CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-018841
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 
Protein Synonyms/Alias
 Inositol polyphosphate-5-phosphatase of 145 kDa; SIP-145; SH2 domain-containing inositol 5'-phosphatase 1; SH2 domain-containing inositol phosphatase 1; SHIP-1; p150Ship; hp51CN 
Gene Name
 INPP5D 
Gene Synonyms/Alias
 SHIP; SHIP1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
14HGNITRSKAEELLSRubiquitination[1]
24ELLSRTGKDGSFLVRubiquitination[1]
141TASSCEAKEVPFSNEubiquitination[1]
371EKEKILRKEYVFADSacetylation[2]
779SEGELVVKFGETLPKubiquitination[3]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983] 
Functional Description
 Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol- 3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways. Acts as a negative regulator of B-cell antigen receptor signaling. Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. Acts as a negative regulator of myeloid cell proliferation/survival and chemotaxis, mast cell degranulation, immune cells homeostasis, integrin alpha-IIb/beta-3 signaling in platelets and JNK signaling in B-cells. Regulates proliferation of osteoclast precursors, macrophage programming, phagocytosis and activation and is required for endotoxin tolerance. Involved in the control of cell-cell junctions, CD32a signaling in neutrophils and modulation of EGF-induced phospholipase C activity. Key regulator of neutrophil migration, by governing the formation of the leading edge and polarization required for chemotaxis. Modulates FCGR3/CD16-mediated cytotoxicity in NK cells. Mediates the activin/TGF-beta-induced apoptosis through its Smad-dependent expression. May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6. 
Sequence Annotation
 DOMAIN 5 101 SH2.
 REGION 1016 1030 Interaction with DAB2 (By similarity).
 MOTIF 124 129 SH3-binding 1.
 MOTIF 912 915 NPXY motif 1.
 MOTIF 969 974 SH3-binding 2.
 MOTIF 1019 1022 NPXY motif 2.
 MOTIF 1040 1051 SH3-binding 3.
 MOD_RES 865 865 Phosphotyrosine (By similarity).
 MOD_RES 915 915 Phosphotyrosine.
 MOD_RES 934 934 Phosphoserine (By similarity).
 MOD_RES 944 944 Phosphotyrosine (By similarity).
 MOD_RES 971 971 Phosphoserine (By similarity).
 MOD_RES 1022 1022 Phosphotyrosine (By similarity).  
Keyword
 3D-structure; Alternative splicing; Apoptosis; Complete proteome; Cytoplasm; Hydrolase; Immunity; Membrane; Phosphoprotein; Polymorphism; Reference proteome; Repeat; SH2 domain; SH3-binding. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1189 AA 
Protein Sequence
MVPCWNHGNI TRSKAEELLS RTGKDGSFLV RASESISRAY ALCVLYRNCV YTYRILPNED 60
DKFTVQASEG VSMRFFTKLD QLIEFYKKEN MGLVTHLQYP VPLEEEDTGD DPEEDTVESV 120
VSPPELPPRN IPLTASSCEA KEVPFSNENP RATETSRPSL SETLFQRLQS MDTSGLPEEH 180
LKAIQDYLST QLAQDSEFVK TGSSSLPHLK KLTTLLCKEL YGEVIRTLPS LESLQRLFDQ 240
QLSPGLRPRP QVPGEANPIN MVSKLSQLTS LLSSIEDKVK ALLHEGPESP HRPSLIPPVT 300
FEVKAESLGI PQKMQLKVDV ESGKLIIKKS KDGSEDKFYS HKKILQLIKS QKFLNKLVIL 360
VETEKEKILR KEYVFADSKK REGFCQLLQQ MKNKHSEQPE PDMITIFIGT WNMGNAPPPK 420
KITSWFLSKG QGKTRDDSAD YIPHDIYVIG TQEDPLSEKE WLEILKHSLQ EITSVTFKTV 480
AIHTLWNIRI VVLAKPEHEN RISHICTDNV KTGIANTLGN KGAVGVSFMF NGTSLGFVNS 540
HLTSGSEKKL RRNQNYMNIL RFLALGDKKL SPFNITHRFT HLFWFGDLNY RVDLPTWEAE 600
TIIQKIKQQQ YADLLSHDQL LTERREQKVF LHFEEEEITF APTYRFERLT RDKYAYTKQK 660
ATGMKYNLPS WCDRVLWKSY PLVHVVCQSY GSTSDIMTSD HSPVFATFEA GVTSQFVSKN 720
GPGTVDSQGQ IEFLRCYATL KTKSQTKFYL EFHSSCLESF VKSQEGENEE GSEGELVVKF 780
GETLPKLKPI ISDPEYLLDQ HILISIKSSD SDESYGEGCI ALRLEATETQ LPIYTPLTHH 840
GELTGHFQGE IKLQTSQGKT REKLYDFVKT ERDESSGPKT LKSLTSHDPM KQWEVTSRAP 900
PCSGSSITEI INPNYMGVGP FGPPMPLHVK QTLSPDQQPT AWSYDQPPKD SPLGPCRGES 960
PPTPPGQPPI SPKKFLPSTA NRGLPPRTQE SRPSDLGKNA GDTLPQEDLP LTKPEMFENP 1020
LYGSLSSFPK PAPRKDQESP KMPRKEPPPC PEPGILSPSI VLTKAQEADR GEGPGKQVPA 1080
PRLRSFTCSS SAEGRAAGGD KSQGKPKTPV SSQAPVPAKR PIKPSRSEIN QQTPPTPTPR 1140
PPLPVKSPAV LHLQHSKGRD YRDNTELPHH GKHRPEEGPP GPLGRTAMQ 1189 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
 GO:0004445; F:inositol-polyphosphate 5-phosphatase activity; TAS:ProtInc.
 GO:0034594; F:phosphatidylinositol trisphosphate phosphatase activity; IEA:Compara.
 GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
 GO:0007596; P:blood coagulation; TAS:Reactome.
 GO:0008340; P:determination of adult lifespan; IEA:Compara.
 GO:0016064; P:immunoglobulin mediated immune response; IEA:Compara.
 GO:0043647; P:inositol phosphate metabolic process; TAS:Reactome.
 GO:0035556; P:intracellular signal transduction; IEA:Compara.
 GO:0050900; P:leukocyte migration; TAS:Reactome.
 GO:0030889; P:negative regulation of B cell proliferation; IEA:Compara.
 GO:0045779; P:negative regulation of bone resorption; IEA:Compara.
 GO:0050777; P:negative regulation of immune response; IEA:Compara.
 GO:0045409; P:negative regulation of interleukin-6 biosynthetic process; IEA:Compara.
 GO:0045656; P:negative regulation of monocyte differentiation; IEA:Compara.
 GO:0045659; P:negative regulation of neutrophil differentiation; IEA:Compara.
 GO:0045671; P:negative regulation of osteoclast differentiation; IEA:Compara.
 GO:0009968; P:negative regulation of signal transduction; IEA:Compara.
 GO:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome.
 GO:0046856; P:phosphatidylinositol dephosphorylation; IEA:InterPro.
 GO:0043065; P:positive regulation of apoptotic process; IEA:Compara.
 GO:0045579; P:positive regulation of B cell differentiation; IEA:Compara.
 GO:0045648; P:positive regulation of erythrocyte differentiation; IEA:Compara.
 GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome. 
Interpro
 IPR005135; Endo/exonuclease/phosphatase.
 IPR000300; IPPc.
 IPR000980; SH2. 
Pfam
 PF03372; Exo_endo_phos
 PF00017; SH2 
SMART
 SM00128; IPPc
 SM00252; SH2 
PROSITE
 PS50001; SH2 
PRINTS
 PR00401; SH2DOMAIN.