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Reviewed, UniProtKB/Swiss-Prot Q9Y4P1 (ATG4B_HUMAN)

Last modified March 2, 2010. Version 86. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
Cysteine protease ATG4B
EC=3.4.22.-
Alternative name(s):
Autophagy-related protein 4 homolog B
Short name=hAPG4B
Autophagin-1
Autophagy-related cysteine endopeptidase 1
AUT-like 1 cysteine endopeptidase
Gene names
Name:ATG4B
Synonyms:APG4B, AUTL1, KIAA0943
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length393 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Cysteine protease required for autophagy, which cleaves the C-terminal part of either MAP1LC3, GABARAPL2 or GABARAP, allowing the liberation of form I. A subpopulation of form I is subsequently converted to a smaller form (form II). Form II, with a revealed C-terminal glycine, is considered to be the phosphatidylethanolamine (PE)-conjugated form, and has the capacity for the binding to autophagosomes. Ref.2

Enzyme regulation

Inhibited by N-ethylmaleimide.

Subcellular location

Cytoplasm Probable.

Tissue specificity

Mainly expressed in the skeletal muscle, followed by brain, heart, liver and pancreas. Ref.2 Ref.1

Sequence similarities

Belongs to the peptidase C54 family.

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Binary interactions

With

Entry

#Exp.

IntAct

Notes

GABARAPL2P605201EBI-712014,EBI-720116

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Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9Y4P1-1)

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: Q9Y4P1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MAHSVPSDSR...GSVGGRTGKM
     370-393: DSSDVERLERFFDSEDEDFEILSL → GESCQVQILLM
Note: No experimental confirmation available.
Isoform 3 (identifier: Q9Y4P1-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-74: Missing.
     321-354: FFCKTEDDFNDWCQQVKKLSLLGGALPMFELVEQ → KQGRLVRSLIPWAPRPSSWCAAVLGAAVVMCGTP
     355-393: Missing.
Note: No experimental confirmation available.
Isoform 4 (identifier: Q9Y4P1-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-74: Missing.
     369-369: L → LGESCQVQVGSLG
Isoform 6 (identifier: Q9Y4P1-6)

The sequence of this isoform differs from the canonical sequence as follows:
     370-393: DSSDVERLERFFDSEDEDFEILSL → GESCQVQILLM
Note: No experimental confirmation available.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 393393Cysteine protease ATG4B
PRO_0000215844

Sites

Active site741Nucleophile
Active site2781 Potential
Active site2801

Amino acid modifications

Modified residue11N-acetylmethionine Ref.12
Modified residue341Phosphoserine By similarity
Modified residue3161Phosphoserine Ref.11
Modified residue3831Phosphoserine Ref.10 Ref.14
Modified residue3921Phosphoserine Ref.10

Natural variations

Alternative sequence1 – 7474Missing in isoform 3 and isoform 4.
VSP_013028
Alternative sequence11M → MAHSVPSDSRTSRRPTTRPH AARGAPRGSRRPGRTPKWRL PRISARAPYRLRRLRRHTYW PPRRPVAASRCWPVGATPLG SVGGRTGKM in isoform 2.
VSP_013029
Alternative sequence321 – 35434FFCKT…ELVEQ → KQGRLVRSLIPWAPRPSSWC AAVLGAAVVMCGTP in isoform 3.
VSP_013031
Alternative sequence355 – 39339Missing in isoform 3.
VSP_013032
Alternative sequence3691L → LGESCQVQVGSLG in isoform 4.
VSP_013033
Alternative sequence370 – 39324DSSDV…EILSL → GESCQVQILLM in isoform 2 and isoform 6.
VSP_013034
Natural variant3541Q → L: dbSNP rs7601000. Ref.5 Ref.7
VAR_021486

Experimental info

Mutagenesis741C → S: Complete loss of protease activity. Ref.2 Ref.15 Ref.16
Mutagenesis1421W → A: Strongly reduced protease activity. Ref.15
Mutagenesis2291R → A: Strongly reduced protease activity. Ref.15
Mutagenesis2781D → A: Complete loss of protease activity. Ref.15 Ref.16
Mutagenesis2801H → A: Complete loss of protease activity. Ref.15 Ref.16
Sequence conflict1361Missing in BAB83890. Ref.2
Sequence conflict1881P → L in BAB55127. Ref.5
Sequence conflict2471F → Y in BAB55353. Ref.5
Sequence conflict2731E → G in BAB55042. Ref.5
Sequence conflict3121E → N in BAB83890. Ref.2

Secondary structure

1 ................................................................ 393
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1999. Version 1.
Checksum: 7E850A192176E0F5

FASTA39344,309
        10         20         30         40         50         60 
MDAATLTYDT LRFAEFEDFP ETSEPVWILG RKYSIFTEKD EILSDVASRL WFTYRKNFPA 

        70         80         90        100        110        120 
IGGTGPTSDT GWGCMLRCGQ MIFAQALVCR HLGRDWRWTQ RKRQPDSYFS VLNAFIDRKD 

       130        140        150        160        170        180 
SYYSIHQIAQ MGVGEGKSIG QWYGPNTVAQ VLKKLAVFDT WSSLAVHIAM DNTVVMEEIR 

       190        200        210        220        230        240 
RLCRTSVPCA GATAFPADSD RHCNGFPAGA EVTNRPSPWR PLVLLIPLRL GLTDINEAYV 

       250        260        270        280        290        300 
ETLKHCFMMP QSLGVIGGKP NSAHYFIGYV GEELIYLDPH TTQPAVEPTD GCFIPDESFH 

       310        320        330        340        350        360 
CQHPPCRMSI AELDPSIAVG FFCKTEDDFN DWCQQVKKLS LLGGALPMFE LVEQQPSHLA 

       370        380        390 
CPDVLNLSLD SSDVERLERF FDSEDEDFEI LSL

« Hide

Isoform 2.

Checksum: F97302AD8D6960D6
Show »

FASTA46852,544
Isoform 3.

Checksum: 0904A795A1B596B3
Show »

FASTA28031,042
Isoform 4.

Checksum: 97592E31055D7882
Show »

FASTA33137,052
Isoform 6.

Checksum: 481414A271E7533D
Show »

FASTA38042,637

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References

« Hide 'large scale' references
[1]"Human autophagins, a family of cysteine proteinases potentially implicated in cell degradation by autophagy."
Marino G., Uria J.A., Puente X.S., Quesada V., Bordallo J., Lopez-Otin C.
J. Biol. Chem. 278:3671-3678(2003) [PubMed: 12446702] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Liver.
[2]"LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation."
Kabeya Y., Mizushima N., Yamamoto A., Oshitani-Okamoto S., Ohsumi Y., Yoshimori T.
J. Cell Sci. 117:2805-2812(2004) [PubMed: 15169837] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, FUNCTION IN GABARAPL2; GABARAP AND MAP1LC3A CLEAVAGE, MUTAGENESIS OF CYS-74.
[3]"Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 6:63-70(1999) [PubMed: 10231032] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[4]Ohara O., Nagase T., Kikuno R.
Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3; 4 AND 6), VARIANT LEU-354.
Tissue: Embryo and Placenta.
[6]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Testis.
[7]"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: 15815621] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT LEU-354.
[8]"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: Placenta.
[9]Bienvenut W.V.
Submitted (JAN-2010) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 1-12; 33-49; 120-137; 185-201 AND 230-244, ACETYLATION AT MET-1, MASS SPECTROMETRY.
Tissue: Ovarian carcinoma.
[10]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed: 17081983] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-383 AND SER-392, MASS SPECTROMETRY.
Tissue: Epithelium.
[11]"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column."
Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y.
Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-316, MASS SPECTROMETRY.
[12]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, MASS SPECTROMETRY.
[13]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-383, MASS SPECTROMETRY.
[14]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-383, MASS SPECTROMETRY.
Tissue: T-cell.
[15]"Structural basis for the specificity and catalysis of human Atg4B responsible for mammalian autophagy."
Sugawara K., Suzuki N.N., Fujioka Y., Mizushima N., Ohsumi Y., Inagaki F.
J. Biol. Chem. 280:40058-40065(2005) [PubMed: 16183633] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS), MUTAGENESIS OF CYS-74; TRP-142; ARG-229; ASP-278 AND HIS-280.
[16]"The crystal structure of human Atg4b, a processing and de-conjugating enzyme for autophagosome-forming modifiers."
Kumanomidou T., Mizushima T., Komatsu M., Suzuki A., Tanida I., Sou Y.-S., Ueno T., Kominami E., Tanaka K., Yamane T.
J. Mol. Biol. 355:612-618(2006) [PubMed: 16325851] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), MUTAGENESIS OF CYS-74; ASP-278 AND HIS-280.
+Additional computationally mapped references.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AJ504652 mRNA. Translation: CAD43219.1.
AB066215 mRNA. Translation: BAB83890.1.
AB023160 mRNA. Translation: BAA76787.2. Different initiation.
AK027332 mRNA. Translation: BAB55042.1.
AK027462 mRNA. Translation: BAB55127.1.
AK027763 mRNA. Translation: BAB55353.1.
AK125277 mRNA. Translation: BAC86110.1.
AL080168 mRNA. Translation: CAB45756.1.
AC133528 Genomic DNA. Translation: AAY14919.1.
BC000719 mRNA. Translation: AAH00719.1.
IPIIPI00554649.
IPI00647200.
IPI00743619.
IPI00746254.
IPI00941681.
PIRT12492.
RefSeqNP_037457.3.
NP_847896.1.
UniGeneHs.283610

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2CY7X-ray1.90A1-393[»]
2D1IX-ray2.00A/B1-393[»]
2Z0DX-ray1.90A1-354[»]
2Z0EX-ray1.90A1-354[»]
2ZZPX-ray2.05A1-354[»]
ModBaseSearch...

Protein-protein interaction databases

IntActQ9Y4P1. 6 interactions.
STRINGQ9Y4P1.

Protein family/group databases

MEROPSC54.003.

PTM databases

PhosphoSiteQ9Y4P1.

Proteomic databases

PRIDEQ9Y4P1.

Genome annotation databases

EnsemblENST00000337606; ENSP00000336547; ENSG00000168397; Homo sapiens. [Genome view]
ENST00000404914; ENSP00000384259; ENSG00000168397; Homo sapiens. [Genome view]
GeneID23192.
KEGGhsa:23192.
UCSCuc002wbu.2. human.
uc002wbw.1. human.
uc002wbx.1. human.

Organism-specific databases

CTD23192.
GeneCardsGC02P242225.
HGNCHGNC:20790. ATG4B.
MIM611338. gene.
PharmGKBPA134898340.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG15184.
HOVERGENHBG050536.
PhylomeDBQ9Y4P1.

Gene expression databases

ArrayExpressQ9Y4P1.
BgeeQ9Y4P1.
CleanExHS_ATG4B.
GenevestigatorQ9Y4P1.
GermOnlineENSG00000168397. Homo sapiens.

Family and domain databases

InterProIPR005078. Peptidase_C54.
[Graphical view]
PANTHERPTHR22624. Peptidase_C54. 1 hit.
PfamPF03416. Peptidase_C54. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio44679.
SOURCESearch...

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Entry information

Entry nameATG4B_HUMAN
AccessionPrimary (citable) accession number: Q9Y4P1
Secondary accession number(s): Q53NU4 expand/collapse secondary AC list , Q6ZUV8, Q8WYM9, Q96K07, Q96K96, Q96SZ1, Q9Y2F2
Entry history
Integrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: November 1, 1999
Last modified: March 2, 2010
This is version 86 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.

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Relevant documents

Human chromosome 2

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

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List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Peptidase families

Classification of peptidase families and list of entries

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents