ID PIN4_HUMAN Reviewed; 131 AA. AC Q9Y237; A8E0G6; Q0D2H3; Q3MHV0; Q52M21; Q5HYW6; Q6IRW4; DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 25-JAN-2012, entry version 97. DE RecName: Full=Peptidyl-prolyl cis-trans isomerase NIMA-interacting 4; DE EC=5.2.1.8; DE AltName: Full=Parvulin-14; DE Short=Par14; DE Short=hPar14; DE AltName: Full=Parvulin-17; DE Short=Par17; DE Short=hPar17; DE AltName: Full=Peptidyl-prolyl cis-trans isomerase Pin4; DE Short=PPIase Pin4; DE AltName: Full=Peptidyl-prolyl cis/trans isomerase EPVH; DE Short=hEPVH; DE AltName: Full=Rotamase Pin4; GN Name=PIN4; 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] (ISOFORM 1), SUBCELLULAR LOCATION, AND RP TISSUE SPECIFICITY. RX MEDLINE=99294627; PubMed=10364457; DOI=10.1006/bbrc.1999.0828; RA Rulten S.L., Thorpe J.R., Kay J.E.; RT "Identification of eukaryotic parvulin homologues: a new subfamily of RT peptidylprolyl cis-trans isomerases."; RL Biochem. Biophys. Res. Commun. 259:557-562(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, AND RP TISSUE SPECIFICITY. RX MEDLINE=99198957; PubMed=10100858; DOI=10.1016/S0014-5793(99)00239-2; RA Uchida T., Fujimori F., Tradler T., Fischer G., Rahfeld J.-U.; RT "Identification and characterization of a 14 kDa human protein as a RT novel parvulin-like peptidyl prolyl cis/trans isomerase."; RL FEBS Lett. 446:278-282(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S., RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., RA Williams G., Williams L., Williamson A., Williamson H., Wilming L., RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND RP VARIANTS GLN-16 AND ARG-18 (ISOFORM 2). RC TISSUE=Brain, Prostate, and Urinary bladder; 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 [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-13 (ISOFORM 1), PARTIAL NUCLEOTIDE RP SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE PROMOTER USAGE, SUMOYLATION, RP TISSUE SPECIFICITY, AND VARIANTS GLN-16 AND ARG-18 (ISOFORM 2). RX PubMed=16522211; DOI=10.1186/1471-2199-7-9; RA Mueller J.W., Kessler D., Neumann D., Stratmann T., Papatheodorou P., RA Hartmann-Fatu C., Bayer P.; RT "Characterization of novel elongated Parvulin isoforms that are RT ubiquitously expressed in human tissues and originate from alternative RT transcription initiation."; RL BMC Mol. Biol. 7:9-9(2006). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-6 AND 48-72, ALTERNATIVE RP PROMOTER USAGE (ISOFORMS 1 AND 2), DNA-BINDING, AND SUBCELLULAR RP LOCATION. RX PubMed=17875217; DOI=10.1186/1741-7007-5-37; RA Kessler D., Papatheodorou P., Stratmann T., Dian E.A., RA Hartmann-Fatu C., Rassow J., Bayer P., Mueller J.W.; RT "The DNA binding parvulin Par17 is targeted to the mitochondrial RT matrix by a recently evolved prepeptide uniquely present in RT Hominidae."; RL BMC Biol. 5:37-37(2007). RN [7] RP PROTEIN SEQUENCE OF 15-25, IDENTIFICATION BY MASS SPECTROMETRY, RP PHOSPHORYLATION AT SER-19, MUTAGENESIS OF SER-19, AND SUBCELLULAR RP LOCATION. RX PubMed=12860119; DOI=10.1016/S0022-2836(03)00713-7; RA Reimer T., Weiwad M., Schierhorn A., Ruecknagel P.-K., Rahfeld J.-U., RA Bayer P., Fischer G.; RT "Phosphorylation of the N-terminal domain regulates subcellular RT localization and DNA binding properties of the peptidyl-prolyl RT cis/trans isomerase hPar14."; RL J. Mol. Biol. 330:955-966(2003). RN [8] RP DNA-BINDING, AND SUBCELLULAR LOCATION. RX PubMed=12144781; DOI=10.1016/S0022-2836(02)00615-0; RA Surmacz T.A., Bayer E., Rahfeld J.-U., Fischer G., Bayer P.; RT "The N-terminal basic domain of human parvulin hPar14 is responsible RT for the entry to the nucleus and high-affinity DNA-binding."; RL J. Mol. Biol. 321:235-247(2002). RN [9] RP FUNCTION, IDENTIFICATION IN PRE-RRNP COMPLEXES, PHOSPHORYLATION, AND RP SUBCELLULAR LOCATION. RX PubMed=19369196; DOI=10.1074/mcp.M900147-MCP200; RA Fujiyama-Nakamura S., Yoshikawa H., Homma K., Hayano T., RA Tsujimura-Takahashi T., Izumikawa K., Ishikawa H., Miyazawa N., RA Yanagida M., Miura Y., Shinkawa T., Yamauchi Y., Isobe T., RA Takahashi N.; RT "Parvulin (Par14), a peptidyl-prolyl cis-trans isomerase, is a novel RT rRNA processing factor that evolved in the metazoan lineage."; RL Mol. Cell. Proteomics 8:1552-1565(2009). RN [10] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-32, AND MASS SPECTROMETRY. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., RA 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 [11] 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 [12] RP STRUCTURE BY NMR OF 36-131. RX MEDLINE=20425097; PubMed=10966801; DOI=10.1006/jmbi.2000.4013; RA Sekerina E., Rahfeld J.-U., Mueller J., Fanghaenel J., Rascher C., RA Fischer G., Bayer P.; RT "NMR solution structure of hPar14 reveals similarity to the peptidyl RT prolyl cis/trans isomerase domain of the mitotic regulator hPin1 but RT indicates a different functionality of the protein."; RL J. Mol. Biol. 301:1003-1017(2000). RN [13] RP STRUCTURE BY NMR OF 28-131. RX MEDLINE=21103679; PubMed=11162102; DOI=10.1006/jmbi.2000.4293; RA Terada T., Shirouzu M., Fukumori Y., Fujimori F., Ito Y., Kigawa T., RA Yokoyama S., Uchida T.; RT "Solution structure of the human parvulin-like peptidyl prolyl RT cis/trans isomerase, hPar14."; RL J. Mol. Biol. 305:917-926(2001). CC -!- FUNCTION: Isoform 1 is involved as a ribosomal RNA processing CC factor in ribosome biogenesis. Binds to tightly bent AT-rich CC stretches of double-stranded DNA. CC -!- FUNCTION: Isoform 2 binds to double-stranded DNA. CC -!- CATALYTIC ACTIVITY: Peptidylproline (omega=180) = peptidylproline CC (omega=0). CC -!- SUBUNIT: Isoform 1 is found in pre-ribosomal ribonucleoprotein CC (pre-rRNP) complexes (By similarity). CC -!- SUBCELLULAR LOCATION: Isoform 1: Nucleus, nucleolus. Cytoplasm, CC cytoskeleton, spindle. Cytoplasm. Note=Colocalizes in the CC nucleolus during interphase and on the spindle apparatus during CC mitosis with NPM1. CC -!- SUBCELLULAR LOCATION: Isoform 2: Mitochondrion. Mitochondrion CC matrix. Note=Imported in a time- and membrane potential-dependent CC manner to the mitochondrial matrix, but without concomitant CC processing of the protein. Directed to mitochondria by a novel N- CC terminal domain that functions as non-cleavable mitochondrial CC targeting peptide. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage; Named isoforms=2; CC Name=1; CC IsoId=Q9Y237-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9Y237-2; Sequence=VSP_037754; CC Note=The first 25 amino acids are sufficient for mitochondrial CC targeting. Variant in position: 16:R->Q (in dbSNP:rs6525589). CC Variant in position: 18:S->R (in dbSNP:rs7058353); CC -!- TISSUE SPECIFICITY: Isoform 2 is much more stable than isoform 1 CC (at protein level). Ubiquitous. Isoform 1 and isoform 2 are CC expressed in kidney, liver, blood vessel, brain, mammary gland, CC skeletal muscle, small intestine and submandibularis. Isoform 1 CC transcripts are much more abundant than isoform 2 in each tissue CC analyzed. CC -!- DOMAIN: The PPIase domain enhances mitochondrial targeting. CC -!- PTM: Phosphorylated. Isoform 1 phosphorylation occurs both in the CC nucleus and the cytoplasm. Isoform 1 phosphorylation at Ser-19 CC does not affect its PPIase activity but is required for nuclear CC localization, and the dephosphorylation is a prerequisite for the CC binding to DNA. The unphosphorylated isoform 1 associates with the CC pre-rRNP complexes in the nucleus. CC -!- PTM: Isoform 2 is sumoylated by SUMO2 and SUMO3. CC -!- SIMILARITY: Belongs to the ppiC/parvulin rotamase family. PIN4 CC subfamily. CC -!- SIMILARITY: Contains 1 PpiC domain. CC -!- SEQUENCE CAUTION: CC Sequence=AAH05234.2; Type=Erroneous initiation; CC Sequence=AAH70288.1; Type=Erroneous initiation; CC Sequence=AAI04654.1; Type=Erroneous initiation; CC Sequence=AAI11395.1; Type=Erroneous initiation; 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; AF143096; AAD27893.1; -; mRNA. DR EMBL; AB009690; BAA82320.1; -; mRNA. DR EMBL; BX119917; CAI39856.1; -; Genomic_DNA. DR EMBL; AL135749; CAI39856.1; JOINED; Genomic_DNA. DR EMBL; BC005234; AAH05234.2; ALT_INIT; mRNA. DR EMBL; BC070288; AAH70288.1; ALT_INIT; mRNA. DR EMBL; BC093700; AAH93700.1; -; mRNA. DR EMBL; BC104653; AAI04654.1; ALT_INIT; mRNA. DR EMBL; BC111394; AAI11395.1; ALT_INIT; mRNA. DR EMBL; BC112281; AAI12282.1; -; mRNA. DR EMBL; AM420633; CAM12362.1; -; Genomic_DNA. DR IPI; IPI00006658; -. DR IPI; IPI00941201; -. DR RefSeq; NP_006214.2; NM_006223.3. DR UniGene; Hs.655623; -. DR PDB; 1EQ3; NMR; -; A=36-131. DR PDB; 1FJD; NMR; -; A=30-131. DR PDBsum; 1EQ3; -. DR PDBsum; 1FJD; -. DR ProteinModelPortal; Q9Y237; -. DR SMR; Q9Y237; 36-131. DR IntAct; Q9Y237; 5. DR STRING; Q9Y237; -. DR PhosphoSite; Q9Y237; -. DR DMDM; 20139299; -. DR PRIDE; Q9Y237; -. DR Ensembl; ENST00000218432; ENSP00000218432; ENSG00000102309. DR Ensembl; ENST00000373669; ENSP00000362773; ENSG00000102309. DR GeneID; 5303; -. DR KEGG; hsa:5303; -. DR UCSC; uc004eam.1; human. DR CTD; 5303; -. DR GeneCards; GC0XP071401; -. DR H-InvDB; HIX0016866; -. DR HGNC; HGNC:8992; PIN4. DR MIM; 300252; gene. DR neXtProt; NX_Q9Y237; -. DR GeneTree; ENSGT00510000047029; -. DR HOGENOM; HBG526275; -. DR HOVERGEN; HBG019150; -. DR InParanoid; Q9Y237; -. DR OMA; TAVKVRH; -. DR PhylomeDB; Q9Y237; -. DR NextBio; 20496; -. DR ArrayExpress; Q9Y237; -. DR Bgee; Q9Y237; -. DR CleanEx; HS_PIN4; -. DR Genevestigator; Q9Y237; -. DR GermOnline; ENSG00000102309; Homo sapiens. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell. DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell. DR GO; GO:0030684; C:preribosome; IDA:UniProtKB. DR GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell. DR GO; GO:0003681; F:bent DNA binding; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0003690; F:double-stranded DNA binding; IDA:UniProtKB. DR GO; GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; IEA:UniProtKB-KW. DR GO; GO:0006457; P:protein folding; IEA:UniProtKB-KW. DR GO; GO:0006364; P:rRNA processing; IMP:UniProtKB. DR InterPro; IPR000297; PPIase_PpiC. DR KO; K09579; -. DR Pfam; PF00639; Rotamase; 1. DR PROSITE; PS01096; PPIC_PPIASE_1; FALSE_NEG. DR PROSITE; PS50198; PPIC_PPIASE_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative promoter usage; KW Complete proteome; Cytoplasm; Cytoskeleton; Direct protein sequencing; KW DNA-binding; Isomerase; Mitochondrion; Nucleus; Phosphoprotein; KW Polymorphism; Reference proteome; Rotamase; Ubl conjugation. FT CHAIN 1 131 Peptidyl-prolyl cis-trans isomerase NIMA- FT interacting 4. FT /FTId=PRO_0000193438. FT DOMAIN 35 129 PpiC. FT REGION 1 41 Necessary for association with the pre- FT rRNP complexes. FT REGION 1 25 Necessary for nuclear localization and FT DNA-binding. FT MOD_RES 19 19 Phosphoserine; by CK2. FT MOD_RES 32 32 N6-acetyllysine. FT VAR_SEQ 1 1 M -> MPMAGLLKGLVRQLERFSVQQQASKM (in FT isoform 2). FT /FTId=VSP_037754. FT MUTAGEN 19 19 S->A: Abolishes phosphorylation and FT reduces strongly nuclear localization. FT MUTAGEN 19 19 S->E: Does not abolish nuclear FT localization and reduces DNA-binding FT ability. FT STRAND 38 45 FT HELIX 51 58 FT TURN 59 62 FT HELIX 64 71 FT TURN 75 77 FT STRAND 80 87 FT STRAND 90 92 FT HELIX 93 100 FT TURN 108 110 FT STRAND 116 118 FT STRAND 121 129 SQ SEQUENCE 131 AA; 13810 MW; 787C15BDB0701258 CRC64; MPPKGKSGSG KAGKGGAASG SDSADKKAQG PKGGGNAVKV RHILCEKHGK IMEAMEKLKS GMRFNEVAAQ YSEDKARQGG DLGWMTRGSM VGPFQEAAFA LPVSGMDKPV FTDPPVKTKF GYHIIMVEGR K //