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Protein

Tyrosine-protein phosphatase non-receptor type 14

Gene

PTPN14

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Protein tyrosine phosphatase which may play a role in the regulation of lymphangiogenesis, cell-cell adhesion, cell-matrix adhesion, cell migration, cell growth and also regulates TGF-beta gene expression, thereby modulating epithelial-mesenchymal transition. Mediates beta-catenin dephosphorylation at adhesion junctions. Acts as a negative regulator of the oncogenic property of YAP, a downstream target of the hippo pathway, in a cell density-dependent manner. May function as a tumor suppressor.7 Publications

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei1079SubstrateBy similarity1
Active sitei1121Phosphocysteine intermediatePROSITE-ProRule annotation1
Binding sitei1165SubstrateBy similarity1

GO - Molecular functioni

  • protein tyrosine phosphatase activity Source: UniProtKB
  • receptor tyrosine kinase binding Source: UniProtKB
  • transcription cofactor activity Source: UniProtKB

GO - Biological processi

  • lymphangiogenesis Source: UniProtKB
  • negative regulation of cell proliferation Source: UniProtKB
  • protein dephosphorylation Source: ProtInc
  • regulation of protein export from nucleus Source: UniProtKB
  • regulation of transcription, DNA-templated Source: UniProtKB-KW
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Keywords - Biological processi

Transcription, Transcription regulation

Enzyme and pathway databases

BioCyciZFISH:HS07792-MONOMER.
BRENDAi3.1.3.48. 2681.
SIGNORiQ15678.

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein phosphatase non-receptor type 14 (EC:3.1.3.48)
Alternative name(s):
Protein-tyrosine phosphatase pez
Gene namesi
Name:PTPN14
Synonyms:PEZ, PTPD2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:9647. PTPN14.

Subcellular locationi

  • Cytoplasm
  • Cytoplasmcytoskeleton By similarity
  • Nucleus

  • Note: Translocation into the nucleus is associated with induction of cell proliferation. Partially colocalized with actin filaments at the plasma membrane.

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytoskeleton Source: UniProtKB-SubCell
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Involvement in diseasei

Choanal atresia and lymphedema (CHATLY)1 Publication
The disease is caused by mutations affecting the gene represented in this entry. A homozygous deletion in PTPN14 predicted to result in frameshift and premature truncation, has been shown to be the cause of choanal atresia and lymphedema in one family.
Disease descriptionA disease characterized by posterior choanal atresia and lymphedema. Additional features are a high-arched palate, hypoplastic nipples, and mild pectus excavatum.
See also OMIM:613611

Influence clinical severity of hereditary haemorragic telagiectasia (HHT).

Organism-specific databases

DisGeNETi5784.
MalaCardsiPTPN14.
MIMi613611. phenotype.
OpenTargetsiENSG00000152104.
PharmGKBiPA33989.

Chemistry databases

ChEMBLiCHEMBL3317332.

Polymorphism and mutation databases

BioMutaiPTPN14.
DMDMi209572662.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002194371 – 1187Tyrosine-protein phosphatase non-receptor type 14Add BLAST1187

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei314PhosphoserineBy similarity1
Modified residuei461PhosphoserineBy similarity1
Modified residuei486PhosphoserineCombined sources1
Modified residuei591PhosphoserineCombined sources1
Modified residuei593PhosphoserineBy similarity1
Modified residuei594PhosphoserineCombined sources1
Modified residuei642PhosphoserineCombined sources1
Modified residuei831PhosphoserineBy similarity1

Post-translational modificationi

Ubiquitinated by the ECS (Elongin BC-CUL2/5-SOCS-box protein)/LRR1 E3 ligase complex and subsequently targeted to proteasomal degradation.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ15678.
MaxQBiQ15678.
PaxDbiQ15678.
PeptideAtlasiQ15678.
PRIDEiQ15678.

PTM databases

DEPODiQ15678.
iPTMnetiQ15678.
PhosphoSitePlusiQ15678.

Expressioni

Tissue specificityi

Ubiquitous.

Inductioni

Up-regulated at protein level by cell density. However, at the mRNA level remains the same regardless of the status of cell density.1 Publication

Gene expression databases

BgeeiENSG00000152104.
CleanExiHS_PTPN14.
ExpressionAtlasiQ15678. baseline and differential.
GenevisibleiQ15678. HS.

Organism-specific databases

HPAiCAB011469.
CAB069441.
HPA053864.

Interactioni

Subunit structurei

Interacts with FLT4; the interaction is enhanced by stimulation with VEGFC. Interacts (via PPxY motifs) with YAP1 (via WW domains); this interaction leads to the cytoplasmic sequestration of YAP1 and inhibits its transcriptional co-activator activity.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
YAP1P469376EBI-1237156,EBI-1044059

GO - Molecular functioni

  • receptor tyrosine kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111748. 43 interactors.
DIPiDIP-38131N.
IntActiQ15678. 17 interactors.
STRINGi9606.ENSP00000355923.

Chemistry databases

BindingDBiQ15678.

Structurei

Secondary structure

11187
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi896 – 903Combined sources8
Helixi909 – 914Combined sources6
Turni926 – 929Combined sources4
Helixi931 – 933Combined sources3
Helixi946 – 948Combined sources3
Beta strandi964 – 972Combined sources9
Beta strandi975 – 982Combined sources8
Turni987 – 989Combined sources3
Helixi990 – 999Combined sources10
Beta strandi1004 – 1007Combined sources4
Beta strandi1011 – 1013Combined sources3
Beta strandi1032 – 1035Combined sources4
Beta strandi1038 – 1047Combined sources10
Beta strandi1049 – 1060Combined sources12
Turni1061 – 1063Combined sources3
Beta strandi1066 – 1074Combined sources9
Beta strandi1079 – 1081Combined sources3
Helixi1086 – 1103Combined sources18
Helixi1105 – 1107Combined sources3
Beta strandi1117 – 1125Combined sources9
Helixi1126 – 1142Combined sources17
Helixi1149 – 1157Combined sources9
Helixi1167 – 1183Combined sources17

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2BZLX-ray1.65A886-1187[»]
ProteinModelPortaliQ15678.
SMRiQ15678.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ15678.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini21 – 306FERMPROSITE-ProRule annotationAdd BLAST286
Domaini909 – 1180Tyrosine-protein phosphatasePROSITE-ProRule annotationAdd BLAST272

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1121 – 1127Substrate bindingBy similarity7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi566 – 573Poly-Pro8
Compositional biasi709 – 716Poly-Glu8

Sequence similaritiesi

Contains 1 FERM domain.PROSITE-ProRule annotation
Contains 1 tyrosine-protein phosphatase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0792. Eukaryota.
COG5599. LUCA.
GeneTreeiENSGT00830000128259.
HOGENOMiHOG000115775.
HOVERGENiHBG053757.
InParanoidiQ15678.
KOiK18025.
OMAiEKVEYSA.
OrthoDBiEOG091G00QP.
PhylomeDBiQ15678.
TreeFamiTF315900.

Family and domain databases

Gene3Di1.20.80.10. 1 hit.
2.30.29.30. 1 hit.
3.90.190.10. 1 hit.
InterProiIPR019749. Band_41_domain.
IPR014352. FERM/acyl-CoA-bd_prot_3-hlx.
IPR019748. FERM_central.
IPR019747. FERM_CS.
IPR000299. FERM_domain.
IPR018979. FERM_N.
IPR018980. FERM_PH-like_C.
IPR011993. PH_dom-like.
IPR029021. Prot-tyrosine_phosphatase-like.
IPR000242. PTPase_domain.
IPR016130. Tyr_Pase_AS.
IPR003595. Tyr_Pase_cat.
IPR014392. Tyr_Pase_non-rcpt_typ-14/21.
IPR000387. TYR_PHOSPHATASE_dom.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PfamiPF09380. FERM_C. 1 hit.
PF00373. FERM_M. 1 hit.
PF09379. FERM_N. 1 hit.
PF00102. Y_phosphatase. 1 hit.
[Graphical view]
PIRSFiPIRSF000934. Tyr-Ptase_nr14. 1 hit.
PRINTSiPR00935. BAND41.
PR00700. PRTYPHPHTASE.
SMARTiSM00295. B41. 1 hit.
SM01196. FERM_C. 1 hit.
SM00194. PTPc. 1 hit.
SM00404. PTPc_motif. 1 hit.
[Graphical view]
SUPFAMiSSF47031. SSF47031. 1 hit.
SSF50729. SSF50729. 1 hit.
SSF52799. SSF52799. 1 hit.
SSF54236. SSF54236. 1 hit.
PROSITEiPS00660. FERM_1. 1 hit.
PS00661. FERM_2. 1 hit.
PS50057. FERM_3. 1 hit.
PS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50055. TYR_PHOSPHATASE_PTP. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q15678-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPFGLKLRRT RRYNVLSKNC FVTRIRLLDS NVIECTLSVE STGQECLEAV
60 70 80 90 100
AQRLELRETH YFGLWFLSKS QQARWVELEK PLKKHLDKFA NEPLLFFGVM
110 120 130 140 150
FYVPNVSWLQ QEATRYQYYL QVKKDVLEGR LRCTLDQVIR LAGLAVQADF
160 170 180 190 200
GDYNQFDSQD FLREYVLFPM DLALEEAVLE ELTQKVAQEH KAHSGILPAE
210 220 230 240 250
AELMYINEVE RLDGFGQEIF PVKDNHGNCV HLGIFFMGIF VRNRIGRQAV
260 270 280 290 300
IYRWNDMGNI THNKSTILVE LINKEETALF HTDDIENAKY ISRLFATRHK
310 320 330 340 350
FYKQNKICTE QSNSPPPIRR QPTWSRSSLP RQQPYILPPV HVQCGEHYSE
360 370 380 390 400
THTSQDSIFH GNEEALYCNS HNSLDLNYLN GTVTNGSVCS VHSVNSLNCS
410 420 430 440 450
QSFIQASPVS SNLSIPGSDI MRADYIPSHR HSAIIVPSYR PTPDYETVMR
460 470 480 490 500
QMKRGILHTD SQSQSLRNLN IINTHAYNQP EDLVYSQPEM RERHPYTVPY
510 520 530 540 550
GPQGVYSNKL VSPSDQRNPK NNVVPSKPGA SAISHTVSTP ELANMQLQGS
560 570 580 590 600
HNYSTAHMLK NYLFRPPPPY PRPRPATSTP DLASHRHKYV SGSSPDLVTR
610 620 630 640 650
KVQLSVKTFQ EDSSPVVHQS LQEVSEPLTA TKHHGTVNKR HSLEVMNSMV
660 670 680 690 700
RGMEAMTLKS LHLPMARRNT LREQGPPEEG SGSHEVPQLP QYHHKKTFSD
710 720 730 740 750
ATMLIHSSES EEEEEEAPES VPQIPMLREK MEYSAQLQAA LARIPNKPPP
760 770 780 790 800
EYPGPRKSVS NGALRQDQAS LPPAMARARV LRHGPAKAIS MSRTDPPAVN
810 820 830 840 850
GASLGPSISE PDLTSVKERV KKEPVKERPV SEMFSLEDSI IEREMMIRNL
860 870 880 890 900
EKQKMAGLEA QKRPLMLAAL NGLSVARVSG REENRVDATR VPMDERFRTL
910 920 930 940 950
KKKLEEGMVF TEYEQIPKKK ANGIFSTAAL PENAERSRIR EVVPYEENRV
960 970 980 990 1000
ELIPTKENNT GYINASHIKV VVGGAEWHYI ATQGPLPHTC HDFWQMVWEQ
1010 1020 1030 1040 1050
GVNVIAMVTA EEEGGRTKSH RYWPKLGSKH SSATYGKFKV TTKFRTDSVC
1060 1070 1080 1090 1100
YATTGLKVKH LLSGQERTVW HLQYTDWPDH GCPEDVQGFL SYLEEIQSVR
1110 1120 1130 1140 1150
RHTNSMLEGT KNRHPPIVVH CSAGVGRTGV LILSELMIYC LEHNEKVEVP
1160 1170 1180
MMLRLLREQR MFMIQTIAQY KFVYQVLIQF LQNSRLI
Length:1,187
Mass (Da):135,261
Last modified:October 14, 2008 - v2
Checksum:i1D22F1C8ED06C096
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti392H → D in CAA57993 (PubMed:7733990).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_035849159Q → E in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_035850360H → P in a breast cancer sample; somatic mutation. 1 PublicationCorresponds to variant rs112523432dbSNPEnsembl.1
Natural variantiVAR_046995505V → F.Corresponds to variant rs12239356dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X82676 mRNA. Translation: CAA57993.1.
AL929236
, AL445305, AL592216, AL603838 Genomic DNA. Translation: CAH70919.1.
AL603838
, AL445305, AL592216, AL929236 Genomic DNA. Translation: CAH72982.1.
AL445305
, AL592216, AL603838, AL929236 Genomic DNA. Translation: CAH73027.1.
AL592216
, AL445305, AL603838, AL929236 Genomic DNA. Translation: CAH73479.1.
CH471100 Genomic DNA. Translation: EAW93351.1.
BC101754 mRNA. Translation: AAI01755.1.
BC104803 mRNA. Translation: AAI04804.1.
CCDSiCCDS1514.1.
PIRiJC4155.
RefSeqiNP_005392.2. NM_005401.4.
XP_016857430.1. XM_017001941.1.
UniGeneiHs.193557.
Hs.688910.

Genome annotation databases

EnsembliENST00000366956; ENSP00000355923; ENSG00000152104.
GeneIDi5784.
KEGGihsa:5784.
UCSCiuc001hkk.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X82676 mRNA. Translation: CAA57993.1.
AL929236
, AL445305, AL592216, AL603838 Genomic DNA. Translation: CAH70919.1.
AL603838
, AL445305, AL592216, AL929236 Genomic DNA. Translation: CAH72982.1.
AL445305
, AL592216, AL603838, AL929236 Genomic DNA. Translation: CAH73027.1.
AL592216
, AL445305, AL603838, AL929236 Genomic DNA. Translation: CAH73479.1.
CH471100 Genomic DNA. Translation: EAW93351.1.
BC101754 mRNA. Translation: AAI01755.1.
BC104803 mRNA. Translation: AAI04804.1.
CCDSiCCDS1514.1.
PIRiJC4155.
RefSeqiNP_005392.2. NM_005401.4.
XP_016857430.1. XM_017001941.1.
UniGeneiHs.193557.
Hs.688910.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2BZLX-ray1.65A886-1187[»]
ProteinModelPortaliQ15678.
SMRiQ15678.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111748. 43 interactors.
DIPiDIP-38131N.
IntActiQ15678. 17 interactors.
STRINGi9606.ENSP00000355923.

Chemistry databases

BindingDBiQ15678.
ChEMBLiCHEMBL3317332.

PTM databases

DEPODiQ15678.
iPTMnetiQ15678.
PhosphoSitePlusiQ15678.

Polymorphism and mutation databases

BioMutaiPTPN14.
DMDMi209572662.

Proteomic databases

EPDiQ15678.
MaxQBiQ15678.
PaxDbiQ15678.
PeptideAtlasiQ15678.
PRIDEiQ15678.

Protocols and materials databases

DNASUi5784.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000366956; ENSP00000355923; ENSG00000152104.
GeneIDi5784.
KEGGihsa:5784.
UCSCiuc001hkk.3. human.

Organism-specific databases

CTDi5784.
DisGeNETi5784.
GeneCardsiPTPN14.
HGNCiHGNC:9647. PTPN14.
HPAiCAB011469.
CAB069441.
HPA053864.
MalaCardsiPTPN14.
MIMi603155. gene.
613611. phenotype.
neXtProtiNX_Q15678.
OpenTargetsiENSG00000152104.
PharmGKBiPA33989.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0792. Eukaryota.
COG5599. LUCA.
GeneTreeiENSGT00830000128259.
HOGENOMiHOG000115775.
HOVERGENiHBG053757.
InParanoidiQ15678.
KOiK18025.
OMAiEKVEYSA.
OrthoDBiEOG091G00QP.
PhylomeDBiQ15678.
TreeFamiTF315900.

Enzyme and pathway databases

BioCyciZFISH:HS07792-MONOMER.
BRENDAi3.1.3.48. 2681.
SIGNORiQ15678.

Miscellaneous databases

ChiTaRSiPTPN14. human.
EvolutionaryTraceiQ15678.
GeneWikiiPTPN14.
GenomeRNAii5784.
PROiQ15678.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000152104.
CleanExiHS_PTPN14.
ExpressionAtlasiQ15678. baseline and differential.
GenevisibleiQ15678. HS.

Family and domain databases

Gene3Di1.20.80.10. 1 hit.
2.30.29.30. 1 hit.
3.90.190.10. 1 hit.
InterProiIPR019749. Band_41_domain.
IPR014352. FERM/acyl-CoA-bd_prot_3-hlx.
IPR019748. FERM_central.
IPR019747. FERM_CS.
IPR000299. FERM_domain.
IPR018979. FERM_N.
IPR018980. FERM_PH-like_C.
IPR011993. PH_dom-like.
IPR029021. Prot-tyrosine_phosphatase-like.
IPR000242. PTPase_domain.
IPR016130. Tyr_Pase_AS.
IPR003595. Tyr_Pase_cat.
IPR014392. Tyr_Pase_non-rcpt_typ-14/21.
IPR000387. TYR_PHOSPHATASE_dom.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PfamiPF09380. FERM_C. 1 hit.
PF00373. FERM_M. 1 hit.
PF09379. FERM_N. 1 hit.
PF00102. Y_phosphatase. 1 hit.
[Graphical view]
PIRSFiPIRSF000934. Tyr-Ptase_nr14. 1 hit.
PRINTSiPR00935. BAND41.
PR00700. PRTYPHPHTASE.
SMARTiSM00295. B41. 1 hit.
SM01196. FERM_C. 1 hit.
SM00194. PTPc. 1 hit.
SM00404. PTPc_motif. 1 hit.
[Graphical view]
SUPFAMiSSF47031. SSF47031. 1 hit.
SSF50729. SSF50729. 1 hit.
SSF52799. SSF52799. 1 hit.
SSF54236. SSF54236. 1 hit.
PROSITEiPS00660. FERM_1. 1 hit.
PS00661. FERM_2. 1 hit.
PS50057. FERM_3. 1 hit.
PS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50055. TYR_PHOSPHATASE_PTP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPTN14_HUMAN
AccessioniPrimary (citable) accession number: Q15678
Secondary accession number(s): Q5VSI0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: October 14, 2008
Last modified: November 30, 2016
This is version 163 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.