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O95630 (STABP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 116. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
STAM-binding protein

EC=3.4.19.-
Alternative name(s):
Associated molecule with the SH3 domain of STAM
Endosome-associated ubiquitin isopeptidase
Gene names
Name:STAMBP
Synonyms:AMSH
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length424 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.5 Ref.7 Ref.10 Ref.12

Cofactor

Binds 2 zinc ions per subunit By similarity.

Enzyme regulation

Inhibited by N-ethylmaleimide.

Subunit structure

Interacts with STAM1. 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. Ref.1 Ref.5 Ref.7 Ref.8 Ref.9 Ref.10

Subcellular location

Nucleus. Membrane; Peripheral membrane protein. Cytoplasm. Early endosome Ref.5 Ref.7 Ref.10.

Tissue specificity

Ubiquitously expressed.

Domain

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

Post-translational modification

Phosphorylated after BMP type I receptor activation. Ref.5

Ubiquitinated by SMURF2 in the presence of RNF11. Ref.8

Involvement in disease

Microcephaly-capillary malformation syndrome (MICCAP) [MIM:614261]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12

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.

Sequence similarities

Belongs to the peptidase M67C family.

Contains 1 MPN (JAB/Mov34) domain.

Ontologies

Keywords
   Biological processUbl conjugation pathway
   Cellular componentCytoplasm
Endosome
Membrane
Nucleus
   DiseaseDisease mutation
   LigandMetal-binding
Zinc
   Molecular functionHydrolase
Metalloprotease
Protease
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processJAK-STAT cascade

Traceable author statement Ref.1. Source: ProtInc

mitotic cytokinesis

Inferred from mutant phenotype PubMed 18388320. Source: MGI

negative regulation of Ras protein signal transduction

Inferred from mutant phenotype Ref.12. Source: UniProtKB

negative regulation of neuron apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of phosphatidylinositol 3-kinase signaling

Inferred from mutant phenotype Ref.12. Source: UniProtKB

positive regulation of cell proliferation

Traceable author statement Ref.1. Source: ProtInc

protein deubiquitination

Inferred from mutant phenotype PubMed 18388320. Source: MGI

proteolysis

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcleavage furrow

Inferred from direct assay PubMed 18388320. Source: MGI

cytoplasm

Inferred from direct assay. Source: HPA

early endosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

nucleus

Inferred from direct assay. Source: HPA

plasma membrane

Inferred from direct assay. Source: HPA

   Molecular_functionmetal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

metallopeptidase activity

Inferred from electronic annotation. Source: UniProtKB-KW

ubiquitin-specific protease activity

Inferred from direct assay PubMed 18388320. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 424424STAM-binding protein
PRO_0000194869

Regions

Domain252 – 361110MPN
Region1 – 127127Interaction with CHMP3
Region227 – 2315Interaction with STAM1
Motif335 – 34814JAMM motif
Compositional bias104 – 17774Glu-rich

Sites

Metal binding3351Zinc 1; catalytic By similarity
Metal binding3371Zinc 1; catalytic By similarity
Metal binding3481Zinc 1; catalytic By similarity
Metal binding3501Zinc 2 By similarity
Metal binding3901Zinc 2 By similarity
Metal binding3961Zinc 2 By similarity
Metal binding3981Zinc 2 By similarity
Site2801Indirect zinc-binding By similarity

Amino acid modifications

Modified residue21Phosphoserine Ref.5
Modified residue481Phosphoserine Ref.5
Modified residue2431Phosphoserine Ref.5
Modified residue2451Phosphoserine Ref.5
Modified residue2471Phosphoserine Ref.5

Natural variations

Natural variant141R → P in MICCAP. Ref.12
VAR_069806
Natural variant381R → C in MICCAP. Ref.12
VAR_069807
Natural variant421E → G in MICCAP. Ref.12
VAR_069808
Natural variant631Y → C in MICCAP. Ref.12
VAR_069809
Natural variant1001F → Y in MICCAP. Ref.12
VAR_069810
Natural variant3131T → I in MICCAP. Ref.12
VAR_069811

Experimental info

Mutagenesis3481D → A: Promotes accumulation of ubiquitin on endosomes, ablates enzymatic activity toward polyubiquitin substrate and allows ubiquitinated STAM stabilization. Ref.7

Secondary structure

............................................... 424
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O95630 [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: 7B6E08A245BD9D43

FASTA42448,077
        10         20         30         40         50         60 
MSDHGDVSLP PEDRVRALSQ LGSAVEVNED IPPRRYFRSG VEIIRMASIY SEEGNIEHAF 

        70         80         90        100        110        120 
ILYNKYITLF IEKLPKHRDY KSAVIPEKKD TVKKLKEIAF PKAEELKAEL LKRYTKEYTE 

       130        140        150        160        170        180 
YNEEKKKEAE ELARNMAIQQ ELEKEKQRVA QQKQQQLEQE QFHAFEEMIR NQELEKERLK 

       190        200        210        220        230        240 
IVQEFGKVDP GLGGPLVPDL EKPSLDVFPT LTVSSIQPSD CHTTVRPAKP PVVDRSLKPG 

       250        260        270        280        290        300 
ALSNSESIPT IDGLRHVVVP GRLCPQFLQL ASANTARGVE TCGILCGKLM RNEFTITHVL 

       310        320        330        340        350        360 
IPKQSAGSDY CNTENEEELF LIQDQQGLIT LGWIHTHPTQ TAFLSSVDLH THCSYQMMLP 

       370        380        390        400        410        420 
ESVAIVCSPK FQETGFFKLT DHGLEEISSC RQKGFHPHSK DPPLFCSCSH VTVVDRAVTI 


TDLR 

« Hide

References

« Hide 'large scale' references
[1]"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: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH STAM1.
Tissue: Peripheral blood lymphocyte.
[2]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE 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. expand/collapse author list , 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].
Tissue: Brain, Eye and Lymph.
[5]"Promoting bone morphogenetic protein signaling through negative regulation of inhibitory Smads."
Itoh F., Asao H., Sugamura K., Heldin C.-H., ten Dijke P., Itoh S.
EMBO J. 20:4132-4142(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH SMAD6 AND SMAD7, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-2; SER-48; SER-243; SER-245 AND SER-247.
[6]"MPN+, a putative catalytic motif found in a subset of MPN domain proteins from eukaryotes and prokaryotes, is critical for Rpn11 function."
Maytal-Kivity V., Reis N., Hofmann K., Glickman M.H.
BMC Biochem. 3:28-28(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT OF GLU-280; HIS-335 AND HIS-337 IN ZINC-BINDING.
[7]"AMSH is an endosome-associated ubiquitin isopeptidase."
McCullough J., Clague M.J., Urbe S.
J. Cell Biol. 166:487-492(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF ASP-348, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH STAM1.
[8]"An RNF11: Smurf2 complex mediates ubiquitination of the AMSH protein."
Li H., Seth A.K.
Oncogene 23:1801-1808(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SMURF2 AND RNF11, UBIQUITINATION.
[9]"Release of autoinhibition converts ESCRT-III components into potent inhibitors of HIV-1 budding."
Zamborlini A., Usami Y., Radoshitzky S.R., Popova E., Palu G., Goettlinger H.
Proc. Natl. Acad. Sci. U.S.A. 103:19140-19145(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CHMP3.
[10]"Targeting of AMSH to endosomes is required for epidermal growth factor receptor degradation."
Ma Y.M., Boucrot E., Villen J., Affar el B., Gygi S.P., Goettlinger H.G., Kirchhausen T.
J. Biol. Chem. 282:9805-9812(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CHMP3, SUBCELLULAR LOCATION.
[11]"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].
[12]"Mutations in STAMBP, encoding a deubiquitinating enzyme, cause microcephaly-capillary malformation syndrome."
FORGE Canada Consortium
McDonell L.M., Mirzaa G.M., Alcantara D., Schwartzentruber J., Carter M.T., Lee L.J., Clericuzio C.L., Graham J.M. Jr., Morris-Rosendahl D.J., Polster T., Acsadi G., Townshend S., Williams S., Halbert A., Isidor B., David A., Smyser C.D., Paciorkowski A.R. expand/collapse author list , Willing M., Woulfe J., Das S., Beaulieu C.L., Marcadier J., Geraghty M.T., Frey B.J., Majewski J., Bulman D.E., Dobyns W.B., O'Driscoll M., Boycott K.M.
Nat. Genet. 45:556-562(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, VARIANTS MICCAP PRO-14; CYS-38; GLY-42; CYS-63; TYR-100 AND ILE-313.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_006454.1. NM_006463.4.
NP_964010.1. NM_201647.2.
NP_998787.1. NM_213622.2.
XP_005264145.1. XM_005264088.1.
UniGeneHs.469018.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2XZEX-ray1.75A/B1-146[»]
3RZUX-ray2.50A/B/C/D/E/F/G243-424[»]
3RZVX-ray1.67A219-424[»]
ProteinModelPortalO95630.
SMRO95630. Positions 2-142, 248-424.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115863. 40 interactions.
DIPDIP-33062N.
IntActO95630. 29 interactions.
MINTMINT-96921.
STRING9606.ENSP00000344742.

Protein family/group databases

MEROPSM67.006.

PTM databases

PhosphoSiteO95630.

2D gel databases

REPRODUCTION-2DPAGEIPI00007943.

Proteomic databases

PaxDbO95630.
PeptideAtlasO95630.
PRIDEO95630.

Protocols and materials databases

DNASU10617.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000339566; ENSP00000344742; ENSG00000124356.
ENST00000394070; ENSP00000377633; ENSG00000124356.
ENST00000394073; ENSP00000377636; ENSG00000124356.
ENST00000409707; ENSP00000386548; ENSG00000124356.
GeneID10617.
KEGGhsa:10617.
UCSCuc002sjs.3. human.

Organism-specific databases

CTD10617.
GeneCardsGC02P074056.
HGNCHGNC:16950. STAMBP.
HPAHPA035800.
MIM606247. gene.
614261. phenotype.
neXtProtNX_O95630.
Orphanet294016. Microcephaly-capillary malformation syndrome.
PharmGKBPA134955569.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1310.
HOGENOMHOG000195792.
HOVERGENHBG058519.
InParanoidO95630.
KOK11866.
OMAPSDCHTT.
OrthoDBEOG7NW698.
PhylomeDBO95630.
TreeFamTF323215.

Enzyme and pathway databases

SignaLinkO95630.

Gene expression databases

ArrayExpressO95630.
BgeeO95630.
CleanExHS_STAMBP.
GenevestigatorO95630.

Family and domain databases

InterProIPR000555. JAMM/MPN+_dom.
IPR015063. USP8_dimer.
[Graphical view]
PfamPF01398. JAB. 1 hit.
PF08969. USP8_dimer. 1 hit.
[Graphical view]
SMARTSM00232. JAB_MPN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSTAMBP.
GenomeRNAi10617.
NextBio40340.
PROO95630.
SOURCESearch...

Entry information

Entry nameSTABP_HUMAN
AccessionPrimary (citable) accession number: O95630
Secondary accession number(s): D6W5H7, Q3MJE7
Entry history
Integrated into UniProtKB/Swiss-Prot: July 19, 2005
Last sequence update: May 1, 1999
Last modified: April 16, 2014
This is version 116 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM