Reviewed, UniProtKB/Swiss-Prot O88811 (STAM2_MOUSE)

Names and origin

Protein names

Recommended name:
    Signal transducing adapter molecule 2
      Short name=STAM-2
Alternative name(s):
    Hrs-binding protein

Gene names

Name:	Stam2
Synonyms:	Hbp

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	523 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Involved in intracellular signal transduction mediated by cytokines and growth factors. Upon IL-2 and GM-CSL stimulation, it plays a role in signaling leading to DNA synthesis and c-myc induction. May also play a role in T-cell development. Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with HGS (ESCRT-0 complex). The ESCRT-0 complex binds ubiquitin and acts as sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes By similarity.
Subunit structure	Component of the ESCRT-0 complex composed of STAM or STAM2 and HGS. Part of a complex at least composed of HSG, STAM2 and EPS15. Interacts with JAK2 and JAK3. Interacts with ubiquitinated proteins and the deubiquitinating enzyme USP8/UBPY. Interacts (via the via the PxVxL motif) with CBX5; the interaction is direct. Interacts with VPS37C. Interacts with ubiquitin; the interaction is direct By similarity.
Subcellular location	Cytoplasm. Early endosome membrane; Peripheral membrane protein; Cytoplasmic side By similarity.
Tissue specificity	Ubiquitously expressed, with highest levels in testis. Ref.1
Domain	The VHS and UIM domains mediate the interaction with ubiquitinated proteins. Ref.1 The SH3 domain mediates the interaction with USP8. Ref.1 Contains one Pro-Xaa-Val-Xaa-Leu (PxVxL) motif, which is required for interaction with chromoshadow domains. This motif requires additional residues -7, -6, +4 and +5 of the central Val which contact the chromoshadow domain. Ref.1
Post-translational modification	Phosphorylated in response to IL-2, GM-CSF, EGF and PDGF By similarity.
Disruption phenotype	Adult mice lacking Stam1 and Stam2 due to inducible gene targeting exhibit significant reduction in T-cell development in the thymus and profound reduction in the peripheral mature T-cells. Ref.6
Sequence similarities	Belongs to the STAM family. Contains 1 ITAM domain. Contains 1 SH3 domain. Contains 1 UIM (ubiquitin-interacting motif) repeat. Contains 1 VHS domain.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Cytoplasm Endosome Membrane
Coding sequence diversity	Alternative splicing
Domain	SH3 domain
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	intracellular protein transport Inferred from electronic annotation. Source: InterPro
Cellular component	endosome Inferred from electronic annotation. Source: UniProtKB-KW internal side of plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
HGS	O14964	1	EBI-2119154,EBI-740220	From a different organism.

Alternative products

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

Isoform 1 (identifier: O88811-1)

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: O88811-2)

The sequence of this isoform differs from the canonical sequence as follows:
     68-100: Missing.
     448-448: S → R
     449-523: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 523

523

Signal transducing adapter molecule 2

PRO_0000190148

Regions

Domain

16 – 144

129

VHS

Repeat

165 – 184

20

UIM

Domain

202 – 261

60

SH3

Domain

360 – 377

18

ITAM

Region

219 – 220

2

Interaction with USP8

Region

334 – 368

35

Interaction with HGS

Motif

54 – 67

14

PxVxL motif

Amino acid modifications

Modified residue

192

1

Phosphotyrosine By similarity

Modified residue

371

1

Phosphotyrosine By similarity

Modified residue

374

1

Phosphotyrosine Ref.9

Natural variations

Alternative sequence

68 – 100

33

Missing in isoform 2.

VSP_014849

Alternative sequence

448

1

S → R in isoform 2.

VSP_014850

Alternative sequence

449 – 523

75

Missing in isoform 2.

VSP_014851

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

523

Helix Strand Turn

Details...

Beta strand

205 – 211

7

Beta strand

228 – 233

6

Beta strand

236 – 244

9

Beta strand

247 – 252

6

Helix

253 – 255

3

Beta strand

256 – 258

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: CE00B59F10BA0161	FASTA	523	57,455
	10 20 30 40 50 60 MPLFTANPFE QDVEKATNEY NTTEDWSLIM DICDRVGSTP SGAKDCLKAI MKRVNHKVPH 70 80 90 100 110 120 VALQALTLLG ACVANCGKIF HLEVCSRDFA TEVRSVIKNK AHPKVCEKLK SLMVEWSEEF 130 140 150 160 170 180 QKDPQFSLIS ATIKSMKEEG VTFPSAGSQT VAAAAKNGTS LNKNKEDEDI AKAIELSLQE 190 200 210 220 230 240 QKQQYTETKA LYPPAESQLN NKAARRVRAL YDFEAVEDNE LTFKHGELIT VLDDSDANWW 250 260 270 280 290 300 QGENHRGTGL FPSNFVTTDL STEVETATVD KLNVIDDDVE EIKKSEPEPV YIDEGKMDRA 310 320 330 340 350 360 LQILQSIDPK ESKPDSQDLL DLEDVCQQMG PMIDEKLEEI DRKHSELSEL NVKVLEALDL 370 380 390 400 410 420 YNKLVNEAPV YSVYSKLHPA HYPPAAAGVP VQTYPVQSHG GNYLGHGIHQ VSVAQNYNLG 430 440 450 460 470 480 PDPMGSLRSL PPNMNSVTAH TVQPPYLSTG QDTVSNPSYM NQSSRLQAAA GTAAYTQPVG 490 500 510 520 MSTDVSSFQN TASGLPQLAG FPVAVPAPVA AQPQASYHQQ PLL
	Isoform 2. Checksum: 305B94A59C0CA08B	FASTA	415	46,260
	10 20 30 40 50 60 MPLFTANPFE QDVEKATNEY NTTEDWSLIM DICDRVGSTP SGAKDCLKAI MKRVNHKVPH 70 80 90 100 110 120 VALQALTAHP KVCEKLKSLM VEWSEEFQKD PQFSLISATI KSMKEEGVTF PSAGSQTVAA 130 140 150 160 170 180 AAKNGTSLNK NKEDEDIAKA IELSLQEQKQ QYTETKALYP PAESQLNNKA ARRVRALYDF 190 200 210 220 230 240 EAVEDNELTF KHGELITVLD DSDANWWQGE NHRGTGLFPS NFVTTDLSTE VETATVDKLN 250 260 270 280 290 300 VIDDDVEEIK KSEPEPVYID EGKMDRALQI LQSIDPKESK PDSQDLLDLE DVCQQMGPMI 310 320 330 340 350 360 DEKLEEIDRK HSELSELNVK VLEALDLYNK LVNEAPVYSV YSKLHPAHYP PAAAGVPVQT 370 380 390 400 410 YPVQSHGGNY LGHGIHQVSV AQNYNLGPDP MGSLRSLPPN MNSVTAHTVQ PPYLR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A hrs binding protein having a Src homology 3 domain is involved in intracellular degradation of growth factors and their receptors." Takata H., Kato M., Denda K., Kitamura N. Genes Cells 5:57-69(2000) [PubMed: 10651905] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INTERACTION WITH HGS, DOMAIN, SUBCELLULAR LOCATION. Tissue: Liver.
[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: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6J. Tissue: Lung.
[3]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed: 19468303] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6.
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: FVB/N. Tissue: Mammary tumor.
[5]	"A deubiquitinating enzyme UBPY interacts with the Src homology 3 domain of Hrs-binding protein via a novel binding motif PX(V/I)(D/N)RXXKP." Kato M., Miyazawa K., Kitamura N. J. Biol. Chem. 275:37481-37487(2000) [PubMed: 10982817] [Abstract] Cited for: INTERACTION WITH USP8.
[6]	"Signal-transducing adaptor molecules STAM1 and STAM2 are required for T-cell development and survival." Yamada M., Ishii N., Asao H., Murata K., Kanazawa C., Sasaki H., Sugamura K. Mol. Cell. Biol. 22:8648-8658(2002) [PubMed: 12446783] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[7]	"STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on early endosomes." Bache K.G., Raiborg C., Mehlum A., Stenmark H. J. Biol. Chem. 278:12513-12521(2003) [PubMed: 12551915] [Abstract] Cited for: INTERACTION WITH HGS; EPS15 AND UBIQUITIN, SUBCELLULAR LOCATION.
[8]	"STAM proteins bind ubiquitinated proteins on the early endosome via the VHS domain and ubiquitin-interacting motif." Mizuno E., Kawahata K., Kato M., Kitamura N., Komada M. Mol. Biol. Cell 14:3675-3689(2003) [PubMed: 12972556] [Abstract] Cited for: INTERACTION WITH UBIQUITIN, FUNCTION.
[9]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-374, MASS SPECTROMETRY.
[10]	"Structural insight into modest binding of a non-PXXP ligand to the signal transducing adaptor molecule-2 Src homology 3 domain." Kaneko T., Kumasaka T., Ganbe T., Sato T., Miyazawa K., Kitamura N., Tanaka N. J. Biol. Chem. 278:48162-48168(2003) [PubMed: 13129930] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 203-260 IN COMPLEX WITH USP8.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AB012611 mRNA. Translation: BAA33547.1.
AK004604 mRNA. Translation: BAB23403.1.
AK044230 mRNA. Translation: BAC31830.1.
AL928960 Genomic DNA. Translation: CAM23666.1.
BC013818 mRNA. Translation: AAH13818.1.

IPI

IPI00468418.
IPI00471128.

RefSeq

NP_062641.1.

UniGene

Mm.263639

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1UJ0	X-ray	1.70	A	204-261	[»]

SMR

O88811. Positions 1-150.

ModBase

Search...

Protein-protein interaction databases

IntAct

O88811. 1 interaction.

STRING

O88811.

PTM databases

PhosphoSite

O88811.

Proteomic databases

PRIDE

O88811.

Genome annotation databases

Ensembl

ENSMUST00000102759; ENSMUSP00000099820; ENSMUSG00000055371; Mus musculus. [Genome view]

GeneID

56324.

KEGG

mmu:56324.

UCSC

uc008jre.1. mouse.
uc008jrf.1. mouse.

Organism-specific databases

CTD

56324.

MGI

MGI:1929100. Stam2.

Phylogenomic databases

HOGENOM

O88811.

HOVERGEN

O88811.

OMA

YQNTTSN.

Gene expression databases

ArrayExpress

O88811.

Bgee

O88811.

Genevestigator

O88811.

GermOnline

ENSMUSG00000055371. Mus musculus.

Family and domain databases

InterPro

IPR008942. ENTH_VHS.
IPR000108. Neu_cyt_fact_2.
IPR001452. SH3_domain.
IPR020473. SH3_region.
IPR003903. Ubiquitin-int_motif.
IPR002014. VHS.
IPR018205. VHS_subgroup.
[Graphical view]

Gene3D

G3DSA:1.25.40.90. ENTH_VHS. 1 hit.

Pfam

PF00018. SH3_1. 1 hit.
PF02809. UIM. 1 hit.
PF00790. VHS. 1 hit.
[Graphical view]

PRINTS

PR00499. P67PHOX.
PR00452. SH3DOMAIN.

ProDom

PD000066. SH3. 1 hit.
PD003686. VHS. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00326. SH3. 1 hit.
SM00726. UIM. 1 hit.
SM00288. VHS. 1 hit.
[Graphical view]

PROSITE

PS51055. ITAM_1. False negative.
PS50002. SH3. 1 hit.
PS50330. UIM. 1 hit.
PS50179. VHS. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

312298.

SOURCE

Search...

Entry information

Entry name

STAM2_MOUSE

Accession

Primary (citable) accession number: O88811
Secondary accession number(s): A2AU00, Q8C8Y4

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2005
Last sequence update:	November 1, 1998
Last modified:	November 3, 2009
This is version 84 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)