Reviewed, UniProtKB/Swiss-Prot Q96FJ0 (STALP_HUMAN)

Names and origin

Protein names

Recommended name:
    AMSH-like protease
      Short name=AMSH-LP
    EC=3.1.2.15
Alternative name(s):
    STAM-binding protein-like 1

Gene names

Name:	STAMBPL1
Synonyms:	AMSHLP, KIAA1373

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	436 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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. Ref.6
Catalytic activity	Ubiquitin C-terminal thioester + H2O = ubiquitin + a thiol.
Cofactor	Binds 2 zinc ions per subunit. Ref.6
Tissue specificity	Ubiquitously expressed. Ref.1
Domain	The JAMM motif is essential for the protease activity By similarity.
Sequence similarities	Belongs to the peptidase M67C family. Contains 1 MPN (JAB/Mov34) domain.
Sequence caution	The sequence CAI13863.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	modification-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	metallopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW ubiquitin thiolesterase activity Inferred from electronic annotation. Source: EC zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96FJ0-1)

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.

Isoform 2 (identifier: Q96FJ0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     420-436: CKHVLVKDIKIIVLDLR → QKFLSGIISGTALEMEPLKIGYGPNGFPLLGISRSSSPSEQL

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 436

436

AMSH-like protease

PRO_0000194874

Regions

Domain

264 – 373

110

MPN

Motif

347 – 360

14

JAMM motif

Sites

Metal binding

347

1

Zinc 1; catalytic

Metal binding

349

1

Zinc 1; catalytic

Metal binding

360

1

Zinc 1; catalytic

Metal binding

362

1

Zinc 2

Metal binding

402

1

Zinc 2

Metal binding

408

1

Zinc 2

Metal binding

410

1

Zinc 2

Site

292

1

Indirect Zinc-binding

Amino acid modifications

Modified residue

25

1

Phosphoserine Ref.5

Modified residue

242

1

Phosphoserine Ref.5

Natural variations

Alternative sequence

420 – 436

17

CKHVL…VLDLR → QKFLSGIISGTALEMEPLKI GYGPNGFPLLGISRSSSPSE QL in isoform 2.

VSP_014648

Natural variant

196

1

S → N: dbSNP rs12254856.

VAR_051817

Natural variant

204

1

E → K: dbSNP rs34270879.

VAR_051818

Natural variant

210

1

A → T: dbSNP rs9988723.

VAR_051819

Experimental info

Mutagenesis

292

1

E → A: Complete loss of catalytic activity. Ref.6

Mutagenesis

329

1

E → A: 3-fold decrease in substrate affinity. Ref.6

Mutagenesis

332

1

F → A: 12-fold decrease in substrate affinity, little effect on catalytic activity. Ref.6

Mutagenesis

353

1

T → A: 19-fold decrease in activity, no change in substrate affinity. Ref.6

Mutagenesis

355

1

F → A: 161-fold decrease in activity, no change in substrate affinity. Ref.6

Mutagenesis

357

1

S → A: 34-fold decrease in activity. Ref.6

Mutagenesis

358

1

S → A: 10-fold decrease in activity, no change in substrate affinity. Ref.6

Mutagenesis

360

1

D → A: Complete loss of catalytic activity. Ref.6

Mutagenesis

370

1

M → A: 18-fold decrease in substrate affinity, little effect on catalytic activity. Ref.6

Mutagenesis

402

1

C → S: 402-fold decrease in activity, slight increase in substrate affinity. Ref.6

Mutagenesis

407

1

F → A: 35-fold decrease in activity, slight increase in substrate affinity. Ref.6

Secondary structure

1

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436

Helix Strand Turn

Details...

Beta strand

269 – 272

4

Helix

275 – 287

13

Beta strand

300 – 302

3

Beta strand

305 – 313

9

Helix

328 – 338

11

Beta strand

346 – 348

3

Beta strand

350 – 352

3

Helix

358 – 370

13

Beta strand

376 – 380

5

Helix

381 – 383

3

Beta strand

389 – 391

3

Helix

397 – 401

5

Beta strand

416 – 419

4

Beta strand

421 – 426

6

Beta strand

431 – 434

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 23, 2004. Version 2. Checksum: 722662C76A734102	FASTA	436	49,783
	10 20 30 40 50 60 MDQPFTVNSL KKLAAMPDHT DVSLSPEERV RALSKLGCNI TISEDITPRR YFRSGVEMER 70 80 90 100 110 120 MASVYLEEGN LENAFVLYNK FITLFVEKLP NHRDYQQCAV PEKQDIMKKL KEIAFPRTDE 130 140 150 160 170 180 LKNDLLKKYN VEYQEYLQSK NKYKAEILKK LEHQRLIEAE RKRIAQMRQQ QLESEQFLFF 190 200 210 220 230 240 EDQLKKQELA RGQMRSQQTS GLSEQIDGSA LSCFSTHQNN SLLNVFADQP NKSDATNYAS 250 260 270 280 290 300 HSPPVNRALT PAATLSAVQN LVVEGLRCVV LPEDLCHKFL QLAESNTVRG IETCGILCGK 310 320 330 340 350 360 LTHNEFTITH VIVPKQSAGP DYCDMENVEE LFNVQDQHDL LTLGWIHTHP TQTAFLSSVD 370 380 390 400 410 420 LHTHCSYQLM LPEAIAIVCS PKHKDTGIFR LTNAGMLEVS ACKKKGFHPH TKEPRLFSIC 430 KHVLVKDIKI IVLDLR
	Isoform 2. Checksum: 266828EB12055970	FASTA	461	52,199
	10 20 30 40 50 60 MDQPFTVNSL KKLAAMPDHT DVSLSPEERV RALSKLGCNI TISEDITPRR YFRSGVEMER 70 80 90 100 110 120 MASVYLEEGN LENAFVLYNK FITLFVEKLP NHRDYQQCAV PEKQDIMKKL KEIAFPRTDE 130 140 150 160 170 180 LKNDLLKKYN VEYQEYLQSK NKYKAEILKK LEHQRLIEAE RKRIAQMRQQ QLESEQFLFF 190 200 210 220 230 240 EDQLKKQELA RGQMRSQQTS GLSEQIDGSA LSCFSTHQNN SLLNVFADQP NKSDATNYAS 250 260 270 280 290 300 HSPPVNRALT PAATLSAVQN LVVEGLRCVV LPEDLCHKFL QLAESNTVRG IETCGILCGK 310 320 330 340 350 360 LTHNEFTITH VIVPKQSAGP DYCDMENVEE LFNVQDQHDL LTLGWIHTHP TQTAFLSSVD 370 380 390 400 410 420 LHTHCSYQLM LPEAIAIVCS PKHKDTGIFR LTNAGMLEVS ACKKKGFHPH TKEPRLFSIQ 430 440 450 460 KFLSGIISGT ALEMEPLKIG YGPNGFPLLG ISRSSSPSEQ L

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of AMSH-LP containing a Jab1/MPN domain metalloenzyme motif." Kikuchi K., Ishii N., Asano H., Sugamura K. Biochem. Biophys. Res. Commun. 306:637-643(2003) [PubMed: 12810066] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, SUBCELLULAR LOCATION. Tissue: Peripheral blood lymphocyte.
[2]	"Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O. DNA Res. 7:65-73(2000) [PubMed: 10718198] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[3]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] 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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Pancreas.
[5]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25 AND SER-242, MASS SPECTROMETRY.
[6]	"Structural basis for specific cleavage of Lys 63-linked polyubiquitin chains." Sato Y., Yoshikawa A., Yamagata A., Mimura H., Yamashita M., Ookata K., Nureki O., Iwai K., Komada M., Fukai S. Nature 455:358-362(2008) [PubMed: 18758443] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) OF 263-436 IN COMPLEXES WITH ZINC IONS AND WITH LYS-63-LINKED DI-UBIQUITIN, FUNCTION, COFACTOR, MUTAGENESIS OF GLU-292; GLU-329; PHE-332; THR-353; PHE-355; SER-357; SER-358; ASP-360; MET-370; CYS-402 AND PHE-407.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AB010120 mRNA. Translation: BAC77766.1.
AB037794 mRNA. Translation: BAA92611.1. Different initiation.
AL157394 Genomic DNA. Translation: CAI13861.1.
AL157394 Genomic DNA. Translation: CAI13862.1.
AL157394 Genomic DNA. Translation: CAI13863.1. Sequence problems.
BC010846 mRNA. Translation: AAH10846.2.

IPI

IPI00002208.
IPI00290975.

RefSeq

NP_065850.1.

UniGene

Hs.16229

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2ZNR	X-ray	1.20	A	264-436	[»]
2ZNV	X-ray	1.60	A/D	264-436	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q96FJ0. 1 interaction.

STRING

Q96FJ0.

Protein family/group databases

MEROPS

M67.003.

PTM databases

PhosphoSite

Q96FJ0.

Proteomic databases

PRIDE

Q96FJ0.

Genome annotation databases

Ensembl

ENST00000371922; ENSP00000360990; ENSG00000138134; Homo sapiens. [Genome view]
ENST00000371924; ENSP00000360992; ENSG00000138134; Homo sapiens. [Genome view]
ENST00000371926; ENSP00000360994; ENSG00000138134; Homo sapiens. [Genome view]
ENST00000371927; ENSP00000360995; ENSG00000138134; Homo sapiens. [Genome view]

GeneID

57559.

KEGG

hsa:57559.

UCSC

uc001kfk.1. human.

Organism-specific databases

CTD

57559.

GeneCards

GC10P090630.

H-InvDB

HIX0009014.

HGNC

HGNC:24105. STAMBPL1.

MIM

612352. gene.

PharmGKB

PA142670864.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q96FJ0.

OMA

FTVNSLK.

Enzyme and pathway databases

BRENDA

3.1.2.15. 247.

Gene expression databases

ArrayExpress

Q96FJ0.

Bgee

Q96FJ0.

CleanEx

HS_STAMBPL1.

Genevestigator

Q96FJ0.

GermOnline

ENSG00000138134. Homo sapiens.

Family and domain databases

InterPro

IPR000555. Mov34_MPN_PAD1.
[Graphical view]

Pfam

PF01398. Mov34. 1 hit.
[Graphical view]

SMART

SM00232. JAB_MPN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

64054.

SOURCE

Search...

Entry information

Entry name

STALP_HUMAN

Accession

Primary (citable) accession number: Q96FJ0
Secondary accession number(s): Q5T9N4 , Q5T9N9, Q7Z420, Q9P2H4

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2005
Last sequence update:	November 23, 2004
Last modified:	November 3, 2009
This is version 59 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.