Full text data of STIP1
STIP1
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Stress-induced-phosphoprotein 1; STI1 (Hsc70/Hsp90-organizing protein; Hop; Renal carcinoma antigen NY-REN-11; Transformation-sensitive protein IEF SSP 3521)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Stress-induced-phosphoprotein 1; STI1 (Hsc70/Hsp90-organizing protein; Hop; Renal carcinoma antigen NY-REN-11; Transformation-sensitive protein IEF SSP 3521)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00013894
IPI00013894 Stress-induced-phosphoprotein 1 Hsc70/Hsp90-organizing protein, Mediates the association of the molecular chaperones HSC70 and HSP90 soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a Cytoplasmic and nuclear n/a expected molecular weight found in band at molecular weight
IPI00013894 Stress-induced-phosphoprotein 1 Hsc70/Hsp90-organizing protein, Mediates the association of the molecular chaperones HSC70 and HSP90 soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a Cytoplasmic and nuclear n/a expected molecular weight found in band at molecular weight
UniProt
P31948
ID STIP1_HUMAN Reviewed; 543 AA.
AC P31948; Q5TZU9;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUL-1993, sequence version 1.
DT 22-JAN-2014, entry version 150.
DE RecName: Full=Stress-induced-phosphoprotein 1;
DE Short=STI1;
DE AltName: Full=Hsc70/Hsp90-organizing protein;
DE Short=Hop;
DE AltName: Full=Renal carcinoma antigen NY-REN-11;
DE AltName: Full=Transformation-sensitive protein IEF SSP 3521;
GN Name=STIP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=1569099;
RA Honore B., Leffers H., Madsen P., Rasmussen H.H., Vandekerckhove J.,
RA Celis J.E.;
RT "Molecular cloning and expression of a transformation-sensitive human
RT protein containing the TPR motif and sharing identity to the stress-
RT inducible yeast protein STI1.";
RL J. Biol. Chem. 267:8485-8491(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 1-10; 110-118; 345-364; 382-389; 479-486 AND
RP 534-543, ACETYLATION AT MET-1, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (OCT-2004) to UniProtKB.
RN [7]
RP PROTEIN SEQUENCE OF 33-44; 64-73; 79-87; 154-160; 253-272; 306-312;
RP 352-364; 407-429; 454-462; 489-513 AND 534-543, AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [8]
RP PROTEIN SEQUENCE OF 101-109; 352-364 AND 374-381.
RC TISSUE=Keratinocyte;
RX PubMed=1286667; DOI=10.1002/elps.11501301199;
RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E.,
RA Vandekerckhove J.;
RT "Microsequences of 145 proteins recorded in the two-dimensional gel
RT protein database of normal human epidermal keratinocytes.";
RL Electrophoresis 13:960-969(1992).
RN [9]
RP INTERACTION WITH HSP90AA1.
RX PubMed=9195923; DOI=10.1074/jbc.272.26.16224;
RA Silverstein A.M., Galigniana M.D., Chen M.S., Owens-Grillo J.K.,
RA Chinkers M., Pratt W.B.;
RT "Protein phosphatase 5 is a major component of glucocorticoid
RT receptor.hsp90 complexes with properties of an FK506-binding
RT immunophilin.";
RL J. Biol. Chem. 272:16224-16230(1997).
RN [10]
RP IDENTIFICATION AS A RENAL CANCER ANTIGEN.
RC TISSUE=Renal cell carcinoma;
RX PubMed=10508479;
RX DOI=10.1002/(SICI)1097-0215(19991112)83:4<456::AID-IJC4>3.0.CO;2-5;
RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H.,
RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T.,
RA Old L.J.;
RT "Antigens recognized by autologous antibody in patients with renal-
RT cell carcinoma.";
RL Int. J. Cancer 83:456-464(1999).
RN [11]
RP INTERACTION WITH PACRG.
RX PubMed=14532270; DOI=10.1074/jbc.M309655200;
RA Imai Y., Soda M., Murakami T., Shoji M., Abe K., Takahashi R.;
RT "A product of the human gene adjacent to parkin is a component of Lewy
RT bodies and suppresses Pael receptor-induced cell death.";
RL J. Biol. Chem. 278:51901-51910(2003).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-354, AND MASS
RP SPECTROMETRY.
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1; LYS-8; LYS-301; LYS-312;
RP LYS-325; LYS-344 AND LYS-446, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [19]
RP INTERACTION WITH METTL21B.
RX PubMed=23349634; DOI=10.1371/journal.pgen.1003210;
RA Cloutier P., Lavallee-Adam M., Faubert D., Blanchette M., Coulombe B.;
RT "A newly uncovered group of distantly related lysine
RT methyltransferases preferentially interact with molecular chaperones
RT to regulate their activity.";
RL PLoS Genet. 9:E1003210-E1003210(2013).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 223-349.
RX PubMed=10786835; DOI=10.1016/S0092-8674(00)80830-2;
RA Scheufler C., Brinker A., Bourenkov G., Pegoraro S., Moroder L.,
RA Bartunik H., Hartl F.U., Moarefi I.;
RT "Structure of TPR domain-peptide complexes: critical elements in the
RT assembly of the Hsp70-Hsp90 multichaperone machine.";
RL Cell 101:199-210(2000).
CC -!- FUNCTION: Mediates the association of the molecular chaperones
CC HSC70 and HSP90 (HSPCA and HSPCB).
CC -!- SUBUNIT: Forms a complex with HSC70 and HSPCA/HSP-86 and
CC HSPCB/HSP-84. Interacts with PACRG. Interacts with METTL21B.
CC Interacts with HSP90/HSP90AA1; the interaction dissociates the
CC PPP5C:HSP90AA1 interaction.
CC -!- INTERACTION:
CC P00533:EGFR; NbExp=2; IntAct=EBI-1054052, EBI-297353;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By
CC similarity).
CC -!- DOMAIN: The TPR 1 repeat interacts with the C-terminal of HSC70.
CC The TPR 4, 5 and 6 repeats (also called TPR2A domain) and TPR 7, 8
CC and 9 repeats (also called TPR2B domain) interact with HSP90.
CC -!- SIMILARITY: Contains 2 STI1 domains.
CC -!- SIMILARITY: Contains 9 TPR repeats.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; M86752; AAA58682.1; -; mRNA.
DR EMBL; BT020010; AAV38813.1; -; mRNA.
DR EMBL; BT020011; AAV38814.1; -; mRNA.
DR EMBL; CR536512; CAG38750.1; -; mRNA.
DR EMBL; CH471076; EAW74196.1; -; Genomic_DNA.
DR EMBL; BC002987; AAH02987.1; -; mRNA.
DR PIR; A38093; A38093.
DR RefSeq; NP_006810.1; NM_006819.2.
DR UniGene; Hs.337295; -.
DR PDB; 1ELR; X-ray; 1.90 A; A=223-352.
DR PDB; 1ELW; X-ray; 1.60 A; A/B=1-118.
DR PDB; 2LNI; NMR; -; A=356-477.
DR PDB; 3ESK; X-ray; 2.05 A; A=223-350.
DR PDB; 3FWV; X-ray; 2.20 A; A/B=223-349.
DR PDBsum; 1ELR; -.
DR PDBsum; 1ELW; -.
DR PDBsum; 2LNI; -.
DR PDBsum; 3ESK; -.
DR PDBsum; 3FWV; -.
DR ProteinModelPortal; P31948; -.
DR SMR; P31948; 2-118, 223-540.
DR DIP; DIP-41085N; -.
DR IntAct; P31948; 23.
DR MINT; MINT-132047; -.
DR STRING; 9606.ENSP00000305958; -.
DR PhosphoSite; P31948; -.
DR DMDM; 400042; -.
DR REPRODUCTION-2DPAGE; IPI00013894; -.
DR UCD-2DPAGE; P31948; -.
DR PaxDb; P31948; -.
DR PRIDE; P31948; -.
DR DNASU; 10963; -.
DR Ensembl; ENST00000305218; ENSP00000305958; ENSG00000168439.
DR GeneID; 10963; -.
DR KEGG; hsa:10963; -.
DR UCSC; uc001nyk.1; human.
DR CTD; 10963; -.
DR GeneCards; GC11P063953; -.
DR HGNC; HGNC:11387; STIP1.
DR MIM; 605063; gene.
DR neXtProt; NX_P31948; -.
DR PharmGKB; PA36196; -.
DR eggNOG; COG0457; -.
DR HOGENOM; HOG000186562; -.
DR HOVERGEN; HBG057820; -.
DR KO; K09553; -.
DR ChiTaRS; STIP1; human.
DR EvolutionaryTrace; P31948; -.
DR GeneWiki; Hop_(protein); -.
DR GenomeRNAi; 10963; -.
DR NextBio; 41662; -.
DR PRO; PR:P31948; -.
DR ArrayExpress; P31948; -.
DR Bgee; P31948; -.
DR CleanEx; HS_STIP1; -.
DR Genevestigator; P31948; -.
DR GO; GO:0005794; C:Golgi apparatus; TAS:ProtInc.
DR GO; GO:0005634; C:nucleus; TAS:UniProtKB.
DR GO; GO:0043234; C:protein complex; IEA:Ensembl.
DR GO; GO:0006950; P:response to stress; TAS:ProtInc.
DR Gene3D; 1.25.40.10; -; 3.
DR InterPro; IPR006636; STI1_HS-bd.
DR InterPro; IPR013026; TPR-contain_dom.
DR InterPro; IPR011990; TPR-like_helical.
DR InterPro; IPR001440; TPR_1.
DR InterPro; IPR019734; TPR_repeat.
DR Pfam; PF00515; TPR_1; 8.
DR Pfam; PF13181; TPR_8; 1.
DR SMART; SM00727; STI1; 2.
DR SMART; SM00028; TPR; 9.
DR PROSITE; PS50005; TPR; 9.
DR PROSITE; PS50293; TPR_REGION; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; TPR repeat.
FT CHAIN 1 543 Stress-induced-phosphoprotein 1.
FT /FTId=PRO_0000106372.
FT REPEAT 4 37 TPR 1.
FT REPEAT 38 71 TPR 2.
FT REPEAT 72 105 TPR 3.
FT DOMAIN 130 169 STI1 1.
FT REPEAT 225 258 TPR 4.
FT REPEAT 259 292 TPR 5.
FT REPEAT 300 333 TPR 6.
FT REPEAT 360 393 TPR 7.
FT REPEAT 394 427 TPR 8.
FT REPEAT 428 461 TPR 9.
FT DOMAIN 492 531 STI1 2.
FT MOTIF 222 239 Bipartite nuclear localization signal
FT (Potential).
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 8 8 N6-acetyllysine.
FT MOD_RES 16 16 Phosphoserine.
FT MOD_RES 301 301 N6-acetyllysine.
FT MOD_RES 312 312 N6-acetyllysine.
FT MOD_RES 325 325 N6-acetyllysine.
FT MOD_RES 344 344 N6-acetyllysine.
FT MOD_RES 354 354 Phosphotyrosine.
FT MOD_RES 446 446 N6-acetyllysine.
FT MOD_RES 481 481 Phosphoserine.
FT HELIX 3 16
FT HELIX 20 33
FT HELIX 38 51
FT HELIX 54 67
FT HELIX 72 84
FT HELIX 88 99
FT HELIX 106 117
FT HELIX 223 237
FT HELIX 241 254
FT HELIX 259 272
FT HELIX 275 291
FT HELIX 296 312
FT HELIX 316 329
FT HELIX 333 348
FT HELIX 359 372
FT HELIX 377 387
FT HELIX 394 404
FT TURN 405 408
FT HELIX 410 423
FT HELIX 428 440
FT HELIX 444 457
FT HELIX 459 462
FT HELIX 463 475
SQ SEQUENCE 543 AA; 62639 MW; 8E58ECA13825CB0E CRC64;
MEQVNELKEK GNKALSVGNI DDALQCYSEA IKLDPHNHVL YSNRSAAYAK KGDYQKAYED
GCKTVDLKPD WGKGYSRKAA ALEFLNRFEE AKRTYEEGLK HEANNPQLKE GLQNMEARLA
ERKFMNPFNM PNLYQKLESD PRTRTLLSDP TYRELIEQLR NKPSDLGTKL QDPRIMTTLS
VLLGVDLGSM DEEEEIATPP PPPPPKKETK PEPMEEDLPE NKKQALKEKE LGNDAYKKKD
FDTALKHYDK AKELDPTNMT YITNQAAVYF EKGDYNKCRE LCEKAIEVGR ENREDYRQIA
KAYARIGNSY FKEEKYKDAI HFYNKSLAEH RTPDVLKKCQ QAEKILKEQE RLAYINPDLA
LEEKNKGNEC FQKGDYPQAM KHYTEAIKRN PKDAKLYSNR AACYTKLLEF QLALKDCEEC
IQLEPTFIKG YTRKAAALEA MKDYTKAMDV YQKALDLDSS CKEAADGYQR CMMAQYNRHD
SPEDVKRRAM ADPEVQQIMS DPAMRLILEQ MQKDPQALSE HLKNPVIAQK IQKLMDVGLI
AIR
//
ID STIP1_HUMAN Reviewed; 543 AA.
AC P31948; Q5TZU9;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUL-1993, sequence version 1.
DT 22-JAN-2014, entry version 150.
DE RecName: Full=Stress-induced-phosphoprotein 1;
DE Short=STI1;
DE AltName: Full=Hsc70/Hsp90-organizing protein;
DE Short=Hop;
DE AltName: Full=Renal carcinoma antigen NY-REN-11;
DE AltName: Full=Transformation-sensitive protein IEF SSP 3521;
GN Name=STIP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=1569099;
RA Honore B., Leffers H., Madsen P., Rasmussen H.H., Vandekerckhove J.,
RA Celis J.E.;
RT "Molecular cloning and expression of a transformation-sensitive human
RT protein containing the TPR motif and sharing identity to the stress-
RT inducible yeast protein STI1.";
RL J. Biol. Chem. 267:8485-8491(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 1-10; 110-118; 345-364; 382-389; 479-486 AND
RP 534-543, ACETYLATION AT MET-1, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (OCT-2004) to UniProtKB.
RN [7]
RP PROTEIN SEQUENCE OF 33-44; 64-73; 79-87; 154-160; 253-272; 306-312;
RP 352-364; 407-429; 454-462; 489-513 AND 534-543, AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [8]
RP PROTEIN SEQUENCE OF 101-109; 352-364 AND 374-381.
RC TISSUE=Keratinocyte;
RX PubMed=1286667; DOI=10.1002/elps.11501301199;
RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E.,
RA Vandekerckhove J.;
RT "Microsequences of 145 proteins recorded in the two-dimensional gel
RT protein database of normal human epidermal keratinocytes.";
RL Electrophoresis 13:960-969(1992).
RN [9]
RP INTERACTION WITH HSP90AA1.
RX PubMed=9195923; DOI=10.1074/jbc.272.26.16224;
RA Silverstein A.M., Galigniana M.D., Chen M.S., Owens-Grillo J.K.,
RA Chinkers M., Pratt W.B.;
RT "Protein phosphatase 5 is a major component of glucocorticoid
RT receptor.hsp90 complexes with properties of an FK506-binding
RT immunophilin.";
RL J. Biol. Chem. 272:16224-16230(1997).
RN [10]
RP IDENTIFICATION AS A RENAL CANCER ANTIGEN.
RC TISSUE=Renal cell carcinoma;
RX PubMed=10508479;
RX DOI=10.1002/(SICI)1097-0215(19991112)83:4<456::AID-IJC4>3.0.CO;2-5;
RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H.,
RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T.,
RA Old L.J.;
RT "Antigens recognized by autologous antibody in patients with renal-
RT cell carcinoma.";
RL Int. J. Cancer 83:456-464(1999).
RN [11]
RP INTERACTION WITH PACRG.
RX PubMed=14532270; DOI=10.1074/jbc.M309655200;
RA Imai Y., Soda M., Murakami T., Shoji M., Abe K., Takahashi R.;
RT "A product of the human gene adjacent to parkin is a component of Lewy
RT bodies and suppresses Pael receptor-induced cell death.";
RL J. Biol. Chem. 278:51901-51910(2003).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-354, AND MASS
RP SPECTROMETRY.
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1; LYS-8; LYS-301; LYS-312;
RP LYS-325; LYS-344 AND LYS-446, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [19]
RP INTERACTION WITH METTL21B.
RX PubMed=23349634; DOI=10.1371/journal.pgen.1003210;
RA Cloutier P., Lavallee-Adam M., Faubert D., Blanchette M., Coulombe B.;
RT "A newly uncovered group of distantly related lysine
RT methyltransferases preferentially interact with molecular chaperones
RT to regulate their activity.";
RL PLoS Genet. 9:E1003210-E1003210(2013).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 223-349.
RX PubMed=10786835; DOI=10.1016/S0092-8674(00)80830-2;
RA Scheufler C., Brinker A., Bourenkov G., Pegoraro S., Moroder L.,
RA Bartunik H., Hartl F.U., Moarefi I.;
RT "Structure of TPR domain-peptide complexes: critical elements in the
RT assembly of the Hsp70-Hsp90 multichaperone machine.";
RL Cell 101:199-210(2000).
CC -!- FUNCTION: Mediates the association of the molecular chaperones
CC HSC70 and HSP90 (HSPCA and HSPCB).
CC -!- SUBUNIT: Forms a complex with HSC70 and HSPCA/HSP-86 and
CC HSPCB/HSP-84. Interacts with PACRG. Interacts with METTL21B.
CC Interacts with HSP90/HSP90AA1; the interaction dissociates the
CC PPP5C:HSP90AA1 interaction.
CC -!- INTERACTION:
CC P00533:EGFR; NbExp=2; IntAct=EBI-1054052, EBI-297353;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By
CC similarity).
CC -!- DOMAIN: The TPR 1 repeat interacts with the C-terminal of HSC70.
CC The TPR 4, 5 and 6 repeats (also called TPR2A domain) and TPR 7, 8
CC and 9 repeats (also called TPR2B domain) interact with HSP90.
CC -!- SIMILARITY: Contains 2 STI1 domains.
CC -!- SIMILARITY: Contains 9 TPR repeats.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; M86752; AAA58682.1; -; mRNA.
DR EMBL; BT020010; AAV38813.1; -; mRNA.
DR EMBL; BT020011; AAV38814.1; -; mRNA.
DR EMBL; CR536512; CAG38750.1; -; mRNA.
DR EMBL; CH471076; EAW74196.1; -; Genomic_DNA.
DR EMBL; BC002987; AAH02987.1; -; mRNA.
DR PIR; A38093; A38093.
DR RefSeq; NP_006810.1; NM_006819.2.
DR UniGene; Hs.337295; -.
DR PDB; 1ELR; X-ray; 1.90 A; A=223-352.
DR PDB; 1ELW; X-ray; 1.60 A; A/B=1-118.
DR PDB; 2LNI; NMR; -; A=356-477.
DR PDB; 3ESK; X-ray; 2.05 A; A=223-350.
DR PDB; 3FWV; X-ray; 2.20 A; A/B=223-349.
DR PDBsum; 1ELR; -.
DR PDBsum; 1ELW; -.
DR PDBsum; 2LNI; -.
DR PDBsum; 3ESK; -.
DR PDBsum; 3FWV; -.
DR ProteinModelPortal; P31948; -.
DR SMR; P31948; 2-118, 223-540.
DR DIP; DIP-41085N; -.
DR IntAct; P31948; 23.
DR MINT; MINT-132047; -.
DR STRING; 9606.ENSP00000305958; -.
DR PhosphoSite; P31948; -.
DR DMDM; 400042; -.
DR REPRODUCTION-2DPAGE; IPI00013894; -.
DR UCD-2DPAGE; P31948; -.
DR PaxDb; P31948; -.
DR PRIDE; P31948; -.
DR DNASU; 10963; -.
DR Ensembl; ENST00000305218; ENSP00000305958; ENSG00000168439.
DR GeneID; 10963; -.
DR KEGG; hsa:10963; -.
DR UCSC; uc001nyk.1; human.
DR CTD; 10963; -.
DR GeneCards; GC11P063953; -.
DR HGNC; HGNC:11387; STIP1.
DR MIM; 605063; gene.
DR neXtProt; NX_P31948; -.
DR PharmGKB; PA36196; -.
DR eggNOG; COG0457; -.
DR HOGENOM; HOG000186562; -.
DR HOVERGEN; HBG057820; -.
DR KO; K09553; -.
DR ChiTaRS; STIP1; human.
DR EvolutionaryTrace; P31948; -.
DR GeneWiki; Hop_(protein); -.
DR GenomeRNAi; 10963; -.
DR NextBio; 41662; -.
DR PRO; PR:P31948; -.
DR ArrayExpress; P31948; -.
DR Bgee; P31948; -.
DR CleanEx; HS_STIP1; -.
DR Genevestigator; P31948; -.
DR GO; GO:0005794; C:Golgi apparatus; TAS:ProtInc.
DR GO; GO:0005634; C:nucleus; TAS:UniProtKB.
DR GO; GO:0043234; C:protein complex; IEA:Ensembl.
DR GO; GO:0006950; P:response to stress; TAS:ProtInc.
DR Gene3D; 1.25.40.10; -; 3.
DR InterPro; IPR006636; STI1_HS-bd.
DR InterPro; IPR013026; TPR-contain_dom.
DR InterPro; IPR011990; TPR-like_helical.
DR InterPro; IPR001440; TPR_1.
DR InterPro; IPR019734; TPR_repeat.
DR Pfam; PF00515; TPR_1; 8.
DR Pfam; PF13181; TPR_8; 1.
DR SMART; SM00727; STI1; 2.
DR SMART; SM00028; TPR; 9.
DR PROSITE; PS50005; TPR; 9.
DR PROSITE; PS50293; TPR_REGION; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; TPR repeat.
FT CHAIN 1 543 Stress-induced-phosphoprotein 1.
FT /FTId=PRO_0000106372.
FT REPEAT 4 37 TPR 1.
FT REPEAT 38 71 TPR 2.
FT REPEAT 72 105 TPR 3.
FT DOMAIN 130 169 STI1 1.
FT REPEAT 225 258 TPR 4.
FT REPEAT 259 292 TPR 5.
FT REPEAT 300 333 TPR 6.
FT REPEAT 360 393 TPR 7.
FT REPEAT 394 427 TPR 8.
FT REPEAT 428 461 TPR 9.
FT DOMAIN 492 531 STI1 2.
FT MOTIF 222 239 Bipartite nuclear localization signal
FT (Potential).
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 8 8 N6-acetyllysine.
FT MOD_RES 16 16 Phosphoserine.
FT MOD_RES 301 301 N6-acetyllysine.
FT MOD_RES 312 312 N6-acetyllysine.
FT MOD_RES 325 325 N6-acetyllysine.
FT MOD_RES 344 344 N6-acetyllysine.
FT MOD_RES 354 354 Phosphotyrosine.
FT MOD_RES 446 446 N6-acetyllysine.
FT MOD_RES 481 481 Phosphoserine.
FT HELIX 3 16
FT HELIX 20 33
FT HELIX 38 51
FT HELIX 54 67
FT HELIX 72 84
FT HELIX 88 99
FT HELIX 106 117
FT HELIX 223 237
FT HELIX 241 254
FT HELIX 259 272
FT HELIX 275 291
FT HELIX 296 312
FT HELIX 316 329
FT HELIX 333 348
FT HELIX 359 372
FT HELIX 377 387
FT HELIX 394 404
FT TURN 405 408
FT HELIX 410 423
FT HELIX 428 440
FT HELIX 444 457
FT HELIX 459 462
FT HELIX 463 475
SQ SEQUENCE 543 AA; 62639 MW; 8E58ECA13825CB0E CRC64;
MEQVNELKEK GNKALSVGNI DDALQCYSEA IKLDPHNHVL YSNRSAAYAK KGDYQKAYED
GCKTVDLKPD WGKGYSRKAA ALEFLNRFEE AKRTYEEGLK HEANNPQLKE GLQNMEARLA
ERKFMNPFNM PNLYQKLESD PRTRTLLSDP TYRELIEQLR NKPSDLGTKL QDPRIMTTLS
VLLGVDLGSM DEEEEIATPP PPPPPKKETK PEPMEEDLPE NKKQALKEKE LGNDAYKKKD
FDTALKHYDK AKELDPTNMT YITNQAAVYF EKGDYNKCRE LCEKAIEVGR ENREDYRQIA
KAYARIGNSY FKEEKYKDAI HFYNKSLAEH RTPDVLKKCQ QAEKILKEQE RLAYINPDLA
LEEKNKGNEC FQKGDYPQAM KHYTEAIKRN PKDAKLYSNR AACYTKLLEF QLALKDCEEC
IQLEPTFIKG YTRKAAALEA MKDYTKAMDV YQKALDLDSS CKEAADGYQR CMMAQYNRHD
SPEDVKRRAM ADPEVQQIMS DPAMRLILEQ MQKDPQALSE HLKNPVIAQK IQKLMDVGLI
AIR
//
MIM
605063
*RECORD*
*FIELD* NO
605063
*FIELD* TI
*605063 STRESS-INDUCED PHOSPHOPROTEIN 1; STIP1
;;STI1, YEAST, HOMOLOG OF;;
HSP70/HSP90-ORGANIZING PROTEIN; HOP
read more*FIELD* TX
DESCRIPTION
STIP1 is an adaptor protein that coordinates the functions of HSP70 (see
HSPA1A; 140550) and HSP90 (see HSP90AA1; 140571) in protein folding. It
is thought to assist in the transfer of proteins from HSP70 to HSP90 by
binding both HSP90 and substrate-bound HSP70. STIP1 also stimulates the
ATPase activity of HSP70 and inhibits the ATPase activity of HSP90,
suggesting that it regulates both the conformations and ATPase cycles of
these chaperones (Song and Masison, 2005).
CLONING
By microsequencing a protein that was upregulated in transformed
embryonic lung fibroblasts and using degenerate PCR primers to screen a
transformed embryonic lung fibroblast cDNA library, Honore et al. (1992)
obtained a cDNA encoding STIP1. The predicted 543-amino acid hydrophilic
protein contains a tetratricopeptide repeat (TPR), a 34-amino acid motif
that is repeated at least 6 times in STIP1. STIP1 is homologous to the
yeast stress-inducible mediator of the heat shock response, Sti1.
Western blot analysis and 2-dimensional gel electrophoresis showed that
STIP1 was expressed as an approximately 61-kD protein. Northern blot
analysis showed that STIP1, which was expressed as an approximately
2.1-kb transcript, was upregulated in transformed cell lines and
psoriatic keratinocytes. Immunofluorescence analysis showed that STIP1
localized to the Golgi in normal fibroblasts, but mainly to the nucleus
in transformed cells.
GENE FUNCTION
Using mutation analysis, Chen and Smith (1998) localized a putative
HSP90-binding domain to a central tetratricopeptide repeat (TPR) of the
HOP sequence, and a putative HSP70-binding domain to an N-terminal TPR.
Using in vitro steroid receptor assembly reactions, they found that
reactions performed with HOP carrying mutations in the putative HSP70-
and HSP90-binding domains resulted in receptor complexes that failed to
incorporate HSP90. Chen and Smith (1998) concluded that HOP acts as an
adaptor that directs HSP90 to preexisting HSP70-progesterone receptor
complexes.
By mutating the TPR regions of yeast Sti1, Song and Masison (2005)
identified separate domains involved in the regulation of Hsp70 and
Hsp90. All Sti1 mutations impaired protein folding, which required both
Hsp70 and Hsp90. Human HOP1 complemented a yeast strain lacking Sti1,
suggesting conservation of HSP70 and HSP90 regulation.
Arruda-Carvalho et al. (2007) stated that STI1 is an extracellular
protein that modulates cell death and differentiation through
interaction with prion protein (PRNP; 176640). They treated rat retinal
explants with mouse Sti1 or with neutralizing antibody and identified
both Prnp-dependent and -independent roles for Sti1 in ganglion and
neuroblastic cell death and differentiation.
Canalization, or developmental robustness, is an organism's ability to
produce the same phenotype despite genotypic variations and
environmental influences. Expression of a gain-of-function allele of
Drosophila Kruppel results in misregulation of genes in the fly eye disc
and generation of eye outgrowths, which are normally repressed via
canalization. Using a fly eye outgrowth assay, Gangaraju et al. (2011)
showed that a protein complex made up of Piwi (see 605571), Hsp83
(HSP90), and Hop was involved in canalization. The results suggested
that canalization may involve Hsp83-mediated phosphorylation of Piwi.
Gangaraju et al. (2011) concluded that the eye outgrowth phenotype is a
defect in epigenetic silencing of a normally suppressed genotype.
BIOCHEMICAL FEATURES
Scheufler et al. (2000) reported the crystal structures of the
N-terminal TPR domain (TPR1) of HOP in the presence of a bound peptide
consisting of the C-terminal 12 amino acids of HSC70 and of a C-terminal
domain (TPR2A) of HOP in complex with a peptide representing the 5
C-terminal residues of HSP90. The structures provided insight into how
TPR domain cochaperones specifically recognize HSP70 and HSP90 proteins
and explained the conservation of the EEVD motif in all HSP70 and HSP90
family members known to interact with TPR proteins.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the STIP1
gene to 11q13 (TMAP stSG137).
*FIELD* RF
1. Arruda-Carvalho, M.; Njaine, B.; Silveira, M. S.; Linden, R.; Chiarini,
L. B.: Hop/STI1 modulates retinal proliferation and cell death independent
of PrPC. Biochem. Biophys. Res. Commun. 361: 474-480, 2007.
2. Chen, S.; Smith, D. F.: Hop as an adaptor in the heat shock protein
70 (Hsp70) and Hsp90 chaperone machinery. J. Biol. Chem. 273: 35194-35200,
1998.
3. Gangaraju, V. K.; Yin, H.; Weiner, M. M.; Wang, J.; Huang, X. A.;
Lin, H.: Drosophila Piwi functions in Hsp90-mediated suppression
of phenotypic variation. Nature Genet. 43: 153-158, 2011.
4. Honore, B.; Leffers, H.; Madsen, P.; Rasmussen, H. H.; Vandekerckhove,
J.; Celis, J. E.: Molecular cloning and expression of a transformation-sensitive
human protein containing the TPR motif and sharing identity to the
stress-inducible yeast protein STI1. J. Biol. Chem. 267: 8485-8491,
1992.
5. Scheufler, C.; Brinker, A.; Bourenkov, G.; Pegoraro, S.; Moroder,
L.; Bartunik, H.; Hartl, F. U.; Moarefi, I.: Structure of TPR domain-peptide
complexes: critical elements in the assembly of the Hsp70-Hsp90 multichaperone
machine. Cell 101: 199-210, 2000.
6. Song, Y.; Masison, D. C.: Independent regulation of Hsp70 and
Hsp90 chaperones by Hsp70/Hsp90-organizing protein Sti1 (Hop1). J.
Biol. Chem. 280: 34178-34185, 2005.
*FIELD* CN
Patricia A. Hartz - updated: 05/05/2011
Patricia A. Hartz - updated: 7/17/2009
Paul J. Converse - updated: 6/22/2000
*FIELD* CD
Stylianos E. Antonarakis: 6/19/2000
*FIELD* ED
mgross: 05/05/2011
mgross: 7/20/2009
terry: 7/17/2009
wwang: 7/17/2007
mgross: 6/22/2000
mgross: 6/19/2000
*RECORD*
*FIELD* NO
605063
*FIELD* TI
*605063 STRESS-INDUCED PHOSPHOPROTEIN 1; STIP1
;;STI1, YEAST, HOMOLOG OF;;
HSP70/HSP90-ORGANIZING PROTEIN; HOP
read more*FIELD* TX
DESCRIPTION
STIP1 is an adaptor protein that coordinates the functions of HSP70 (see
HSPA1A; 140550) and HSP90 (see HSP90AA1; 140571) in protein folding. It
is thought to assist in the transfer of proteins from HSP70 to HSP90 by
binding both HSP90 and substrate-bound HSP70. STIP1 also stimulates the
ATPase activity of HSP70 and inhibits the ATPase activity of HSP90,
suggesting that it regulates both the conformations and ATPase cycles of
these chaperones (Song and Masison, 2005).
CLONING
By microsequencing a protein that was upregulated in transformed
embryonic lung fibroblasts and using degenerate PCR primers to screen a
transformed embryonic lung fibroblast cDNA library, Honore et al. (1992)
obtained a cDNA encoding STIP1. The predicted 543-amino acid hydrophilic
protein contains a tetratricopeptide repeat (TPR), a 34-amino acid motif
that is repeated at least 6 times in STIP1. STIP1 is homologous to the
yeast stress-inducible mediator of the heat shock response, Sti1.
Western blot analysis and 2-dimensional gel electrophoresis showed that
STIP1 was expressed as an approximately 61-kD protein. Northern blot
analysis showed that STIP1, which was expressed as an approximately
2.1-kb transcript, was upregulated in transformed cell lines and
psoriatic keratinocytes. Immunofluorescence analysis showed that STIP1
localized to the Golgi in normal fibroblasts, but mainly to the nucleus
in transformed cells.
GENE FUNCTION
Using mutation analysis, Chen and Smith (1998) localized a putative
HSP90-binding domain to a central tetratricopeptide repeat (TPR) of the
HOP sequence, and a putative HSP70-binding domain to an N-terminal TPR.
Using in vitro steroid receptor assembly reactions, they found that
reactions performed with HOP carrying mutations in the putative HSP70-
and HSP90-binding domains resulted in receptor complexes that failed to
incorporate HSP90. Chen and Smith (1998) concluded that HOP acts as an
adaptor that directs HSP90 to preexisting HSP70-progesterone receptor
complexes.
By mutating the TPR regions of yeast Sti1, Song and Masison (2005)
identified separate domains involved in the regulation of Hsp70 and
Hsp90. All Sti1 mutations impaired protein folding, which required both
Hsp70 and Hsp90. Human HOP1 complemented a yeast strain lacking Sti1,
suggesting conservation of HSP70 and HSP90 regulation.
Arruda-Carvalho et al. (2007) stated that STI1 is an extracellular
protein that modulates cell death and differentiation through
interaction with prion protein (PRNP; 176640). They treated rat retinal
explants with mouse Sti1 or with neutralizing antibody and identified
both Prnp-dependent and -independent roles for Sti1 in ganglion and
neuroblastic cell death and differentiation.
Canalization, or developmental robustness, is an organism's ability to
produce the same phenotype despite genotypic variations and
environmental influences. Expression of a gain-of-function allele of
Drosophila Kruppel results in misregulation of genes in the fly eye disc
and generation of eye outgrowths, which are normally repressed via
canalization. Using a fly eye outgrowth assay, Gangaraju et al. (2011)
showed that a protein complex made up of Piwi (see 605571), Hsp83
(HSP90), and Hop was involved in canalization. The results suggested
that canalization may involve Hsp83-mediated phosphorylation of Piwi.
Gangaraju et al. (2011) concluded that the eye outgrowth phenotype is a
defect in epigenetic silencing of a normally suppressed genotype.
BIOCHEMICAL FEATURES
Scheufler et al. (2000) reported the crystal structures of the
N-terminal TPR domain (TPR1) of HOP in the presence of a bound peptide
consisting of the C-terminal 12 amino acids of HSC70 and of a C-terminal
domain (TPR2A) of HOP in complex with a peptide representing the 5
C-terminal residues of HSP90. The structures provided insight into how
TPR domain cochaperones specifically recognize HSP70 and HSP90 proteins
and explained the conservation of the EEVD motif in all HSP70 and HSP90
family members known to interact with TPR proteins.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the STIP1
gene to 11q13 (TMAP stSG137).
*FIELD* RF
1. Arruda-Carvalho, M.; Njaine, B.; Silveira, M. S.; Linden, R.; Chiarini,
L. B.: Hop/STI1 modulates retinal proliferation and cell death independent
of PrPC. Biochem. Biophys. Res. Commun. 361: 474-480, 2007.
2. Chen, S.; Smith, D. F.: Hop as an adaptor in the heat shock protein
70 (Hsp70) and Hsp90 chaperone machinery. J. Biol. Chem. 273: 35194-35200,
1998.
3. Gangaraju, V. K.; Yin, H.; Weiner, M. M.; Wang, J.; Huang, X. A.;
Lin, H.: Drosophila Piwi functions in Hsp90-mediated suppression
of phenotypic variation. Nature Genet. 43: 153-158, 2011.
4. Honore, B.; Leffers, H.; Madsen, P.; Rasmussen, H. H.; Vandekerckhove,
J.; Celis, J. E.: Molecular cloning and expression of a transformation-sensitive
human protein containing the TPR motif and sharing identity to the
stress-inducible yeast protein STI1. J. Biol. Chem. 267: 8485-8491,
1992.
5. Scheufler, C.; Brinker, A.; Bourenkov, G.; Pegoraro, S.; Moroder,
L.; Bartunik, H.; Hartl, F. U.; Moarefi, I.: Structure of TPR domain-peptide
complexes: critical elements in the assembly of the Hsp70-Hsp90 multichaperone
machine. Cell 101: 199-210, 2000.
6. Song, Y.; Masison, D. C.: Independent regulation of Hsp70 and
Hsp90 chaperones by Hsp70/Hsp90-organizing protein Sti1 (Hop1). J.
Biol. Chem. 280: 34178-34185, 2005.
*FIELD* CN
Patricia A. Hartz - updated: 05/05/2011
Patricia A. Hartz - updated: 7/17/2009
Paul J. Converse - updated: 6/22/2000
*FIELD* CD
Stylianos E. Antonarakis: 6/19/2000
*FIELD* ED
mgross: 05/05/2011
mgross: 7/20/2009
terry: 7/17/2009
wwang: 7/17/2007
mgross: 6/22/2000
mgross: 6/19/2000