Q92783 (STAM1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Signal transducing adapter molecule 1
Short name=STAM-1

Gene names

Name:	STAM
Synonyms:	STAM1

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	540 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
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.
Subunit structure	Component of the ESCRT-0 complex composed of STAM or STAM2 and HGS. Probably part of a complex at least composed of HSG, STAM and EPS15. Interacts with STAMBP/AMSH. Interacts with PDGFRB. Ref.5 Ref.6 Ref.7 Ref.8 Ref.10 Ref.13
Subcellular location	Cytoplasm Probable. Early endosome membrane; Peripheral membrane protein; Cytoplasmic side Probable.
Tissue specificity	Ubiquitously expressed. Ref.1
Domain	The VHS domain mediates high-avidity binding to Lys63-linked and Lys48-linked polyubiquitinated cargos. Ref.13
Post-translational modification	Phosphorylated on Tyr-198. Phosphorylated in response to IL2, IL3, IL4, IL7, CSF2/GM-CSF, EGF and PDGFB. Phosphorylated by activated PDGFRB. Ref.5 Ref.10
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 Polymorphism
Domain	SH3 domain
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing 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
Molecular_function	SH3/SH2 adaptor activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
STAMBP	O95630	3	EBI-752333,EBI-396676

Alternative products

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

Isoform 1 (identifier: Q92783-1)

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: Q92783-2)

The sequence of this isoform differs from the canonical sequence as follows:
     392-403: YYMQSSGVSGSQ → GSGPTIRKPSPS
     404-540: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.1 Ref.5

Chain

2 – 540

539

Signal transducing adapter molecule 1

PRO_0000190145

Regions

Domain

16 – 143

128

VHS

Repeat

171 – 190

20

UIM

Domain

210 – 269

60

SH3

Domain

370 – 387

18

ITAM

Amino acid modifications

Modified residue

156

1

Phosphoserine Ref.11

Modified residue

198

1

Phosphotyrosine Ref.5

Modified residue

381

1

Phosphotyrosine

Modified residue

384

1

Phosphotyrosine

Natural variations

Alternative sequence

392 – 403

12

YYMQS…VSGSQ → GSGPTIRKPSPS in isoform 2.

VSP_014846

Alternative sequence

404 – 540

137

Missing in isoform 2.

VSP_014847

Natural variant

212

1

G → D in a colorectal cancer sample; somatic mutation. Ref.14

VAR_036348

Experimental info

Sequence conflict

267

1

D → Y in AAH30586. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

540

Helix Strand Turn

Details...

Helix

10 – 16

7

Beta strand

21 – 23

3

Helix

26 – 36

11

Helix

42 – 54

13

Helix

59 – 75

17

Helix

78 – 84

7

Helix

87 – 99

13

Helix

102 – 119

18

Helix

123 – 125

3

Helix

127 – 137

11

Beta strand

213 – 219

7

Beta strand

236 – 244

9

Beta strand

247 – 251

5

Beta strand

256 – 258

3

Beta strand

264 – 266

3

Helix

304 – 315

12

Helix

327 – 375

49

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 8D6F07FAE538F36F	FASTA	540	59,180
	10 20 30 40 50 60 MPLFATNPFD QDVEKATSEM NTAEDWGLIL DICDKVGQSR TGPKDCLRSI MRRVNHKDPH 70 80 90 100 110 120 VAMQALTLLG ACVSNCGKIF HLEVCSRDFA SEVSNVLNKG HPKVCEKLKA LMVEWTDEFK 130 140 150 160 170 180 NDPQLSLISA MIKNLKEQGV TFPAIGSQAA EQAKASPALV AKDPGTVANK KEEEDLAKAI 190 200 210 220 230 240 ELSLKEQRQQ STTLSTLYPS TSSLLTNHQH EGRKVRAIYD FEAAEDNELT FKAGEIITVL 250 260 270 280 290 300 DDSDPNWWKG ETHQGIGLFP SNFVTADLTA EPEMIKTEKK TVQFSDDVQV ETIEPEPEPA 310 320 330 340 350 360 FIDEDKMDQL LQMLQSTDPS DDQPDLPELL HLEAMCHQMG PLIDEKLEDI DRKHSELSEL 370 380 390 400 410 420 NVKVMEALSL YTKLMNEDPM YSMYAKLQNQ PYYMQSSGVS GSQVYAGPPP SGAYLVAGNA 430 440 450 460 470 480 QMSHLQSYSL PPEQLSSLSQ AVVPPSANPA LPSQQTQAAY PNTMVSSVQG NTYPSQAPVY 490 500 510 520 530 540 SPPPAATAAA ATADVTLYQN AGPNMPQVPN YNLTSSTLPQ PGGSQQPPQP QQPYSQKALL
	Isoform 2 [UniParc]. Checksum: 91E858BF4FADC8B5	FASTA	403	44,972
	10 20 30 40 50 60 MPLFATNPFD QDVEKATSEM NTAEDWGLIL DICDKVGQSR TGPKDCLRSI MRRVNHKDPH 70 80 90 100 110 120 VAMQALTLLG ACVSNCGKIF HLEVCSRDFA SEVSNVLNKG HPKVCEKLKA LMVEWTDEFK 130 140 150 160 170 180 NDPQLSLISA MIKNLKEQGV TFPAIGSQAA EQAKASPALV AKDPGTVANK KEEEDLAKAI 190 200 210 220 230 240 ELSLKEQRQQ STTLSTLYPS TSSLLTNHQH EGRKVRAIYD FEAAEDNELT FKAGEIITVL 250 260 270 280 290 300 DDSDPNWWKG ETHQGIGLFP SNFVTADLTA EPEMIKTEKK TVQFSDDVQV ETIEPEPEPA 310 320 330 340 350 360 FIDEDKMDQL LQMLQSTDPS DDQPDLPELL HLEAMCHQMG PLIDEKLEDI DRKHSELSEL 370 380 390 400 NVKVMEALSL YTKLMNEDPM YSMYAKLQNQ PGSGPTIRKP SPS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of a novel signal-transducing adaptor molecule containing an SH3 domain and ITAM." Takeshita T., Arita T., Asao H., Tanaka N., Higuchi M., Kuroda H., Kaneko K., Munakata H., Endo Y., Fujita T., Sugamura K. Biochem. Biophys. Res. Commun. 225:1035-1039(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 2-15; 110-119; 137-154; 215-223; 233-247 AND 364-373, TISSUE SPECIFICITY. Tissue: T-cell.
[2]	NHLBI resequencing and genotyping service (RS&G) Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	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].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[5]	"Tyrosine phosphorylation mapping of the epidermal growth factor receptor signaling pathway." Steen H., Kuster B., Fernandez M., Pandey A., Mann M. J. Biol. Chem. 277:1031-1039(2002) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 189-213, INTERACTION WITH HGS, CLEAVAGE OF INITIATOR METHIONINE, PHOSPHORYLATION AT TYR-198, MASS SPECTROMETRY.
[6]	"Hrs is associated with STAM, a signal-transducing adaptor molecule. Its suppressive effect on cytokine-induced cell growth." Asao H., Sasaki Y., Arita T., Tanaka N., Endo K., Kasai H., Takeshita T., Endo Y., Fujita T., Sugamura K. J. Biol. Chem. 272:32785-32791(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HGS.
[7]	"Possible involvement of a novel STAM-associated molecule 'AMSH' in intracellular signal transduction mediated by cytokines." Tanaka N., Kaneko K., Asao H., Kasai H., Endo Y., Fujita T., Takeshita T., Sugamura K. J. Biol. Chem. 274:19129-19135(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH STAMBP.
[8]	"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, IDENTIFICATION IN A COMPLEX WITH HGS AND EPS15.
[9]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[10]	"Mutation of tyrosine residue 857 in the PDGF beta-receptor affects cell proliferation but not migration." Wardega P., Heldin C.H., Lennartsson J. Cell. Signal. 22:1363-1368(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION, INTERACTION WITH PDGFRB.
[11]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-156, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"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].
[13]	"VHS domains of ESCRT-0 cooperate in high-avidity binding to polyubiquitinated cargo." Ren X., Hurley J.H. EMBO J. 29:1045-1054(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 4-143 IN COMPLEX WITH UBIQUITIN, DOMAIN VHS, SUBUNIT.
[14]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ASP-212.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U43899 mRNA. Translation: AAC50734.1.
EF445033 Genomic DNA. Translation: ACA06077.1.
EF445033 Genomic DNA. Translation: ACA06078.1.
CH471072 Genomic DNA. Translation: EAW86207.1.
CH471072 Genomic DNA. Translation: EAW86209.1.
BC030586 mRNA. Translation: AAH30586.1.

IPI

IPI00020178.
IPI00607769.

PIR

JC4916.

RefSeq

NP_003464.1. NM_003473.3.

UniGene

Hs.335391.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2L0A	NMR	-	A	207-267	[»]
3F1I	X-ray	2.30	C/S	301-377	[»]
3LDZ	X-ray	2.60	A/B/C/D	4-143	[»]

ProteinModelPortal

Q92783.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-37761N.

IntAct

Q92783. 4 interactions.

MINT

MINT-734093.

STRING

9606.ENSP00000366746.

PTM databases

PhosphoSite

Q92783.

Polymorphism databases

DMDM

71153545.

Proteomic databases

PaxDb

Q92783.

PRIDE

Q92783.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000377524; ENSP00000366746; ENSG00000136738.
ENST00000565101; ENSP00000456885; ENSG00000260045.

GeneID

8027.

KEGG

hsa:8027.

UCSC

uc001ipj.2. human.

Organism-specific databases

CTD

8027.

GeneCards

GC10P017686.

HGNC

HGNC:11357. STAM.

HPA

CAB034399.

MIM

601899. gene.

neXtProt

NX_Q92783.

PharmGKB

PA36179.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG309509.

HOGENOM

HOG000231952.

HOVERGEN

HBG053175.

InParanoid

Q92783.

KO

K04705.

OMA

VAGSAQM.

OrthoDB

EOG4HT8S1.

PhylomeDB

Q92783.

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

ArrayExpress

Q92783.

Bgee

Q92783.

CleanEx

HS_STAM.

Genevestigator

Q92783.

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

Q92783.

GenomeRNAi

8027.

NextBio

30597.

SOURCE

Search...

Entry information

Entry name

STAM1_HUMAN

Accession

Primary (citable) accession number: Q92783
Secondary accession number(s): B0YJ99, D3DRU5, Q8N6D9

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2005
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 115 of the entry and version 3 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.