Reviewed, UniProtKB/Swiss-Prot Q9Y4P1 (ATG4B_HUMAN)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	393 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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.
Enzyme regulation	Inhibited by N-ethylmaleimide.
Subcellular location	CytoplasmProbable.
Tissue specificity	Mainly expressed in the skeletal muscle, followed by brain, heart, liver and pancreas.
Sequence similarities	Belongs to the peptidase C54 family.

Ontologies

Keywords
Biological process	Autophagy Protein transport Transport Ubl conjugation pathway
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Hydrolase Protease Thiol protease
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	autophagosome formation Ref.1 Inferred from sequence or structural similarity. Source: UniProtKB protein targeting to membrane Ref.1 Inferred from sequence or structural similarity. Source: UniProtKB proteolysis Ref.2 Inferred from direct assay. Source: UniProtKB
Cellular component	cytosol Ref.1 Inferred from sequence or structural similarity. Source: UniProtKB microtubule associated complex Ref.1 Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	cysteine-type peptidase activity Ref.2 Inferred from direct assay. Source: UniProtKB protein binding Ref.1 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GABARAPL2	P60520	1	EBI-712014,EBI-720116

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

Notes: 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.

Notes: 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

Notes: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 393

393

Cysteine protease ATG4B

PRO_0000215844

Sites

Active site

74

1

Nucleophile

Active site

278

1

Potential

Active site

280

1

Amino acid modifications

Modified residue

34

1

Phosphoserine By similarity

Modified residue

316

1

Phosphoserine

Modified residue

383

1

Phosphoserine

Modified residue

392

1

Phosphoserine

Natural variations

Alternative sequence

1 – 74

74

Missing in isoform 3 and isoform 4.

VSP_013028

Alternative sequence

1

1

M → MAHSVPSDSRTSRRPTTRPH AARGAPRGSRRPGRTPKWRL PRISARAPYRLRRLRRHTYW PPRRPVAASRCWPVGATPLG SVGGRTGKM in isoform 2.

VSP_013029

Alternative sequence

321 – 354

34

FFCKT…ELVEQ → KQGRLVRSLIPWAPRPSSWC AAVLGAAVVMCGTP in isoform 3.

VSP_013031

Alternative sequence

355 – 393

39

Missing in isoform 3.

VSP_013032

Alternative sequence

369

1

L → LGESCQVQVGSLG in isoform 4.

VSP_013033

Alternative sequence

370 – 393

24

DSSDV…EILSL → GESCQVQILLM in isoform 2 and isoform 6.

VSP_013034

Natural variant

354

1

Q → L: dbSNP rs7601000.

VAR_021486

Experimental info

Mutagenesis

74

1

C → S: Complete loss of protease activity

Mutagenesis

142

1

W → A: Strongly reduced protease activity

Mutagenesis

229

1

R → A: Strongly reduced protease activity

Mutagenesis

278

1

D → A: Complete loss of protease activity

Mutagenesis

280

1

H → A: Complete loss of protease activity

Sequence conflict

136

1

Missing in BAB83890. Ref.2

Sequence conflict

188

1

P → L in BAB55127. Ref.5

Sequence conflict

247

1

F → Y in BAB55353. Ref.5

Sequence conflict

273

1

E → G in BAB55042. Ref.5

Sequence conflict

312

1

E → N in BAB83890. Ref.2

Secondary structure

1

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393

Helix Strand Turn

Details...

Helix

10 – 13

4

Beta strand

26 – 28

3

Beta strand

31 – 33

3

Turn

35 – 37

3

Helix

39 – 48

10

Beta strand

54 – 57

4

Turn

61 – 64

4

Turn

70 – 72

3

Helix

74 – 91

18

Helix

106 – 113

8

Beta strand

116 – 118

3

Helix

125 – 133

9

Turn

134 – 136

3

Helix

145 – 156

12

Turn

160 – 162

3

Beta strand

165 – 168

4

Beta strand

173 – 175

3

Helix

176 – 183

8

Beta strand

184 – 186

3

Beta strand

222 – 229

8

Beta strand

232 – 234

3

Helix

237 – 239

3

Helix

240 – 246

7

Beta strand

252 – 257

6

Beta strand

264 – 270

7

Beta strand

273 – 277

5

Beta strand

281 – 284

4

Helix

297 – 299

3

Beta strand

306 – 309

4

Helix

310 – 312

3

Beta strand

315 – 325

11

Helix

326 – 341

16

Beta strand

349 – 353

5

Beta strand

364 – 370

7

Helix

371 – 376

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 7E850A192176E0F5	FASTA	393	44,309
	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
	Isoform 2 [UniParc]. Checksum: F97302AD8D6960D6		468	52,544
	10 20 30 40 50 60 MAHSVPSDSR TSRRPTTRPH AARGAPRGSR RPGRTPKWRL PRISARAPYR LRRLRRHTYW 70 80 90 100 110 120 PPRRPVAASR CWPVGATPLG SVGGRTGKMD AATLTYDTLR FAEFEDFPET SEPVWILGRK 130 140 150 160 170 180 YSIFTEKDEI LSDVASRLWF TYRKNFPAIG GTGPTSDTGW GCMLRCGQMI FAQALVCRHL 190 200 210 220 230 240 GRDWRWTQRK RQPDSYFSVL NAFIDRKDSY YSIHQIAQMG VGEGKSIGQW YGPNTVAQVL 250 260 270 280 290 300 KKLAVFDTWS SLAVHIAMDN TVVMEEIRRL CRTSVPCAGA TAFPADSDRH CNGFPAGAEV 310 320 330 340 350 360 TNRPSPWRPL VLLIPLRLGL TDINEAYVET LKHCFMMPQS LGVIGGKPNS AHYFIGYVGE 370 380 390 400 410 420 ELIYLDPHTT QPAVEPTDGC FIPDESFHCQ HPPCRMSIAE LDPSIAVGFF CKTEDDFNDW 430 440 450 460 CQQVKKLSLL GGALPMFELV EQQPSHLACP DVLNLSLGES CQVQILLM
	Isoform 3 [UniParc]. Checksum: 0904A795A1B596B3		280	31,042
	10 20 30 40 50 60 MLRCGQMIFA QALVCRHLGR DWRWTQRKRQ PDSYFSVLNA FIDRKDSYYS IHQIAQMGVG 70 80 90 100 110 120 EGKSIGQWYG PNTVAQVLKK LAVFDTWSSL AVHIAMDNTV VMEEIRRLCR TSVPCAGATA 130 140 150 160 170 180 FPADSDRHCN GFPAGAEVTN RPSPWRPLVL LIPLRLGLTD INEAYVETLK HCFMMPQSLG 190 200 210 220 230 240 VIGGKPNSAH YFIGYVGEEL IYLDPHTTQP AVEPTDGCFI PDESFHCQHP PCRMSIAELD 250 260 270 280 PSIAVGKQGR LVRSLIPWAP RPSSWCAAVL GAAVVMCGTP
	Isoform 4 [UniParc]. Checksum: 97592E31055D7882		331	37,052
	10 20 30 40 50 60 MLRCGQMIFA QALVCRHLGR DWRWTQRKRQ PDSYFSVLNA FIDRKDSYYS IHQIAQMGVG 70 80 90 100 110 120 EGKSIGQWYG PNTVAQVLKK LAVFDTWSSL AVHIAMDNTV VMEEIRRLCR TSVPCAGATA 130 140 150 160 170 180 FPADSDRHCN GFPAGAEVTN RPSPWRPLVL LIPLRLGLTD INEAYVETLK HCFMMPQSLG 190 200 210 220 230 240 VIGGKPNSAH YFIGYVGEEL IYLDPHTTQP AVEPTDGCFI PDESFHCQHP PCRMSIAELD 250 260 270 280 290 300 PSIAVGFFCK TEDDFNDWCQ QVKKLSLLGG ALPMFELVEQ QPSHLACPDV LNLSLGESCQ 310 320 330 VQVGSLGDSS DVERLERFFD SEDEDFEILS L
	Isoform 6 [UniParc]. Checksum: 481414A271E7533D		380	42,637
	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 CPDVLNLSLG ESCQVQILLM

References

	« Hide 'large scale' referencesShow '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.,