UniProt Accession

 FKBP4_HUMAN; Q02790; D3DUQ1; Q9UCP1; Q9UCV7 

Genbank Protein ID

 M88279; AC005841; CH471116; CH471116; BC001786; BC007924 

Genbank Nucleotide ID

 AAA36111.1; EAW88889.1; EAW88890.1; AAH01786.1; AAH07924.1 

Protein Name

 Peptidyl-prolyl cis-trans isomerase FKBP4 

Protein Synonyms/Alias

 PPIase FKBP4; 51 kDa FK506-binding protein; FKBP51; 52 kDa FK506-binding protein; 52 kDa FKBP; FKBP-52; 59 kDa immunophilin; p59; FK506-binding protein 4; FKBP-4; FKBP59; HSP-binding immunophilin; HBI; Immunophilin FKBP52; Rotamase; Peptidyl-prolyl cis-trans isomerase FKBP4, N-terminally processed 

Gene Name

 FKBP4 

Gene Synonyms/Alias

 FKBP52 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
28	EGVDISPKQDEGVLK	ubiquitination	[1, 2, 3]
76	SSLDRKDKFSFDLGK	ubiquitination	[2, 4, 5, 6]
83	KFSFDLGKGEVIKAW	ubiquitination	[2, 3, 4, 5, 6]
88	LGKGEVIKAWDIAIA	ubiquitination	[4, 6]
181	LEGYYKDKLFDQREL	ubiquitination	[1, 4, 6]
222	EHSIVYLKPSYAFGS	ubiquitination	[3, 4, 5, 6]
244	IPPNAELKYELHLKS	ubiquitination	[4, 6]
250	LKYELHLKSFEKAKE	ubiquitination	[4, 6]
274	LEQSTIVKERGTVYF	acetylation	[7, 8, 9]
274	LEQSTIVKERGTVYF	ubiquitination	[3, 4, 6]
282	ERGTVYFKEGKYKQA	acetylation	[10]
282	ERGTVYFKEGKYKQA	ubiquitination	[2]
287	YFKEGKYKQALLQYK	ubiquitination	[5]
313	FSNEEAQKAQALRLA	ubiquitination	[11]
354	ELDSNNEKGLFRRGE	acetylation	[9, 12]
354	ELDSNNEKGLFRRGE	ubiquitination	[2, 3, 4, 5, 6, 12]
378	LARADFQKVLQLYPN	ubiquitination	[2, 3, 4, 5, 6]
387	LQLYPNNKAAKTQLA	ubiquitination	[2, 4, 6, 13]
390	YPNNKAAKTQLAVCQ	ubiquitination	[2]
409	RQLAREKKLYANMFE	ubiquitination	[2, 4, 6]
426	AEEENKAKAEASSGD	ubiquitination	[1, 2]
441	HPTDTEMKEEQKSNT	ubiquitination	[12]

Reference

 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [4] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [5] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [6] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [7] Substrate and functional diversity of lysine acetylation revealed by a proteomics survey.
 Kim SC, Sprung R, Chen Y, Xu Y, Ball H, Pei J, Cheng T, Kho Y, Xiao H, Xiao L, Grishin NV, White M, Yang XJ, Zhao Y.
 Mol Cell. 2006 Aug;23(4):607-18. [PMID: 16916647]
 [8] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [9] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [10] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [11] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
 [12] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [13] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724] 

Functional Description

 Immunophilin protein with PPIase and co-chaperone activities (By similarity). Component of unligated steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). May play a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors between cytoplasm and nuclear compartments (By similarity). The isomerase activity controls neuronal growth cones via regulation of TRPC1 channel opening. Acts also as a regulator of microtubule dynamics by inhibiting MAPT/TAU ability to promote microtubule assembly. May have a protective role against oxidative stress in mitochondria. 

Sequence Annotation

 DOMAIN 50 138 PPIase FKBP-type 1.
 DOMAIN 167 253 PPIase FKBP-type 2.
 REPEAT 270 303 TPR 1.
 REPEAT 319 352 TPR 2.
 REPEAT 353 386 TPR 3.
 REGION 267 400 Interaction with tubulin (By similarity).
 MOD_RES 1 1 N-acetylmethionine; in peptidyl-prolyl
 MOD_RES 2 2 N-acetylthreonine; in peptidyl-prolyl
 MOD_RES 143 143 Phosphothreonine; by CK2 (By similarity).
 MOD_RES 282 282 N6-acetyllysine.
 MOD_RES 451 451 Phosphoserine.
 MOD_RES 453 453 Phosphoserine.  

Keyword

 3D-structure; Acetylation; Chaperone; Complete proteome; Cytoplasm; Cytoskeleton; Direct protein sequencing; Isomerase; Microtubule; Mitochondrion; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Rotamase; TPR repeat. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 459 AA 

Protein Sequence

Gene Ontology

 GO:0044295; C:axonal growth cone; ISS:UniProtKB.
 GO:0005829; C:cytosol; ISS:UniProtKB.
 GO:0016020; C:membrane; IBA:RefGenome.
 GO:0005874; C:microtubule; IEA:UniProtKB-KW.
 GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
 GO:0043025; C:neuronal cell body; IEA:Compara.
 GO:0005634; C:nucleus; IDA:HPA.
 GO:0048471; C:perinuclear region of cytoplasm; IEA:Compara.
 GO:0005524; F:ATP binding; IEA:Compara.
 GO:0005528; F:FK506 binding; TAS:UniProtKB.
 GO:0005525; F:GTP binding; IEA:Compara.
 GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; IDA:UniProtKB.
 GO:0030674; F:protein binding, bridging; TAS:ProtInc.
 GO:0030521; P:androgen receptor signaling pathway; IEA:Compara.
 GO:0061077; P:chaperone-mediated protein folding; IDA:UniProtKB.
 GO:0006825; P:copper ion transport; IEA:Compara.
 GO:0007566; P:embryo implantation; IEA:Compara.
 GO:0046661; P:male sex differentiation; IEA:Compara.
 GO:0031115; P:negative regulation of microtubule polymerization; IEA:Compara.
 GO:0031111; P:negative regulation of microtubule polymerization or depolymerization; ISS:UniProtKB.
 GO:0010977; P:negative regulation of neuron projection development; ISS:UniProtKB.
 GO:0030850; P:prostate gland development; IEA:Compara.
 GO:0031503; P:protein complex localization; IEA:Compara.
 GO:0006463; P:steroid hormone receptor complex assembly; IEA:Compara. 

Interpro

 IPR023566; PPIase_FKBP.
 IPR001179; PPIase_FKBP_dom.
 IPR001440; TPR-1.
 IPR013026; TPR-contain_dom.
 IPR011990; TPR-like_helical.
 IPR019734; TPR_repeat. 

Pfam

 PF00254; FKBP_C
 PF00515; TPR_1 

SMART

 SM00028; TPR 

PROSITE

 PS50059; FKBP_PPIASE
 PS50005; TPR
 PS50293; TPR_REGION 

PRINTS