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Protein

Proline-serine-threonine phosphatase-interacting protein 1

Gene

PSTPIP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Involved in regulation of the actin cytoskeleton. May regulate WAS actin-bundling activity. Bridges the interaction between ABL1 and PTPN18 leading to ABL1 dephosphorylation. May play a role as a scaffold protein between PTPN12 and WAS and allow PTPN12 to dephosphorylate WAS. Has the potential to physically couple CD2 and CD2AP to WAS. Acts downstream of CD2 and CD2AP to recruit WAS to the T-cell:APC contact site so as to promote the actin polymerization required for synapse induction during T-cell activation (By similarity). Down-regulates CD2-stimulated adhesion through the coupling of PTPN12 to CD2. Also has a role in innate immunity and the inflammatory response. Recruited to inflammasomes by MEFV. Induces formation of pyroptosomes, large supramolecular structures composed of oligomerized PYCARD dimers which form prior to inflammatory apoptosis. Binding to MEFV allows MEFV to bind to PYCARD and facilitates pyroptosome formation. Regulates endocytosis and cell migration in neutrophils.By similarity5 Publications

GO - Molecular functioni

  • identical protein binding Source: IntAct

GO - Biological processi

  • cell adhesion Source: ProtInc
  • endocytosis Source: UniProtKB-KW
  • inflammatory response Source: UniProtKB-KW
  • innate immune response Source: UniProtKB-KW
  • signal transduction Source: ProtInc

Keywordsi

Biological processCell adhesion, Endocytosis, Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-HSA-844456 The NLRP3 inflammasome
SignaLinkiO43586
SIGNORiO43586

Names & Taxonomyi

Protein namesi
Recommended name:
Proline-serine-threonine phosphatase-interacting protein 1
Short name:
PEST phosphatase-interacting protein 1
Alternative name(s):
CD2-binding protein 1
H-PIP
Gene namesi
Name:PSTPIP1
Synonyms:CD2BP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000140368.12
HGNCiHGNC:9580 PSTPIP1
MIMi606347 gene
neXtProtiNX_O43586

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

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane

Pathology & Biotechi

Involvement in diseasei

PAPA syndrome (PAPAS)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionCharacterized by autosomal dominant inheritance of early-onset, primarily affecting skin and joint tissues. Recurring inflammatory episodes lead to accumulation of sterile, pyogenic, neutrophil-rich material within the affected joints, ultimately resulting in significant destruction.
See also OMIM:604416
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_023522230A → T in PAPAS; severely reduced binding with PTPN12; markedly increased binding to MEFV; accentuates IL1B secretion; no effect on filament formation; increased induction of MEFV in response to retroviral infection. 5 PublicationsCorresponds to variant dbSNP:rs121908130EnsemblClinVar.1
Natural variantiVAR_070635250E → K in PAPAS. 1 PublicationCorresponds to variant dbSNP:rs28939089EnsemblClinVar.1
Natural variantiVAR_023523250E → Q in PAPAS; severely reduced binding with PTPN12; markedly increased binding to MEFV; accentuates IL1B secretion; increased induction of MEFV in response to retroviral infection. 5 PublicationsCorresponds to variant dbSNP:rs28939089EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi232W → A: Abolishes binding to MEFV. Cytoplasmic filaments are finer with fewer branches. 2 Publications1
Mutagenesisi266D → N: No effect on filament formation. 1 Publication1
Mutagenesisi345Y → F: Decreases binding to MEFV. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi9051
MalaCardsiPSTPIP1
MIMi604416 phenotype
OpenTargetsiENSG00000140368
Orphaneti69126 Pyogenic arthritis - pyoderma gangrenosum - acne
PharmGKBiPA33931

Polymorphism and mutation databases

BioMutaiPSTPIP1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000585391 – 416Proline-serine-threonine phosphatase-interacting protein 1Add BLAST416

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei318PhosphoserineBy similarity1
Modified residuei345PhosphotyrosineBy similarity1

Post-translational modificationi

Dephosphorylated on Tyr-345 by PTPN18, this event negatively regulates the association of PSTPIP1 with SH2 domain-containing proteins as tyrosine kinase. Phosphorylation of Tyr-345 is probably required for subsequent phosphorylation at other tyrosine residues. Phosphorylation is induced by activation of the EGFR and PDGFR in a ABL1 dependent manner. The phosphorylation regulates the interaction with WAS and with MEFV (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO43586
MaxQBiO43586
PaxDbiO43586
PeptideAtlasiO43586
PRIDEiO43586
ProteomicsDBi49064
49065 [O43586-2]

PTM databases

iPTMnetiO43586
PhosphoSitePlusiO43586
SwissPalmiO43586

Expressioni

Tissue specificityi

Highly expressed in the peripheral blood leukocytes, granulocytes and monocytes, namely in T-cells and natural killer cells, and in spleen. Weakly expressed in the thymus, small intestine, lung and placenta.2 Publications

Gene expression databases

BgeeiENSG00000140368
CleanExiHS_PSTPIP1
ExpressionAtlasiO43586 baseline and differential
GenevisibleiO43586 HS

Organism-specific databases

HPAiHPA010600

Interactioni

Subunit structurei

Homodimer (PubMed:19584923). Homotrimer (PubMed:17964261). Interacts (via coiled-coil domain) with CD2AP, PTPN12 and PTPN18. Interacts (via SH3 domain) with ABL1 and WAS. Interacts (via SH3 and coiled-coil domains) with MEFV (via B-box zinc finger); the interaction allows binding of MEFV to PYCARD and facilitates formation of PYCARD pyroptosomes. Interacts with CD2, DNM2 and FASLG.7 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi114513, 54 interactors
IntActiO43586, 88 interactors
MINTiO43586
STRINGi9606.ENSP00000452746

Structurei

Secondary structure

1416
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi363 – 365Combined sources3
Beta strandi373 – 377Combined sources5
Beta strandi385 – 390Combined sources6
Beta strandi393 – 401Combined sources9
Beta strandi404 – 409Combined sources6
Helixi410 – 412Combined sources3

3D structure databases

ProteinModelPortaliO43586
SMRiO43586
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO43586

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini5 – 264F-BARPROSITE-ProRule annotationAdd BLAST260
Domaini359 – 416SH3PROSITE-ProRule annotationAdd BLAST58

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili166 – 212Sequence analysisAdd BLAST47

Domaini

The F-BAR domain is important for filament formation. The SH3 domain is not required for filament formation or localization to the uropod.

Keywords - Domaini

Coiled coil, SH3 domain

Phylogenomic databases

eggNOGiENOG410IU8N Eukaryota
ENOG410XR8X LUCA
GeneTreeiENSGT00860000133756
HOGENOMiHOG000294218
HOVERGENiHBG052960
InParanoidiO43586
KOiK12804
OMAiYYDREVT
OrthoDBiEOG091G09F9
PhylomeDBiO43586
TreeFamiTF313677

Family and domain databases

CDDicd11824 SH3_PSTPIP1, 1 hit
Gene3Di1.20.1270.60, 1 hit
InterProiView protein in InterPro
IPR027267 AH/BAR_dom_sf
IPR031160 F_BAR
IPR001060 FCH_dom
IPR030777 PSTPIP1_SH3
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PfamiView protein in Pfam
PF00611 FCH, 1 hit
PF14604 SH3_9, 1 hit
PRINTSiPR00452 SH3DOMAIN
SMARTiView protein in SMART
SM00055 FCH, 1 hit
SM00326 SH3, 1 hit
SUPFAMiSSF103657 SSF103657, 1 hit
SSF50044 SSF50044, 1 hit
PROSITEiView protein in PROSITE
PS51741 F_BAR, 1 hit
PS50002 SH3, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O43586-1) [UniParc]FASTAAdd to basket
Also known as: CD2BP1L

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
MMPQLQFKDA FWCRDFTAHT GYEVLLQRLL DGRKMCKDME ELLRQRAQAE
60 70 80 90 100
ERYGKELVQI ARKAGGQTEI NSLRASFDSL KQQMENVGSS HIQLALTLRE
110 120 130 140 150
ELRSLEEFRE RQKEQRKKYE AVMDRVQKSK LSLYKKAMES KKTYEQKCRD
160 170 180 190 200
ADDAEQAFER ISANGHQKQV EKSQNKARQC KDSATEAERV YRQSIAQLEK
210 220 230 240 250
VRAEWEQEHR TTCEAFQLQE FDRLTILRNA LWVHSNQLSM QCVKDDELYE
260 270 280 290 300
EVRLTLEGCS IDADIDSFIQ AKSTGTEPPA PVPYQNYYDR EVTPLTSSPG
310 320 330 340 350
IQPSCGMIKR FSGLLHGSPK TTSLAASAAS TETLTPTPER NEGVYTAIAV
360 370 380 390 400
QEIQGNPASP AQEYRALYDY TAQNPDELDL SAGDILEVIL EGEDGWWTVE
410
RNGQRGFVPG SYLEKL
Length:416
Mass (Da):47,591
Last modified:June 1, 1998 - v1
Checksum:i97818150B3D5D600
GO
Isoform 2 (identifier: O43586-2) [UniParc]FASTAAdd to basket
Also known as: CD2BP1S

The sequence of this isoform differs from the canonical sequence as follows:
     280-309: APVPYQNYYDREVTPLTSSPGIQPSCGMIK → GEVRLADSAAS

Show »
Length:397
Mass (Da):45,354
Checksum:i54D64A3AAE16A2FC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti367L → F in AAD00762 (Ref. 2) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02351548Q → H1 PublicationCorresponds to variant dbSNP:rs1141038Ensembl.1
Natural variantiVAR_023516106E → K1 PublicationCorresponds to variant dbSNP:rs1141039Ensembl.1
Natural variantiVAR_023517146Q → H1 PublicationCorresponds to variant dbSNP:rs1141041Ensembl.1
Natural variantiVAR_023518149R → L1 PublicationCorresponds to variant dbSNP:rs1141042Ensembl.1
Natural variantiVAR_023519151A → S1 PublicationCorresponds to variant dbSNP:rs1141043Ensembl.1
Natural variantiVAR_023520155E → D1 PublicationCorresponds to variant dbSNP:rs1141044Ensembl.1
Natural variantiVAR_023521156Q → H1 PublicationCorresponds to variant dbSNP:rs1141045Ensembl.1
Natural variantiVAR_023522230A → T in PAPAS; severely reduced binding with PTPN12; markedly increased binding to MEFV; accentuates IL1B secretion; no effect on filament formation; increased induction of MEFV in response to retroviral infection. 5 PublicationsCorresponds to variant dbSNP:rs121908130EnsemblClinVar.1
Natural variantiVAR_070635250E → K in PAPAS. 1 PublicationCorresponds to variant dbSNP:rs28939089EnsemblClinVar.1
Natural variantiVAR_023523250E → Q in PAPAS; severely reduced binding with PTPN12; markedly increased binding to MEFV; accentuates IL1B secretion; increased induction of MEFV in response to retroviral infection. 5 PublicationsCorresponds to variant dbSNP:rs28939089EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_015627280 – 309APVPY…CGMIK → GEVRLADSAAS in isoform 2. 1 PublicationAdd BLAST30

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF038602 mRNA Translation: AAD11958.1
AF038603 mRNA Translation: AAD11959.1
U94778 mRNA Translation: AAD00762.1
AB451310 mRNA Translation: BAG70124.1
AB451440 mRNA Translation: BAG70254.1
CH471136 Genomic DNA Translation: EAW99213.1
BC008602 mRNA Translation: AAH08602.1
CCDSiCCDS45312.1 [O43586-1]
CCDS81910.1 [O43586-2]
RefSeqiNP_001308064.1, NM_001321135.1 [O43586-2]
NP_001308066.1, NM_001321137.1
NP_003969.2, NM_003978.4 [O43586-1]
UniGeneiHs.129758

Genome annotation databases

EnsembliENST00000558012; ENSP00000452746; ENSG00000140368 [O43586-1]
ENST00000559295; ENSP00000452743; ENSG00000140368 [O43586-2]
GeneIDi9051
KEGGihsa:9051
UCSCiuc002bcf.3 human [O43586-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPPIP1_HUMAN
AccessioniPrimary (citable) accession number: O43586
Secondary accession number(s): B5BU74
, B5BUK4, O43585, O95657
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 13, 2005
Last sequence update: June 1, 1998
Last modified: July 18, 2018
This is version 166 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 15
    Human chromosome 15: 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

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