O75886 (STAM2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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

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	525 AA.
Sequence status	Complete.
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 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 By similarity. Interacts (via the via the PxVxL motif) with CBX5; the interaction is direct. Interacts with VPS37C. Interacts with ubiquitin; the interaction is direct. Ref.1 Ref.7 Ref.9 Ref.10
Subcellular location	Cytoplasm By similarity. Early endosome membrane; Peripheral membrane protein; Cytoplasmic side Ref.7.
Tissue specificity	Ubiquitously expressed. Ref.1
Domain	The VHS and UIM domains mediate the interaction with ubiquitinated proteins. The SH3 domain mediates the interaction with USP8. 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.
Post-translational modification	Phosphorylated in response to IL-2, GM-CSF, EGF and PDGF.
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 Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular membrane organization Traceable author statement. Source: Reactome endosomal transport Traceable author statement. Source: Reactome epidermal growth factor receptor signaling pathway Traceable author statement. Source: Reactome intracellular protein transport Inferred from electronic annotation. Source: InterPro negative regulation of epidermal growth factor receptor signaling pathway Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome early endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay. Source: HPA
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RIN1	Q13671	4	EBI-373258,EBI-366017
STAMBP	O95630	3	EBI-373258,EBI-396676

Alternative products

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

Isoform 1 (identifier: O75886-1)

Also known as: STAM2A;

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: O75886-2)

Also known as: STAM2B;

The sequence of this isoform differs from the canonical sequence as follows:
     343-525: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 525

525

Signal transducing adapter molecule 2

PRO_0000190147

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 By similarity

Region

334 – 368

35

Interaction with HGS By similarity

Motif

54 – 67

14

PxVxL motif

Amino acid modifications

Modified residue

374

1

Phosphotyrosine By similarity

Natural variations

Alternative sequence

343 – 525

183

Missing in isoform 2.

VSP_014848

Experimental info

Sequence conflict

81 – 83

3

HLE → RLG in CAB63735. Ref.2

Sequence conflict

254

1

N → D in CAB63735. Ref.2

Sequence conflict

266

1

A → V in CAB63735. Ref.2

Secondary structure

1

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525

Helix Strand Turn

Details...

Helix

10 – 16

7

Helix

26 – 38

13

Beta strand

39 – 41

3

Helix

42 – 54

13

Helix

59 – 75

17

Helix

78 – 84

7

Helix

87 – 98

12

Helix

103 – 119

17

Turn

120 – 122

3

Turn

124 – 126

3

Helix

127 – 137

11

Turn

138 – 140

3

Beta strand

205 – 211

7

Beta strand

217 – 219

3

Beta strand

228 – 233

6

Beta strand

237 – 244

8

Beta strand

247 – 251

5

Helix

253 – 255

3

Beta strand

256 – 258

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (STAM2A) [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 408D484544DD9403	FASTA	525	58,164
	10 20 30 40 50 60 MPLFTANPFE QDVEKATNEY NTTEDWSLIM DICDKVGSTP NGAKDCLKAI MKRVNHKVPH 70 80 90 100 110 120 VALQALTLLG ACVANCGKIF HLEVCSRDFA TEVRAVIKNK AHPKVCEKLK SLMVEWSEEF 130 140 150 160 170 180 QKDPQFSLIS ATIKSMKEEG ITFPPAGSQT VSAAAKNGTS SNKNKEDEDI AKAIELSLQE 190 200 210 220 230 240 QKQQHTETKS LYPSSEIQLN NKVARKVRAL YDFEAVEDNE LTFKHGEIII VLDDSDANWW 250 260 270 280 290 300 KGENHRGIGL FPSNFVTTNL NIETEAAAVD KLNVIDDDVE EIKKSEPEPV YIDEDKMDRA 310 320 330 340 350 360 LQVLQSIDPT DSKPDSQDLL DLEDICQQMG PMIDEKLEEI DRKHSELSEL NVKVLEALEL 370 380 390 400 410 420 YNKLVNEAPV YSVYSKLHPP AHYPPASSGV PMQTYPVQSH GGNYMGQSIH QVTVAQSYSL 430 440 450 460 470 480 GPDQIGPLRS LPPNVNSSVT AQPAQTSYLS TGQDTVSNPT YMNQNSNLQS ATGTTAYTQQ 490 500 510 520 MGMSVDMSSY QNTTSNLPQL AGFPVTVPAH PVAQQHTNYH QQPLL
	Isoform 2 (STAM2B) [UniParc]. Checksum: E54540C48B6CD1B3	FASTA	342	38,370
	10 20 30 40 50 60 MPLFTANPFE QDVEKATNEY NTTEDWSLIM DICDKVGSTP NGAKDCLKAI MKRVNHKVPH 70 80 90 100 110 120 VALQALTLLG ACVANCGKIF HLEVCSRDFA TEVRAVIKNK AHPKVCEKLK SLMVEWSEEF 130 140 150 160 170 180 QKDPQFSLIS ATIKSMKEEG ITFPPAGSQT VSAAAKNGTS SNKNKEDEDI AKAIELSLQE 190 200 210 220 230 240 QKQQHTETKS LYPSSEIQLN NKVARKVRAL YDFEAVEDNE LTFKHGEIII VLDDSDANWW 250 260 270 280 290 300 KGENHRGIGL FPSNFVTTNL NIETEAAAVD KLNVIDDDVE EIKKSEPEPV YIDEDKMDRA 310 320 330 340 LQVLQSIDPT DSKPDSQDLL DLEDICQQMG PMIDEKLEEI DR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"STAM2, a new member of the STAM family, binding to the Janus kinases." Endo K., Takeshita T., Kasai H., Sasaki Y., Tanaka N., Asao H., Kikuchi K., Yamada M., Chenb M., O'Shea J.J., Sugamura K. FEBS Lett. 477:55-61(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, INTERACTION WITH JAK2 AND JAK3. Tissue: Fetal brain.
[2]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[3]	"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] (ISOFORM 1). Tissue: Testis and Trachea.
[4]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	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].
[6]	"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.
[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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HGS AND UBIQUITIN, IDENTIFICATION IN A COMPLEX WITH HSG AND EPS15, SUBCELLULAR LOCATION.
[8]	"Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry." Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C. Anal. Chem. 76:2763-2772(2004) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[9]	"The mammalian heterochromatin protein 1 binds diverse nuclear proteins through a common motif that targets the chromoshadow domain." Lechner M.S., Schultz D.C., Negorev D., Maul G.G., Rauscher F.J. III Biochem. Biophys. Res. Commun. 331:929-937(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CBX5.
[10]	"Identification of human VPS37C, a component of endosomal sorting complex required for transport-I important for viral budding." Eastman S.W., Martin-Serrano J., Chung W., Zang T., Bieniasz P.D. J. Biol. Chem. 280:628-636(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH VPS37C.
[11]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]	"The solution structure of the VHS and SH3 domains of human signal transducing adaptor molecule 2." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 1-269.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF042273 mRNA. Translation: AAC63963.1.
AF042274 mRNA. Translation: AAC63964.1.
AL133600 mRNA. Translation: CAB63735.1.
AK292265 mRNA. Translation: BAF84954.1.
AK292847 mRNA. Translation: BAF85536.1.
AC079790 Genomic DNA. Translation: AAY14712.1.
CH471058 Genomic DNA. Translation: EAX11490.1.
CH471058 Genomic DNA. Translation: EAX11492.1.
BC028740 mRNA. Translation: AAH28740.1.

IPI

IPI00290542.
IPI00607771.

PIR

T43437.

RefSeq

NP_005834.4. NM_005843.4.

UniGene

Hs.17200.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1X2Q	NMR	-	A	195-269	[»]
1X5B	NMR	-	A	1-150	[»]
2L0T	NMR	-	B	1-150	[»]

ProteinModelPortal

O75886.

ModBase

Search...

Protein-protein interaction databases

IntAct

O75886. 14 interactions.

MINT

MINT-145850.

STRING

9606.ENSP00000263904.

PTM databases

PhosphoSite

O75886.

Proteomic databases

PaxDb

O75886.

PRIDE

O75886.

Protocols and materials databases

DNASU

10254.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000263904; ENSP00000263904; ENSG00000115145.

GeneID

10254.

KEGG

hsa:10254.

UCSC

uc002tyc.4. human.

Organism-specific databases

CTD

10254.

GeneCards

GC02M152939.

HGNC

HGNC:11358. STAM2.

HPA

HPA035528.
HPA035529.

MIM

606244. gene.

neXtProt

NX_O75886.

PharmGKB

PA36180.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG309509.

HOGENOM

HOG000231952.

HOVERGEN

HBG053175.

InParanoid

O75886.

KO

K04705.

OMA

QHTETKS.

OrthoDB

EOG4GTKCN.

PhylomeDB

O75886.

Enzyme and pathway databases

Pathway_Interaction_DB

il2_1pathway. IL2-mediated signaling events.

Reactome

REACT_111102. Signal Transduction.
REACT_11123. Membrane Trafficking.
REACT_116125. Disease.

Gene expression databases

Bgee

O75886.

CleanEx

HS_STAM2.

Genevestigator

O75886.

GermOnline

ENSG00000115145. Homo sapiens.

Family and domain databases

Gene3D

1.25.40.90. 1 hit.

InterPro

IPR008942. ENTH_VHS.
IPR000108. p67phox.
IPR001452. SH3_domain.
IPR003903. Ubiquitin-int_motif.
IPR002014. VHS.
IPR018205. VHS_subgr.
[Graphical view]

Pfam

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

PRINTS

PR00499. P67PHOX.
PR00452. SH3DOMAIN.

SMART

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

SUPFAM

SSF48464. ENTH_VHS. 1 hit.
SSF50044. SH3. 1 hit.

PROSITE

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

ProtoNet

Search...

Other

EvolutionaryTrace

O75886.

GenomeRNAi

10254.

NextBio

38856.

SOURCE

Search...

Entry information

Entry name

STAM2_HUMAN

Accession

Primary (citable) accession number: O75886
Secondary accession number(s): A8K8A0 , D3DPA1, Q7LDQ0, Q9UF58

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2005
Last sequence update:	November 1, 1998
Last modified:	May 1, 2013
This is version 127 of the entry and version 1 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.