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Protein

Signal transducing adapter molecule 1

Gene

STAM

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  1. SH3/SH2 adaptor activity Source: ProtInc

GO - Biological processi

  1. endosomal transport Source: Reactome
  2. epidermal growth factor receptor signaling pathway Source: Reactome
  3. intracellular protein transport Source: InterPro
  4. membrane organization Source: Reactome
  5. negative regulation of epidermal growth factor receptor signaling pathway Source: Reactome
  6. positive regulation of exosomal secretion Source: UniProtKB
  7. positive regulation of signal transduction Source: GOC
  8. regulation of extracellular vesicular exosome assembly Source: UniProtKB
  9. signal transduction Source: ProtInc
Complete GO annotation...

Keywords - Biological processi

Protein transport, Transport

Enzyme and pathway databases

ReactomeiREACT_12484. EGFR downregulation.
REACT_27258. Endosomal Sorting Complex Required For Transport (ESCRT).
SignaLinkiQ92783.

Names & Taxonomyi

Protein namesi
Recommended name:
Signal transducing adapter molecule 1
Short name:
STAM-1
Gene namesi
Name:STAM
Synonyms:STAM1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 10

Organism-specific databases

HGNCiHGNC:11357. STAM.

Subcellular locationi

GO - Cellular componenti

  1. cytosol Source: Reactome
  2. early endosome membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endosome, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA36179.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed2 Publications
Chaini2 – 540539Signal transducing adapter molecule 1PRO_0000190145Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei156 – 1561Phosphoserine1 Publication
Modified residuei198 – 1981Phosphotyrosine1 Publication
Modified residuei381 – 3811Phosphotyrosine1 Publication
Modified residuei384 – 3841Phosphotyrosine1 Publication

Post-translational modificationi

Phosphorylated on Tyr-198. Phosphorylated in response to IL2, IL3, IL4, IL7, CSF2/GM-CSF, EGF and PDGFB. Phosphorylated by activated PDGFRB.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ92783.
PaxDbiQ92783.
PRIDEiQ92783.

PTM databases

PhosphoSiteiQ92783.

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Gene expression databases

BgeeiQ92783.
CleanExiHS_STAM.
ExpressionAtlasiQ92783. baseline and differential.
GenevestigatoriQ92783.

Organism-specific databases

HPAiCAB034399.
HPA043882.

Interactioni

Subunit structurei

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.6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
LCP2Q130943EBI-752333,EBI-346946
STAMBPO956306EBI-752333,EBI-396676
UBBP0CG539EBI-752333,EBI-5333021From a different organism.
UBCP0CG482EBI-752333,EBI-3390054

Protein-protein interaction databases

BioGridi113722. 56 interactions.
DIPiDIP-37761N.
IntActiQ92783. 13 interactions.
MINTiMINT-734093.
STRINGi9606.ENSP00000366746.

Structurei

Secondary structure

1
540
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi10 – 167Combined sources
Beta strandi21 – 233Combined sources
Helixi26 – 3611Combined sources
Helixi42 – 5413Combined sources
Helixi59 – 7517Combined sources
Helixi78 – 847Combined sources
Helixi87 – 9913Combined sources
Helixi102 – 11918Combined sources
Helixi123 – 1253Combined sources
Helixi127 – 13711Combined sources
Beta strandi213 – 2197Combined sources
Beta strandi236 – 2449Combined sources
Beta strandi247 – 2515Combined sources
Beta strandi256 – 2583Combined sources
Beta strandi264 – 2663Combined sources
Helixi304 – 31512Combined sources
Helixi327 – 37549Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2L0ANMR-A207-267[»]
3F1IX-ray2.30C/S301-377[»]
3LDZX-ray2.60A/B/C/D4-143[»]
ProteinModelPortaliQ92783.
SMRiQ92783. Positions 4-143, 211-267, 301-377.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ92783.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini16 – 143128VHSPROSITE-ProRule annotationAdd
BLAST
Domaini171 – 19020UIMPROSITE-ProRule annotationAdd
BLAST
Domaini210 – 26960SH3PROSITE-ProRule annotationAdd
BLAST
Domaini370 – 38718ITAMAdd
BLAST

Domaini

The VHS domain mediates high-avidity binding to Lys63-linked and Lys48-linked polyubiquitinated cargos.1 Publication

Sequence similaritiesi

Belongs to the STAM family.Curated
Contains 1 ITAM domain.Curated
Contains 1 SH3 domain.PROSITE-ProRule annotation
Contains 1 UIM (ubiquitin-interacting motif) domain.PROSITE-ProRule annotation
Contains 1 VHS domain.PROSITE-ProRule annotation

Keywords - Domaini

SH3 domain

Phylogenomic databases

eggNOGiNOG309509.
GeneTreeiENSGT00700000104139.
HOGENOMiHOG000231952.
HOVERGENiHBG053175.
InParanoidiQ92783.
KOiK04705.
OMAiPDVTIYQ.
PhylomeDBiQ92783.
TreeFamiTF315007.

Family and domain databases

Gene3Di1.25.40.90. 1 hit.
InterProiIPR008942. ENTH_VHS.
IPR001452. SH3_domain.
IPR003903. Ubiquitin-int_motif.
IPR002014. VHS.
IPR018205. VHS_subgr.
[Graphical view]
PfamiPF00018. SH3_1. 1 hit.
PF02809. UIM. 1 hit.
PF00790. VHS. 1 hit.
[Graphical view]
PRINTSiPR00452. SH3DOMAIN.
SMARTiSM00326. SH3. 1 hit.
SM00726. UIM. 1 hit.
SM00288. VHS. 1 hit.
[Graphical view]
SUPFAMiSSF48464. SSF48464. 1 hit.
SSF50044. SSF50044. 1 hit.
PROSITEiPS50002. SH3. 1 hit.
PS50330. UIM. 1 hit.
PS50179. VHS. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q92783-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MPLFATNPFD QDVEKATSEM NTAEDWGLIL DICDKVGQSR TGPKDCLRSI
60 70 80 90 100
MRRVNHKDPH VAMQALTLLG ACVSNCGKIF HLEVCSRDFA SEVSNVLNKG
110 120 130 140 150
HPKVCEKLKA LMVEWTDEFK NDPQLSLISA MIKNLKEQGV TFPAIGSQAA
160 170 180 190 200
EQAKASPALV AKDPGTVANK KEEEDLAKAI ELSLKEQRQQ STTLSTLYPS
210 220 230 240 250
TSSLLTNHQH EGRKVRAIYD FEAAEDNELT FKAGEIITVL DDSDPNWWKG
260 270 280 290 300
ETHQGIGLFP SNFVTADLTA EPEMIKTEKK TVQFSDDVQV ETIEPEPEPA
310 320 330 340 350
FIDEDKMDQL LQMLQSTDPS DDQPDLPELL HLEAMCHQMG PLIDEKLEDI
360 370 380 390 400
DRKHSELSEL NVKVMEALSL YTKLMNEDPM YSMYAKLQNQ PYYMQSSGVS
410 420 430 440 450
GSQVYAGPPP SGAYLVAGNA QMSHLQSYSL PPEQLSSLSQ AVVPPSANPA
460 470 480 490 500
LPSQQTQAAY PNTMVSSVQG NTYPSQAPVY SPPPAATAAA ATADVTLYQN
510 520 530 540
AGPNMPQVPN YNLTSSTLPQ PGGSQQPPQP QQPYSQKALL
Length:540
Mass (Da):59,180
Last modified:January 23, 2007 - v3
Checksum:i8D6F07FAE538F36F
GO
Isoform 2 (identifier: Q92783-2) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.

Show »
Length:403
Mass (Da):44,972
Checksum:i91E858BF4FADC8B5
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti267 – 2671D → Y in AAH30586 (PubMed:15489334).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti212 – 2121G → D in a colorectal cancer sample; somatic mutation. 1 Publication
VAR_036348

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei392 – 40312YYMQS…VSGSQ → GSGPTIRKPSPS in isoform 2. 1 PublicationVSP_014846Add
BLAST
Alternative sequencei404 – 540137Missing in isoform 2. 1 PublicationVSP_014847Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS7122.1. [Q92783-1]
PIRiJC4916.
RefSeqiNP_003464.1. NM_003473.3. [Q92783-1]
UniGeneiHs.335391.

Genome annotation databases

EnsembliENST00000377524; ENSP00000366746; ENSG00000136738. [Q92783-1]
GeneIDi8027.
KEGGihsa:8027.
UCSCiuc001ipj.2. human. [Q92783-1]

Polymorphism databases

DMDMi71153545.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS7122.1. [Q92783-1]
PIRiJC4916.
RefSeqiNP_003464.1. NM_003473.3. [Q92783-1]
UniGeneiHs.335391.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2L0ANMR-A207-267[»]
3F1IX-ray2.30C/S301-377[»]
3LDZX-ray2.60A/B/C/D4-143[»]
ProteinModelPortaliQ92783.
SMRiQ92783. Positions 4-143, 211-267, 301-377.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113722. 56 interactions.
DIPiDIP-37761N.
IntActiQ92783. 13 interactions.
MINTiMINT-734093.
STRINGi9606.ENSP00000366746.

PTM databases

PhosphoSiteiQ92783.

Polymorphism databases

DMDMi71153545.

Proteomic databases

MaxQBiQ92783.
PaxDbiQ92783.
PRIDEiQ92783.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000377524; ENSP00000366746; ENSG00000136738. [Q92783-1]
GeneIDi8027.
KEGGihsa:8027.
UCSCiuc001ipj.2. human. [Q92783-1]

Organism-specific databases

CTDi8027.
GeneCardsiGC10P017686.
HGNCiHGNC:11357. STAM.
HPAiCAB034399.
HPA043882.
MIMi601899. gene.
neXtProtiNX_Q92783.
PharmGKBiPA36179.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG309509.
GeneTreeiENSGT00700000104139.
HOGENOMiHOG000231952.
HOVERGENiHBG053175.
InParanoidiQ92783.
KOiK04705.
OMAiPDVTIYQ.
PhylomeDBiQ92783.
TreeFamiTF315007.

Enzyme and pathway databases

ReactomeiREACT_12484. EGFR downregulation.
REACT_27258. Endosomal Sorting Complex Required For Transport (ESCRT).
SignaLinkiQ92783.

Miscellaneous databases

EvolutionaryTraceiQ92783.
GeneWikiiSignal_transducing_adaptor_molecule.
GenomeRNAii8027.
NextBioi30597.
PROiQ92783.
SOURCEiSearch...

Gene expression databases

BgeeiQ92783.
CleanExiHS_STAM.
ExpressionAtlasiQ92783. baseline and differential.
GenevestigatoriQ92783.

Family and domain databases

Gene3Di1.25.40.90. 1 hit.
InterProiIPR008942. ENTH_VHS.
IPR001452. SH3_domain.
IPR003903. Ubiquitin-int_motif.
IPR002014. VHS.
IPR018205. VHS_subgr.
[Graphical view]
PfamiPF00018. SH3_1. 1 hit.
PF02809. UIM. 1 hit.
PF00790. VHS. 1 hit.
[Graphical view]
PRINTSiPR00452. SH3DOMAIN.
SMARTiSM00326. SH3. 1 hit.
SM00726. UIM. 1 hit.
SM00288. VHS. 1 hit.
[Graphical view]
SUPFAMiSSF48464. SSF48464. 1 hit.
SSF50044. SSF50044. 1 hit.
PROSITEiPS50002. SH3. 1 hit.
PS50330. UIM. 1 hit.
PS50179. VHS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. 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, IDENTIFICATION BY 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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  12. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  13. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  14. "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.
  15. Cited for: VARIANT [LARGE SCALE ANALYSIS] ASP-212.

Entry informationi

Entry nameiSTAM1_HUMAN
AccessioniPrimary (citable) accession number: Q92783
Secondary accession number(s): B0YJ99, D3DRU5, Q8N6D9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2005
Last sequence update: January 23, 2007
Last modified: March 4, 2015
This is version 135 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.