Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

STAM-binding protein

Gene

STAMBP

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

Functioni

Zinc metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains. Does not cleave 'Lys-48'-linked polyubiquitin chains (By similarity). Plays a role in signal transduction for cell growth and MYC induction mediated by IL-2 and GM-CSF. Potentiates BMP (bone morphogenetic protein) signaling by antagonizing the inhibitory action of SMAD6 and SMAD7. Has a key role in regulation of cell surface receptor-mediated endocytosis and ubiquitin-dependent sorting of receptors to lysosomes. Endosomal localization of STAMBP is required for efficient EGFR degradation but not for its internalization (By similarity). Involved in the negative regulation of PI3K-AKT-mTOR and RAS-MAP signaling pathways.By similarity5 Publications

Cofactori

Zn2+By similarityNote: Binds 2 Zn2+ ions per subunit.By similarity

Enzyme regulationi

Inhibited by N-ethylmaleimide.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei280Indirect zinc-bindingBy similarity1
Metal bindingi335Zinc 1; catalyticBy similarity1
Metal bindingi337Zinc 1; catalyticBy similarity1
Metal bindingi348Zinc 1; catalyticBy similarity1
Metal bindingi350Zinc 2By similarity1
Metal bindingi390Zinc 2By similarity1
Metal bindingi396Zinc 2By similarity1
Metal bindingi398Zinc 2By similarity1

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • metallopeptidase activity Source: UniProtKB-KW
  • protein domain specific binding Source: UniProtKB
  • thiol-dependent ubiquitin-specific protease activity Source: MGI

GO - Biological processi

  • JAK-STAT cascade Source: ProtInc
  • mitotic cytokinesis Source: MGI
  • negative regulation of neuron apoptotic process Source: Ensembl
  • negative regulation of phosphatidylinositol 3-kinase signaling Source: UniProtKB
  • negative regulation of Ras protein signal transduction Source: UniProtKB
  • positive regulation of cell proliferation Source: ProtInc
  • protein deubiquitination Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:HS04762-MONOMER.
ReactomeiR-HSA-5689901. Metalloprotease DUBs.
SignaLinkiO95630.
SIGNORiO95630.

Protein family/group databases

MEROPSiM67.006.

Names & Taxonomyi

Protein namesi
Recommended name:
STAM-binding protein (EC:3.4.19.-)
Alternative name(s):
Associated molecule with the SH3 domain of STAM
Endosome-associated ubiquitin isopeptidase
Gene namesi
Name:STAMBP
Synonyms:AMSH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:16950. STAMBP.

Subcellular locationi

GO - Cellular componenti

  • cleavage furrow Source: MGI
  • cytoplasm Source: HPA
  • early endosome Source: UniProtKB-SubCell
  • extracellular exosome Source: UniProtKB
  • nucleoplasm Source: HPA
  • nucleus Source: ProtInc
  • plasma membrane Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endosome, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

Microcephaly-capillary malformation syndrome (MICCAP)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA congenital disorder characterized by severe progressive microcephaly, early-onset refractory epilepsy, profound developmental delay, and multiple small capillary malformations spread diffusely on the body. Additional more variable features include dysmorphic facial features, distal limb abnormalities, and mild heart defects.
See also OMIM:614261
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06980614R → P in MICCAP. 1 Publication1
Natural variantiVAR_06980738R → C in MICCAP. 1 PublicationCorresponds to variant rs143739249dbSNPEnsembl.1
Natural variantiVAR_06980842E → G in MICCAP. 1 PublicationCorresponds to variant rs397509387dbSNPEnsembl.1
Natural variantiVAR_06980963Y → C in MICCAP. 1 PublicationCorresponds to variant rs781694797dbSNPEnsembl.1
Natural variantiVAR_069810100F → Y in MICCAP. 1 PublicationCorresponds to variant rs397514697dbSNPEnsembl.1
Natural variantiVAR_069811313T → I in MICCAP. 1 PublicationCorresponds to variant rs202100019dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi348D → A: Promotes accumulation of ubiquitin on endosomes, ablates enzymatic activity toward polyubiquitin substrate and allows ubiquitinated STAM stabilization. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi10617.
MalaCardsiSTAMBP.
MIMi614261. phenotype.
OpenTargetsiENSG00000124356.
Orphaneti294016. Microcephaly-capillary malformation syndrome.
PharmGKBiPA134955569.

Polymorphism and mutation databases

BioMutaiSTAMBP.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001948691 – 424STAM-binding proteinAdd BLAST424

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2PhosphoserineCombined sources1 Publication1
Modified residuei48Phosphoserine1 Publication1
Modified residuei243PhosphoserineCombined sources1 Publication1
Modified residuei245Phosphoserine1 Publication1
Modified residuei247PhosphoserineCombined sources1 Publication1

Post-translational modificationi

Phosphorylated after BMP type I receptor activation.1 Publication
Ubiquitinated by SMURF2 in the presence of RNF11.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO95630.
MaxQBiO95630.
PaxDbiO95630.
PeptideAtlasiO95630.
PRIDEiO95630.

2D gel databases

REPRODUCTION-2DPAGEIPI00007943.

PTM databases

iPTMnetiO95630.
PhosphoSitePlusiO95630.

Expressioni

Tissue specificityi

Ubiquitously expressed.

Gene expression databases

BgeeiENSG00000124356.
CleanExiHS_STAMBP.
ExpressionAtlasiO95630. baseline and differential.
GenevisibleiO95630. HS.

Organism-specific databases

HPAiHPA035800.

Interactioni

Subunit structurei

Interacts with STAM. Interacts with SMAD6 and SMAD7. Interacts with CHMP3; the interaction appears to relieve the autoinhibition of CHMP3. Interacts with SMURF2 and RNF11; this interaction promotes ubiquitination.6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CHMP1AQ9HD426EBI-396676,EBI-1057156
CHMP1BQ7LBR115EBI-396676,EBI-2118090
CHMP3Q9Y3E719EBI-396676,EBI-2118119
CHMP4BQ9H4443EBI-396676,EBI-749627
CHMP5Q9NZZ32EBI-396676,EBI-751303
GRB2P629939EBI-396676,EBI-401755
RNF11Q9Y3C52EBI-396676,EBI-396669
SMAD6O43541-22EBI-396676,EBI-4324970
STAMQ927837EBI-396676,EBI-752333
STAM2O758864EBI-396676,EBI-373258

GO - Molecular functioni

  • protein domain specific binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115863. 64 interactors.
DIPiDIP-33062N.
IntActiO95630. 40 interactors.
MINTiMINT-96921.
STRINGi9606.ENSP00000344742.

Structurei

Secondary structure

1424
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi11 – 22Combined sources12
Helixi33 – 53Combined sources21
Helixi56 – 71Combined sources16
Helixi74 – 76Combined sources3
Turni78 – 82Combined sources5
Helixi88 – 97Combined sources10
Helixi99 – 137Combined sources39
Beta strandi257 – 260Combined sources4
Helixi263 – 276Combined sources14
Beta strandi282 – 290Combined sources9
Beta strandi293 – 301Combined sources9
Beta strandi304 – 306Combined sources3
Beta strandi311 – 313Combined sources3
Helixi316 – 326Combined sources11
Beta strandi329 – 336Combined sources8
Beta strandi338 – 340Combined sources3
Helixi346 – 358Combined sources13
Beta strandi363 – 368Combined sources6
Turni369 – 372Combined sources4
Beta strandi373 – 379Combined sources7
Helixi381 – 389Combined sources9
Beta strandi404 – 407Combined sources4
Beta strandi409 – 414Combined sources6
Beta strandi419 – 422Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2XZEX-ray1.75A/B1-146[»]
3RZUX-ray2.50A/B/C/D/E/F/G243-424[»]
3RZVX-ray1.67A219-424[»]
ProteinModelPortaliO95630.
SMRiO95630.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini252 – 361MPNAdd BLAST110

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 127Interaction with CHMP3Add BLAST127
Regioni227 – 231Interaction with STAM5

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi335 – 348JAMM motifAdd BLAST14

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi104 – 177Glu-richAdd BLAST74

Domaini

The JAMM motif is essential for the protease activity.By similarity

Sequence similaritiesi

Belongs to the peptidase M67C family.Curated
Contains 1 MPN (JAB/Mov34) domain.Curated

Phylogenomic databases

eggNOGiKOG2880. Eukaryota.
COG1310. LUCA.
GeneTreeiENSGT00390000015439.
HOGENOMiHOG000195792.
HOVERGENiHBG058519.
InParanoidiO95630.
KOiK11866.
OMAiSIQPSDC.
OrthoDBiEOG091G06CJ.
PhylomeDBiO95630.
TreeFamiTF323215.

Family and domain databases

Gene3Di1.20.58.280. 1 hit.
InterProiIPR000555. JAMM/MPN+_dom.
IPR007330. MIT.
IPR015063. USP8_dimer.
[Graphical view]
PfamiPF01398. JAB. 1 hit.
PF08969. USP8_dimer. 1 hit.
[Graphical view]
SMARTiSM00232. JAB_MPN. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: O95630-1) [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
MSDHGDVSLP PEDRVRALSQ LGSAVEVNED IPPRRYFRSG VEIIRMASIY
60 70 80 90 100
SEEGNIEHAF ILYNKYITLF IEKLPKHRDY KSAVIPEKKD TVKKLKEIAF
110 120 130 140 150
PKAEELKAEL LKRYTKEYTE YNEEKKKEAE ELARNMAIQQ ELEKEKQRVA
160 170 180 190 200
QQKQQQLEQE QFHAFEEMIR NQELEKERLK IVQEFGKVDP GLGGPLVPDL
210 220 230 240 250
EKPSLDVFPT LTVSSIQPSD CHTTVRPAKP PVVDRSLKPG ALSNSESIPT
260 270 280 290 300
IDGLRHVVVP GRLCPQFLQL ASANTARGVE TCGILCGKLM RNEFTITHVL
310 320 330 340 350
IPKQSAGSDY CNTENEEELF LIQDQQGLIT LGWIHTHPTQ TAFLSSVDLH
360 370 380 390 400
THCSYQMMLP ESVAIVCSPK FQETGFFKLT DHGLEEISSC RQKGFHPHSK
410 420
DPPLFCSCSH VTVVDRAVTI TDLR
Length:424
Mass (Da):48,077
Last modified:May 1, 1999 - v1
Checksum:i7B6E08A245BD9D43
GO
Isoform 2 (identifier: O95630-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     336-424: THPTQTAFLS...DRAVTITDLR → VETLWSLKSLHAP

Show »
Length:348
Mass (Da):39,596
Checksum:iEE94242C85A11070
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06980614R → P in MICCAP. 1 Publication1
Natural variantiVAR_06980738R → C in MICCAP. 1 PublicationCorresponds to variant rs143739249dbSNPEnsembl.1
Natural variantiVAR_06980842E → G in MICCAP. 1 PublicationCorresponds to variant rs397509387dbSNPEnsembl.1
Natural variantiVAR_06980963Y → C in MICCAP. 1 PublicationCorresponds to variant rs781694797dbSNPEnsembl.1
Natural variantiVAR_069810100F → Y in MICCAP. 1 PublicationCorresponds to variant rs397514697dbSNPEnsembl.1
Natural variantiVAR_069811313T → I in MICCAP. 1 PublicationCorresponds to variant rs202100019dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_057197336 – 424THPTQ…ITDLR → VETLWSLKSLHAP in isoform 2. 1 PublicationAdd BLAST89

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U73522 mRNA. Translation: AAD05037.1.
AC073046 Genomic DNA. Translation: AAX88908.1.
CH471053 Genomic DNA. Translation: EAW99715.1.
CH471053 Genomic DNA. Translation: EAW99716.1.
BC007682 mRNA. Translation: AAH07682.1.
BC065574 mRNA. Translation: AAH65574.1.
BC101467 mRNA. Translation: AAI01468.1.
BC101469 mRNA. Translation: AAI01470.1.
EU927390 mRNA. Translation: ACH57452.1.
CCDSiCCDS1929.1. [O95630-1]
RefSeqiNP_006454.1. NM_006463.4. [O95630-1]
NP_964010.1. NM_201647.2. [O95630-1]
NP_998787.1. NM_213622.2. [O95630-1]
XP_005264145.1. XM_005264088.3. [O95630-1]
XP_011530785.1. XM_011532483.2. [O95630-1]
XP_016858664.1. XM_017003175.1. [O95630-1]
UniGeneiHs.469018.

Genome annotation databases

EnsembliENST00000339566; ENSP00000344742; ENSG00000124356. [O95630-1]
ENST00000394070; ENSP00000377633; ENSG00000124356. [O95630-1]
ENST00000394073; ENSP00000377636; ENSG00000124356. [O95630-1]
ENST00000409707; ENSP00000386548; ENSG00000124356. [O95630-1]
GeneIDi10617.
KEGGihsa:10617.
UCSCiuc002sjs.3. human. [O95630-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U73522 mRNA. Translation: AAD05037.1.
AC073046 Genomic DNA. Translation: AAX88908.1.
CH471053 Genomic DNA. Translation: EAW99715.1.
CH471053 Genomic DNA. Translation: EAW99716.1.
BC007682 mRNA. Translation: AAH07682.1.
BC065574 mRNA. Translation: AAH65574.1.
BC101467 mRNA. Translation: AAI01468.1.
BC101469 mRNA. Translation: AAI01470.1.
EU927390 mRNA. Translation: ACH57452.1.
CCDSiCCDS1929.1. [O95630-1]
RefSeqiNP_006454.1. NM_006463.4. [O95630-1]
NP_964010.1. NM_201647.2. [O95630-1]
NP_998787.1. NM_213622.2. [O95630-1]
XP_005264145.1. XM_005264088.3. [O95630-1]
XP_011530785.1. XM_011532483.2. [O95630-1]
XP_016858664.1. XM_017003175.1. [O95630-1]
UniGeneiHs.469018.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2XZEX-ray1.75A/B1-146[»]
3RZUX-ray2.50A/B/C/D/E/F/G243-424[»]
3RZVX-ray1.67A219-424[»]
ProteinModelPortaliO95630.
SMRiO95630.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115863. 64 interactors.
DIPiDIP-33062N.
IntActiO95630. 40 interactors.
MINTiMINT-96921.
STRINGi9606.ENSP00000344742.

Protein family/group databases

MEROPSiM67.006.

PTM databases

iPTMnetiO95630.
PhosphoSitePlusiO95630.

Polymorphism and mutation databases

BioMutaiSTAMBP.

2D gel databases

REPRODUCTION-2DPAGEIPI00007943.

Proteomic databases

EPDiO95630.
MaxQBiO95630.
PaxDbiO95630.
PeptideAtlasiO95630.
PRIDEiO95630.

Protocols and materials databases

DNASUi10617.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000339566; ENSP00000344742; ENSG00000124356. [O95630-1]
ENST00000394070; ENSP00000377633; ENSG00000124356. [O95630-1]
ENST00000394073; ENSP00000377636; ENSG00000124356. [O95630-1]
ENST00000409707; ENSP00000386548; ENSG00000124356. [O95630-1]
GeneIDi10617.
KEGGihsa:10617.
UCSCiuc002sjs.3. human. [O95630-1]

Organism-specific databases

CTDi10617.
DisGeNETi10617.
GeneCardsiSTAMBP.
GeneReviewsiSTAMBP.
HGNCiHGNC:16950. STAMBP.
HPAiHPA035800.
MalaCardsiSTAMBP.
MIMi606247. gene.
614261. phenotype.
neXtProtiNX_O95630.
OpenTargetsiENSG00000124356.
Orphaneti294016. Microcephaly-capillary malformation syndrome.
PharmGKBiPA134955569.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2880. Eukaryota.
COG1310. LUCA.
GeneTreeiENSGT00390000015439.
HOGENOMiHOG000195792.
HOVERGENiHBG058519.
InParanoidiO95630.
KOiK11866.
OMAiSIQPSDC.
OrthoDBiEOG091G06CJ.
PhylomeDBiO95630.
TreeFamiTF323215.

Enzyme and pathway databases

BioCyciZFISH:HS04762-MONOMER.
ReactomeiR-HSA-5689901. Metalloprotease DUBs.
SignaLinkiO95630.
SIGNORiO95630.

Miscellaneous databases

ChiTaRSiSTAMBP. human.
GeneWikiiSTAMBP.
GenomeRNAii10617.
PROiO95630.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000124356.
CleanExiHS_STAMBP.
ExpressionAtlasiO95630. baseline and differential.
GenevisibleiO95630. HS.

Family and domain databases

Gene3Di1.20.58.280. 1 hit.
InterProiIPR000555. JAMM/MPN+_dom.
IPR007330. MIT.
IPR015063. USP8_dimer.
[Graphical view]
PfamiPF01398. JAB. 1 hit.
PF08969. USP8_dimer. 1 hit.
[Graphical view]
SMARTiSM00232. JAB_MPN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSTABP_HUMAN
AccessioniPrimary (citable) accession number: O95630
Secondary accession number(s): B5M0B6, D6W5H7, Q3MJE7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2005
Last sequence update: May 1, 1999
Last modified: November 30, 2016
This is version 144 of the entry and version 1 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

Miscellaneous

X-ray crystallography studies of STAMBPL1, another member of the peptidase M67C family, has shown that Glu-280 binds zinc indirectly via a water molecule. Nevertheless, this residue is essential for catalytic activity.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: 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. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

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 one 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.