRL LLLPLLLAVS GLRPVQAQAQ SDCSCSTVSP GVLAGIVMGD
60 70 80 90 100
LVLTVLIALA VYFLGRLVPR GRGAAEAATR KQRITETESP YQELQGQRSD
110
VYSDLNTQRP YYK
Length:113
Mass (Da):12,179
Last modified:June 1, 1998 - v1
Checksum:i267CB1C1756F89F0
GO
Isoform 2 (identifier: O43914-2) [UniParc]FASTAAdd to basket
Also known as: KARAP-b

The sequence of this isoform differs from the canonical sequence as follows:
     77-77: Missing.

Show »
Length:112
Mass (Da):12,108
Checksum:iD89003C4B50874D0
GO
Isoform 3 (identifier: O43914-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     20-30: Missing.

Note: No experimental confirmation available.
Show »
Length:102
Mass (Da):11,043
Checksum:i4DB742FB830E8C48
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_011985111Y → H.Corresponds to variant rs14714dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04606620 – 30Missing in isoform 3. 1 PublicationAdd BLAST11
Alternative sequenceiVSP_01290977Missing in isoform 2. 3 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF019562 mRNA. Translation: AAD09436.1.
AF019563 Genomic DNA. Translation: AAD09437.1.
AJ010098 mRNA. Translation: CAB52288.1.
AY074782 mRNA. Translation: AAL74017.1.
BT009851 mRNA. Translation: AAP88853.1.
AK290385 mRNA. Translation: BAF83074.1.
CR450342 mRNA. Translation: CAG29338.1.
CR542202 mRNA. Translation: CAG46999.1.
BP295666 mRNA. No translation available.
AD000833 Genomic DNA. No translation available.
AD000864 Genomic DNA. No translation available.
BC011175 mRNA. Translation: AAH11175.1.
CCDSiCCDS12482.1. [O43914-1]
CCDS46058.1. [O43914-2]
CCDS54255.1. [O43914-3]
RefSeqiNP_001166985.1. NM_001173514.1. [O43914-3]
NP_003323.1. NM_003332.3. [O43914-1]
NP_937758.1. NM_198125.2. [O43914-2]
UniGeneiHs.515369.

Genome annotation databases

EnsembliENST00000262629; ENSP00000262629; ENSG00000011600. [O43914-1]
ENST00000544690; ENSP00000445332; ENSG00000011600. [O43914-3]
ENST00000589517; ENSP00000468447; ENSG00000011600. [O43914-2]
GeneIDi7305.
KEGGihsa:7305.
UCSCiuc002ocm.4. human. [O43914-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF019562 mRNA. Translation: AAD09436.1.
AF019563 Genomic DNA. Translation: AAD09437.1.
AJ010098 mRNA. Translation: CAB52288.1.
AY074782 mRNA. Translation: AAL74017.1.
BT009851 mRNA. Translation: AAP88853.1.
AK290385 mRNA. Translation: BAF83074.1.
CR450342 mRNA. Translation: CAG29338.1.
CR542202 mRNA. Translation: CAG46999.1.
BP295666 mRNA. No translation available.
AD000833 Genomic DNA. No translation available.
AD000864 Genomic DNA. No translation available.
BC011175 mRNA. Translation: AAH11175.1.
CCDSiCCDS12482.1. [O43914-1]
CCDS46058.1. [O43914-2]
CCDS54255.1. [O43914-3]
RefSeqiNP_001166985.1. NM_001173514.1. [O43914-3]
NP_003323.1. NM_003332.3. [O43914-1]
NP_937758.1. NM_198125.2. [O43914-2]
UniGeneiHs.515369.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2L34NMR-A/B35-67[»]
2L35NMR-A35-67[»]
B35-66[»]
4WO1X-ray2.14A/B/C/D35-67[»]
4WOLX-ray1.77A/B/C35-67[»]
ProteinModelPortaliO43914.
SMRiO43914.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113155. 7 interactors.
IntActiO43914. 8 interactors.
STRINGi9606.ENSP00000262629.

PTM databases

iPTMnetiO43914.
PhosphoSitePlusiO43914.

Polymorphism and mutation databases

BioMutaiTYROBP.

Proteomic databases

EPDiO43914.
PaxDbiO43914.
PeptideAtlasiO43914.
PRIDEiO43914.

Protocols and materials databases

DNASUi7305.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262629; ENSP00000262629; ENSG00000011600. [O43914-1]
ENST00000544690; ENSP00000445332; ENSG00000011600. [O43914-3]
ENST00000589517; ENSP00000468447; ENSG00000011600. [O43914-2]
GeneIDi7305.
KEGGihsa:7305.
UCSCiuc002ocm.4. human. [O43914-1]

Organism-specific databases

CTDi7305.
DisGeNETi7305.
GeneCardsiTYROBP.
GeneReviewsiTYROBP.
HGNCiHGNC:12449. TYROBP.
HPAiCAB009493.
HPA041899.
MalaCardsiTYROBP.
MIMi221770. phenotype.
604142. gene.
neXtProtiNX_O43914.
OpenTargetsiENSG00000011600.
Orphaneti2770. Nasu-Hakola disease.
PharmGKBiPA37100.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J1XS. Eukaryota.
ENOG410Z4TN. LUCA.
GeneTreeiENSGT00390000016786.
HOGENOMiHOG000056440.
HOVERGENiHBG061468.
InParanoidiO43914.
KOiK07992.
PhylomeDBiO43914.
TreeFamiTF336898.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000011600-MONOMER.
ReactomeiR-HSA-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
R-HSA-2172127. DAP12 interactions.
R-HSA-2424491. DAP12 signaling.
R-HSA-391160. Signal regulatory protein (SIRP) family interactions.
R-HSA-416700. Other semaphorin interactions.
R-HSA-6798695. Neutrophil degranulation.
SignaLinkiO43914.

Miscellaneous databases

EvolutionaryTraceiO43914.
GeneWikiiTYROBP.
GenomeRNAii7305.
PROiO43914.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000011600.
CleanExiHS_TYROBP.
ExpressionAtlasiO43914. baseline and differential.
GenevisibleiO43914. HS.

Family and domain databases

InterProiIPR026200. Tyrobp.
[Graphical view]
PANTHERiPTHR17554. PTHR17554. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiTYOBP_HUMAN
AccessioniPrimary (citable) accession number: O43914
Secondary accession number(s): A8K2X0
, F5H389, Q6FGA5, Q9UMT3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: June 1, 1998
Last modified: November 30, 2016
This is version 144 of the entry and version 1 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  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.