PTN5_MOUSE
ID PTN5_MOUSE Reviewed; 541 AA.
AC P54830; Q64694; Q8CAN0;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2009, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Tyrosine-protein phosphatase non-receptor type 5;
DE EC=3.1.3.48;
DE AltName: Full=Neural-specific protein-tyrosine phosphatase;
DE AltName: Full=Striatum-enriched protein-tyrosine phosphatase;
DE Short=STEP;
GN Name=Ptpn5;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS STEP20; STEP38; STEP46 AND STEP61).
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=7494467; DOI=10.1016/0169-328x(95)00066-2;
RA Sharma E., Zhao F., Bult A., Lombroso P.J.;
RT "Identification of two alternatively spliced transcripts of STEP: a
RT subfamily of brain-enriched protein tyrosine phosphatases.";
RL Brain Res. Mol. Brain Res. 32:87-93(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM STEP61).
RC STRAIN=C57BL/6J; TISSUE=Hypothalamus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM STEP61).
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=8987810; DOI=10.1523/jneurosci.16-24-07821.1996;
RA Bult A., Zhao F., Dirkx R. Jr., Sharma E., Lukacsi E., Solimena M.,
RA Naegele J.R., Lombroso P.J.;
RT "STEP61: a member of a family of brain-enriched PTPs is localized to the
RT endoplasmic reticulum.";
RL J. Neurosci. 16:7821-7831(1996).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: May regulate the activity of several effector molecules
CC involved in synaptic plasticity and neuronal cell survival, including
CC MAPKs, Src family kinases and NMDA receptors. {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] +
CC phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620; EC=3.1.3.48; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU10044};
CC -!- INTERACTION:
CC P54830-1; Q16539-1: MAPK14; Xeno; NbExp=6; IntAct=EBI-16067443, EBI-15834191;
CC -!- SUBCELLULAR LOCATION: [Isoform STEP61]: Endoplasmic reticulum membrane;
CC Multi-pass membrane protein.
CC -!- SUBCELLULAR LOCATION: [Isoform STEP46]: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Comment=Additional isoforms seem to exist.;
CC Name=STEP61;
CC IsoId=P54830-1; Sequence=Displayed;
CC Name=STEP46;
CC IsoId=P54830-2; Sequence=VSP_005126;
CC Name=STEP38;
CC IsoId=P54830-3; Sequence=VSP_005127, VSP_005128;
CC Name=STEP20;
CC IsoId=P54830-4; Sequence=VSP_005126, VSP_005127, VSP_005128;
CC -!- TISSUE SPECIFICITY: STEP20 is expressed only in the CNS.
CC -!- PTM: Phosphorylation at Ser-221 by PKA deactivates PTPN5.
CC Phosphorylation at Thr-231 and Ser-244 by MAPKs stabilizes the
CC phosphatase, dephosphorylation of these sites results in ubiquitin-
CC mediated degradation of the active phosphatase (By similarity).
CC {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform STEP38]: Lacks the catalytic domain.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform STEP20]: Lacks the catalytic domain.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U28217; AAA73574.1; -; mRNA.
DR EMBL; U28216; AAA73573.1; -; mRNA.
DR EMBL; S80329; AAB35656.2; -; mRNA.
DR EMBL; AK038416; BAC29993.1; -; mRNA.
DR EMBL; CH466603; EDL22958.1; -; Genomic_DNA.
DR EMBL; BC079592; AAH79592.1; -; mRNA.
DR CCDS; CCDS21294.1; -. [P54830-1]
DR RefSeq; NP_001157037.1; NM_001163565.1. [P54830-1]
DR RefSeq; NP_038671.2; NM_013643.2. [P54830-1]
DR RefSeq; XP_006540776.1; XM_006540713.3. [P54830-1]
DR RefSeq; XP_006540777.1; XM_006540714.3. [P54830-1]
DR RefSeq; XP_006540778.1; XM_006540715.3. [P54830-1]
DR RefSeq; XP_017177535.1; XM_017322046.1. [P54830-1]
DR PDB; 6H8S; X-ray; 1.77 A; A=244-539.
DR PDBsum; 6H8S; -.
DR AlphaFoldDB; P54830; -.
DR BMRB; P54830; -.
DR SMR; P54830; -.
DR BioGRID; 202488; 13.
DR DIP; DIP-32453N; -.
DR ELM; P54830; -.
DR IntAct; P54830; 2.
DR MINT; P54830; -.
DR STRING; 10090.ENSMUSP00000033142; -.
DR ChEMBL; CHEMBL4523242; -.
DR iPTMnet; P54830; -.
DR PhosphoSitePlus; P54830; -.
DR MaxQB; P54830; -.
DR PaxDb; P54830; -.
DR PeptideAtlas; P54830; -.
DR PRIDE; P54830; -.
DR ProteomicsDB; 301876; -. [P54830-1]
DR ProteomicsDB; 301877; -. [P54830-2]
DR ProteomicsDB; 301878; -. [P54830-3]
DR ProteomicsDB; 301879; -. [P54830-4]
DR Antibodypedia; 25176; 303 antibodies from 29 providers.
DR DNASU; 19259; -.
DR Ensembl; ENSMUST00000033142; ENSMUSP00000033142; ENSMUSG00000030854. [P54830-1]
DR Ensembl; ENSMUST00000102626; ENSMUSP00000099686; ENSMUSG00000030854. [P54830-1]
DR GeneID; 19259; -.
DR KEGG; mmu:19259; -.
DR UCSC; uc009gzz.2; mouse. [P54830-1]
DR UCSC; uc009hac.1; mouse. [P54830-3]
DR CTD; 84867; -.
DR MGI; MGI:97807; Ptpn5.
DR VEuPathDB; HostDB:ENSMUSG00000030854; -.
DR eggNOG; KOG0789; Eukaryota.
DR GeneTree; ENSGT00940000159916; -.
DR HOGENOM; CLU_001645_10_2_1; -.
DR InParanoid; P54830; -.
DR OMA; GWPQGYG; -.
DR OrthoDB; 411281at2759; -.
DR PhylomeDB; P54830; -.
DR TreeFam; TF331016; -.
DR BioGRID-ORCS; 19259; 4 hits in 74 CRISPR screens.
DR ChiTaRS; Ptpn5; mouse.
DR PRO; PR:P54830; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P54830; protein.
DR Bgee; ENSMUSG00000030854; Expressed in caudate-putamen and 125 other tissues.
DR Genevisible; P54830; MM.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0030054; C:cell junction; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0043204; C:perikaryon; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:1990635; C:proximal dendrite; ISO:MGI.
DR GO; GO:0097060; C:synaptic membrane; ISO:MGI.
DR GO; GO:0008021; C:synaptic vesicle; ISO:MGI.
DR GO; GO:0035254; F:glutamate receptor binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0051019; F:mitogen-activated protein kinase binding; ISO:MGI.
DR GO; GO:0001784; F:phosphotyrosine residue binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IMP:MGI.
DR GO; GO:0035640; P:exploration behavior; ISO:MGI.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; ISO:MGI.
DR GO; GO:0035335; P:peptidyl-tyrosine dephosphorylation; ISO:MGI.
DR GO; GO:1900273; P:positive regulation of long-term synaptic potentiation; ISO:MGI.
DR GO; GO:1901216; P:positive regulation of neuron death; ISO:MGI.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:1903955; P:positive regulation of protein targeting to mitochondrion; ISO:MGI.
DR GO; GO:0002092; P:positive regulation of receptor internalization; ISO:MGI.
DR GO; GO:2001025; P:positive regulation of response to drug; ISO:MGI.
DR GO; GO:0006470; P:protein dephosphorylation; IMP:MGI.
DR GO; GO:0035902; P:response to immobilization stress; ISO:MGI.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR Gene3D; 3.90.190.10; -; 1.
DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR InterPro; IPR000242; PTP_cat.
DR InterPro; IPR016130; Tyr_Pase_AS.
DR InterPro; IPR003595; Tyr_Pase_cat.
DR InterPro; IPR000387; Tyr_Pase_dom.
DR InterPro; IPR008356; Tyr_Pase_KIM-con.
DR InterPro; IPR016334; Tyr_Pase_rcpt_R/non-rcpt_5.
DR PANTHER; PTHR46198; PTHR46198; 1.
DR Pfam; PF00102; Y_phosphatase; 1.
DR PIRSF; PIRSF001997; PTPRR; 1.
DR PRINTS; PR01778; KIMPTPASE.
DR PRINTS; PR00700; PRTYPHPHTASE.
DR SMART; SM00194; PTPc; 1.
DR SMART; SM00404; PTPc_motif; 1.
DR SUPFAM; SSF52799; SSF52799; 1.
DR PROSITE; PS00383; TYR_PHOSPHATASE_1; 1.
DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 1.
DR PROSITE; PS50055; TYR_PHOSPHATASE_PTP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Endoplasmic reticulum;
KW Hydrolase; Membrane; Phosphoprotein; Protein phosphatase;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..541
FT /note="Tyrosine-protein phosphatase non-receptor type 5"
FT /id="PRO_0000094756"
FT TRANSMEM 64..84
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 122..142
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 276..531
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT REGION 1..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 29..47
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 472
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160,
FT ECO:0000255|PROSITE-ProRule:PRU10044"
FT BINDING 437
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 472..478
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 516
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 221
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:P54829"
FT MOD_RES 231
FT /note="Phosphothreonine; by MAPK"
FT /evidence="ECO:0000250|UniProtKB:P54829"
FT MOD_RES 244
FT /note="Phosphoserine; by MAPK"
FT /evidence="ECO:0000250|UniProtKB:P54829"
FT VAR_SEQ 1..172
FT /note="Missing (in isoform STEP20 and isoform STEP46)"
FT /evidence="ECO:0000303|PubMed:7494467"
FT /id="VSP_005126"
FT VAR_SEQ 337..346
FT /note="GYSGEEKVYI -> VCSSIPRAFH (in isoform STEP38 and
FT isoform STEP20)"
FT /evidence="ECO:0000303|PubMed:7494467"
FT /id="VSP_005127"
FT VAR_SEQ 347..541
FT /note="Missing (in isoform STEP38 and isoform STEP20)"
FT /evidence="ECO:0000303|PubMed:7494467"
FT /id="VSP_005128"
FT CONFLICT 426
FT /note="S -> T (in Ref. 1; AAA73574)"
FT /evidence="ECO:0000305"
FT HELIX 250..256
FT /evidence="ECO:0007829|PDB:6H8S"
FT HELIX 263..270
FT /evidence="ECO:0007829|PDB:6H8S"
FT HELIX 273..282
FT /evidence="ECO:0007829|PDB:6H8S"
FT HELIX 290..292
FT /evidence="ECO:0007829|PDB:6H8S"
FT HELIX 295..297
FT /evidence="ECO:0007829|PDB:6H8S"
FT TURN 299..301
FT /evidence="ECO:0007829|PDB:6H8S"
FT HELIX 311..313
FT /evidence="ECO:0007829|PDB:6H8S"
FT TURN 325..328
FT /evidence="ECO:0007829|PDB:6H8S"
FT STRAND 331..335
FT /evidence="ECO:0007829|PDB:6H8S"
FT HELIX 338..340
FT /evidence="ECO:0007829|PDB:6H8S"
FT STRAND 344..348
FT /evidence="ECO:0007829|PDB:6H8S"
FT HELIX 353..355
FT /evidence="ECO:0007829|PDB:6H8S"
FT HELIX 356..366
FT /evidence="ECO:0007829|PDB:6H8S"
FT STRAND 370..374
FT /evidence="ECO:0007829|PDB:6H8S"
FT HELIX 377..379
FT /evidence="ECO:0007829|PDB:6H8S"
FT TURN 380..382
FT /evidence="ECO:0007829|PDB:6H8S"
FT STRAND 390..395
FT /evidence="ECO:0007829|PDB:6H8S"
FT STRAND 398..407
FT /evidence="ECO:0007829|PDB:6H8S"
FT STRAND 409..420
FT /evidence="ECO:0007829|PDB:6H8S"
FT STRAND 423..432
FT /evidence="ECO:0007829|PDB:6H8S"
FT HELIX 441..443
FT /evidence="ECO:0007829|PDB:6H8S"
FT HELIX 444..459
FT /evidence="ECO:0007829|PDB:6H8S"
FT STRAND 468..471
FT /evidence="ECO:0007829|PDB:6H8S"
FT STRAND 473..476
FT /evidence="ECO:0007829|PDB:6H8S"
FT HELIX 477..495
FT /evidence="ECO:0007829|PDB:6H8S"
FT HELIX 500..510
FT /evidence="ECO:0007829|PDB:6H8S"
FT HELIX 518..536
FT /evidence="ECO:0007829|PDB:6H8S"
SQ SEQUENCE 541 AA; 60815 MW; 31A0D2C9139F90A4 CRC64;
MCCSERLLGL PQPVEMEAPD EAEGLPSKQK EMPPPPPPSP PSEPAQKLPP QGAGSHSLTV
RSSLCLFAAS QFLLACGVLW LSGHGHSWLQ NTTDLISSSL TVLNHLGPVA WLGSGTWGIP
SLLLVSLTVS LVIVTTLVWH LLKAPPEPPA PLPPEDRRQS VSRQPSFTYS EWMEEKVEDD
FLDLDAVPET PVFDCVMDIK PETDPASLTV KSMGLQERRG SNVSLTLDMC TPGCNEEGFG
YLVSPREESA HEYLLSASRV LRAEELHEKA LDPFLLQAEF FEIPMNFVDP KEYDIPGLVR
KNRYKTILPN PHSRVRLTSP DPEDPLSSYI NANYIRGYSG EEKVYIATQG PIVSTVADFW
RMVWQERTPI IVMITNIEEM NEKCTEYWPE EQVVHDGVEI TVQKVIHTED YRLRLISLRR
GTEERSLKHY WFTSWPDQKT PDRAPPLLHL VREVEEAAQQ EGPHCSPIIV HCSAGIGRTG
CFIATSICCQ QLRREGVVDI LKTTCQLRQD RGGMIQTCEQ YQFVHHAMSL YEKQLSLQSS
E
