P54829 (PTN5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	565 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Molecular function	Hydrolase Protein phosphatase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Traceable author statement PubMed 2263249. Source: UniProtKB
Molecular_function	phosphotyrosine binding Inferred from direct assay Ref.8. Source: UniProtKB protein tyrosine phosphatase activity Traceable author statement Ref.6. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 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.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 565

565

Tyrosine-protein phosphatase non-receptor type 5

PRO_0000363657

Regions

Transmembrane

88 – 108

21

Helical; Potential

Transmembrane

146 – 166

21

Helical; Potential

Domain

300 – 555

256

Tyrosine-protein phosphatase

Region

496 – 502

7

Substrate binding

Sites

Active site

496

1

Phosphocysteine intermediate By similarity

Binding site

461

1

Substrate By similarity

Binding site

540

1

Substrate By similarity

Amino acid modifications

Modified residue

245

1

Phosphoserine; by PKA Ref.7

Modified residue

255

1

Phosphothreonine; by MAPK Ref.7

Modified residue

268

1

Phosphoserine; by MAPK Ref.7

Natural variations

Alternative sequence

98 – 129

32

Missing in isoform 2.

VSP_042654

Natural variant

170

1

P → A. Ref.1 Ref.4
Corresponds to variant rs4757707 [ dbSNP | Ensembl ].

VAR_054369

Natural variant

561

1

H → R.
Corresponds to variant rs11024773 [ dbSNP | Ensembl ].

VAR_054370

Experimental info

Sequence conflict

32 – 34

3

PGL → LGR in AAA87555. Ref.6

Sequence conflict

104

1

W → R in BAC03548. Ref.1

Sequence conflict

107

1

G → A in CAD38632. Ref.2

Sequence conflict

110

1

H → D in CAD38632. Ref.2

Sequence conflict

111

1

I → M in AAA87555. Ref.6

Sequence conflict

134

1

A → S in AAA87555. Ref.6

Sequence conflict

145

1

S → G in AAA87555. Ref.6

Sequence conflict

162

1

V → L in CAD38632. Ref.2

Sequence conflict

313

1

D → V in AAA87555. Ref.6

Sequence conflict

322 – 323

2

LV → RC in AAA87555. Ref.6

Sequence conflict

541

1

T → H in AAA87555. Ref.6

Secondary structure

1

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565

Helix Strand Turn

Details...

Helix

287 – 293

7

Helix

297 – 304

8

Helix

314 – 316

3

Helix

322 – 325

4

Helix

335 – 337

3

Beta strand

338 – 340

3

Turn

349 – 352

4

Beta strand

355 – 359

5

Helix

362 – 364

3

Beta strand

368 – 373

6

Helix

377 – 379

3

Helix

380 – 390

11

Beta strand

394 – 398

5

Helix

401 – 403

3

Turn

404 – 406

3

Beta strand

414 – 419

6

Beta strand

422 – 431

10

Beta strand

433 – 443

11

Beta strand

448 – 456

9

Helix

465 – 467

3

Helix

468 – 484

17

Beta strand

492 – 500

9

Helix

501 – 519

19

Helix

524 – 534

11

Helix

542 – 559

18

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (STEP61) [UniParc]. Last modified January 11, 2011. Version 4. Checksum: DE32BEFFEFF7C494	FASTA	565	63,538
	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
	Isoform 2 [UniParc]. Checksum: A27BA66C3292C132	FASTA	533	60,035
	10 20 30 40 50 60 MNYEGARSER ENHAADDSEG GALDMCCSER LPGLPQPIVM EALDEAEGLQ DSQREMPPPP 70 80 90 100 110 120 PPSPPSDPAQ KPPPRGAGSH SLTVRSSLCL FAASQFLLEP TAWLDSGTWG VPSLLLVFLS 130 140 150 160 170 180 VGLVLVTTLV WHLLRTPPEP PTPLPPEDRR QSVSRQPSFT YSEWMEEKIE DDFLDLDPVP 190 200 210 220 230 240 ETPVFDCVMD IKPEADPTSL TVKSMGLQER RGSNVSLTLD MCTPGCNEEG FGYLMSPREE 250 260 270 280 290 300 SAREYLLSAS RVLQAEELHE KALDPFLLQA EFFEIPMNFV DPKEYDIPGL VRKNRYKTIL 310 320 330 340 350 360 PNPHSRVCLT SPDPDDPLSS YINANYIRGY GGEEKVYIAT QGPIVSTVAD FWRMVWQEHT 370 380 390 400 410 420 PIIVMITNIE EMNEKCTEYW PEEQVAYDGV EITVQKVIHT EDYRLRLISL KSGTEERGLK 430 440 450 460 470 480 HYWFTSWPDQ KTPDRAPPLL HLVREVEEAA QQEGPHCAPI IVHCSAGIGR TGCFIATSIC 490 500 510 520 530 CQQLRQEGVV DILKTTCQLR QDRGGMIQTC EQYQFVHHVM SLYEKQLSHQ SPE

References

	« Hide 'large scale' referencesShow '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. , 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 AND 2), VARIANT ALA-170. Tissue: Amygdala 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. , 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. , 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.
AL832541 mRNA. Translation: CAD38632.2.
AC103974 Genomic DNA. No translation available.
CH471064 Genomic DNA. Translation: EAW68363.1.
CH471064 Genomic DNA. Translation: EAW68367.1.
BC064807 mRNA. Translation: AAH64807.1.
U27831 mRNA. Translation: AAA87555.1.

IPI

IPI00008837.
IPI00743309.

RefSeq

NP_001035059.1. NM_001039970.1.
NP_008837.1. NM_006906.1.
NP_116170.3. NM_032781.3.

UniGene

Hs.79092.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2BIJ	X-ray	2.05	A	282-563	[»]
2BV5	X-ray	1.80	A	282-561	[»]
2CJZ	X-ray	1.70	A	282-563	[»]

ProteinModelPortal

P54829.

SMR

P54829. Positions 280-561.

ModBase

Search...

Protein-protein interaction databases

IntAct

P54829. 5 interactions.

STRING

9606.ENSP00000351342.

PTM databases

PhosphoSite

P54829.

Polymorphism databases

DMDM

223590258.

Proteomic databases

PaxDb

P54829.

PRIDE

P54829.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000358540; ENSP00000351342; ENSG00000110786.
ENST00000396167; ENSP00000379470; ENSG00000110786.
ENST00000396170; ENSP00000379473; ENSG00000110786.
ENST00000396171; ENSP00000379474; ENSG00000110786.

GeneID

84867.

KEGG

hsa:84867.

UCSC

uc001mpc.3. human.

Organism-specific databases

CTD

84867.

GeneCards

GC11M018706.

HGNC

HGNC:9657. PTPN5.

HPA

HPA031014.

MIM

176879. gene.

neXtProt

NX_P54829.

PharmGKB

PA34001.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5599.

HOGENOM

HOG000294188.

HOVERGEN

HBG001594.

InParanoid

P54829.

KO

K04458.

OMA

CTPGCSE.

OrthoDB

EOG4229JX.

Enzyme and pathway databases

BRENDA

3.1.3.48. 2681.

Gene expression databases

ArrayExpress

P54829.

Bgee

P54829.

CleanEx

HS_PTPN5.

Genevestigator

P54829.

GermOnline

ENSG00000110786. Homo sapiens.

Family and domain databases

InterPro

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]

Pfam

PF00102. Y_phosphatase. 1 hit.
[Graphical view]

PIRSF

PIRSF001997. PTPRR. 1 hit.

PRINTS

PR01778. KIMPTPASE.
PR00700. PRTYPHPHTASE.

SMART

SM00194. PTPc. 1 hit.
[Graphical view]

PROSITE

PS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50055. TYR_PHOSPHATASE_PTP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P54829.

ChEMBL

CHEMBL2007628.

EvolutionaryTrace

P54829.

GenomeRNAi

84867.

NextBio

75139.

SOURCE

Search...

Entry information

Entry name

PTN5_HUMAN

Accession

Primary (citable) accession number: P54829
Secondary accession number(s): B3KXG7 , B7Z386, D3DQY7, Q6P1Z2, Q8N2A1, Q8NDP8

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	January 11, 2011
Last modified:	April 3, 2013
This is version 114 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.