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UniProtKB/Swiss-Prot O75475 (PSIP1_HUMAN)
Last modified
November 25, 2008.
Version 70.
History...
Clusters with 100%,
90%,
50% identity |
Documents (4) |
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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 |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 530 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
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. |
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 organismsInferred from electronic annotation. Source: UniProtKB-KW provirus integrationInferred from Experiment. Source: Reactome regulation of transcription, DNA-dependentInferred from electronic annotation. Source: UniProtKB-KW |
| Cellular component | cytosol Inferred from Experiment. Source: Reactome nucleusInferred from electronic annotation. Source: InterPro |
| Molecular function | DNA binding 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: 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 | |||||
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 | |||||||||||||||||||
Helix Strand Turn | |||||||||||||||||||
| Helix | 347 – 362 | 16 | |||||||||||||||||
| Helix | 370 – 381 | 12 | |||||||||||||||||
| Helix | 387 – 391 | 5 | |||||||||||||||||
| Helix | 394 – 403 | 10 | |||||||||||||||||
| Helix | 410 – 425 | 16 | |||||||||||||||||
Sequences
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References
| « Hide '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. |
Cross-references
Sequence databases | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| AF098483 mRNA. Translation: AAC97946.1. AF098482 mRNA. Translation: AAC97945.1. AF063020 mRNA. Translation: AAC25167.1. AF199339 Genomic DNA. Translation: AAF25870.1. AF199339 Genomic DNA. Translation: AAF25871.1. AF432220 mRNA. Translation: AAL99926.1. AL359998, AL441925, AL513423 Genomic DNA. Translation: CAH71355.1. AL441925, AL359998, AL513423 Genomic DNA. Translation: CAI13287.1. BC044568 mRNA. Translation: AAH44568.2. BC064135 mRNA. Translation: AAH64135.1. U94319 mRNA. Translation: AAB52589.1. | |||||||||||||||||||
| PIR | JC7168. | ||||||||||||||||||
| RefSeq | NP_001121689.1. NP_066967.3. NP_150091.2. | ||||||||||||||||||
| UniGene | Hs.658434 | ||||||||||||||||||
3D structure databases | |||||||||||||||||||
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| SMR | O75475. Positions 4-87. | ||||||||||||||||||
| ModBase | Search... | ||||||||||||||||||
Proteomic databases | |||||||||||||||||||
| PeptideAtlas | O75475. | ||||||||||||||||||
Genome annotation databases | |||||||||||||||||||
| Ensembl | ENSG00000164985. Homo sapiens. [ | ||||||||||||||||||

Clusters with