TYROBP TYRO protein tyrosine kinase binding protein [Homo sapiens (human)] - Gene

Summary

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Official Symbol: TYROBPprovided by HGNC
Official Full Name: TYRO protein tyrosine kinase binding proteinprovided by HGNC
Primary source: HGNC:12449
See related: Ensembl:ENSG00000011600; HPRD:04996; MIM:604142; Vega:OTTHUMG00000181739
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: DAP12; KARAP; PLOSL
Summary: This gene encodes a transmembrane signaling polypeptide which contains an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain. The encoded protein may associate with the killer-cell inhibitory receptor (KIR) family of membrane glycoproteins and may act as an activating signal transduction element. This protein may bind zeta-chain (TCR) associated protein kinase 70kDa (ZAP-70) and spleen tyrosine kinase (SYK) and play a role in signal transduction, bone modeling, brain myelination, and inflammation. Mutations within this gene have been associated with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), also known as Nasu-Hakola disease. Its putative receptor, triggering receptor expressed on myeloid cells 2 (TREM2), also causes PLOSL. Multiple alternative transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Mar 2010]

Genomic context

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Location :: 19q13.1

Sequence :: Chromosome: 19; NC_000019.9 (36395303..36399211, complement)

See TYROBP in Epigenomics, MapViewer

Chromosome 19 - NC_000019.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

A molecular defect of DAP12 in human monocytes deregulates the gene network pivotal for maintenance of myeloid cell function in Nasu-Hakola disease.
Title: Gene expression profile of THP-1 monocytes following knockdown of DAP12, a causative gene for Nasu-Hakola disease.
the putative periodontal pathogen P. gingivalis can positively regulate the expression of the TREM-1/DAP12 pathway in monocytic cells.
Title: Involvement of the TREM-1/DAP12 pathway in the innate immune responses to Porphyromonas gingivalis.
DAP12 gene levels were not increased in the monocytes of schizophrenic, bioplar or major depressive disorder patients.
Title: TREM-1 and DAP12 expression in monocytes of patients with severe psychiatric disorders. EGR3, ATF3 and PU.1 as important transcription factors.
Data suggest that OSCAR is a collagen receptor that binds to specific collagen motifs and costimulates osteoclastogenesis in DAP12-deficient humans and mice.
Title: OSCAR is a collagen receptor that costimulates osteoclastogenesis in DAP12-deficient humans and mice.
A transgenic mouse model demonstrates that induction of tolerance in Ly49H-positive natural killer (NK) cells by chronic exposure to virus-encoded ligand m157 requires signaling through the Ly49H adaptor protein DAP12, not the DAP10 adaptor protein.
Title: Activation receptor-induced tolerance of mature NK cells in vivo requires signaling through the receptor and is reversible.
Meta-analysis of gene-disease association. (HuGE Navigator)
Title: Evaluation of candidate stromal epithelial cross-talk genes identifies association between risk of serous ovarian cancer and TERT, a cancer susceptibility "hot-spot".
These findings indicate that DAP12, possibly through association with TREM2, contributes to alveolar macrophage chemotaxis and recruitment to the lung and may mediate macrophage accumulation in lung diseases such as emphysema.
Title: DAP12 is required for macrophage recruitment to the lung in response to cigarette smoke and chemotaxis toward CCL2.
DAP12-associating lectin (MDL)-1 receptor is a key regulator of synovial injury and bone erosion in autoimmune joint inflammation.
Title: Myeloid DAP12-associating lectin (MDL)-1 regulates synovial inflammation and bone erosion associated with autoimmune arthritis.
describe the generation and the characterization of an anti-DAP12 monoclonal antibody. Using this novel reagent, we show that DAP12 expression is restricted to innate immune cells in basal condition
Title: Pattern of DAP12 expression in leukocytes from both healthy and systemic lupus erythematosus patients.
loss of function mutation results in recessive genetic disorder, Nasu-Hakola disease (bone development abnormalities and dementia at adolescence)
Title: DAP10- and DAP12-associated receptors in innate immunity.

Submit: New GeneRIF Correction See all (28)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy

MIM: 221770

Genetic Testing Registry

Summary from GeneReviews: PLOSL

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) is characterized by fractures (resulting from radiologically demonstrable polycystic osseous lesions), frontal lobe syndrome, and progressive presenile dementia beginning in the fourth decade. The clinical course of PLOSL can be divided into four stages: (1) The latent stage is characterized by normal early development. (2) The osseous stage (3rd decade of life) is characterized by pain and tenderness, mostly in ankles and feet, usually following strain or injury. Fractures are typically diagnosed several years later, most commonly in the bones of the extremities. (3) In the early neurologic stage (4th decade of life), a change of personality begins to develop insidiously. Affected individuals show a frontal lobe syndrome (loss of judgment, euphoria, loss of social inhibitions, disturbance of concentration, and lack of insight, libido, and motor persistence) leading to serious social problems. (4) The late neurologic stage is characterized by progressive dementia and loss of mobility. Death usually occurs before age 50 years.

Diagnosis Testing

The combination of radiologically demonstrable polycystic osseous lesions, frontal lobe syndrome, and progressive presenile dementia beginning in the fourth decade is diagnostic. Fractures of the wrists or ankles after minor trauma with typical polycystic osseous lesions identified on x-ray examination suggest the possibility of PLOSL. In uncertain cases, molecular genetic testing helps to establish the diagnosis. Molecular genetic testing of TYROBP (DAP12) and TREM2, the only two genes known to be associated with PLOSL, is available in clinical laboratories.

Genetic Counseling

PLOSL is inherited in an autosomal recessive manner. Each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once an at-risk sib is known to be unaffected, the risk of his/her being a carrier is 2/3. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the disease-causing mutations in the family have been identified.

References

PMID: 20301376

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
O43914	Immune receptor expressed on myeloid cells 2	CD300E	HPRD	PubMed
O43914	Q9NY25	CLEC5A	HPRD	PubMed
O43914	P43631	KIR2DS2	HPRD	PubMed
O43914	Q14943	KIR3DS1	HPRD	PubMed
O43914	Q07444	KLRC3	HPRD	PubMed
O43914	O43908	KLRC4	HPRD	PubMed
O43914	P26718	KLRK1	HPRD	PubMed
O43914	O95944	NCR2	HPRD	PubMed
O43914	Sialic acid binding Ig-like lectin 14	SIGLEC14	HPRD	PubMed
O43914	O00241	SIRPB1	HPRD	PubMed
O43914	P43405	SYK	HPRD	PubMed
O43914	Q9NP99	TREM1	HPRD	PubMed
O43914	Q9NZC2	TREM2	HPRD	PubMed
O43914	P43403	ZAP70	HPRD	PubMed
BioGRID:113155	BioGRID:110008	KIR2DS2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:113155	BioGRID:115971	KLRAP1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:113155	BioGRID:114827	NCR2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:113155	BioGRID:115609	SIRPB1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:113155	BioGRID:112717	SYK	BioGRID	PubMed	Reconstituted Complex
BioGRID:113155	BioGRID:119926	TREM1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:113155	BioGRID:113367	ZAP70	BioGRID	PubMed	Protein-peptide

Pathways from BioSystems

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Adaptive Immune System, organism-specific biosystem (from REACTOME)
Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
Axon guidance, organism-specific biosystem (from REACTOME)
Axon guidance, organism-specific biosystemAxon guidance / axon pathfinding is the process by which neurons send out axons to reach the correct targets. Growing axons have a highly motile structure at the growing tip called the growth cone, w...
Cell-Cell communication, organism-specific biosystem (from REACTOME)
Cell-Cell communication, organism-specific biosystemCell-to-Cell communication is crucial for multicellular organisms because it allows organisms to coordinate the activity of their cells. Some cell-to-cell communication requires direct cell-cell cont...
DAP12 interactions, organism-specific biosystem (from REACTOME)
DAP12 interactions, organism-specific biosystemDNAX activation protein of 12kDa (DAP12) is an immunoreceptor tyrosine-based activation motif (ITAM)-bearing adapter molecule that transduces activating signals in natural killer (NK) and myeloid cel...
DAP12 signaling, organism-specific biosystem (from REACTOME)
DAP12 signaling, organism-specific biosystemIn response to receptor ligation, the tyrosine residues in DAP12's immunoreceptor tyrosine-based activation motif (ITAM) are phosphorylated by Src family kinases. These phosphotyrosines form the dock...
Developmental Biology, organism-specific biosystem (from REACTOME)
Developmental Biology, organism-specific biosystemAs a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are a...
Immune System, organism-specific biosystem (from REACTOME)
Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell, organism-specific biosystem (from REACTOME)
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell, organism-specific biosystemA number of receptors and cell adhesion molecules play a key role in modifying the response of cells of lymphoid origin (such as B-, T- and NK cells) to self and tumor antigens, as well as to pathoge...
Innate Immune System, organism-specific biosystem (from REACTOME)
Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
Natural killer cell mediated cytotoxicity, organism-specific biosystem (from KEGG)
Natural killer cell mediated cytotoxicity, organism-specific biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...
Natural killer cell mediated cytotoxicity, conserved biosystem (from KEGG)
Natural killer cell mediated cytotoxicity, conserved biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...
Osteoclast differentiation, organism-specific biosystem (from KEGG)
Osteoclast differentiation, organism-specific biosystemThe osteoclasts, multinucleared cells originating from the hematopoietic monocyte-macrophage lineage, are responsible for bone resorption. Osteoclastogenesis is mainly regulated by signaling pathways...
Osteoclast differentiation, conserved biosystem (from KEGG)
Osteoclast differentiation, conserved biosystemThe osteoclasts, multinucleared cells originating from the hematopoietic monocyte-macrophage lineage, are responsible for bone resorption. Osteoclastogenesis is mainly regulated by signaling pathways...
Other semaphorin interactions, organism-specific biosystem (from REACTOME)
Other semaphorin interactions, organism-specific biosystem
Other semaphorin interactions
Semaphorin interactions, organism-specific biosystem (from REACTOME)
Semaphorin interactions, organism-specific biosystemSemaphorins are a large family of cell surface and secreted guidance molecules divided into eight classes on the basis of their structures. They all have an N-terminal conserved sema domain. Semaphor...
Signal regulatory protein (SIRP) family interactions, organism-specific biosystem (from REACTOME)
Signal regulatory protein (SIRP) family interactions, organism-specific biosystemSignal regulatory protein (SIRP)alpha, also known as SHPS-1 or SIRPA or CD172a, is a transmembrane protein expressed mostly on myeloid cells. CD47, a widely expressed transmembrane protein, is a liga...

General gene information

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Markers

A006G29 (e-PCR)
- UniSTS:39994

D19S844E (e-PCR)
- UniSTS:153967

G32347 (e-PCR)
- UniSTS:116938

Genotypes

See TYROBP SNP Geneview Report
See TYROBP SNP Genotype Report
See TYROBP SNP Variation Viewer Report

Homology

Homologs of the TYROBP gene: The TYROBP gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, and rat.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
identical protein binding	IPI Inferred from Physical Interaction more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
receptor signaling protein activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
axon guidance	TAS Traceable Author Statement more info
cellular defense response	TAS Traceable Author Statement more info	PubMed
innate immune response	TAS Traceable Author Statement more info
integrin-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
intracellular signal transduction	TAS Traceable Author Statement more info	PubMed
macrophage activation involved in immune response	IEA Inferred from Electronic Annotation more info
neutrophil activation involved in immune response	IEA Inferred from Electronic Annotation more info
regulation of immune response	TAS Traceable Author Statement more info
signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
integral to plasma membrane	TAS Traceable Author Statement more info	PubMed
plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: TYRO protein tyrosine kinase-binding protein

Names: TYRO protein tyrosine kinase-binding protein; KAR-associated protein; DNAX-activation protein 12; killer activating receptor associated protein; killer-activating receptor-associated protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009304.1 RefSeqGene

Range

4976..8884

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001173514.1 → NP_001166985.1 TYRO protein tyrosine kinase-binding protein isoform 3 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (3) is shorter compared to isoform 1.

Source sequence(s)

BP295666, BP302545, BQ576278

Consensus CDS

CCDS54255.1

UniProtKB/Swiss-Prot

O43914

Related

ENSP00000445332, ENST00000544690
NM_001173515.1 → NP_001166986.1 TYRO protein tyrosine kinase-binding protein isoform 4 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks an alternate in-frame exon and uses an alternate in-frame splice site in the coding region, compared to variant 1. The resulting isoform (4) is shorter compared to isoform 1.

Source sequence(s)

BP302545, BP305672, BQ576278

Consensus CDS

CCDS59378.1

Related

ENSP00000402371, OTTHUMP00000267347, ENST00000424586, OTTHUMT00000457395
NM_003332.3 → NP_003323.1 TYRO protein tyrosine kinase-binding protein isoform 1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AF019562, BP302545, BQ576278

Consensus CDS

CCDS12482.1

UniProtKB/Swiss-Prot

O43914

Related

ENSP00000262629, OTTHUMP00000267349, ENST00000262629, OTTHUMT00000457397
NM_198125.2 → NP_937758.1 TYRO protein tyrosine kinase-binding protein isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2), also known as 112DAP12, uses an alternate in-frame splice site in the coding region, compared to variant 1. The resulting isoform (2) is 1 aa shorter compared to isoform 1.

Source sequence(s)

AK290385, BP302545, BQ576278

Consensus CDS

CCDS46058.1

UniProtKB/Swiss-Prot

O43914

RNA

NR_033390.1 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks an alternate in-frame exon and uses an alternate splice junction compared to variant 1, that causes a frameshift. This variant is not thought to be protein-coding.

Source sequence(s)

BI908458, BP302545, BQ576278

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000019.9 Reference GRCh37.p10 Primary Assembly

Range

36395303..36399211, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000151.1 Alternate HuRef

Range

32900548..32904456, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018930.1 Alternate CHM1_1.0

Range

36554314..36558222, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01018772.1 (34995..38903)	None
genomic	AD000833.1 (3078..6826)	None
genomic	AD000864.1 (39012..39146)	None
genomic	AF019563.1	AAD09437.1
genomic	AMYH01009736.1 (4312..8220)	None
mRNA	AF019562.1	AAD09436.1
mRNA	AJ010098.1	CAB52288.1
mRNA	AK290385.1	BAF83074.1
mRNA	AY074782.1	AAL74017.1
mRNA	BC011175.1	AAH11175.1
mRNA	BI908458.1	None
mRNA	BP295666.1	None
mRNA	BP302545.1	None
mRNA	BP305672.1	None
mRNA	BQ576278.1	None
mRNA	BT009851.1	AAP88853.1
mRNA	CR450342.1	CAG29338.1
mRNA	CR542202.1	CAG46999.1
other-genetic	DQ891092.2	ABM82018.1
other-genetic	DQ894274.2	ABM85200.1