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Protein

Proline-serine-threonine phosphatase-interacting protein 1

Gene

PSTPIP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 - Biological processi

  • cell adhesion Source: ProtInc
  • cell migration Source: InterPro
  • endocytosis Source: UniProtKB-KW
  • inflammatory response Source: UniProtKB-KW
  • innate immune response Source: UniProtKB-KW
  • signal transduction Source: ProtInc
Complete GO annotation...

Keywords - Biological processi

Cell adhesion, Endocytosis, Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

BioCyciZFISH:ENSG00000140368-MONOMER.
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

HGNCiHGNC:9580. PSTPIP1.

Subcellular locationi

GO - Cellular componenti

  • cleavage furrow Source: UniProtKB-SubCell
  • cytoskeleton Source: UniProtKB-SubCell
  • cytosol Source: Reactome
  • lamellipodium Source: UniProtKB-SubCell
  • membrane Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB-SubCell
  • plasma membrane Source: UniProtKB-SubCell
  • uropod Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane

Pathology & Biotechi

Involvement in diseasei

PAPA syndrome (PAPAS)2 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 rs28939381dbSNPEnsembl.1
Natural variantiVAR_070635250E → K in PAPAS. 1 PublicationCorresponds to variant rs28939089dbSNPEnsembl.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 rs28939089dbSNPEnsembl.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

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.

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

WithEntry#Exp.IntActNotes
BUB3O436843EBI-1050964,EBI-1050987
FAM90A1Q86YD75EBI-1050964,EBI-6658203
FASLGP480235EBI-1050964,EBI-495538
FBXL18Q96D163EBI-1050964,EBI-744419
LSM4Q9Y4Z05EBI-1050964,EBI-372521
PCDHB14Q9Y5E93EBI-1050964,EBI-10329013
PRPF31F1T0A53EBI-1050964,EBI-10177194
PTPN12Q052094EBI-1050964,EBI-2266035
PTPN18Q999524EBI-1050964,EBI-1384210
PTPN22Q9Y2R26EBI-1050964,EBI-1211241
RTP5Q14D335EBI-1050964,EBI-10217913
SDCBPO005603EBI-1050964,EBI-727004
SH2D4AQ9H7883EBI-1050964,EBI-747035
SPG7Q9UQ903EBI-1050964,EBI-717201
TRAF3IP3Q9Y2283EBI-1050964,EBI-765817
TULP3O753865EBI-1050964,EBI-5357290
UBE2WQ96B024EBI-1050964,EBI-716589
ZNF175Q9Y4733EBI-1050964,EBI-3438881

Protein-protein interaction databases

BioGridi114513. 51 interactors.
IntActiO43586. 41 interactors.
MINTiMINT-1130527.
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

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DILNMR-A361-416[»]
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.

Sequence similaritiesi

Contains 1 F-BAR domain.PROSITE-ProRule annotation
Contains 1 SH3 domain.PROSITE-ProRule annotation

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

InterProiIPR031160. F_BAR.
IPR001060. FCH_dom.
IPR030777. PSTPIP1.
IPR001452. SH3_domain.
IPR013315. Spectrin_alpha_SH3.
[Graphical view]
PANTHERiPTHR23065:SF3. PTHR23065:SF3. 1 hit.
PfamiPF00611. FCH. 1 hit.
PF14604. SH3_9. 1 hit.
[Graphical view]
PRINTSiPR00452. SH3DOMAIN.
PR01887. SPECTRNALPHA.
SMARTiSM00055. FCH. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
PROSITEiPS51741. F_BAR. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

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 → H.1 PublicationCorresponds to variant rs1141038dbSNPEnsembl.1
Natural variantiVAR_023516106E → K.1 PublicationCorresponds to variant rs1141039dbSNPEnsembl.1
Natural variantiVAR_023517146Q → H.1 PublicationCorresponds to variant rs1141041dbSNPEnsembl.1
Natural variantiVAR_023518149R → L.1 PublicationCorresponds to variant rs1141042dbSNPEnsembl.1
Natural variantiVAR_023519151A → S.1 PublicationCorresponds to variant rs1141043dbSNPEnsembl.1
Natural variantiVAR_023520155E → D.1 PublicationCorresponds to variant rs1141044dbSNPEnsembl.1
Natural variantiVAR_023521156Q → H.1 PublicationCorresponds to variant rs1141045dbSNPEnsembl.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 rs28939381dbSNPEnsembl.1
Natural variantiVAR_070635250E → K in PAPAS. 1 PublicationCorresponds to variant rs28939089dbSNPEnsembl.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 rs28939089dbSNPEnsembl.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

Cross-referencesi

Web resourcesi

INFEVERS

Repertory of FMF and hereditary autoinflammatory disorders mutations

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DILNMR-A361-416[»]
ProteinModelPortaliO43586.
SMRiO43586.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114513. 51 interactors.
IntActiO43586. 41 interactors.
MINTiMINT-1130527.
STRINGi9606.ENSP00000452746.

PTM databases

iPTMnetiO43586.
PhosphoSitePlusiO43586.
SwissPalmiO43586.

Polymorphism and mutation databases

BioMutaiPSTPIP1.

Proteomic databases

EPDiO43586.
MaxQBiO43586.
PaxDbiO43586.
PeptideAtlasiO43586.
PRIDEiO43586.

Protocols and materials databases

DNASUi9051.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi9051.
DisGeNETi9051.
GeneCardsiPSTPIP1.
HGNCiHGNC:9580. PSTPIP1.
HPAiHPA010600.
MalaCardsiPSTPIP1.
MIMi604416. phenotype.
606347. gene.
neXtProtiNX_O43586.
OpenTargetsiENSG00000140368.
Orphaneti69126. Pyogenic arthritis - pyoderma gangrenosum - acne.
PharmGKBiPA33931.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000140368-MONOMER.
ReactomeiR-HSA-844456. The NLRP3 inflammasome.
SignaLinkiO43586.
SIGNORiO43586.

Miscellaneous databases

EvolutionaryTraceiO43586.
GeneWikiiPSTPIP1.
GenomeRNAii9051.
PROiO43586.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000140368.
CleanExiHS_PSTPIP1.
ExpressionAtlasiO43586. baseline and differential.
GenevisibleiO43586. HS.

Family and domain databases

InterProiIPR031160. F_BAR.
IPR001060. FCH_dom.
IPR030777. PSTPIP1.
IPR001452. SH3_domain.
IPR013315. Spectrin_alpha_SH3.
[Graphical view]
PANTHERiPTHR23065:SF3. PTHR23065:SF3. 1 hit.
PfamiPF00611. FCH. 1 hit.
PF14604. SH3_9. 1 hit.
[Graphical view]
PRINTSiPR00452. SH3DOMAIN.
PR01887. SPECTRNALPHA.
SMARTiSM00055. FCH. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
PROSITEiPS51741. F_BAR. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPPIP1_HUMAN
AccessioniPrimary (citable) accession number: O43586
Secondary accession number(s): B5BU74
, B5BUK4, O43585, O95657
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 13, 2005
Last sequence update: June 1, 1998
Last modified: November 30, 2016
This is version 149 of the entry and version 1 of the sequence. [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
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.