PEX16_HUMAN
ID PEX16_HUMAN Reviewed; 336 AA.
AC Q9Y5Y5; Q9BWB9;
DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 03-MAY-2011, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Peroxisomal membrane protein PEX16;
DE AltName: Full=Peroxin-16;
DE AltName: Full=Peroxisomal biogenesis factor 16;
GN Name=PEX16;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INVOLVEMENT IN PBD-CG9 AND PBD8A,
RP AND VARIANT ILE-116.
RX PubMed=9837814; DOI=10.1086/302161;
RA Honsho M., Tamura S., Shimozawa N., Suzuki Y., Kondo N., Fujiki Y.;
RT "Mutation in PEX16 is causal in the peroxisome-deficient Zellweger syndrome
RT of complementation group D.";
RL Am. J. Hum. Genet. 63:1622-1630(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ILE-116.
RX PubMed=9922452; DOI=10.1083/jcb.144.2.255;
RA South S.T., Gould S.J.;
RT "Peroxisome synthesis in the absence of preexisting peroxisomes.";
RL J. Cell Biol. 144:255-266(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP ILE-116.
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, AND INTERACTION WITH PEX19.
RX PubMed=10704444; DOI=10.1083/jcb.148.5.931;
RA Sacksteder K.A., Jones J.M., South S.T., Li X., Liu Y., Gould S.J.;
RT "PEX19 binds multiple peroxisomal membrane proteins, is predominantly
RT cytoplasmic, and is required for peroxisome membrane synthesis.";
RL J. Cell Biol. 148:931-944(2000).
RN [6]
RP INTERACTION WITH PEX19, AND SUBCELLULAR LOCATION.
RX PubMed=11390669; DOI=10.1128/mcb.21.13.4413-4424.2001;
RA Fransen M., Wylin T., Brees C., Mannaerts G.P., Van Veldhoven P.P.;
RT "Human pex19p binds peroxisomal integral membrane proteins at regions
RT distinct from their sorting sequences.";
RL Mol. Cell. Biol. 21:4413-4424(2001).
RN [7]
RP FUNCTION, AND TOPOLOGY.
RX PubMed=12223482; DOI=10.1074/jbc.m206139200;
RA Honsho M., Hiroshige T., Fujiki Y.;
RT "The membrane biogenesis peroxin Pex16p. Topogenesis and functional roles
RT in peroxisomal membrane assembly.";
RL J. Biol. Chem. 277:44513-44524(2002).
RN [8]
RP INTERACTION WITH PEX19.
RX PubMed=14709540; DOI=10.1083/jcb.200304111;
RA Jones J.M., Morrell J.C., Gould S.J.;
RT "PEX19 is a predominantly cytosolic chaperone and import receptor for class
RT 1 peroxisomal membrane proteins.";
RL J. Cell Biol. 164:57-67(2004).
RN [9]
RP FUNCTION.
RX PubMed=16717127; DOI=10.1083/jcb.200601036;
RA Kim P.K., Mullen R.T., Schumann U., Lippincott-Schwartz J.;
RT "The origin and maintenance of mammalian peroxisomes involves a de novo
RT PEX16-dependent pathway from the ER.";
RL J. Cell Biol. 173:521-532(2006).
RN [10]
RP SUBCELLULAR LOCATION.
RX PubMed=21768384; DOI=10.1073/pnas.1103283108;
RA Yonekawa S., Furuno A., Baba T., Fujiki Y., Ogasawara Y., Yamamoto A.,
RA Tagaya M., Tani K.;
RT "Sec16B is involved in the endoplasmic reticulum export of the peroxisomal
RT membrane biogenesis factor peroxin 16 (Pex16) in mammalian cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:12746-12751(2011).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [13]
RP VARIANTS PBD8B VAL-252 DEL; THR-289 AND CYS-331.
RX PubMed=20647552; DOI=10.1136/jmg.2009.074302;
RA Ebberink M.S., Csanyi B., Chong W.K., Denis S., Sharp P., Mooijer P.A.,
RA Dekker C.J., Spooner C., Ngu L.H., De Sousa C., Wanders R.J., Fietz M.J.,
RA Clayton P.T., Waterham H.R., Ferdinandusse S.;
RT "Identification of an unusual variant peroxisome biogenesis disorder caused
RT by mutations in the PEX16 gene.";
RL J. Med. Genet. 47:608-615(2010).
CC -!- FUNCTION: Required for peroxisome membrane biogenesis. May play a role
CC in early stages of peroxisome assembly. Can recruit other peroxisomal
CC proteins, such as PEX3 and PMP34, to de novo peroxisomes derived from
CC the endoplasmic reticulum (ER). May function as receptor for PEX3.
CC {ECO:0000269|PubMed:10704444, ECO:0000269|PubMed:12223482,
CC ECO:0000269|PubMed:16717127}.
CC -!- SUBUNIT: Interacts with PEX19. {ECO:0000269|PubMed:10704444,
CC ECO:0000269|PubMed:11390669, ECO:0000269|PubMed:14709540}.
CC -!- INTERACTION:
CC Q9Y5Y5; Q13520: AQP6; NbExp=3; IntAct=EBI-981985, EBI-13059134;
CC Q9Y5Y5; Q8IUN9: CLEC10A; NbExp=3; IntAct=EBI-981985, EBI-2873246;
CC Q9Y5Y5; Q96BA8: CREB3L1; NbExp=3; IntAct=EBI-981985, EBI-6942903;
CC Q9Y5Y5; O95424: DEXI; NbExp=3; IntAct=EBI-981985, EBI-724515;
CC Q9Y5Y5; O00559: EBAG9; NbExp=3; IntAct=EBI-981985, EBI-8787095;
CC Q9Y5Y5; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-981985, EBI-781551;
CC Q9Y5Y5; O15552: FFAR2; NbExp=3; IntAct=EBI-981985, EBI-2833872;
CC Q9Y5Y5; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-981985, EBI-13345167;
CC Q9Y5Y5; P48051: KCNJ6; NbExp=3; IntAct=EBI-981985, EBI-12017638;
CC Q9Y5Y5; O95214: LEPROTL1; NbExp=3; IntAct=EBI-981985, EBI-750776;
CC Q9Y5Y5; Q5SR56: MFSD14B; NbExp=3; IntAct=EBI-981985, EBI-373355;
CC Q9Y5Y5; Q8N4V1: MMGT1; NbExp=3; IntAct=EBI-981985, EBI-6163737;
CC Q9Y5Y5; Q96CV9: OPTN; NbExp=3; IntAct=EBI-981985, EBI-748974;
CC Q9Y5Y5; Q13113: PDZK1IP1; NbExp=3; IntAct=EBI-981985, EBI-716063;
CC Q9Y5Y5; P40855: PEX19; NbExp=20; IntAct=EBI-981985, EBI-594747;
CC Q9Y5Y5; P56589: PEX3; NbExp=4; IntAct=EBI-981985, EBI-594885;
CC Q9Y5Y5; O15173: PGRMC2; NbExp=3; IntAct=EBI-981985, EBI-1050125;
CC Q9Y5Y5; Q9H6H4: REEP4; NbExp=3; IntAct=EBI-981985, EBI-7545592;
CC Q9Y5Y5; Q14973: SLC10A1; NbExp=3; IntAct=EBI-981985, EBI-3923031;
CC Q9Y5Y5; Q3KNW5: SLC10A6; NbExp=3; IntAct=EBI-981985, EBI-18159983;
CC Q9Y5Y5; P54219-3: SLC18A1; NbExp=3; IntAct=EBI-981985, EBI-17595455;
CC Q9Y5Y5; Q9NQQ7-3: SLC35C2; NbExp=3; IntAct=EBI-981985, EBI-17295964;
CC Q9Y5Y5; Q9Y320: TMX2; NbExp=3; IntAct=EBI-981985, EBI-6447886;
CC Q9Y5Y5; Q02223: TNFRSF17; NbExp=3; IntAct=EBI-981985, EBI-519945;
CC Q9Y5Y5; Q96MV8: ZDHHC15; NbExp=3; IntAct=EBI-981985, EBI-12837904;
CC -!- SUBCELLULAR LOCATION: Peroxisome membrane {ECO:0000269|PubMed:11390669,
CC ECO:0000269|PubMed:21768384}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:11390669}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y5Y5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y5Y5-2; Sequence=VSP_036593;
CC -!- DISEASE: Peroxisome biogenesis disorder complementation group 9 (PBD-
CC CG9) [MIM:614876]: A peroxisomal disorder arising from a failure of
CC protein import into the peroxisomal membrane or matrix. The peroxisome
CC biogenesis disorders (PBD group) are genetically heterogeneous with at
CC least 14 distinct genetic groups as concluded from complementation
CC studies. Include disorders are: Zellweger syndrome (ZWS), neonatal
CC adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and
CC classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and
CC IRD are distinct from RCDP and constitute a clinical continuum of
CC overlapping phenotypes known as the Zellweger spectrum (PBD-ZSS).
CC {ECO:0000269|PubMed:9837814}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Peroxisome biogenesis disorder 8A (PBD8A) [MIM:614876]: A
CC fatal peroxisome biogenesis disorder belonging to the Zellweger disease
CC spectrum and clinically characterized by severe neurologic dysfunction
CC with profound psychomotor retardation, severe hypotonia and neonatal
CC seizures, craniofacial abnormalities, liver dysfunction, and
CC biochemically by the absence of peroxisomes. Additional features
CC include cardiovascular and skeletal defects, renal cysts, ocular
CC abnormalities, and hearing impairment. Most severely affected
CC individuals with the classic form of the disease (classic Zellweger
CC syndrome) die within the first year of life.
CC {ECO:0000269|PubMed:9837814}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Peroxisome biogenesis disorder 8B (PBD8B) [MIM:614877]: A
CC relatively mild peroxisome biogenesis disorder. Affected individuals
CC manifest lower limb spasticity and ataxia resulting in wheelchair
CC dependence. Other features include optic atrophy, cataracts,
CC dysarthria, dysphagia, constipation, and a peripheral demyelinating
CC motor and sensory neuropathy. Cognition is relatively preserved.
CC Biochemical abnormalities are mild and include increased very-long-
CC chain fatty acids (VLCFA), increased bile acid intermediates, and
CC increased branched chain fatty acids. Phytanic acid alpha-oxidation,
CC pristanic acid beta-oxidation, and red cell plasmalogen are normal.
CC {ECO:0000269|PubMed:20647552}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the peroxin-16 family. {ECO:0000305}.
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DR EMBL; AB016531; BAA88826.1; -; mRNA.
DR EMBL; AF118240; AAD22466.1; -; mRNA.
DR EMBL; AC068385; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC004356; AAH04356.1; -; mRNA.
DR EMBL; BC000467; AAH00467.1; -; mRNA.
DR CCDS; CCDS31472.1; -. [Q9Y5Y5-1]
DR CCDS; CCDS7917.1; -. [Q9Y5Y5-2]
DR RefSeq; NP_004804.1; NM_004813.2. [Q9Y5Y5-1]
DR RefSeq; NP_476515.1; NM_057174.2. [Q9Y5Y5-2]
DR AlphaFoldDB; Q9Y5Y5; -.
DR BioGRID; 114804; 55.
DR IntAct; Q9Y5Y5; 36.
DR MINT; Q9Y5Y5; -.
DR STRING; 9606.ENSP00000241041; -.
DR ChEMBL; CHEMBL3774297; -.
DR TCDB; 9.A.17.1.2; the integral membrane peroxisomal protein importer-2 (ppi2) family.
DR iPTMnet; Q9Y5Y5; -.
DR PhosphoSitePlus; Q9Y5Y5; -.
DR BioMuta; PEX16; -.
DR DMDM; 332278135; -.
DR EPD; Q9Y5Y5; -.
DR jPOST; Q9Y5Y5; -.
DR MassIVE; Q9Y5Y5; -.
DR MaxQB; Q9Y5Y5; -.
DR PaxDb; Q9Y5Y5; -.
DR PeptideAtlas; Q9Y5Y5; -.
DR PRIDE; Q9Y5Y5; -.
DR ProteomicsDB; 86541; -. [Q9Y5Y5-1]
DR ProteomicsDB; 86542; -. [Q9Y5Y5-2]
DR Antibodypedia; 26211; 132 antibodies from 27 providers.
DR DNASU; 9409; -.
DR Ensembl; ENST00000241041.7; ENSP00000241041.3; ENSG00000121680.16. [Q9Y5Y5-2]
DR Ensembl; ENST00000378750.10; ENSP00000368024.5; ENSG00000121680.16. [Q9Y5Y5-1]
DR GeneID; 9409; -.
DR KEGG; hsa:9409; -.
DR MANE-Select; ENST00000378750.10; ENSP00000368024.5; NM_004813.4; NP_004804.2.
DR UCSC; uc001nbt.4; human. [Q9Y5Y5-1]
DR CTD; 9409; -.
DR DisGeNET; 9409; -.
DR GeneCards; PEX16; -.
DR GeneReviews; PEX16; -.
DR HGNC; HGNC:8857; PEX16.
DR HPA; ENSG00000121680; Low tissue specificity.
DR MalaCards; PEX16; -.
DR MIM; 603360; gene.
DR MIM; 614876; phenotype.
DR MIM; 614877; phenotype.
DR neXtProt; NX_Q9Y5Y5; -.
DR OpenTargets; ENSG00000121680; -.
DR Orphanet; 772; Infantile Refsum disease.
DR Orphanet; 44; Neonatal adrenoleukodystrophy.
DR Orphanet; 912; Zellweger syndrome.
DR PharmGKB; PA33199; -.
DR VEuPathDB; HostDB:ENSG00000121680; -.
DR eggNOG; KOG4546; Eukaryota.
DR GeneTree; ENSGT00390000017790; -.
DR HOGENOM; CLU_070601_0_0_1; -.
DR InParanoid; Q9Y5Y5; -.
DR OMA; GQRSWKQ; -.
DR OrthoDB; 883624at2759; -.
DR TreeFam; TF324139; -.
DR PathwayCommons; Q9Y5Y5; -.
DR Reactome; R-HSA-9603798; Class I peroxisomal membrane protein import.
DR SignaLink; Q9Y5Y5; -.
DR BioGRID-ORCS; 9409; 33 hits in 1084 CRISPR screens.
DR ChiTaRS; PEX16; human.
DR GeneWiki; PEX16; -.
DR GenomeRNAi; 9409; -.
DR Pharos; Q9Y5Y5; Tbio.
DR PRO; PR:Q9Y5Y5; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9Y5Y5; protein.
DR Bgee; ENSG00000121680; Expressed in prefrontal cortex and 190 other tissues.
DR ExpressionAtlas; Q9Y5Y5; baseline and differential.
DR Genevisible; Q9Y5Y5; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005779; C:integral component of peroxisomal membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005778; C:peroxisomal membrane; HDA:UniProtKB.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0106101; P:ER-dependent peroxisome localization; IDA:UniProtKB.
DR GO; GO:0032581; P:ER-dependent peroxisome organization; IDA:UniProtKB.
DR GO; GO:0016557; P:peroxisome membrane biogenesis; IMP:UniProtKB.
DR GO; GO:0007031; P:peroxisome organization; IMP:UniProtKB.
DR GO; GO:0016558; P:protein import into peroxisome matrix; IMP:MGI.
DR GO; GO:0045046; P:protein import into peroxisome membrane; IMP:UniProtKB.
DR GO; GO:0006625; P:protein targeting to peroxisome; IMP:UniProtKB.
DR GO; GO:0022615; P:protein to membrane docking; IDA:UniProtKB.
DR InterPro; IPR013919; Pex16.
DR PANTHER; PTHR13299; PTHR13299; 1.
DR Pfam; PF08610; Pex16; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Membrane; Peroxisome;
KW Peroxisome biogenesis; Peroxisome biogenesis disorder; Reference proteome;
KW Transmembrane; Transmembrane helix; Zellweger syndrome.
FT CHAIN 1..336
FT /note="Peroxisomal membrane protein PEX16"
FT /id="PRO_0000058330"
FT TOPO_DOM 1..84
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 85..105
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 106..110
FT /note="Peroxisomal"
FT /evidence="ECO:0000255"
FT TRANSMEM 111..131
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 132..336
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 66..81
FT /note="Required for peroxisomal location"
FT /evidence="ECO:0000269|PubMed:11390669"
FT REGION 142..171
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 184..210
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 221..336
FT /note="Interaction with PEX19"
FT /evidence="ECO:0000269|PubMed:11390669"
FT VAR_SEQ 318..336
FT /note="RPLMDYLPTWQKIYFYSWG -> TSQRAASPCLPARPHTQPWSPPAFLPGHP
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_036593"
FT VARIANT 103
FT /note="V -> M (in dbSNP:rs11553094)"
FT /id="VAR_051272"
FT VARIANT 116
FT /note="V -> I (in dbSNP:rs10742772)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:9837814, ECO:0000269|PubMed:9922452"
FT /id="VAR_061841"
FT VARIANT 252
FT /note="Missing (in PBD8B)"
FT /evidence="ECO:0000269|PubMed:20647552"
FT /id="VAR_069208"
FT VARIANT 254
FT /note="V -> L (in dbSNP:rs35214605)"
FT /id="VAR_034145"
FT VARIANT 289
FT /note="P -> T (in PBD8B)"
FT /evidence="ECO:0000269|PubMed:20647552"
FT /id="VAR_069209"
FT VARIANT 331
FT /note="Y -> C (in PBD8B; dbSNP:rs397514472)"
FT /evidence="ECO:0000269|PubMed:20647552"
FT /id="VAR_069210"
FT CONFLICT 107
FT /note="V -> L (in Ref. 4; AAH00467)"
FT /evidence="ECO:0000305"
FT CONFLICT 125
FT /note="M -> I (in Ref. 4; AAH00467)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 336 AA; 38629 MW; 57243AEE0B165C59 CRC64;
MEKLRLLGLR YQEYVTRHPA ATAQLETAVR GFSYLLAGRF ADSHELSELV YSASNLLVLL
NDGILRKELR KKLPVSLSQQ KLLTWLSVLE CVEVFMEMGA AKVWGEVGRW LVIALVQLAK
AVLRMLLLLW FKAGLQTSPP IVPLDRETQA QPPDGDHSPG NHEQSYVGKR SNRVVRTLQN
TPSLHSRHWG APQQREGRQQ QHHEELSATP TPLGLQETIA EFLYIARPLL HLLSLGLWGQ
RSWKPWLLAG VVDVTSLSLL SDRKGLTRRE RRELRRRTIL LLYYLLRSPF YDRFSEARIL
FLLQLLADHV PGVGLVTRPL MDYLPTWQKI YFYSWG
