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Protein

STAM-binding protein

Gene

STAMBP

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

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.

Cofactori

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

Activity regulationi

Inhibited by N-ethylmaleimide.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei280Indirect zinc-bindingBy similarity1
Metal bindingi335Zinc 1; catalyticPROSITE-ProRule annotation1
Metal bindingi337Zinc 1; catalyticPROSITE-ProRule annotation1
Metal bindingi348Zinc 1; catalyticPROSITE-ProRule annotation1
Metal bindingi350Zinc 2By similarity1
Metal bindingi390Zinc 2By similarity1
Metal bindingi396Zinc 2By similarity1
Metal bindingi398Zinc 2By similarity1

GO - Molecular functioni

  • Lys63-specific deubiquitinase activity Source: GO_Central
  • 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

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
Biological processUbl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000124356.15
HGNCiHGNC:16950 STAMBP
MIMi606247 gene
neXtProtiNX_O95630

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, 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 dbSNP:rs143739249EnsemblClinVar.1
Natural variantiVAR_06980842E → G in MICCAP. 1 PublicationCorresponds to variant dbSNP:rs397509387EnsemblClinVar.1
Natural variantiVAR_06980963Y → C in MICCAP. 1 PublicationCorresponds to variant dbSNP:rs781694797Ensembl.1
Natural variantiVAR_069810100F → Y in MICCAP. 1 PublicationCorresponds to variant dbSNP:rs397514697EnsemblClinVar.1
Natural variantiVAR_069811313T → I in MICCAP. 1 PublicationCorresponds to variant dbSNP:rs202100019EnsemblClinVar.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
GeneReviewsiSTAMBP
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
ProteomicsDBi50966

2D gel databases

REPRODUCTION-2DPAGEiIPI00007943

PTM databases

iPTMnetiO95630
PhosphoSitePlusiO95630

Expressioni

Tissue specificityi

Ubiquitously expressed.

Gene expression databases

BgeeiENSG00000124356 Expressed in 237 organ(s), highest expression level in C1 segment of cervical spinal cord
CleanExiHS_STAMBP
ExpressionAtlasiO95630 baseline and differential
GenevisibleiO95630 HS

Organism-specific databases

HPAiHPA035800
HPA035801

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi115863, 68 interactors
CORUMiO95630
DIPiDIP-33062N
IntActiO95630, 41 interactors
MINTiO95630
STRINGi9606.ENSP00000344742

Chemistry databases

BindingDBiO95630

Structurei

Secondary structure

1424
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO95630
SMRiO95630
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini257 – 388MPNPROSITE-ProRule annotationAdd BLAST132

Region

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

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi335 – 348JAMM motifPROSITE-ProRule annotationAdd 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

Phylogenomic databases

eggNOGiKOG2880 Eukaryota
COG1310 LUCA
GeneTreeiENSGT00930000150927
HOGENOMiHOG000195792
HOVERGENiHBG058519
InParanoidiO95630
KOiK11866
OMAiCNTMHEE
OrthoDBiEOG091G06CJ
PhylomeDBiO95630
TreeFamiTF323215

Family and domain databases

InterProiView protein in InterPro
IPR000555 JAMM/MPN+_dom
IPR037518 MPN
IPR015063 USP8_dimer
PfamiView protein in Pfam
PF01398 JAB, 1 hit
PF08969 USP8_dimer, 1 hit
SMARTiView protein in SMART
SM00232 JAB_MPN, 1 hit
PROSITEiView protein in PROSITE
PS50249 MPN, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9JK83C9JK83_HUMAN
STAM-binding protein
STAMBP
318Annotation score:
F5H5B9F5H5B9_HUMAN
STAM-binding protein
STAMBP
209Annotation score:
C9JEK5C9JEK5_HUMAN
STAM-binding protein
STAMBP
163Annotation score:
C9JZ93C9JZ93_HUMAN
STAM-binding protein
STAMBP
137Annotation score:

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 dbSNP:rs143739249EnsemblClinVar.1
Natural variantiVAR_06980842E → G in MICCAP. 1 PublicationCorresponds to variant dbSNP:rs397509387EnsemblClinVar.1
Natural variantiVAR_06980963Y → C in MICCAP. 1 PublicationCorresponds to variant dbSNP:rs781694797Ensembl.1
Natural variantiVAR_069810100F → Y in MICCAP. 1 PublicationCorresponds to variant dbSNP:rs397514697EnsemblClinVar.1
Natural variantiVAR_069811313T → I in MICCAP. 1 PublicationCorresponds to variant dbSNP:rs202100019EnsemblClinVar.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
XP_011530785.1, XM_011532483.2 [O95630-1]
XP_016858664.1, XM_017003175.1
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

Similar proteinsi

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
XP_011530785.1, XM_011532483.2 [O95630-1]
XP_016858664.1, XM_017003175.1
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[»]
5IXFNMR-B228-241[»]
ProteinModelPortaliO95630
SMRiO95630
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115863, 68 interactors
CORUMiO95630
DIPiDIP-33062N
IntActiO95630, 41 interactors
MINTiO95630
STRINGi9606.ENSP00000344742

Chemistry databases

BindingDBiO95630

Protein family/group databases

MEROPSiM67.006

PTM databases

iPTMnetiO95630
PhosphoSitePlusiO95630

Polymorphism and mutation databases

BioMutaiSTAMBP

2D gel databases

REPRODUCTION-2DPAGEiIPI00007943

Proteomic databases

EPDiO95630
MaxQBiO95630
PaxDbiO95630
PeptideAtlasiO95630
PRIDEiO95630
ProteomicsDBi50966

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
EuPathDBiHostDB:ENSG00000124356.15
GeneCardsiSTAMBP
GeneReviewsiSTAMBP
HGNCiHGNC:16950 STAMBP
HPAiHPA035800
HPA035801
MalaCardsiSTAMBP
MIMi606247 gene
614261 phenotype
neXtProtiNX_O95630
OpenTargetsiENSG00000124356
Orphaneti294016 Microcephaly-capillary malformation syndrome
PharmGKBiPA134955569
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2880 Eukaryota
COG1310 LUCA
GeneTreeiENSGT00930000150927
HOGENOMiHOG000195792
HOVERGENiHBG058519
InParanoidiO95630
KOiK11866
OMAiCNTMHEE
OrthoDBiEOG091G06CJ
PhylomeDBiO95630
TreeFamiTF323215

Enzyme and pathway databases

ReactomeiR-HSA-5689901 Metalloprotease DUBs
SignaLinkiO95630
SIGNORiO95630

Miscellaneous databases

ChiTaRSiSTAMBP human
GeneWikiiSTAMBP
GenomeRNAii10617
PROiPR:O95630
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000124356 Expressed in 237 organ(s), highest expression level in C1 segment of cervical spinal cord
CleanExiHS_STAMBP
ExpressionAtlasiO95630 baseline and differential
GenevisibleiO95630 HS

Family and domain databases

InterProiView protein in InterPro
IPR000555 JAMM/MPN+_dom
IPR037518 MPN
IPR015063 USP8_dimer
PfamiView protein in Pfam
PF01398 JAB, 1 hit
PF08969 USP8_dimer, 1 hit
SMARTiView protein in SMART
SM00232 JAB_MPN, 1 hit
PROSITEiView protein in PROSITE
PS50249 MPN, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSTABP_HUMAN
AccessioniPrimary (citable) accession number: O95630
Secondary accession number(s): B5M0B6, D6W5H7, Q3MJE7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2005
Last sequence update: May 1, 1999
Last modified: November 7, 2018
This is version 161 of the entry and version 1 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, Reference proteome

Documents

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