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P54829 (PTN5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tyrosine-protein phosphatase non-receptor type 5

EC=3.1.3.48
Alternative name(s):
Neural-specific protein-tyrosine phosphatase
Striatum-enriched protein-tyrosine phosphatase
Short name=STEP
Gene names
Name:PTPN5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length565 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May regulate the activity of several effector molecules involved in synaptic plasticity and neuronal cell survival, including MAPKs, Src family kinases and NMDA receptors. Ref.7

Catalytic activity

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.

Subcellular location

Endoplasmic reticulum membrane; Multi-pass membrane protein By similarity.

Post-translational modification

Phosphorylation at Ser-245 by PKA deactivates PTPN5. Phosphorylation at Thr-255 and Ser-268 by MAPKs stabilizes the phosphatase, dephosphorylation of these sites results in ubiquitin-mediated degradation of the active phosphatase.

Sequence similarities

Belongs to the protein-tyrosine phosphatase family. Non-receptor class subfamily.

Contains 1 tyrosine-protein phosphatase domain.

Caution

It is uncertain whether Met-1 or Met-25 is the initiator.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P54829-1)

Also known as: STEP61;

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.
Isoform 2 (identifier: P54829-2)

The sequence of this isoform differs from the canonical sequence as follows:
     98-129: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: P54829-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-24: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 565565Tyrosine-protein phosphatase non-receptor type 5
PRO_0000363657

Regions

Transmembrane88 – 10821Helical; Potential
Transmembrane146 – 16621Helical; Potential
Domain300 – 555256Tyrosine-protein phosphatase
Region496 – 5027Substrate binding

Sites

Active site4961Phosphocysteine intermediate By similarity
Binding site4611Substrate By similarity
Binding site5401Substrate By similarity

Amino acid modifications

Modified residue2451Phosphoserine; by PKA Ref.7
Modified residue2551Phosphothreonine; by MAPK Ref.7
Modified residue2681Phosphoserine; by MAPK Ref.7

Natural variations

Alternative sequence1 – 2424Missing in isoform 3.
VSP_054561
Alternative sequence98 – 12932Missing in isoform 2.
VSP_042654
Natural variant1701P → A. Ref.1 Ref.4
Corresponds to variant rs4757707 [ dbSNP | Ensembl ].
VAR_054369
Natural variant5611H → R.
Corresponds to variant rs11024773 [ dbSNP | Ensembl ].
VAR_054370

Experimental info

Sequence conflict32 – 343PGL → LGR in AAA87555. Ref.6
Sequence conflict1041W → R in BAC03548. Ref.1
Sequence conflict1071G → A in CAD38632. Ref.2
Sequence conflict1101H → D in CAD38632. Ref.2
Sequence conflict1111I → M in AAA87555. Ref.6
Sequence conflict1341A → S in AAA87555. Ref.6
Sequence conflict1451S → G in AAA87555. Ref.6
Sequence conflict1621V → L in CAD38632. Ref.2
Sequence conflict3131D → V in AAA87555. Ref.6
Sequence conflict322 – 3232LV → RC in AAA87555. Ref.6
Sequence conflict5411T → H in AAA87555. Ref.6

Secondary structure

.............................................. 565
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (STEP61) [UniParc].

Last modified January 11, 2011. Version 4.
Checksum: DE32BEFFEFF7C494

FASTA56563,538
        10         20         30         40         50         60 
MNYEGARSER ENHAADDSEG GALDMCCSER LPGLPQPIVM EALDEAEGLQ DSQREMPPPP 

        70         80         90        100        110        120 
PPSPPSDPAQ KPPPRGAGSH SLTVRSSLCL FAASQFLLAC GVLWFSGYGH IWSQNATNLV 

       130        140        150        160        170        180 
SSLLTLLKQL EPTAWLDSGT WGVPSLLLVF LSVGLVLVTT LVWHLLRTPP EPPTPLPPED 

       190        200        210        220        230        240 
RRQSVSRQPS FTYSEWMEEK IEDDFLDLDP VPETPVFDCV MDIKPEADPT SLTVKSMGLQ 

       250        260        270        280        290        300 
ERRGSNVSLT LDMCTPGCNE EGFGYLMSPR EESAREYLLS ASRVLQAEEL HEKALDPFLL 

       310        320        330        340        350        360 
QAEFFEIPMN FVDPKEYDIP GLVRKNRYKT ILPNPHSRVC LTSPDPDDPL SSYINANYIR 

       370        380        390        400        410        420 
GYGGEEKVYI ATQGPIVSTV ADFWRMVWQE HTPIIVMITN IEEMNEKCTE YWPEEQVAYD 

       430        440        450        460        470        480 
GVEITVQKVI HTEDYRLRLI SLKSGTEERG LKHYWFTSWP DQKTPDRAPP LLHLVREVEE 

       490        500        510        520        530        540 
AAQQEGPHCA PIIVHCSAGI GRTGCFIATS ICCQQLRQEG VVDILKTTCQ LRQDRGGMIQ 

       550        560 
TCEQYQFVHH VMSLYEKQLS HQSPE 

« Hide

Isoform 2 [UniParc].

Checksum: A27BA66C3292C132
Show »

FASTA53360,035
Isoform 3 [UniParc].

Checksum: FE808E1908C2AB58
Show »

FASTA54160,961

References

« Hide 'large scale' references
[1]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), VARIANT ALA-170.
Tissue: Amygdala, Brain and Hippocampus.
[2]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[3]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ALA-170.
[5]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[6]"Molecular cloning of the human homolog of a striatum-enriched phosphatase (STEP) gene and chromosomal mapping of the human and murine loci."
Li X., Luna J., Lombroso P.J., Francke U.
Genomics 28:442-449(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 29-565 (ISOFORM 1).
Tissue: Brain.
[7]"Dephosphorylation of specific sites in the kinase-specificity sequence domain leads to ubiquitin-mediated degradation of the tyrosine phosphatase STEP."
Mukherjee S., Poddar R., Deb I., Paul S.
Biochem. J. 440:115-125(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-245; THR-255 AND SER-268, FUNCTION.
[8]"Crystal structures and inhibitor identification for PTPN5, PTPRR and PTPN7: a family of human MAPK-specific protein tyrosine phosphatases."
Eswaran J., von Kries J.P., Marsden B., Longman E., Debreczeni J.E., Ugochukwu E., Turnbull A., Lee W.H., Knapp S., Barr A.J.
Biochem. J. 395:483-491(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 280-563 IN COMPLEX WITH SUBSTRATE ANALOG.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK090923 mRNA. Translation: BAC03548.1.
AK127312 mRNA. Translation: BAG54479.1.
AK295604 mRNA. Translation: BAH12122.1.
AK316270 mRNA. Translation: BAH14641.1.
AL832541 mRNA. Translation: CAD38632.2.
AC103974 Genomic DNA. No translation available.
CH471064 Genomic DNA. Translation: EAW68363.1.
CH471064 Genomic DNA. Translation: EAW68365.1.
CH471064 Genomic DNA. Translation: EAW68367.1.
BC064807 mRNA. Translation: AAH64807.1.
U27831 mRNA. Translation: AAA87555.1.
CCDSCCDS41626.1. [P54829-2]
CCDS7845.1. [P54829-1]
RefSeqNP_001035059.1. NM_001039970.1. [P54829-2]
NP_001265165.1. NM_001278236.1. [P54829-2]
NP_001265167.1. NM_001278238.1. [P54829-3]
NP_001265168.1. NM_001278239.1.
NP_008837.1. NM_006906.1. [P54829-1]
NP_116170.3. NM_032781.3. [P54829-1]
UniGeneHs.79092.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2BIJX-ray2.05A282-563[»]
2BV5X-ray1.80A280-561[»]
2CJZX-ray1.70A282-563[»]
ProteinModelPortalP54829.
SMRP54829. Positions 280-561.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid124312. 10 interactions.
IntActP54829. 5 interactions.
STRING9606.ENSP00000351342.

Chemistry

BindingDBP54829.
ChEMBLCHEMBL2007628.

PTM databases

PhosphoSiteP54829.

Polymorphism databases

DMDM317373540.

Proteomic databases

PaxDbP54829.
PRIDEP54829.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000358540; ENSP00000351342; ENSG00000110786. [P54829-1]
ENST00000396167; ENSP00000379470; ENSG00000110786. [P54829-2]
ENST00000396168; ENSP00000379471; ENSG00000110786.
ENST00000396170; ENSP00000379473; ENSG00000110786. [P54829-2]
ENST00000396171; ENSP00000379474; ENSG00000110786. [P54829-1]
GeneID84867.
KEGGhsa:84867.
UCSCuc001mpb.4. human. [P54829-2]
uc001mpc.4. human. [P54829-1]

Organism-specific databases

CTD84867.
GeneCardsGC11M018706.
HGNCHGNC:9657. PTPN5.
HPAHPA031014.
MIM176879. gene.
neXtProtNX_P54829.
PharmGKBPA34001.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5599.
HOGENOMHOG000294188.
HOVERGENHBG001594.
InParanoidP54829.
KOK18018.
OMACTPGCSE.
OrthoDBEOG7288QX.
PhylomeDBP54829.
TreeFamTF331016.

Enzyme and pathway databases

BRENDA3.1.3.48. 2681.

Gene expression databases

ArrayExpressP54829.
BgeeP54829.
CleanExHS_PTPN5.
GenevestigatorP54829.

Family and domain databases

Gene3D3.90.190.10. 1 hit.
InterProIPR029021. Prot-tyrosine_phosphatase-like.
IPR000387. Tyr/Dual-sp_Pase.
IPR016130. Tyr_Pase_AS.
IPR008356. Tyr_Pase_KIM-con.
IPR000242. Tyr_Pase_rcpt/non-rcpt.
IPR016334. Tyr_Pase_rcpt_R/non-rcpt_5.
[Graphical view]
PfamPF00102. Y_phosphatase. 1 hit.
[Graphical view]
PIRSFPIRSF001997. PTPRR. 1 hit.
PRINTSPR01778. KIMPTPASE.
PR00700. PRTYPHPHTASE.
SMARTSM00194. PTPc. 1 hit.
[Graphical view]
SUPFAMSSF52799. SSF52799. 1 hit.
PROSITEPS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50055. TYR_PHOSPHATASE_PTP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP54829.
GeneWikiPTPN5.
GenomeRNAi84867.
NextBio35480892.
PROP54829.
SOURCESearch...

Entry information

Entry namePTN5_HUMAN
AccessionPrimary (citable) accession number: P54829
Secondary accession number(s): B3KXG7 expand/collapse secondary AC list , B7Z386, B7ZAF5, D3DQY7, Q6P1Z2, Q8N2A1, Q8NDP8
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 11, 2011
Last modified: July 9, 2014
This is version 127 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM