PC4 and SFRS1-interacting protein - Homo sapiens (Human)

Names and origin

Protein names

Recommended name:
    PC4 and SFRS1-interacting protein
Alternative name(s):
    Lens epithelium-derived growth factor
    Transcriptional coactivator p75/p52
    Dense fine speckles 70 kDa protein
      Short name=DFS 70
    CLL-associated antigen KW-7

Gene names

Name:	PSIP1
Synonyms:	DFS70, LEDGF, PSIP2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

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Protein attributes

Sequence length	530 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Transcriptional coactivator involved in neuroepithelial stem cell differentiation and neurogenesis. Involved in particular in lens epithelial cell gene regulation and stress responses. May play an important role in lens epithelial to fiber cell terminal differentiation. May play a protective role during stress-induced apoptosis. Isoform 2 is a more general and stronger transcriptional coactivator. Isoform 2 may also act as an adapter to coordinate pre-mRNA splicing. Cellular cofactor for lentiviral integration.
Subunit structure	Monomer. Interacts with IFRD1/PC4. Isoform 2 interacts with SFRS1. Isoform 1 interacts with lentiviral integrase and acts as a chromatin tethering factor to the chromosomal DNA. Isoform 1 interacts in particular with the human HIV-1 integrase protein (HIV-1 IN), determining its nuclear localization, its tight association with chromatin and its protection from the proteasome. Isoform 1 interacts also with HIV-2 IN. Isoform 2 does not interact with HIV-1 IN.
Subcellular location	Nucleus. Note= Remains chromatin-associated throughout the cell cycle.
Tissue specificity	Widely expressed. Expressed at high level in the thymus. Expressed in fetal and adult brain. Expressed in neurons, but not astrocytes. Markedly elevated in fetal as compared to adult brain. In the adult brain, expressed in the subventricular zone (SVZ), in hippocampus, and undetectable elsewhere. In the fetal brain, expressed in the germinal neuroepithelium and cortical plate regions.
Domain	Residues 340-417 are necessary and sufficient for the interaction with HIV-1 IN (IBD domain).
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR.
Involvement in disease	A chromosomal aberration involving PSIP1 is associated with pediatric acute myeloid leukemia (AML) with intermediate characteristics between M2-M3 French-American-British (FAB) subtypes. Translocation t(9;11)(p22;p15) with NUP98. The chimeric transcript is an in-frame fusion of NUP98 exon 8 to PSIP1/LEDGF exon 4.
Sequence similarities	Belongs to the HDGF family. Contains 1 PWWP domain.

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Ontologies

Keywords
Biological process	Host-virus interaction Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Chromosomal rearrangement
Domain	Coiled coil
Ligand	DNA-binding
PTM	Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	initiation of viral infection Inferred from Experiment. Source: Reactome interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW provirus integration Inferred from Experiment. Source: Reactome regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Inferred from Experiment. Source: Reactome nucleus Inferred from electronic annotation. Source: InterPro
Molecular function	DNA binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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Alternative products

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

Isoform 1 (identifier: O75475-1)

Also known as: p75; PSIP1;

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.

Notes: Less active than isoform 2 as transcriptional coactivator, but more abundant in cells.

Isoform 2 (identifier: O75475-2)

Also known as: p52; PSIP2;

The sequence of this isoform differs from the canonical sequence as follows:
326-333: QQNKDEGK → HQTTCNLQ
334-530: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Sequence conflict

327 – 333

7

QTTCNLQ → FAL in AAH44568. Ref.6

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 530

530

PC4 and SFRS1-interacting protein

PRO_0000191708

Regions

Domain

1 – 64

64

PWWP

Coiled coil

306 – 334

29

Potential

Coiled coil

371 – 395

25

Potential

Motif

146 – 156

11

Nuclear localization signal

Amino acid modifications

Modified residue

106

1

Phosphoserine

Modified residue

122

1

Phosphothreonine

Modified residue

129

1

Phosphoserine

Modified residue

134

1

Phosphothreonine By similarity

Modified residue

141

1

Phosphothreonine

Modified residue

177

1

Phosphoserine By similarity

Modified residue

273

1

Phosphoserine

Modified residue

275

1

Phosphoserine

Modified residue

437

1

Phosphothreonine

Natural variations

Alternative sequence

326 – 333

8

QQNKDEGK → HQTTCNLQ in isoform 2.

VSP_014297

Alternative sequence

334 – 530

197

Missing in isoform 2.

VSP_014298

Experimental info

Mutagenesis

365

1

I → A: Loss of interaction with human HIV-1 integrase

Mutagenesis

366

1

D → A or N: Loss of interaction with human HIV-1 integrase

Mutagenesis

406

1

F → A: Loss of interaction with human HIV-1 integrase

Mutagenesis

408

1

V → A: Reduced interaction with human HIV-1 integrase

Sequence conflict

153 – 161

9

Missing in AAH64135. Ref.6

Sequence conflict

224

1

E → G in AAC97946 and AAC97945. Ref.1

Sequence conflict

272

1

T → P in AAB52589. Ref.7

Sequence conflict

420

1

Y → F Ref.1 Ref.7

Secondary structure

1

.

530

Helix Strand Turn

Details...

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Sequences

Sequence		Length	Mass (Da)
Isoform 1 (p75) (PSIP1) [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 4B653D02B1D0E174 Show »	FASTA	530	60,103
10 20 30 40 50 60 MTRDFKPGDL IFAKMKGYPH WPARVDEVPD GAVKPPTNKL PIFFFGTHET AFLGPKDIFP 70 80 90 100 110 120 YSENKEKYGK PNKRKGFNEG LWEIDNNPKV KFSSQQAATK QSNASSDVEV EEKETSVSKE 130 140 150 160 170 180 DTDHEEKASN EDVTKAVDIT TPKAARRGRK RKAEKQVETE EAGVVTTATA SVNLKVSPKR 190 200 210 220 230 240 GRPAATEVKI PKPRGRPKMV KQPCPSESDI ITEEDKSKKK GQEEKQPKKQ PKKDEEGQKE 250 260 270 280 290 300 EDKPRKEPDK KEGKKEVESK RKNLAKTGVT STSDSEEEGD DQEGEKKRKG GRNFQTAHRR 310 320 330 340 350 360 NMLKGQHEKE AADRKRKQEE QMETEQQNKD EGKKPEVKKV EKKRETSMDS RLQRIHAEIK 370 380 390 400 410 420 NSLKIDNLDV NRCIEALDEL ASLQVTMQQA QKHTEMITTL KKIRRFKVSQ VIMEKSTMLY 430 440 450 460 470 480 NKFKNMFLVG EGDSVITQVL NKSLAEQRQH EEANKTKDQG KKGPNKKLEK EQTGSKTLNG 490 500 510 520 530 GSDAQDGNQP QHNGESNEDS KDNHEASTKK KPSSEERETE ISLKDSTLDN « Hide
Isoform 2 (p52) (PSIP2) [UniParc]. Checksum: DAFEC8F815C06FCD Show »		333	37,725
10 20 30 40 50 60 MTRDFKPGDL IFAKMKGYPH WPARVDEVPD GAVKPPTNKL PIFFFGTHET AFLGPKDIFP 70 80 90 100 110 120 YSENKEKYGK PNKRKGFNEG LWEIDNNPKV KFSSQQAATK QSNASSDVEV EEKETSVSKE 130 140 150 160 170 180 DTDHEEKASN EDVTKAVDIT TPKAARRGRK RKAEKQVETE EAGVVTTATA SVNLKVSPKR 190 200 210 220 230 240 GRPAATEVKI PKPRGRPKMV KQPCPSESDI ITEEDKSKKK GQEEKQPKKQ PKKDEEGQKE 250 260 270 280 290 300 EDKPRKEPDK KEGKKEVESK RKNLAKTGVT STSDSEEEGD DQEGEKKRKG GRNFQTAHRR 310 320 330 NMLKGQHEKE AADRKRKQEE QMETEHQTTC NLQ « Hide

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation of cDNAs encoding novel transcription coactivators p52 and p75 reveals an alternate regulatory mechanism of transcriptional activation." Ge H., Si Y., Roeder R.G. EMBO J. 17:6723-6729(1998) [PubMed: 9822615] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PROTEIN SEQUENCE OF 4-39 AND 76-89, TISSUE SPECIFICITY, INTERACTION WITH PC4. Tissue: Cervix carcinoma.
[2]	"Lens epithelium-derived growth factor: effects on growth and survival of lens epithelial cells, keratinocytes, and fibroblasts." Singh D.P., Ohguro N., Kikuchi T., Sueno T., Reddy V.N., Yuge K., Chylack L.T. Jr., Shinohara T. Biochem. Biophys. Res. Commun. 267:373-381(2000) [PubMed: 10623627] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Lens.
[3]	"Lens epithelium-derived growth factor (LEDGF/p75) and p52 are derived from a single gene by alternative splicing." Singh D.P., Kimura A., Chylack L.T. Jr., Shinohara T. Gene 242:265-273(2000) [PubMed: 10721720] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2).
[4]	"Identification of tumor-associated antigens in chronic lymphocytic leukemia by SEREX." Krackhardt A.M., Witzens M., Harig S., Hodi F.S., Zauls A.J., Chessia M., Barrett P., Gribben J.G. Blood 100:2123-2131(2002) [PubMed: 12200376] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Leukemia.
[5]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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 2). Tissue: Testis and Uterus.
[7]	"Autoantibodies to DFS 70 kd/transcription coactivator p75 in atopic dermatitis and other conditions." Ochs R.L., Muro Y., Si Y., Ge H., Chan E.K.L., Tan E.M. J. Allergy Clin. Immunol. 105:1211-1220(2000) [PubMed: 10856157] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 180-530 (ISOFORM 1).
[8]	"Lens epithelium-derived growth factor (LEDGF/p75) expression in fetal and adult human brain." Chylack L.T. Jr., Fu L., Mancini R., Martin-Rehrmann M.D., Saunders A.J., Konopka G., Tian D., Hedley-Whyte E.T., Folkerth R.D., Goldstein L.E. Exp. Eye Res. 79:941-948(2004) [PubMed: 15642333] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[9]	"Lens epithelium-derived growth factor/p75 prevents proteasomal degradation of HIV-1 integrase." Llano M., Delgado S., Vanegas M., Poeschla E.M. J. Biol. Chem. 279:55570-55577(2004) [PubMed: 15475359] [Abstract] Cited for: INTERACTION WITH HUMAN HIV-1 INTEGRASE (ISOFORM 1).
[10]	"The interaction of LEDGF/p75 with integrase is lentiviral-specific and promotes DNA binding." Busschots K., Vercammen J., Emiliani S., Benarous R., Engelborghs Y., Christ F., Debyser Z. J. Biol. Chem. 280:17841-17847(2005) [PubMed: 15749713] [Abstract] Cited for: INTERACTION WITH HUMAN HIV-1 AND HIV-2 INTEGRASE (ISOFORM 1).
[11]	"Identification of the LEDGF/p75 HIV-1 integrase-interaction domain and NLS reveals NLS-independent chromatin tethering." Vanegas M., Llano M., Delgado S., Thompson D., Peretz M., Poeschla E.M. J. Cell Sci. 118:1733-1743(2005) [PubMed: 15797927] [Abstract] Cited for: INTERACTION WITH HUMAN HIV-1 INTEGRASE (ISOFORM 1), NUCLEAR LOCALIZATION SIGNAL.
[12]	"A novel transcriptional coactivator, p52, functionally interacts with the essential splicing factor ASF/SF2." Ge H., Si Y., Wolffe A.P. Mol. Cell 2:751-759(1998) [PubMed: 9885563] [Abstract] Cited for: INTERACTION WITH SFRS1, SUBCELLULAR LOCATION.
[13]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-106, MASS SPECTROMETRY. Tissue: Epithelium.
[14]	"Global phosphoproteome of HT-29 human colon adenocarcinoma cells." Kim J.-E., Tannenbaum S.R., White F.M. J. Proteome Res. 4:1339-1346(2005) [PubMed: 16083285] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-275, MASS SPECTROMETRY.
[15]	"t(9;11)(p22;p15) with NUP98-LEDGF fusion gene in pediatric acute myeloid leukemia." Morerio C., Acquila M., Rosanda C., Rapella A., Tassano E., Micalizzi C., Panarello C. Leuk. Res. 29:467-470(2005) [PubMed: 15725483] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION WITH NUP98.
[16]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-122; SER-273 AND SER-275, MASS SPECTROMETRY. Tissue: Epithelium.
[17]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-141, MASS SPECTROMETRY. Tissue: Epithelium.
[18]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-106; THR-122; SER-129; SER-273 AND SER-275, MASS SPECTROMETRY.
[19]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-437, MASS SPECTROMETRY.
[20]	"Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography." Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., Zou H., Gu J. Proteomics 8:1346-1361(2008) [PubMed: 18318008] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-273 AND SER-275, MASS SPECTROMETRY. Tissue: Liver.
[21]	"Solution structure of the HIV-1 integrase-binding domain in LEDGF/p75." Cherepanov P., Sun Z.-Y., Rahman S., Maertens G., Wagner G., Engelman A. Nat. Struct. Mol. Biol. 12:526-532(2005) [PubMed: 15895093] [Abstract] Cited for: STRUCTURE BY NMR OF 347-471, SUBUNIT, MUTAGENESIS OF ILE-365; ASP-366; PHE-406 AND VAL-408.
[22]	"Structural basis for the recognition between HIV-1 integrase and transcriptional coactivator p75." Cherepanov P., Ambrosio A.L.B., Rahman S., Ellenberger T., Engelman A. Proc. Natl. Acad. Sci. U.S.A. 102:17308-17313(2005) [PubMed: 16260736] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.02 ANGSTROMS) OF 347-442 IN COMPLEX WITH HUMAN HIV-1 INTEGRASE.
+	Additional computationally mapped references.