Gene and Protein Information
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	-	1189	2q37.1	INPP5D	inositol polyphosphate-5-phosphatase D
Mouse	-	1191	1 44.44 cM	Inpp5d	inositol polyphosphate-5-phosphatase D
Rat	-	1190	9q35	Inpp5d	inositol polyphosphate-5-phosphatase D
Gene and Protein Information Comments
Alternative transcripts and protein isoforms for the human and mouse genes have been identified. We provide details and links for the longest transcripts and isoforms. Further information is available from the Entrez gene links below.

Previous and Unofficial Names

Inositol polyphosphate-5-phosphatase 145 kDa | inositol polyphosphate-5-phosphatase D | phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 | SH2 domain-containing inositol 5'-phosphatase 1 | Src homology 2 domain-containing inositol-5-phosphatase | inositol polyphosphate-5-phosphatase, 145kDa

Database Links
Alphafold	Q92835 (Hs), Q9ES52 (Mm), P97573 (Rn)
BRENDA	3.1.3.86
CATH/Gene3D	3.30.505.10, 3.60.10.10
ChEMBL Target	CHEMBL1781870 (Hs)
Ensembl Gene	ENSG00000168918 (Hs), ENSMUSG00000026288 (Mm), ENSRNOG00000017020 (Rn)
Entrez Gene	3635 (Hs), 16331 (Mm), 54259 (Rn)
Human Protein Atlas	ENSG00000168918 (Hs)
KEGG Enzyme	3.1.3.86
KEGG Gene	hsa:3635 (Hs), mmu:16331 (Mm), rno:54259 (Rn)
OMIM	601582 (Hs)
Pharos	Q92835 (Hs)
RefSeq Nucleotide	NM_001017915 (Hs), NM_019311 (Rn)
RefSeq Protein	NP_001017915 (Hs), NP_034696 (Mm), NM_010566 (Mm), NP_062184 (Rn)
UniProtKB	Q92835 (Hs), Q9ES52 (Mm), P97573 (Rn)
Wikipedia	INPP5D (Hs)

Enzyme Reaction
EC Number: 3.1.3.86 Description Reaction Reference Hydrolysis of the 5' phosphate of phosphatidylinositol (PtdIns) trisphosphate to PtdIns 3,4 biphosphate 1-phosphatidyl-1D-myo-inositol 3,4,5-triphosphate + H(2)O <=>> 1-phosphatidyl-1D-myo-inositol 3,4-diphosphate + phosphate

Download all structure-activity data for this target as a CSV file

Activators
Key to terms and symbols	View all chemical structures	Click column headers to sort
Ligand Sp. Action Value Parameter Reference rosiptor Hs Activation - - 5 ⤷ [5]

Inhibitors
Key to terms and symbols	View all chemical structures	Click column headers to sort
Ligand Sp. Action Value Parameter Reference 3 alpha-aminocholestane Hs Inhibition - - 1 ⤷ [1]

Immunopharmacology Comments

SHIP1 activators are proposed as novel anti-inflammatory agents e.g. rosiptor (AQX-1125) which is in Phase 2 and 3 clinical trials [3,5]. In contrast, SHIP1 inhibitors may have clinical utility in allogeneic transplantation via upregulation of immune regulatory cell numbers [1].

Immuno Process Associations

Immuno Process:  Inflammation

Immuno Process:  Immune regulation

Immuno Process:  Chemotaxis & migration

Immuno Process:  Cellular signalling

Immuno Process:  T cell (activation)

Immuno Process:  B cell (activation)

Immuno Process:  Immune system development

Immuno Process:  Cytokine production & signalling

Immuno Disease Associations

Disease Name:  Interstitial cystitis Disease Synonyms:  no synonynms Comment:  Phase 3 evaluating the SHIP1 activator rosiptor is underway (see NCT02858453). Disease X-refs:  Disease Ontology: DOID:13949 References:

Disease Name:  Atopic dermatitis Disease Synonyms:  no synonynms Comment:  Target of activating compounds with potential immunosuppressant action. Phase 2 with rosiptor has been completed for atopic dermatitis. Disease X-refs:  Disease Ontology: DOID:3310 OMIM: 603165 References:

Physiological Consequences of Altering Gene Expression
SHIP-deficient mice accept allogeneic bone marrow transplants without significant graft-vs-host disease. They produce elevated levels of myeloid suppressor cells which impairs priming of allogeneic T cells, hence the improved tolerance seen in transplant experiments. Species:  Mouse Tissue:  Technique:  References:  2,4

General Comments
Expression of this protein is restricted to hematopoietic cells. It functions as a negative regulator of myeloid cell proliferation and survival. The phosphatase activity of SHIP1 negatively regulates phosphoinositide 3-kinase (PI3K) signalling pathways.