Reviewed, UniProtKB/Swiss-Prot O43586 (PPIP1_HUMAN)

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) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	416 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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.
Subunit structure	Interacts with PTPN18, ABL1, CD2AP and WAS By similarity. Interacts with CD2, PTPN12 and MEFV/pyrin.
Subcellular location	Cytoplasm By similarity. Cytoplasm › cytoskeleton By similarity. Cell projection › lamellipodium By similarity. Cytoplasm › perinuclear region 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.
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.5
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	Defects in PSTPIP1 are the cause of PAPA syndrome (PAPAS) [MIM:604416]; also known as pyogenic sterile arthritis, pyoderma gangrenosum and acne or familial recurrent arthritis (FRA). PAPAS is 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. Ref.5 Ref.7
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
Gene Ontology (GO)
Biological process	cell adhesion Ref.1 Traceable author statement. Source: ProtInc signal transduction Ref.1 Traceable author statement. Source: ProtInc
Cellular component	cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell lamellipodium Inferred from electronic annotation. Source: UniProtKB-SubCell perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	catalytic activity Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ATIC	P31939	1	EBI-1050964,EBI-1048599
BZW1	Q7L1Q6	1	EBI-1050964,EBI-1046727
BZW2	Q9Y6E2	1	EBI-1050964,EBI-1051021
DDX21	Q9NR30	1	EBI-1050964,EBI-357942
FDFT1	P37268	1	EBI-1050964,EBI-714550
RPL18A	Q02543	1	EBI-1050964,EBI-350523
RPL23A	P62750	1	EBI-1050964,EBI-353254
RPL26	P61254	1	EBI-1050964,EBI-352405
RPL29	P47914	1	EBI-1050964,EBI-714039
RPL3	P39023	1	EBI-1050964,EBI-1056348
RPL31	P62899	1	EBI-1050964,EBI-1053664
RPL32	P62910	1	EBI-1050964,EBI-438408
RPL34	P49207	1	EBI-1050964,EBI-1051893
RPL35	P42766	1	EBI-1050964,EBI-356819
RPL35A	P18077	1	EBI-1050964,EBI-353383
RPL36	Q9Y3U8	1	EBI-1050964,EBI-1057689
RPL36A	P83881	1	EBI-1050964,EBI-1054835
RPL37A	P61513	1	EBI-1050964,EBI-356793
RUVBL1	Q9Y265	1	EBI-1050964,EBI-353675

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

Natural variations

Alternative sequence

280 – 309

30

APVPY…CGMIK → GEVRLADSAAS in isoform 2.

VSP_015627

Natural variant

48

1

Q → H: dbSNP rs1141038. Ref.2

VAR_023515

Natural variant

106

1

E → K: dbSNP rs1141039. Ref.2

VAR_023516

Natural variant

146

1

Q → H: dbSNP rs1141041. Ref.2

VAR_023517

Natural variant

149

1

R → L: dbSNP rs1141042. Ref.2

VAR_023518

Natural variant

151

1

A → S: dbSNP rs1141043. Ref.2

VAR_023519

Natural variant

155

1

E → D: dbSNP rs1141044. Ref.2

VAR_023520

Natural variant

156

1

Q → H: dbSNP rs1141045. Ref.2

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.5 Ref.7

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.5 Ref.7

VAR_023523

Experimental info

Mutagenesis

232

1

W → A: Abolishes binding to MEFV. Ref.5

Mutagenesis

345

1

Y → F: Decreases binding to MEFV. Ref.5

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). 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: 9857189] [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: 19054851] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[5]	"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: 14595024] [Abstract] Cited for: INTERACTION WITH MEFV, TISSUE SPECIFICITY, CHARACTERIZATION OF VARIANTS PAPAS THR-230 AND GLN-250, MUTAGENESIS OF TRP-232 AND TYR-345.
[6]	"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.
[7]	"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: 11971877] [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

EMBLGenBankDDBJ

AF038602 mRNA. Translation: AAD11958.1.
AF038603 mRNA. Translation: AAD11959.1.
U94778 mRNA. Translation: AAD00762.1.
AB451440 mRNA. Translation: BAG70254.1.
BC008602 mRNA. Translation: AAH08602.1.

IPI

IPI00022606.
IPI00643697.

RefSeq

NP_003969.2.

UniGene

Hs.129758

3D structure databases

PDBPDBe

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

ModBase

Search...

Protein-protein interaction databases

IntAct

O43586. 39 interactions.

STRING

O43586.

PTM databases

PhosphoSite

O43586.

Proteomic databases

PRIDE

O43586.

Genome annotation databases

Ensembl

ENST00000267939; ENSP00000267939; ENSG00000140368; Homo sapiens. [Genome view]
ENST00000379595; ENSP00000368914; ENSG00000140368; Homo sapiens. [Genome view]
ENST00000455844; ENSP00000390203; ENSG00000140368; Homo sapiens. [Genome view]

GeneID

9051.

KEGG

hsa:9051.

UCSC

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

Organism-specific databases

CTD

9051.

GeneCards

GC15P075074.

H-InvDB

HIX0012460.

HGNC

HGNC:9580. PSTPIP1.

HPA

HPA010600.

MIM

604416. phenotype.
606347. gene.

Orphanet

69126. Pyogenic arthritis - pyoderma gangrenosum - acne.

PharmGKB

PA33931.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

O43586.

HOVERGEN

O43586.

Gene expression databases

ArrayExpress

O43586.

Bgee

O43586.

CleanEx

HS_PSTPIP1.

Genevestigator

O43586.

GermOnline

ENSG00000140368. Homo sapiens.

Family and domain databases

InterPro

IPR001060. FCH.
IPR001452. SH3_domain.
IPR020473. SH3_region.
IPR013315. Spectrin_alpha_SH3.
[Graphical view]

Pfam

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

PRINTS

PR00452. SH3DOMAIN.
PR01887. SPECTRNALPHA.

ProDom

PD000066. SH3. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

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

PROSITE

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

ProtoNet

Search...

Other Resources

NextBio

33911.

SOURCE

Search...

Entry information

Entry name

PPIP1_HUMAN

Accession

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

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 13, 2005
Last sequence update:	June 1, 1998
Last modified:	November 3, 2009
This is version 82 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.