Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

TYRO protein tyrosine kinase-binding protein

Gene

TYROBP

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

  • identical protein binding Source: IntAct
  • signaling receptor binding Source: UniProtKB
  • signal transducer activity, downstream of receptor Source: ProtInc

GO - Biological processi

  • cellular defense response Source: ProtInc
  • innate immune response Source: Reactome
  • integrin-mediated signaling pathway Source: Ensembl
  • intracellular signal transduction Source: ProtInc
  • macrophage activation involved in immune response Source: Ensembl
  • neutrophil degranulation Source: Reactome
  • osteoclast differentiation Source: MGI
  • regulation of immune response Source: Reactome
  • regulation of osteoclast development Source: Ensembl
  • signal transduction Source: ProtInc

Enzyme and pathway databases

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 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

EuPathDBiHostDB:ENSG00000011600.11
HGNCiHGNC:12449 TYROBP
MIMi604142 gene
neXtProtiNX_O43914

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 domaini22 – 40ExtracellularSequence analysisAdd BLAST19
Transmembranei41 – 61HelicalSequence analysisAdd BLAST21
Topological domaini62 – 113CytoplasmicSequence analysisAdd BLAST52

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
GeneReviewsiTYROBP
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 (PubMed:20890284). Interacts with SIRPB1 and TREM1 (PubMed:10799849). Interacts with CLECSF5 (PubMed:10449773). Interacts with SIGLEC14 (PubMed:17012248). Interacts with CD300LB and CD300E (PubMed:15557162, PubMed:16920917, PubMed:17928527). 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, KIR2DS3 and KIR2DS5 (PubMed:18624290, PubMed:20890284).By similarity8 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • signaling receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi113155, 19 interactors
CORUMiO43914
IntActiO43914, 11 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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410J1XS Eukaryota
ENOG410Z4TN LUCA
GeneTreeiENSGT00390000016786
HOGENOMiHOG000056440
HOVERGENiHBG061468
InParanoidiO43914
KOiK07992
PhylomeDBiO43914
TreeFamiTF336898

Family and domain databases

InterProiView protein in InterPro
IPR026200 Tyrobp
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 dbSNP:rs14714Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiTYOBP_HUMAN
AccessioniPrimary (citable) accession number: O43914
Secondary accession number(s): A8K2X0
, F5H389, Q6FGA5, Q9UMT3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: June 1, 1998
Last modified: May 23, 2018
This is version 153 of the entry and version 1 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

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

Cookie policy

We would like to use anonymized google analytics cookies to gather statistics on how uniprot.org is used in aggregate. Learn more

UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health