O43586 (PPIP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	PSTPIP1
Synonyms:	CD2BP1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	416 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in regulation of the actin cytoskeleton. May regulate the WAS actin-bundling activity. Bridges the interaction between ABL1 and PTPN18 leading to the ABL1 dephosphorylation. May play a role as a scaffold protein between PTPN12 and WAS and allows 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. Ref.1
Subunit structure	Interacts with PTPN18, ABL1, CD2AP and WAS By similarity. Interacts with CD2, PTPN12 and MEFV/pyrin. Interacts with FASLG. Ref.1 Ref.6 Ref.7
Subcellular location	Cytoplasm By similarity. Cytoplasm › cytoskeleton By similarity. Cell projection › lamellipodium By similarity. Cytoplasm › perinuclear region By similarity. Cleavage furrow By similarity. Note: Colocalized with the cortical actin cytoskeleton during interphase, lamellipodia and actin-rich cytokinetic cleavage furrow. Colocalized with WAS to filamentous structures within the cytoplasm. Colocalized with PTPN12 in the cytoplasm and the perinuclear region. Colocalized with CD2AP and WAS in the actin cytoskeleton. Colocalized with CD2, CD2AP and WAS at the site of T-cell:APC contact By similarity. Ref.1
Tissue specificity	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. Ref.1 Ref.6
Domain	The coiled domain mediates interaction with PTPN18, PTPN12 and CD2AP. The SH3 domain mediates interaction with WAS and ABL1 By similarity. The SH3 and coiled-coil domains are necessary for the interaction with MEFV.
Post-translational modification	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.
Involvement in disease	PAPA syndrome (PAPAS) [MIM:604416]: Characterized 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.9
Sequence similarities	Contains 1 FCH domain. Contains 1 SH3 domain.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cell projection Cytoplasm Cytoskeleton
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Coiled coil SH3 domain
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell adhesion Traceable author statement Ref.1. Source: ProtInc innate immune response Traceable author statement. Source: Reactome nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway Traceable author statement. Source: Reactome
Cellular_component	actomyosin contractile ring Inferred from electronic annotation. Source: Compara cleavage furrow Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Traceable author statement. Source: Reactome lamellipodium Inferred from electronic annotation. Source: UniProtKB-SubCell perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell stress fiber Inferred from electronic annotation. Source: Compara
Molecular_function	oxidoreductase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O43586-1)

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.

Isoform 2 (identifier: O43586-2)

Also known as: CD2BP1S;

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 416

416

Proline-serine-threonine phosphatase-interacting protein 1

PRO_0000058539

Regions

Domain

5 – 82

78

FCH

Domain

359 – 416

58

SH3

Coiled coil

166 – 212

47

Potential

Amino acid modifications

Modified residue

345

1

Phosphotyrosine By similarity

Natural variations

Alternative sequence

280 – 309

30

APVPY…CGMIK → GEVRLADSAAS in isoform 2.

VSP_015627

Natural variant

48

1

Q → H. Ref.2
Corresponds to variant rs1141038 [ dbSNP | Ensembl ].

VAR_023515

Natural variant

106

1

E → K. Ref.2
Corresponds to variant rs1141039 [ dbSNP | Ensembl ].

VAR_023516

Natural variant

146

1

Q → H. Ref.2
Corresponds to variant rs1141041 [ dbSNP | Ensembl ].

VAR_023517

Natural variant

149

1

R → L. Ref.2
Corresponds to variant rs1141042 [ dbSNP | Ensembl ].

VAR_023518

Natural variant

151

1

A → S. Ref.2
Corresponds to variant rs1141043 [ dbSNP | Ensembl ].

VAR_023519

Natural variant

155

1

E → D. Ref.2
Corresponds to variant rs1141044 [ dbSNP | Ensembl ].

VAR_023520

Natural variant

156

1

Q → H. Ref.2
Corresponds to variant rs1141045 [ dbSNP | Ensembl ].

VAR_023521

Natural variant

230

1

A → T in PAPAS; severely reduced binding with PTPN12; markedly increased binding to MEFV; accentuates the IL1B secretion. Ref.6 Ref.9
Corresponds to variant rs28939381 [ dbSNP | Ensembl ].

VAR_023522

Natural variant

250

1

E → Q in PAPAS; severely reduced binding with PTPN12; markedly increased binding to MEFV; accentuates the IL1B secretion. Ref.6 Ref.9
Corresponds to variant rs28939089 [ dbSNP | Ensembl ].

VAR_023523

Experimental info

Mutagenesis

232

1

W → A: Abolishes binding to MEFV. Ref.6

Mutagenesis

345

1

Y → F: Decreases binding to MEFV. Ref.6

Sequence conflict

367

1

L → F in AAD00762. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

416

Helix Strand Turn

Details...

Beta strand

363 – 365

3

Beta strand

373 – 377

5

Beta strand

385 – 390

6

Beta strand

393 – 401

9

Beta strand

404 – 409

6

Helix

410 – 412

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (CD2BP1L) [UniParc]. Last modified June 1, 1998. Version 1. Checksum: 97818150B3D5D600	FASTA	416	47,591
	10 20 30 40 50 60 MMPQLQFKDA FWCRDFTAHT GYEVLLQRLL DGRKMCKDME ELLRQRAQAE ERYGKELVQI 70 80 90 100 110 120 ARKAGGQTEI NSLRASFDSL KQQMENVGSS HIQLALTLRE ELRSLEEFRE RQKEQRKKYE 130 140 150 160 170 180 AVMDRVQKSK LSLYKKAMES KKTYEQKCRD ADDAEQAFER ISANGHQKQV EKSQNKARQC 190 200 210 220 230 240 KDSATEAERV YRQSIAQLEK VRAEWEQEHR TTCEAFQLQE FDRLTILRNA LWVHSNQLSM 250 260 270 280 290 300 QCVKDDELYE EVRLTLEGCS IDADIDSFIQ AKSTGTEPPA PVPYQNYYDR EVTPLTSSPG 310 320 330 340 350 360 IQPSCGMIKR FSGLLHGSPK TTSLAASAAS TETLTPTPER NEGVYTAIAV QEIQGNPASP 370 380 390 400 410 AQEYRALYDY TAQNPDELDL SAGDILEVIL EGEDGWWTVE RNGQRGFVPG SYLEKL
	Isoform 2 (CD2BP1S) [UniParc]. Checksum: 54D64A3AAE16A2FC	FASTA	397	45,354
	10 20 30 40 50 60 MMPQLQFKDA FWCRDFTAHT GYEVLLQRLL DGRKMCKDME ELLRQRAQAE ERYGKELVQI 70 80 90 100 110 120 ARKAGGQTEI NSLRASFDSL KQQMENVGSS HIQLALTLRE ELRSLEEFRE RQKEQRKKYE 130 140 150 160 170 180 AVMDRVQKSK LSLYKKAMES KKTYEQKCRD ADDAEQAFER ISANGHQKQV EKSQNKARQC 190 200 210 220 230 240 KDSATEAERV YRQSIAQLEK VRAEWEQEHR TTCEAFQLQE FDRLTILRNA LWVHSNQLSM 250 260 270 280 290 300 QCVKDDELYE EVRLTLEGCS IDADIDSFIQ AKSTGTEPPG EVRLADSAAS RFSGLLHGSP 310 320 330 340 350 360 KTTSLAASAA STETLTPTPE RNEGVYTAIA VQEIQGNPAS PAQEYRALYD YTAQNPDELD 370 380 390 LSAGDILEVI LEGEDGWWTV ERNGQRGFVP GSYLEKL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A cdc15-like adaptor protein (CD2BP1) interacts with the CD2 cytoplasmic domain and regulates CD2-triggered adhesion." Li J., Nishizawa K., An W., Hussey R.E., Lialios F.E., Salgia R., Sunder-Plassmann R., Reinherz E.L. EMBO J. 17:7320-7336(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, INTERACTION WITH CD2 AND PTPN12, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]	"The human homologue of mouse PTP-PIP interactor protein." Wilson L.A., Fields D., Cruz L., Lasky L., Friesen J., Siminovitch K.A. Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS HIS-48; LYS-106; HIS-146; LEU-149; SER-151; ASP-155 AND HIS-156.
[3]	"Human protein factory for converting the transcriptome into an in vitro-expressed proteome." Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B. , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N. Nat. Methods 5:1011-1017(2008) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[6]	"Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway." Shoham N.G., Centola M., Mansfield E., Hull K.M., Wood G., Wise C.A., Kastner D.L. Proc. Natl. Acad. Sci. U.S.A. 100:13501-13506(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MEFV, TISSUE SPECIFICITY, CHARACTERIZATION OF VARIANTS PAPAS THR-230 AND GLN-250, MUTAGENESIS OF TRP-232 AND TYR-345.
[7]	"Identification of SH3 domain interaction partners of human FasL (CD178) by phage display screening." Voss M., Lettau M., Janssen O. BMC Immunol. 10:53-53(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FASLG.
[8]	"Solution structure of the SH3 domain of the human proline-serine-threonine phosphatase-interacting protein 1." RIKEN structural genomics initiative (RSGI) Submitted (FEB-2007) to the PDB data bank Cited for: STRUCTURE BY NMR OF 358-416.
[9]	"Mutations in CD2BP1 disrupt binding to PTP PEST and are responsible for PAPA syndrome, an autoinflammatory disorder." Wise C.A., Gillum J.D., Seidman C.E., Lindor N.M., Veile R., Bashiardes S., Lovett M. Hum. Mol. Genet. 11:961-969(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PAPAS THR-230 AND GLN-250, CHARACTERIZATION OF VARIANTS PAPAS THR-230 AND GLN-250.
+	Additional computationally mapped references.

Web resources

INFEVERS

Repertory of FMF and hereditary autoinflammatory disorders mutations

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00022606.
IPI00643697.

RefSeq

NP_003969.2. NM_003978.3.

UniGene

Hs.129758.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2DIL	NMR	-	A	361-416	[»]

ProteinModelPortal

O43586.

ModBase

Search...

Protein-protein interaction databases

IntAct

O43586. 1 interaction.

MINT

MINT-1130527.

STRING

9606.ENSP00000368914.

PTM databases

PhosphoSite

O43586.

Proteomic databases

PaxDb

O43586.

PRIDE

O43586.

Protocols and materials databases

DNASU

9051.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000558012; ENSP00000452746; ENSG00000140368.
ENST00000559295; ENSP00000452743; ENSG00000140368.

GeneID

9051.

KEGG

hsa:9051.

UCSC

uc002bcf.2. human.
uc010bkw.1. human.

Organism-specific databases

CTD

9051.

GeneCards

GC15P077287.

HGNC

HGNC:9580. PSTPIP1.

HPA

HPA010600.

MIM

604416. phenotype.
606347. gene.

neXtProt

NX_O43586.

Orphanet

69126. Pyogenic arthritis - pyoderma gangrenosum - acne.

PharmGKB

PA33931.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG303711.

HOGENOM

HOG000294218.

HOVERGEN

HBG052960.

InParanoid

O43586.

KO

K12804.

OMA

NYYDREV.

OrthoDB

EOG4PZJ6T.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

SignaLink

O43586.

Gene expression databases

ArrayExpress

O43586.

Bgee

O43586.

CleanEx

HS_PSTPIP1.

Genevestigator

O43586.

GermOnline

ENSG00000140368. Homo sapiens.

Family and domain databases

InterPro

IPR001060. FCH_dom.
IPR011254. Prismane-like.
IPR001452. SH3_domain.
IPR013315. Spectrin_alpha_SH3.
[Graphical view]

Pfam

PF00611. FCH. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]

PRINTS

PR00452. SH3DOMAIN.
PR01887. SPECTRNALPHA.

SMART

SM00055. FCH. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]

SUPFAM

SSF56821. Prismane_like. 1 hit.
SSF50044. SH3. 1 hit.

PROSITE

PS50133. FCH. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O43586.

GenomeRNAi

9051.

NextBio

33911.

SOURCE

Search...

Entry information

Entry name

PPIP1_HUMAN

Accession

Primary (citable) accession number: O43586
Secondary accession number(s): B5BU74 , B5BUK4, O43585, O95657

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 13, 2005
Last sequence update:	June 1, 1998
Last modified:	May 29, 2013
This is version 112 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.