Q8BGG7 (UBS3B_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ubiquitin-associated and SH3 domain-containing protein B
EC=3.1.3.48

Alternative name(s):
Cbl-interacting protein p70
Suppressor of T-cell receptor signaling 1
Short name=STS-1
T-cell ubiquitin ligand 2
Short name=TULA-2
Tyrosine-protein phosphatase STS1/TULA2

Gene names

Name:	Ubash3b
Synonyms:	Sts1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	638 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Interferes with CBL-mediated down-regulation and degradation of receptor-type tyrosine kinases. Promotes accumulation of activated target receptors, such as T-cell receptors and EGFR, on the cell surface. Exhibits tyrosine phosphatase activity toward several substrates including EGFR, FAK, SYK, and ZAP70. Down-regulates proteins that are dually modified by both protein tyrosine phosphorylation and ubiquitination. Ref.5 Ref.6 Ref.7 Ref.10
Catalytic activity	Protein tyrosine phosphate + H2O = protein tyrosine + phosphate. Ref.8
Subunit structure	Homodimer. Interacts with JAK2 (in vitro). Interacts with CBL. Part of a complex containing CBL and activated EGFR. Interacts with ubiquitin and with mono-ubiquitinated proteins By similarity. Ref.4 Ref.9 Ref.10
Subcellular location	Cytoplasm By similarity. Nucleus Potential.
Tissue specificity	Detected in splenic T-cells and B-cells, total spleen, skeletal muscle, heart, lung, kidney, thymus, brain and liver (at protein level). Highly expressed in brain. Detected in heart, spleen, lung, liver, kidney and testis. Ref.4 Ref.5
Disruption phenotype	Mice display strikingly elevated levels of tyrosine phosphorylated, ubiquitinated proteins following TCR stimulation. They are prothrombotic and have shorter bleeding times, which is attributed to insufficient SYK dephosphorylation in platelets. Ref.6 Ref.7
Sequence similarities	Contains 1 SH3 domain. Contains 1 UBA domain.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Domain	SH3 domain
Molecular function	Hydrolase Protein phosphatase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of platelet aggregation Inferred from mutant phenotype Ref.7. Source: MGI negative regulation of protein kinase activity Inferred from mutant phenotype Ref.7. Source: MGI peptidyl-tyrosine dephosphorylation Inferred from mutant phenotype Ref.7. Source: MGI regulation of release of sequestered calcium ion into cytosol Inferred from mutant phenotype Ref.7. Source: MGI
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	protein tyrosine phosphatase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8BGG7-1)

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.

Isoform 2 (identifier: Q8BGG7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-122: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 638

638

Ubiquitin-associated and SH3 domain-containing protein B

PRO_0000245509

Regions

Domain

23 – 65

43

UBA

Domain

243 – 308

66

SH3

Region

369 – 638

270

Protein tyrosine phosphatase

Compositional bias

325 – 328

4

Poly-Ser

Sites

Active site

379

1

Ref.9 Ref.10

Active site

380

1

Tele-phosphohistidine intermediate Ref.9 Ref.10

Active site

565

1

Ref.9 Ref.10

Amino acid modifications

Modified residue

9

1

Phosphoserine By similarity

Modified residue

12

1

Phosphothreonine By similarity

Natural variations

Alternative sequence

1 – 122

122

Missing in isoform 2.

VSP_019716

Experimental info

Sequence conflict

300

1

E → G in BAE30779. Ref.2

Sequence conflict

300

1

E → G in BAE30875. Ref.2

Secondary structure

1

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638

Helix Strand Turn

Details...

Beta strand

374 – 379

6

Helix

384 – 388

5

Helix

392 – 395

4

Helix

421 – 424

4

Helix

432 – 447

16

Beta strand

454 – 457

4

Helix

461 – 473

13

Turn

477 – 479

3

Beta strand

482 – 484

3

Helix

486 – 488

3

Helix

492 – 494

3

Beta strand

495 – 499

5

Helix

506 – 511

6

Helix

526 – 528

3

Helix

535 – 553

19

Turn

554 – 556

3

Beta strand

558 – 564

7

Helix

568 – 571

4

Turn

572 – 574

3

Helix

575 – 577

3

Helix

584 – 591

8

Beta strand

599 – 604

6

Beta strand

606 – 608

3

Beta strand

611 – 614

4

Helix

631 – 635

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2003. Version 1. Checksum: 9B665F45AF208EF6	FASTA	638	71,443
	10 20 30 40 50 60 MAAREELYSK VTPRRDRLQR PGTVKHGSAL DVLLSMGFPR ARAQKALAST GGRSVQAACD 70 80 90 100 110 120 WLFSHVGDPF LDDPLPREYV LYLRPTGPLA QKLSDFWQQS KQICGKNKAH NIFPHITLCQ 130 140 150 160 170 180 FFMCEDSKVD ALGEALQTTV SRWKCKFSAP LPLELYTSSN FIGLFVKEDS AEVLKKFAAD 190 200 210 220 230 240 FAAEAASKTE VHVEPHKKQL HVTLAYHFQA SHLPTLEKLA QNIDVKLGCD WVATIFSRDI 250 260 270 280 290 300 RFANHETLQV IYPYSPQNDD ELELVPGDFI FMSPMEQTST SEGWIYGTSL TTGCSGLLPE 310 320 330 340 350 360 NYITKADECS TWIFHGSYSI LNTVSSSSLA FGDGALERRQ YEDQGLGETT PLTIICQPMQ 370 380 390 400 410 420 PLRVNSQPGP QKRCLFVCRH GERMDVVFGK YWLSQCFDAK GRYIRTNLNM PHSLPQRSGG 430 440 450 460 470 480 FRDYEKDAPI TVFGCMQARL VGEALLESNT VIDHVYCSPS LRCVQTAHNI LKGLQQDNHL 490 500 510 520 530 540 KIRVEPGLFE WTKWVAGSTL PAWIPPSELA AANLSVDTTY RPHIPVSKLA ISESYDTYIN 550 560 570 580 590 600 RSFQVTKEII SECKSKGNNI LIVAHASSLE ACTCQLQGLS PQNSKDFVQM VRKIPYLGFC 610 620 630 SCEELGETGI WQLTDPPILP LTHGPTGGFN WRETLLQE
	Isoform 2 [UniParc]. Checksum: 2F00BDB1F01C31FD	FASTA	516	57,693
	10 20 30 40 50 60 MCEDSKVDAL GEALQTTVSR WKCKFSAPLP LELYTSSNFI GLFVKEDSAE VLKKFAADFA 70 80 90 100 110 120 AEAASKTEVH VEPHKKQLHV TLAYHFQASH LPTLEKLAQN IDVKLGCDWV ATIFSRDIRF 130 140 150 160 170 180 ANHETLQVIY PYSPQNDDEL ELVPGDFIFM SPMEQTSTSE GWIYGTSLTT GCSGLLPENY 190 200 210 220 230 240 ITKADECSTW IFHGSYSILN TVSSSSLAFG DGALERRQYE DQGLGETTPL TIICQPMQPL 250 260 270 280 290 300 RVNSQPGPQK RCLFVCRHGE RMDVVFGKYW LSQCFDAKGR YIRTNLNMPH SLPQRSGGFR 310 320 330 340 350 360 DYEKDAPITV FGCMQARLVG EALLESNTVI DHVYCSPSLR CVQTAHNILK GLQQDNHLKI 370 380 390 400 410 420 RVEPGLFEWT KWVAGSTLPA WIPPSELAAA NLSVDTTYRP HIPVSKLAIS ESYDTYINRS 430 440 450 460 470 480 FQVTKEIISE CKSKGNNILI VAHASSLEAC TCQLQGLSPQ NSKDFVQMVR KIPYLGFCSC 490 500 510 EELGETGIWQ LTDPPILPLT HGPTGGFNWR ETLLQE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"NF-E2 inducible megakaryocyte specific novel gene." Nagata Y., Oda M., Haruta H., Todokoro K. Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Megakaryocyte.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6J and NOD. Tissue: Bone marrow, Cerebellum, Dendritic cell, Diencephalon and Embryo.
[3]	"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: Embryonic limb.
[4]	"Identification, cDNA cloning, and targeted deletion of p70, a novel, ubiquitously expressed SH3 domain-containing protein." Carpino N., Kobayashi R., Zang H., Takahashi Y., Jou S.-T., Feng J., Nakajima H., Ihle J.N. Mol. Cell. Biol. 22:7491-7500(2002) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 93-101; 199-215; 403-410; 482-493 AND 495-515, INTERACTION WITH JAK2, TISSUE SPECIFICITY.
[5]	"Regulation of ZAP-70 activation and TCR signaling by two related proteins, Sts-1 and Sts-2." Carpino N., Turner S., Mekala D., Takahashi Y., Zang H., Geiger T.L., Doherty P., Ihle J.N. Immunity 20:37-46(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[6]	"The Sts proteins target tyrosine phosphorylated, ubiquitinated proteins within TCR signaling pathways." Carpino N., Chen Y., Nassar N., Oh H.W. Mol. Immunol. 46:3224-3231(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[7]	"A novel histidine tyrosine phosphatase, TULA-2, associates with Syk and negatively regulates GPVI signaling in platelets." Thomas D.H., Getz T.M., Newman T.N., Dangelmaier C.A., Carpino N., Kunapuli S.P., Tsygankov A.Y., Daniel J.L. Blood 116:2570-2578(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[8]	"Determination of the substrate specificity of protein-tyrosine phosphatase TULA-2 and identification of Syk as a TULA-2 substrate." Chen X., Ren L., Kim S., Carpino N., Daniel J.L., Kunapuli S.P., Tsygankov A.Y., Pei D. J. Biol. Chem. 285:31268-31276(2010) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY.
[9]	"The 1.35 A resolution structure of the phosphatase domain of the suppressor of T-cell receptor signaling protein in complex with sulfate." Jakoncic J., Sondgeroth B., Carpino N., Nassar N. Acta Crystallogr. F 66:643-647(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 373-636 IN COMPLEX WITH SULFATE, SUBUNIT, ACTIVE SITE.
[10]	"A phosphatase activity of Sts-1 contributes to the suppression of TCR signaling." Mikhailik A., Ford B., Keller J., Chen Y., Nassar N., Carpino N. Mol. Cell 27:486-497(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.82 ANGSTROMS) OF 373-633, SUBUNIT, FUNCTION, PHOSPHATASE ACTIVITY, ACTIVE SITE.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB075602 mRNA. Translation: BAD06450.1.
AK013361 mRNA. Translation: BAC25403.1.
AK034450 mRNA. Translation: BAC28714.1.
AK035764 mRNA. Translation: BAC29178.1.
AK133948 mRNA. Translation: BAE21945.1.
AK151895 mRNA. Translation: BAE30779.1.
AK152013 mRNA. Translation: BAE30875.1.
AK154576 mRNA. Translation: BAE32688.1.
BC053436 mRNA. Translation: AAH53436.1.

IPI

IPI00331539.
IPI00761651.

RefSeq

NP_789830.1. NM_176860.5.

UniGene

Mm.133615.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2H0Q	X-ray	1.82	A/B/C	373-633	[»]
2IKQ	X-ray	2.61	A/B/M	369-638	[»]
3MBK	X-ray	1.35	A/B	373-636	[»]

ProteinModelPortal

Q8BGG7.

SMR

Q8BGG7. Positions 15-67, 238-317, 373-636.

ModBase

Search...

Protein-protein interaction databases

STRING

10090.ENSMUSP00000043865.

PTM databases

PhosphoSite

Q8BGG7.

Proteomic databases

PaxDb

Q8BGG7.

PRIDE

Q8BGG7.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000044155; ENSMUSP00000043865; ENSMUSG00000032020.
ENSMUST00000151485; ENSMUSP00000116038; ENSMUSG00000032020.

GeneID

72828.

KEGG

mmu:72828.

UCSC

uc009pag.1. mouse.

Organism-specific databases

CTD

84959.

MGI

MGI:1920078. Ubash3b.

Phylogenomic databases

eggNOG

NOG276661.

GeneTree

ENSGT00390000018249.

HOGENOM

HOG000012936.

HOVERGEN

HBG018025.

InParanoid

Q8BGG7.

OMA

LSMGFPK.

OrthoDB

EOG4NKBV1.

Gene expression databases

ArrayExpress

Q8BGG7.

Bgee

Q8BGG7.

CleanEx

MM_UBASH3B.

Genevestigator

Q8BGG7.

GermOnline

ENSMUSG00000032020. Mus musculus.

Family and domain databases

InterPro

IPR013078. His_Pase_superF_clade-1.
IPR001452. SH3_domain.
IPR009060. UBA-like.
IPR000449. UBA/transl_elong_EF1B_N.
IPR015940. UBA/transl_elong_EF1B_N_euk.
[Graphical view]

Pfam

PF00300. His_Phos_1. 1 hit.
PF00627. UBA. 1 hit.
[Graphical view]

SMART

SM00326. SH3. 1 hit.
SM00165. UBA. 1 hit.
[Graphical view]

SUPFAM

SSF50044. SH3. 1 hit.
SSF46934. UBA_like. 1 hit.

PROSITE

PS50002. SH3. 1 hit.
PS50030. UBA. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q8BGG7.

NextBio

337005.

SOURCE

Search...

Entry information

Entry name

UBS3B_MOUSE

Accession

Primary (citable) accession number: Q8BGG7
Secondary accession number(s): Q3U8Z2, Q8BMW9

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 11, 2006
Last sequence update:	March 1, 2003
Last modified:	April 3, 2013
This is version 89 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program