Seroatlas · Human Serome Atlas

INPP5D

Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1

Also known as: hp51CN, SHIP, SHIP1, SHIP1_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q92835
Gene: INPP5D
Ensembl: ENSG00000168918
Chromosome: 2
Canonical length: 1189 aa
Protein class: Enzymes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins
Subcellular location: Cytosol

OverviewNCBI Gene

This gene is a member of the inositol polyphosphate-5-phosphatase (INPP5) family and encodes a protein with an N-terminal SH2 domain, an inositol phosphatase domain, and two C-terminal protein interaction domains. Expression of this protein is restricted to hematopoietic cells where its movement from the cytosol to the plasma membrane is mediated by tyrosine phosphorylation. At the plasma membrane, the protein hydrolyzes the 5' phosphate from phosphatidylinositol (3,4,5)-trisphosphate and inositol-1,3,4,5-tetrakisphosphate, thereby affecting multiple signaling pathways. The protein is also partly localized to the nucleus, where it may be involved in nuclear inositol phosphate signaling processes. Overall, the protein functions as a negative regulator of myeloid cell proliferation and survival. Mutations in this gene are associated with defects and cancers of the immune system. Deficiencies in the encoded protein, SHIP1, have been associated with Inflammatory Bowel Disease types such as Crohn's Disease and Ulcerative Colitis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2020]

Canonical amino-acid sequenceUniProt

1189 residues, UniProt reviewed canonical sequence.

>Q92835|INPP5D
     1  MVPCWNHGNI TRSKAEELLS RTGKDGSFLV RASESISRAY ALCVLYRNCV YTYRILPNED
    61  DKFTVQASEG VSMRFFTKLD QLIEFYKKEN MGLVTHLQYP VPLEEEDTGD DPEEDTVESV
   121  VSPPELPPRN IPLTASSCEA KEVPFSNENP RATETSRPSL SETLFQRLQS MDTSGLPEEH
   181  LKAIQDYLST QLAQDSEFVK TGSSSLPHLK KLTTLLCKEL YGEVIRTLPS LESLQRLFDQ
   241  QLSPGLRPRP QVPGEANPIN MVSKLSQLTS LLSSIEDKVK ALLHEGPESP HRPSLIPPVT
   301  FEVKAESLGI PQKMQLKVDV ESGKLIIKKS KDGSEDKFYS HKKILQLIKS QKFLNKLVIL
   361  VETEKEKILR KEYVFADSKK REGFCQLLQQ MKNKHSEQPE PDMITIFIGT WNMGNAPPPK
   421  KITSWFLSKG QGKTRDDSAD YIPHDIYVIG TQEDPLSEKE WLEILKHSLQ EITSVTFKTV
   481  AIHTLWNIRI VVLAKPEHEN RISHICTDNV KTGIANTLGN KGAVGVSFMF NGTSLGFVNS
   541  HLTSGSEKKL RRNQNYMNIL RFLALGDKKL SPFNITHRFT HLFWFGDLNY RVDLPTWEAE
   601  TIIQKIKQQQ YADLLSHDQL LTERREQKVF LHFEEEEITF APTYRFERLT RDKYAYTKQK
   661  ATGMKYNLPS WCDRVLWKSY PLVHVVCQSY GSTSDIMTSD HSPVFATFEA GVTSQFVSKN
   721  GPGTVDSQGQ IEFLRCYATL KTKSQTKFYL EFHSSCLESF VKSQEGENEE GSEGELVVKF
   781  GETLPKLKPI ISDPEYLLDQ HILISIKSSD SDESYGEGCI ALRLEATETQ LPIYTPLTHH
   841  GELTGHFQGE IKLQTSQGKT REKLYDFVKT ERDESSGPKT LKSLTSHDPM KQWEVTSRAP
   901  PCSGSSITEI INPNYMGVGP FGPPMPLHVK QTLSPDQQPT AWSYDQPPKD SPLGPCRGES
   961  PPTPPGQPPI SPKKFLPSTA NRGLPPRTQE SRPSDLGKNA GDTLPQEDLP LTKPEMFENP
  1021  LYGSLSSFPK PAPRKDQESP KMPRKEPPPC PEPGILSPSI VLTKAQEADR GEGPGKQVPA
  1081  PRLRSFTCSS SAEGRAAGGD KSQGKPKTPV SSQAPVPAKR PIKPSRSEIN QQTPPTPTPR
  1141  PPLPVKSPAV LHLQHSKGRD YRDNTELPHH GKHRPEEGPP GPLGRTAMQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against INPP5D can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Cell surface
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.41
Highest tissue expression: 96 nTPM

Expression across tissuesHPA

Tissue

spleen: 96 nTPM
small intestine: 48 nTPM
lymph node: 32 nTPM
bone marrow: 31 nTPM
tonsil: 30 nTPM
salivary gland: 27 nTPM

Single-cell type

microglia: 1,021 nCPM
b-cells: 98 nCPM
nk-cells: 74 nCPM
tuft cells: 69 nCPM
macrophages: 42 nCPM
papillary tip epithelial cells: 38 nCPM

Immune cell

non-classical monocyte: 20 nTPM
total PBMC: 18 nTPM
gdT-cell: 16 nTPM
intermediate monocyte: 16 nTPM
memory B-cell: 14 nTPM
basophil: 13 nTPM

Brain region

medulla oblongata: 18 nTPM
thalamus: 17 nTPM
white matter: 16 nTPM
midbrain: 15 nTPM
pons: 15 nTPM
spinal cord: 15 nTPM

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.31
gnomAD pLI: 0.97
gnomAD missense Z: 4.15

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of INPP5D in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads INPP5D as an antibody target. Whether an autoantibody or antibody against INPP5D could matter depends on whether native INPP5D is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

INPP5D is annotated at the cell surface, where native INPP5D is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label INPP5D as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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