O95630 (STABP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	STAMBP
Synonyms:	AMSH

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	424 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Functions at the endosome and is able to oppose the ubiquitin-dependent sorting of receptors to lysosomes. 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. Ref.1 Ref.5 Ref.7 Ref.10
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
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 process	Ubl conjugation pathway
Cellular component	Cytoplasm Endosome Membrane Nucleus
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	JAK-STAT cascade Traceable author statement Ref.1. Source: ProtInc cytokinesis after mitosis Inferred from mutant phenotype PubMed 18388320. Source: MGI negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara 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_component	cleavage 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 nucleus Inferred from direct assay. Source: HPA plasma membrane Inferred from direct assay. Source: HPA
Molecular_function	metal 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...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CHMP1A	Q9HD42	3	EBI-396676,EBI-1057156
CHMP1B	Q7LBR1	5	EBI-396676,EBI-2118090
CHMP3	Q9Y3E7	5	EBI-396676,EBI-2118119
CHMP5	Q9NZZ3	2	EBI-396676,EBI-751303
GRB2	P62993	3	EBI-396676,EBI-401755
RNF11	Q9Y3C5	2	EBI-396676,EBI-396669
SMAD6	O43541-2	2	EBI-396676,EBI-4324970
STAM	Q92783	3	EBI-396676,EBI-752333
STAM2	O75886	3	EBI-396676,EBI-373258

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 424

424

STAM-binding protein

PRO_0000194869

Regions

Domain

252 – 361

110

MPN

Region

1 – 127

127

Interaction with CHMP3

Region

227 – 231

5

Interaction with STAM1

Motif

335 – 348

14

JAMM motif

Compositional bias

104 – 177

74

Glu-rich

Sites

Metal binding

335

1

Zinc 1; catalytic By similarity

Metal binding

337

1

Zinc 1; catalytic By similarity

Metal binding

348

1

Zinc 1; catalytic By similarity

Metal binding

350

1

Zinc 2 By similarity

Metal binding

390

1

Zinc 2 By similarity

Metal binding

396

1

Zinc 2 By similarity

Metal binding

398

1

Zinc 2 By similarity

Site

280

1

Indirect zinc-binding By similarity

Amino acid modifications

Modified residue

2

1

Phosphoserine Ref.5

Modified residue

48

1

Phosphoserine Ref.5

Modified residue

243

1

Phosphoserine Ref.5

Modified residue

245

1

Phosphoserine Ref.5

Modified residue

247

1

Phosphoserine Ref.5

Experimental info

Mutagenesis

348

1

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

Secondary structure

1

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424

Helix Strand Turn

Details...

Helix

11 – 22

12

Helix

33 – 53

21

Helix

56 – 71

16

Helix

74 – 76

3

Turn

78 – 82

5

Helix

88 – 97

10

Helix

99 – 137

39

Beta strand

257 – 260

4

Helix

263 – 276

14

Beta strand

282 – 290

9

Beta strand

293 – 301

9

Beta strand

304 – 306

3

Beta strand

311 – 313

3

Helix

316 – 326

11

Beta strand

329 – 336

8

Beta strand

338 – 340

3

Helix

346 – 358

13

Beta strand

363 – 368

6

Turn

369 – 372

4

Beta strand

373 – 379

7

Helix

381 – 389

9

Beta strand

404 – 407

4

Beta strand

409 – 414

6

Beta strand

419 – 422

4

Sequences

	Sequence		Length	Mass (Da)
	O95630 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: 7B6E08A245BD9D43	FASTA	424	48,077
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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].
+	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.

IPI

IPI00007943.

RefSeq

NP_006454.1. NM_006463.4.
NP_964010.1. NM_201647.2.
NP_998787.1. NM_213622.2.

UniGene

Hs.469018.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2XZE	X-ray	1.75	A/B	1-146	[»]
3RZU	X-ray	2.50	A/B/C/D/E/F/G	243-424	[»]
3RZV	X-ray	1.67	A	219-424	[»]

ProteinModelPortal

O95630.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-33062N.

IntAct

O95630. 28 interactions.

MINT

MINT-96921.

STRING

9606.ENSP00000344742.

Protein family/group databases

MEROPS

M67.006.

PTM databases

PhosphoSite

O95630.

2D gel databases

REPRODUCTION-2DPAGE

IPI00007943.

Proteomic databases

PaxDb

O95630.

PeptideAtlas

O95630.

PRIDE

O95630.

Protocols and materials databases

DNASU

10617.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000339566; ENSP00000344742; ENSG00000124356.
ENST00000394070; ENSP00000377633; ENSG00000124356.
ENST00000394073; ENSP00000377636; ENSG00000124356.
ENST00000409707; ENSP00000386548; ENSG00000124356.

GeneID

10617.

KEGG

hsa:10617.

UCSC

uc002sjs.3. human.

Organism-specific databases

CTD

10617.

GeneCards

GC02P074056.

HGNC

HGNC:16950. STAMBP.

HPA

HPA035800.

MIM

606247. gene.

neXtProt

NX_O95630.

PharmGKB

PA134955569.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1310.

HOGENOM

HOG000195792.

HOVERGEN

HBG058519.

InParanoid

O95630.

KO

K11866.

OMA

DVPPRRY.

OrthoDB

EOG4B5P58.

PhylomeDB

O95630.

Gene expression databases

ArrayExpress

O95630.

Bgee

O95630.

CleanEx

HS_STAMBP.

Genevestigator

O95630.

Family and domain databases

InterPro

IPR000555. JAB1_Mov34_MPN_PAD1.
[Graphical view]

Pfam

PF01398. JAB. 1 hit.
[Graphical view]

SMART

SM00232. JAB_MPN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

10617.

NextBio

40340.

SOURCE

Search...

Entry information

Entry name

STABP_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 106 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.