Reviewed, UniProtKB/Swiss-Prot Q9Y237 (PIN4_HUMAN)

Names and origin

Protein names

Recommended name:
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 4
EC=5.2.1.8

Alternative name(s):
Peptidyl-prolyl cis-trans isomerase Pin4
Short name=PPIase Pin4
Rotamase Pin4
Parvulin-14
Short name=Par14
Short name=hPar14
Parvulin-17
Short name=Par17
Short name=hPar17
Peptidyl-prolyl cis/trans isomerase EPVH
Short name=hEPVH

Gene names

Name:

PIN4

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	131 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Isoform 1 is involved as a ribosomal RNA processing factor in ribosome biogenesis. Binds to tightly bent AT-rich stretches of double-stranded DNA. Ref.10 Isoform 2 binds to double-stranded DNA. Ref.10
Catalytic activity	Peptidylproline (omega=180) = peptidylproline (omega=0).
Subunit structure	Isoform 1 is found in pre-ribosomal ribonucleoprotein (pre-rRNP) complexes By similarity.
Subcellular location	Isoform 1: Nucleus › nucleolus. Cytoplasm › cytoskeleton › spindle. Cytoplasm. Note: Colocalizes in the nucleolus during interphase and on the spindle apparatus during mitosis with NPM1. Ref.10 Ref.1 Ref.2 Ref.6 Ref.7 Ref.8 Isoform 2: Mitochondrion. Mitochondrion matrix. Note: Imported in a time- and membrane potential-dependent manner to the mitochondrial matrix, but without concomitant processing of the protein. Directed to mitochondria by a novel N-terminal domain that functions as non-cleavable mitochondrial targeting peptide. Ref.10 Ref.1 Ref.2 Ref.6 Ref.7 Ref.8
Tissue specificity	Isoform 2 is much more stable than isoform 1 (at protein level). Ubiquitous. Isoform 1 and isoform 2 are expressed in kidney, liver, blood vessel, brain, mammary gland, skeletal muscle, small intestine and submandibularis. Isoform 1 transcripts are much more abundant than isoform 2 in each tissue analyzed. Ref.1 Ref.2 Ref.5
Domain	The PPIase domain enhances mitochondrial targeting.
Post-translational modification	Phosphorylated. Isoform 1 phosphorylation occurs both in the nucleus and the cytoplasm. Isoform 1 phosphorylation at Ser-19 does not affect its PPIase activity but is required for nuclear localization, and the dephosphorylation is a prerequisite for the binding to DNA. The unphosphorylated isoform 1 associates with the pre-rRNP complexes in the nucleus. Ref.10 Ref.7 Isoform 2 is sumoylated by SUMO2 and SUMO3. Ref.5
Sequence similarities	Belongs to the ppiC/parvulin rotamase family. PIN4 subfamily. Contains 1 PpiC domain.

Ontologies

Keywords
Cellular component	Cytoplasm Cytoskeleton Mitochondrion Nucleus
Coding sequence diversity	Alternative promoter usage Polymorphism
Ligand	DNA-binding
Molecular function	Isomerase Rotamase
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	protein folding Inferred from electronic annotation. Source: UniProtKB-KW rRNA processing Inferred from mutant phenotype. Source: UniProtKB
Cellular component	cytoplasm Inferred from direct assay. Source: UniProtKB mitochondrial matrix Inferred from direct assay. Source: UniProtKB nucleolus Inferred from direct assay. Source: UniProtKB preribosome Inferred from direct assay. Source: UniProtKB spindle Inferred from direct assay. Source: UniProtKB
Molecular function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW bent DNA binding Inferred from direct assay. Source: UniProtKB double-stranded DNA binding Inferred from direct assay. Source: UniProtKB peptidyl-prolyl cis-trans isomerase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative promoter usage. [Align] [Select]
Isoform 1 (identifier: Q9Y237-1) 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.
Note: Colocalizes in the nucleolus during interphase and on the spindle apparatus during mitosis with NPM1. Ref.10 Ref.1 Ref.2 Ref.6 Ref.7 Ref.8
Isoform 2 (identifier: Q9Y237-2) The sequence of this isoform differs from the canonical sequence as follows:      1-1: M → MPMAGLLKGLVRQLERFSVQQQASKM
Note: Imported in a time- and membrane potential-dependent manner to the mitochondrial matrix, but without concomitant processing of the protein. Directed to mitochondria by a novel N-terminal domain that functions as non-cleavable mitochondrial targeting peptide. Ref.10 Ref.1 Ref.2 Ref.6 Ref.7 Ref.8 The first 25 amino acids are sufficient for mitochondrial targeting.
Sequence annotation (Features)
	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
	Natural variant	16	1	R → Q: dbSNP rs6525589.
	Natural variant	18	1	S → R: dbSNP rs7058353.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 131

131

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 4

PRO_0000193438

Regions

Domain

35 – 129

95

PpiC

Region

1 – 41

41

Necessary for association with the pre-rRNP complexes

Region

1 – 25

25

Necessary for nuclear localization and DNA-binding

Amino acid modifications

Modified residue

19

1

Phosphoserine; by CK2 Ref.7

Modified residue

32

1

N6-acetyllysine Ref.11

Natural variations

Alternative sequence

1

1

M → MPMAGLLKGLVRQLERFSVQ QQASKM in isoform 2.

VSP_037754

Experimental info

Mutagenesis

19

1

S → A: Abolishes phosphorylation and reduces strongly nuclear localization. Ref.7

Mutagenesis

19

1

S → E: Does not abolish nuclear localization and reduces DNA-binding ability. Ref.7

Secondary structure

1

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131

Helix Strand Turn

Details...

Beta strand

38 – 45

8

Helix

51 – 58

8

Turn

59 – 62

4

Helix

64 – 71

8

Turn

75 – 77

3

Beta strand

80 – 87

8

Beta strand

90 – 92

3

Helix

93 – 100

8

Turn

108 – 110

3

Beta strand

116 – 118

3

Beta strand

121 – 129

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 787C15BDB0701258	FASTA	131	13,810
	10 20 30 40 50 60 MPPKGKSGSG KAGKGGAASG SDSADKKAQG PKGGGNAVKV RHILCEKHGK IMEAMEKLKS 70 80 90 100 110 120 GMRFNEVAAQ YSEDKARQGG DLGWMTRGSM VGPFQEAAFA LPVSGMDKPV FTDPPVKTKF 130 GYHIIMVEGR K
	Isoform 2. Checksum: 8D4668D3ADB24740	FASTA	156	16,608
	10 20 30 40 50 60 MPMAGLLKGL VRQLERFSVQ QQASKMPPKG KSGSGKAGKG GAASGSDSAD KKAQGPKGGG 70 80 90 100 110 120 NAVKVRHILC EKHGKIMEAM EKLKSGMRFN EVAAQYSEDK ARQGGDLGWM TRGSMVGPFQ 130 140 150 EAAFALPVSG MDKPVFTDPP VKTKFGYHII MVEGRK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of eukaryotic parvulin homologues: a new subfamily of peptidylprolyl cis-trans isomerases." Rulten S.L., Thorpe J.R., Kay J.E. Biochem. Biophys. Res. Commun. 259:557-562(1999) [PubMed: 10364457] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]	"Identification and characterization of a 14 kDa human protein as a novel parvulin-like peptidyl prolyl cis/trans isomerase." Uchida T., Fujimori F., Tradler T., Fischer G., Rahfeld J.-U. FEBS Lett. 446:278-282(1999) [PubMed: 10100858] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[3]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed: 15772651] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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] (ISOFORMS 1 AND 2), VARIANTS GLN-16 AND ARG-18 (ISOFORM 2). Tissue: Brain, Prostate and Urinary bladder.
[5]	"Characterization of novel elongated Parvulin isoforms that are ubiquitously expressed in human tissues and originate from alternative transcription initiation." Mueller J.W., Kessler D., Neumann D., Stratmann T., Papatheodorou P., Hartmann-Fatu C., Bayer P. BMC Mol. Biol. 7:9-9(2006) [PubMed: 16522211] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-13 (ISOFORM 1), PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE PROMOTER USAGE, SUMOYLATION, TISSUE SPECIFICITY, VARIANTS GLN-16 AND ARG-18 (ISOFORM 2).
[6]	"The DNA binding parvulin Par17 is targeted to the mitochondrial matrix by a recently evolved prepeptide uniquely present in Hominidae." Kessler D., Papatheodorou P., Stratmann T., Dian E.A., Hartmann-Fatu C., Rassow J., Bayer P., Mueller J.W. BMC Biol. 5:37-37(2007) [PubMed: 17875217] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-6 AND 48-72, ALTERNATIVE PROMOTER USAGE (ISOFORMS 1 AND 2), DNA-BINDING, SUBCELLULAR LOCATION.
[7]	"Phosphorylation of the N-terminal domain regulates subcellular localization and DNA binding properties of the peptidyl-prolyl cis/trans isomerase hPar14." Reimer T., Weiwad M., Schierhorn A., Ruecknagel P.-K., Rahfeld J.-U., Bayer P., Fischer G. J. Mol. Biol. 330:955-966(2003) [PubMed: 12860119] [Abstract] Cited for: PROTEIN SEQUENCE OF 15-25, IDENTIFICATION BY MASS SPECTROMETRY, PHOSPHORYLATION AT SER-19, MUTAGENESIS OF SER-19, SUBCELLULAR LOCATION.
[8]	"The N-terminal basic domain of human parvulin hPar14 is responsible for the entry to the nucleus and high-affinity DNA-binding." Surmacz T.A., Bayer E., Rahfeld J.-U., Fischer G., Bayer P. J. Mol. Biol. 321:235-247(2002) [PubMed: 12144781] [Abstract] Cited for: DNA-BINDING, SUBCELLULAR LOCATION.
[9]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[10]	"Parvulin (Par14), a peptidyl-prolyl cis-trans isomerase, is a novel rRNA processing factor that evolved in the metazoan lineage." Fujiyama-Nakamura S., Yoshikawa H., Homma K., Hayano T., Tsujimura-Takahashi T., Izumikawa K., Ishikawa H., Miyazawa N., Yanagida M., Miura Y., Shinkawa T., Yamauchi Y., Isobe T., Takahashi N. Mol. Cell. Proteomics 8:1552-1565(2009) [PubMed: 19369196] [Abstract] Cited for: FUNCTION, IDENTIFICATION IN PRE-RRNP COMPLEXES, PHOSPHORYLATION, SUBCELLULAR LOCATION.
[11]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-32, MASS SPECTROMETRY.
[12]	"NMR solution structure of hPar14 reveals similarity to the peptidyl prolyl cis/trans isomerase domain of the mitotic regulator hPin1 but indicates a different functionality of the protein." Sekerina E., Rahfeld J.-U., Mueller J., Fanghaenel J., Rascher C., Fischer G., Bayer P. J. Mol. Biol. 301:1003-1017(2000) [PubMed: 10966801] [Abstract] Cited for: STRUCTURE BY NMR OF 36-131.
[13]	"Solution structure of the human parvulin-like peptidyl prolyl cis/trans isomerase, hPar14." Terada T., Shirouzu M., Fukumori Y., Fujimori F., Ito Y., Kigawa T., Yokoyama S., Uchida T. J. Mol. Biol. 305:917-926(2001) [PubMed: 11162102] [Abstract] Cited for: STRUCTURE BY NMR OF 28-131.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF143096 mRNA. Translation: AAD27893.1.
AB009690 mRNA. Translation: BAA82320.1.
BX119917, AL135749 Genomic DNA. Translation: CAI39856.1.
BC005234 mRNA. Translation: AAH05234.2. Different initiation.
BC070288 mRNA. Translation: AAH70288.1. Different initiation.
BC093700 mRNA. Translation: AAH93700.1.
BC104653 mRNA. Translation: AAI04654.1. Different initiation.
BC111394 mRNA. Translation: AAI11395.1. Different initiation.
BC112281 mRNA. Translation: AAI12282.1.
AM420633 Genomic DNA. Translation: CAM12362.1.

IPI

IPI00006658.
IPI00941201.

RefSeq

NP_006214.2.

UniGene

Hs.655623

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EQ3	NMR	-	A	36-131	[»]
1FJD	NMR	-	A	30-131	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9Y237. 6 interactions.

STRING

Q9Y237.

PTM databases

PhosphoSite

Q9Y237.

Proteomic databases

PRIDE

Q9Y237.

Genome annotation databases

Ensembl

ENST00000218432; ENSP00000218432; ENSG00000102309; Homo sapiens. [Genome view]
ENST00000373669; ENSP00000362773; ENSG00000102309; Homo sapiens. [Genome view]

GeneID

5303.

KEGG

hsa:5303.

UCSC

uc004eam.1. human.

Organism-specific databases

CTD

5303.

GeneCards

GC0XP071318.

H-InvDB

HIX0012195.
HIX0016866.

HGNC

HGNC:8992. PIN4.

MIM

300252. gene.

PharmGKB

PA33324.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HBG526275.

HOVERGEN

HBG019150.

InParanoid

Q9Y237.

OMA

VYTDPPV.

Enzyme and pathway databases

BRENDA

5.2.1.8. 247.

Gene expression databases

ArrayExpress

Q9Y237.

Bgee

Q9Y237.

CleanEx

HS_PIN4.

Genevestigator

Q9Y237.

GermOnline

ENSG00000102309. Homo sapiens.

Family and domain databases

InterPro

IPR000297. PPIase_PpiC.
[Graphical view]

Pfam

PF00639. Rotamase. 1 hit.
[Graphical view]

PROSITE

PS01096. PPIC_PPIASE_1. False negative.
PS50198. PPIC_PPIASE_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

20496.

SOURCE

Search...

Entry information

Entry name

PIN4_HUMAN

Accession

Primary (citable) accession number: Q9Y237
Secondary accession number(s): A8E0G6 , Q0D2H3, Q3MHV0, Q52M21, Q5HYW6, Q6IRW4

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 23, 2002
Last sequence update:	November 1, 1999
Last modified:	March 2, 2010
This is version 80 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.