Q9Y5Y5 (PEX16_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Peroxisomal membrane protein PEX16

Alternative name(s):
Peroxin-16
Peroxisomal biogenesis factor 16

Gene names

Name:

PEX16

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	336 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Required for peroxisome membrane biogenesis. May play a role in early stages of peroxisome assembly. Can recruit other peroxisomal proteins, such as PEX3 and PMP34, to de novo peroxisomes derived from the endoplasmic reticulum (ER). May function as receptor for PEX3. Ref.5 Ref.7 Ref.9
Subunit structure	Interacts with PEX19. Ref.5 Ref.6 Ref.8
Subcellular location	Peroxisome membrane; Multi-pass membrane protein. Endoplasmic reticulum membrane Ref.6.
Involvement in disease	Peroxisome biogenesis disorder complementation group 9 (PBD-CG9) [MIM:614876]: A peroxisomal disorder arising from a failure of protein import into the peroxisomal membrane or matrix. The peroxisome biogenesis disorders (PBD group) are genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies. Include disorders are: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum (PBD-ZSS). Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Peroxisome biogenesis disorder 8A (PBD8A) [MIM:614876]: A fatal peroxisome biogenesis disorder belonging to the Zellweger disease spectrum and clinically characterized by severe neurologic dysfunction with profound psychomotor retardation, severe hypotonia and neonatal seizures, craniofacial abnormalities, liver dysfunction, and biochemically by the absence of peroxisomes. Additional features include cardiovascular and skeletal defects, renal cysts, ocular abnormalities, and hearing impairment. Most severely affected individuals with the classic form of the disease (classic Zellweger syndrome) die within the first year of life. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Peroxisome biogenesis disorder 8B (PBD8B) [MIM:614877]: A relatively mild peroxisome biogenesis disorder. Affected individuals manifest lower limb spasticity and ataxia resulting in wheelchair dependence. Other features include optic atrophy, cataracts, dysarthria, dysphagia, constipation, and a peripheral demyelinating motor and sensory neuropathy. Cognition is relatively preserved. Biochemical abnormalities are mild and include increased very-long-chain fatty acids (VLCFA), increased bile acid intermediates, and increased branched chain fatty acids. Phytanic acid alpha-oxidation, pristanic acid beta-oxidation, and red cell plasmalogen are normal. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10
Sequence similarities	Belongs to the peroxin-16 family.

Ontologies

Keywords
Biological process	Peroxisome biogenesis
Cellular component	Endoplasmic reticulum Membrane Peroxisome
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Peroxisome biogenesis disorder Zellweger syndrome
Domain	Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ER-dependent peroxisome organization Inferred from direct assay Ref.9. Source: UniProtKB peroxisome membrane biogenesis Inferred from mutant phenotype Ref.7Ref.1. Source: UniProtKB protein import into peroxisome matrix Inferred from mutant phenotype Ref.2. Source: MGI protein import into peroxisome membrane Inferred from mutant phenotype Ref.7. Source: UniProtKB protein localization to endoplasmic reticulum Inferred from direct assay PubMed 19479899. Source: UniProtKB protein to membrane docking Inferred from direct assay PubMed 19114594. Source: UniProtKB
Cellular_component	endoplasmic reticulum membrane Inferred from direct assay Ref.9. Source: UniProtKB integral to peroxisomal membrane Inferred from direct assay Ref.7. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q9Y5Y5-1)

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: Q9Y5Y5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     318-336: RPLMDYLPTWQKIYFYSWG → TSQRAASPCLPARPHTQPWSPPAFLPGHP

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 336	336	Peroxisomal membrane protein PEX16		PRO_0000058330
Regions
	Topological domain	1 – 84	84	Cytoplasmic Potential
	Transmembrane	85 – 105	21	Helical; Potential
	Topological domain	106 – 110	5	Peroxisomal Potential
	Transmembrane	111 – 131	21	Helical; Potential
	Topological domain	132 – 336	205	Cytoplasmic Potential
	Region	66 – 81	16	Required for peroxisomal location
	Region	221 – 336	116	Interaction with PEX19
Natural variations
	Alternative sequence	318 – 336	19	RPLMD…FYSWG → TSQRAASPCLPARPHTQPWS PPAFLPGHP in isoform 2.		VSP_036593
	Natural variant	103	1	V → M. Corresponds to variant rs11553094 [ dbSNP | Ensembl ].		VAR_051272
	Natural variant	116	1	V → I. Ref.1 Ref.2 Ref.4 Corresponds to variant rs10742772 [ dbSNP | Ensembl ].		VAR_061841
	Natural variant	252	1	Missing in PBD8B. Ref.10		VAR_069208
	Natural variant	254	1	V → L. Corresponds to variant rs35214605 [ dbSNP | Ensembl ].		VAR_034145
	Natural variant	289	1	P → T in PBD8B. Ref.10		VAR_069209
	Natural variant	331	1	Y → C in PBD8B. Ref.10		VAR_069210
Experimental info
	Sequence conflict	107	1	V → L in AAH00467. Ref.4
	Sequence conflict	125	1	M → I in AAH00467. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 3, 2011. Version 2. Checksum: 57243AEE0B165C59	FASTA	336	38,629
	10 20 30 40 50 60 MEKLRLLGLR YQEYVTRHPA ATAQLETAVR GFSYLLAGRF ADSHELSELV YSASNLLVLL 70 80 90 100 110 120 NDGILRKELR KKLPVSLSQQ KLLTWLSVLE CVEVFMEMGA AKVWGEVGRW LVIALVQLAK 130 140 150 160 170 180 AVLRMLLLLW FKAGLQTSPP IVPLDRETQA QPPDGDHSPG NHEQSYVGKR SNRVVRTLQN 190 200 210 220 230 240 TPSLHSRHWG APQQREGRQQ QHHEELSATP TPLGLQETIA EFLYIARPLL HLLSLGLWGQ 250 260 270 280 290 300 RSWKPWLLAG VVDVTSLSLL SDRKGLTRRE RRELRRRTIL LLYYLLRSPF YDRFSEARIL 310 320 330 FLLQLLADHV PGVGLVTRPL MDYLPTWQKI YFYSWG
	Isoform 2 [UniParc]. Checksum: 2C7FE986CF33B64B	FASTA	346	39,270
	10 20 30 40 50 60 MEKLRLLGLR YQEYVTRHPA ATAQLETAVR GFSYLLAGRF ADSHELSELV YSASNLLVLL 70 80 90 100 110 120 NDGILRKELR KKLPVSLSQQ KLLTWLSVLE CVEVFMEMGA AKVWGEVGRW LVIALVQLAK 130 140 150 160 170 180 AVLRMLLLLW FKAGLQTSPP IVPLDRETQA QPPDGDHSPG NHEQSYVGKR SNRVVRTLQN 190 200 210 220 230 240 TPSLHSRHWG APQQREGRQQ QHHEELSATP TPLGLQETIA EFLYIARPLL HLLSLGLWGQ 250 260 270 280 290 300 RSWKPWLLAG VVDVTSLSLL SDRKGLTRRE RRELRRRTIL LLYYLLRSPF YDRFSEARIL 310 320 330 340 FLLQLLADHV PGVGLVTTSQ RAASPCLPAR PHTQPWSPPA FLPGHP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mutation in PEX16 is causal in the peroxisome-deficient Zellweger syndrome of complementation group D." Honsho M., Tamura S., Shimozawa N., Suzuki Y., Kondo N., Fujiki Y. Am. J. Hum. Genet. 63:1622-1630(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INVOLVEMENT IN PBD-CG9 AND PBD8A, VARIANT ILE-116.
[2]	"Peroxisome synthesis in the absence of preexisting peroxisomes." South S.T., Gould S.J. J. Cell Biol. 144:255-266(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ILE-116.
[3]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT ILE-116. Tissue: Lung.
[5]	"PEX19 binds multiple peroxisomal membrane proteins, is predominantly cytoplasmic, and is required for peroxisome membrane synthesis." Sacksteder K.A., Jones J.M., South S.T., Li X., Liu Y., Gould S.J. J. Cell Biol. 148:931-944(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PEX19.
[6]	"Human pex19p binds peroxisomal integral membrane proteins at regions distinct from their sorting sequences." Fransen M., Wylin T., Brees C., Mannaerts G.P., Van Veldhoven P.P. Mol. Cell. Biol. 21:4413-4424(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PEX19, SUBCELLULAR LOCATION.
[7]	"The membrane biogenesis peroxin Pex16p. Topogenesis and functional roles in peroxisomal membrane assembly." Honsho M., Hiroshige T., Fujiki Y. J. Biol. Chem. 277:44513-44524(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TOPOLOGY.
[8]	"PEX19 is a predominantly cytosolic chaperone and import receptor for class 1 peroxisomal membrane proteins." Jones J.M., Morrell J.C., Gould S.J. J. Cell Biol. 164:57-67(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PEX19.
[9]	"The origin and maintenance of mammalian peroxisomes involves a de novo PEX16-dependent pathway from the ER." Kim P.K., Mullen R.T., Schumann U., Lippincott-Schwartz J. J. Cell Biol. 173:521-532(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"Identification of an unusual variant peroxisome biogenesis disorder caused by mutations in the PEX16 gene." Ebberink M.S., Csanyi B., Chong W.K., Denis S., Sharp P., Mooijer P.A., Dekker C.J., Spooner C., Ngu L.H., De Sousa C., Wanders R.J., Fietz M.J., Clayton P.T., Waterham H.R., Ferdinandusse S. J. Med. Genet. 47:608-615(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PBD8B VAL-252 DEL; THR-289 AND CYS-331.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB016531 mRNA. Translation: BAA88826.1. AF118240 mRNA. Translation: AAD22466.1. AC068385 Genomic DNA. No translation available. BC004356 mRNA. Translation: AAH04356.1. BC000467 mRNA. Translation: AAH00467.1.
IPI	IPI00006722. IPI00386861.
RefSeq	NP_004804.1. NM_004813.2. NP_476515.1. NM_057174.2.
UniGene	Hs.100915.
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y5Y5. 3 interactions.
MINT	MINT-241739.
STRING	9606.ENSP00000241041.
Protein family/group databases
TCDB	9.A.17.1.2. integral membrane peroxisomal protein importer-2 (PPI2) family.
PTM databases
PhosphoSite	Q9Y5Y5.
Polymorphism databases
DMDM	20178039.
Proteomic databases
PaxDb	Q9Y5Y5.
PRIDE	Q9Y5Y5.
Protocols and materials databases
DNASU	9409.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000241041; ENSP00000241041; ENSG00000121680. ENST00000378750; ENSP00000368024; ENSG00000121680.
GeneID	9409.
KEGG	hsa:9409.
UCSC	uc001nbt.3. human. uc001nbu.3. human.
Organism-specific databases
CTD	9409.
GeneCards	GC11M045931.
HGNC	HGNC:8857. PEX16.
HPA	HPA043286.
MIM	603360. gene. 614876. phenotype. 614877. phenotype.
neXtProt	NX_Q9Y5Y5.
Orphanet	772. Infantile Refsum disease. 44. Neonatal adrenoleukodystrophy. 912. Zellweger syndrome.
PharmGKB	PA33199.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG289038.
HOGENOM	HOG000008062.
HOVERGEN	HBG053572.
KO	K13335.
OMA	WGQRSWT.
Gene expression databases
ArrayExpress	Q9Y5Y5.
Bgee	Q9Y5Y5.
CleanEx	HS_PEX16.
Genevestigator	Q9Y5Y5.
GermOnline	ENSG00000121680. Homo sapiens.
Family and domain databases
InterPro	IPR013919. Pex16. [Graphical view]
Pfam	PF08610. Pex16. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	9409.
NextBio	35246.
SOURCE	Search...

Entry information

Entry name

PEX16_HUMAN

Accession

Primary (citable) accession number: Q9Y5Y5
Secondary accession number(s): Q9BWB9

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 16, 2002
Last sequence update:	May 3, 2011
Last modified:	May 29, 2013
This is version 111 of the entry and version 2 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.