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Protein

Signal transducing adapter molecule 1

Gene

STAM

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

  • SH3/SH2 adaptor activity Source: ProtInc
  • ubiquitin-like protein ligase binding Source: UniProtKB

GO - Biological processi

  • endosomal transport Source: Reactome
  • intracellular protein transport Source: InterPro
  • macroautophagy Source: ParkinsonsUK-UCL
  • membrane organization Source: Reactome
  • multivesicular body assembly Source: ParkinsonsUK-UCL
  • negative regulation of epidermal growth factor receptor signaling pathway Source: Reactome
  • positive regulation of exosomal secretion Source: UniProtKB
  • protein deubiquitination Source: Reactome
  • regulation of extracellular exosome assembly Source: UniProtKB
  • signal transduction Source: ProtInc

Keywordsi

Biological processProtein transport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-182971 EGFR downregulation
R-HSA-5689901 Metalloprotease DUBs
R-HSA-6807004 Negative regulation of MET activity
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828 Clathrin-mediated endocytosis
R-HSA-8875360 InlB-mediated entry of Listeria monocytogenes into host cell
R-HSA-917729 Endosomal Sorting Complex Required For Transport (ESCRT)
SignaLinkiQ92783
SIGNORiQ92783

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
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000136738.14
HGNCiHGNC:11357 STAM
MIMi601899 gene
neXtProtiNX_Q92783

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endosome, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi8027
OpenTargetsiENSG00000136738
PharmGKBiPA36179

Polymorphism and mutation databases

BioMutaiSTAM
DMDMi71153545

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved2 Publications
ChainiPRO_00001901452 – 540Signal transducing adapter molecule 1Add BLAST539

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei156PhosphoserineCombined sources1
Modified residuei198Phosphotyrosine1 Publication1
Cross-linki276Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei381Phosphotyrosine1 Publication1
Modified residuei384Phosphotyrosine1 Publication1

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
Ubiquitinated by ITCH.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ92783
MaxQBiQ92783
PaxDbiQ92783
PeptideAtlasiQ92783
PRIDEiQ92783

PTM databases

iPTMnetiQ92783
PhosphoSitePlusiQ92783
SwissPalmiQ92783

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Gene expression databases

BgeeiENSG00000136738
CleanExiHS_STAM
ExpressionAtlasiQ92783 baseline and differential
GenevisibleiQ92783 HS

Organism-specific databases

HPAiCAB034399
HPA043882

Interactioni

Subunit structurei

Component of the ESCRT-0 complex composed of STAM or STAM2 and HGS (PubMed:11687594, PubMed:9407053, PubMed:19278655). Probably part of a complex at least composed of HSG, STAM and EPS15 (PubMed:12551915). Found in a complex with HGS and E3 ligase ITCH and DTX3L (PubMed:24790097). Interacts with E3 ligase DTX3L; the interaction brings together STAM and HSG, promotes their recruitment to early endosomes and decreases STAM and HGS ubiquitination by ITCH (PubMed:24790097). Interacts with STAMBP/AMSH (PubMed:10383417). Interacts with PDGFRB (PubMed:20494825). Interacts with LITAF; the interaction is direct (PubMed:23166352). Identified in a complex with HGS and LITAF (PubMed:23166352).9 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • SH3/SH2 adaptor activity Source: ProtInc
  • ubiquitin-like protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi113722, 69 interactors
CORUMiQ92783
DIPiDIP-37761N
IntActiQ92783, 17 interactors
MINTiQ92783
STRINGi9606.ENSP00000366746

Structurei

Secondary structure

1540
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi10 – 16Combined sources7
Beta strandi21 – 23Combined sources3
Helixi26 – 36Combined sources11
Helixi42 – 54Combined sources13
Helixi59 – 75Combined sources17
Helixi78 – 84Combined sources7
Helixi87 – 99Combined sources13
Helixi102 – 119Combined sources18
Helixi123 – 125Combined sources3
Helixi127 – 137Combined sources11
Beta strandi213 – 219Combined sources7
Beta strandi236 – 244Combined sources9
Beta strandi247 – 251Combined sources5
Beta strandi256 – 258Combined sources3
Beta strandi264 – 266Combined sources3
Helixi304 – 315Combined sources12
Helixi327 – 375Combined sources49

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiQ92783

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini16 – 143VHSPROSITE-ProRule annotationAdd BLAST128
Domaini171 – 190UIMPROSITE-ProRule annotationAdd BLAST20
Domaini210 – 269SH3PROSITE-ProRule annotationAdd BLAST60
Domaini370 – 387ITAMAdd BLAST18

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

Keywords - Domaini

SH3 domain

Phylogenomic databases

eggNOGiKOG2199 Eukaryota
ENOG410XTSY LUCA
GeneTreeiENSGT00870000136415
HOGENOMiHOG000231952
HOVERGENiHBG053175
InParanoidiQ92783
KOiK04705
OMAiGIMEQAY
OrthoDBiEOG091G0H1Y
PhylomeDBiQ92783
TreeFamiTF315007

Family and domain databases

CDDicd11964 SH3_STAM1, 1 hit
Gene3Di1.25.40.90, 1 hit
InterProiView protein in InterPro
IPR008942 ENTH_VHS
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
IPR035657 STAM1_SH3
IPR003903 UIM_dom
IPR002014 VHS_dom
PfamiView protein in Pfam
PF00018 SH3_1, 1 hit
PF02809 UIM, 1 hit
PF00790 VHS, 1 hit
PRINTSiPR00452 SH3DOMAIN
SMARTiView protein in SMART
SM00326 SH3, 1 hit
SM00288 VHS, 1 hit
SUPFAMiSSF48464 SSF48464, 1 hit
SSF50044 SSF50044, 1 hit
PROSITEiView protein in PROSITE
PS50002 SH3, 1 hit
PS50330 UIM, 1 hit
PS50179 VHS, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti267D → Y in AAH30586 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_036348212G → D in a colorectal cancer sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_014846392 – 403YYMQS…VSGSQ → GSGPTIRKPSPS in isoform 2. 1 PublicationAdd BLAST12
Alternative sequenceiVSP_014847404 – 540Missing in isoform 2. 1 PublicationAdd BLAST137

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.3 human [Q92783-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSTAM1_HUMAN
AccessioniPrimary (citable) accession number: Q92783
Secondary accession number(s): B0YJ99, D3DRU5, Q8N6D9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2005
Last sequence update: January 23, 2007
Last modified: March 28, 2018
This is version 166 of the entry and version 3 of the sequence. See 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health