AP3B2_HUMAN
ID AP3B2_HUMAN Reviewed; 1082 AA.
AC Q13367; A4Z4T7; B7ZKR7; B7ZKS0; O14808; Q52LY8;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 26-SEP-2001, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=AP-3 complex subunit beta-2;
DE AltName: Full=Adaptor protein complex AP-3 subunit beta-2;
DE AltName: Full=Adaptor-related protein complex 3 subunit beta-2;
DE AltName: Full=Beta-3B-adaptin;
DE AltName: Full=Clathrin assembly protein complex 3 beta-2 large chain;
DE AltName: Full=Neuron-specific vesicle coat protein beta-NAP;
GN Name=AP3B2;
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).
RC TISSUE=Cerebellum, and Hippocampus;
RX PubMed=7671305; DOI=10.1016/0092-8674(95)90474-3;
RA Newman L.S., McKeever M.O., Okano H.J., Darnell R.B.;
RT "Beta-NAP, a cerebellar degeneration antigen, is a neuron-specific vesicle
RT coat protein.";
RL Cell 82:773-783(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING, AND TISSUE
RP SPECIFICITY.
RX PubMed=17453999; DOI=10.1080/10425170600842121;
RA Chen C., Zou X., Ji C., Zhao S., Lv L., Gu S., Xie Y., Mao Y.;
RT "Characterization of AP3B2_v2, a novel splice variant of human AP3B2.";
RL DNA Seq. 18:165-168(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Peden A.A., Robinson M.S.;
RT "Correction of beta3B.";
RL Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Colon;
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 [6]
RP TISSUE SPECIFICITY.
RX PubMed=1851215; DOI=10.1523/jneurosci.11-05-01224.1991;
RA Darnell R.B., Furneaux H.M., Posner J.B.;
RT "Antiserum from a patient with cerebellar degeneration identifies a novel
RT protein in Purkinje cells, cortical neurons, and neuroectodermal tumors.";
RL J. Neurosci. 11:1224-1230(1991).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-272, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [8]
RP INVOLVEMENT IN DEE48.
RX PubMed=27889060; DOI=10.1016/j.ajhg.2016.10.009;
RA Assoum M., Philippe C., Isidor B., Perrin L., Makrythanasis P.,
RA Sondheimer N., Paris C., Douglas J., Lesca G., Antonarakis S., Hamamy H.,
RA Jouan T., Duffourd Y., Auvin S., Saunier A., Begtrup A., Nowak C.,
RA Chatron N., Ville D., Mireskandari K., Milani P., Jonveaux P., Lemeur G.,
RA Milh M., Amamoto M., Kato M., Nakashima M., Miyake N., Matsumoto N.,
RA Masri A., Thauvin-Robinet C., Riviere J.B., Faivre L., Thevenon J.;
RT "Autosomal-recessive mutations in AP3B2, adaptor-related protein complex 3
RT beta 2 subunit, cause an early-onset epileptic encephalopathy with optic
RT atrophy.";
RL Am. J. Hum. Genet. 99:1368-1376(2016).
RN [9]
RP INVOLVEMENT IN DEE48.
RX PubMed=27431290; DOI=10.1038/mp.2016.113;
RA Anazi S., Maddirevula S., Faqeih E., Alsedairy H., Alzahrani F.,
RA Shamseldin H.E., Patel N., Hashem M., Ibrahim N., Abdulwahab F., Ewida N.,
RA Alsaif H.S., Al Sharif H., Alamoudi W., Kentab A., Bashiri F.A.,
RA Alnaser M., AlWadei A.H., Alfadhel M., Eyaid W., Hashem A., Al Asmari A.,
RA Saleh M.M., AlSaman A., Alhasan K.A., Alsughayir M., Al Shammari M.,
RA Mahmoud A., Al-Hassnan Z.N., Al-Husain M., Osama Khalil R.,
RA Abd El Meguid N., Masri A., Ali R., Ben-Omran T., El Fishway P.,
RA Hashish A., Ercan Sencicek A., State M., Alazami A.M., Salih M.A.,
RA Altassan N., Arold S.T., Abouelhoda M., Wakil S.M., Monies D., Shaheen R.,
RA Alkuraya F.S.;
RT "Clinical genomics expands the morbid genome of intellectual disability and
RT offers a high diagnostic yield.";
RL Mol. Psychiatry 22:615-624(2017).
CC -!- FUNCTION: Subunit of non-clathrin- and clathrin-associated adaptor
CC protein complex 3 (AP-3) that plays a role in protein sorting in the
CC late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes
CC mediate both the recruitment of clathrin to membranes and the
CC recognition of sorting signals within the cytosolic tails of
CC transmembrane cargo molecules. AP-3 appears to be involved in the
CC sorting of a subset of transmembrane proteins targeted to lysosomes and
CC lysosome-related organelles. In concert with the BLOC-1 complex, AP-3
CC is required to target cargos into vesicles assembled at cell bodies for
CC delivery into neurites and nerve terminals.
CC -!- SUBUNIT: AP-3 associates with the BLOC-1 complex (By similarity).
CC Adaptor protein complex 3 (AP-3) is a heterotetramer composed of two
CC large adaptins (delta-type subunit AP3D1 and beta-type subunit AP3B1 or
CC AP3B2), a medium adaptin (mu-type subunit AP3M1 or AP3M2) and a small
CC adaptin (sigma-type subunit APS1 or AP3S2). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, clathrin-coated vesicle
CC membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250};
CC Cytoplasmic side {ECO:0000250}. Golgi apparatus {ECO:0000250}.
CC Note=Component of the coat surrounding the cytoplasmic face of coated
CC vesicles located at the Golgi complex. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=AP3B2_v1;
CC IsoId=Q13367-1; Sequence=Displayed;
CC Name=2; Synonyms=AP3B2_v2;
CC IsoId=Q13367-2; Sequence=VSP_043905;
CC Name=3;
CC IsoId=Q13367-3; Sequence=VSP_054918;
CC Name=4;
CC IsoId=Q13367-4; Sequence=VSP_054919;
CC -!- TISSUE SPECIFICITY: Isoform 1 expression is specific to nervous system.
CC Expressed in nerve terminal and cell body, and is associated with
CC nerve-terminal vesicles. Expression seen in Purkinje cells, cortical
CC neurons, neuroectodermal tumors and graded in cerebral cortex (deeper
CC layers exhibit stronger expression) (PubMed:1851215). Isoform 2 is
CC expressed at high levels in brain and testis (PubMed:17453999).
CC {ECO:0000269|PubMed:17453999, ECO:0000269|PubMed:1851215}.
CC -!- DEVELOPMENTAL STAGE: Expressed from early in development through
CC adulthood.
CC -!- DISEASE: Developmental and epileptic encephalopathy 48 (DEE48)
CC [MIM:617276]: A form of epileptic encephalopathy, a heterogeneous group
CC of severe early-onset epilepsies characterized by refractory seizures,
CC neurodevelopmental impairment, and poor prognosis. Development is
CC normal prior to seizure onset, after which cognitive and motor delays
CC become apparent. DEE48 is an autosomal recessive form characterized by
CC onset of seizures in the first year of life. Affected individuals
CC manifest global developmental delay, intellectual disability, absent
CC speech, and poor, if any, motor development.
CC {ECO:0000269|PubMed:27431290, ECO:0000269|PubMed:27889060}. Note=The
CC disease may be caused by variants affecting the gene represented in
CC this entry.
CC -!- SIMILARITY: Belongs to the adaptor complexes large subunit family.
CC {ECO:0000305}.
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DR EMBL; U37673; AAC50219.1; -; mRNA.
DR EMBL; AF022152; AAB71894.1; -; mRNA.
DR EMBL; DQ092369; AAZ38147.1; -; mRNA.
DR EMBL; AC105339; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; FJ695193; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC093739; AAH93739.1; -; mRNA.
DR EMBL; BC143342; AAI43343.1; -; mRNA.
DR EMBL; BC143346; AAI43347.1; -; mRNA.
DR CCDS; CCDS45331.1; -. [Q13367-1]
DR CCDS; CCDS61736.1; -. [Q13367-3]
DR CCDS; CCDS61737.1; -. [Q13367-4]
DR PIR; T50650; T50650.
DR RefSeq; NP_001265440.1; NM_001278511.1. [Q13367-3]
DR RefSeq; NP_001265441.1; NM_001278512.1. [Q13367-4]
DR RefSeq; NP_001335370.1; NM_001348441.1. [Q13367-2]
DR RefSeq; NP_004635.2; NM_004644.4. [Q13367-1]
DR AlphaFoldDB; Q13367; -.
DR SMR; Q13367; -.
DR BioGRID; 113788; 24.
DR ComplexPortal; CPX-5053; Neuronal AP-3 Adaptor complex, sigma3b variant.
DR ComplexPortal; CPX-5055; Neuronal AP-3 Adaptor complex, sigma3a variant.
DR CORUM; Q13367; -.
DR ELM; Q13367; -.
DR IntAct; Q13367; 11.
DR MINT; Q13367; -.
DR STRING; 9606.ENSP00000440984; -.
DR iPTMnet; Q13367; -.
DR PhosphoSitePlus; Q13367; -.
DR SwissPalm; Q13367; -.
DR BioMuta; AP3B2; -.
DR DMDM; 18202497; -.
DR EPD; Q13367; -.
DR jPOST; Q13367; -.
DR MassIVE; Q13367; -.
DR MaxQB; Q13367; -.
DR PaxDb; Q13367; -.
DR PeptideAtlas; Q13367; -.
DR PRIDE; Q13367; -.
DR ProteomicsDB; 59351; -. [Q13367-1]
DR ProteomicsDB; 59352; -. [Q13367-2]
DR ProteomicsDB; 7189; -.
DR ProteomicsDB; 7190; -.
DR Antibodypedia; 28110; 141 antibodies from 27 providers.
DR DNASU; 8120; -.
DR Ensembl; ENST00000535348.5; ENSP00000438721.1; ENSG00000103723.17. [Q13367-3]
DR Ensembl; ENST00000535359.6; ENSP00000440984.1; ENSG00000103723.17. [Q13367-4]
DR Ensembl; ENST00000668990.2; ENSP00000499235.1; ENSG00000103723.17. [Q13367-1]
DR GeneID; 8120; -.
DR KEGG; hsa:8120; -.
DR MANE-Select; ENST00000535359.6; ENSP00000440984.1; NM_001278512.2; NP_001265441.1. [Q13367-4]
DR UCSC; uc010uoh.4; human. [Q13367-1]
DR CTD; 8120; -.
DR DisGeNET; 8120; -.
DR GeneCards; AP3B2; -.
DR HGNC; HGNC:567; AP3B2.
DR HPA; ENSG00000103723; Tissue enhanced (brain, pituitary gland, retina).
DR MalaCards; AP3B2; -.
DR MIM; 602166; gene.
DR MIM; 617276; phenotype.
DR neXtProt; NX_Q13367; -.
DR OpenTargets; ENSG00000103723; -.
DR Orphanet; 442835; Non-specific early-onset epileptic encephalopathy.
DR PharmGKB; PA24858; -.
DR VEuPathDB; HostDB:ENSG00000103723; -.
DR eggNOG; KOG1060; Eukaryota.
DR GeneTree; ENSGT00940000156817; -.
DR HOGENOM; CLU_006320_3_1_1; -.
DR InParanoid; Q13367; -.
DR OrthoDB; 323029at2759; -.
DR PhylomeDB; Q13367; -.
DR TreeFam; TF314605; -.
DR PathwayCommons; Q13367; -.
DR SignaLink; Q13367; -.
DR SIGNOR; Q13367; -.
DR BioGRID-ORCS; 8120; 11 hits in 1071 CRISPR screens.
DR ChiTaRS; AP3B2; human.
DR GeneWiki; AP3B2; -.
DR GenomeRNAi; 8120; -.
DR Pharos; Q13367; Tbio.
DR PRO; PR:Q13367; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q13367; protein.
DR Bgee; ENSG00000103723; Expressed in right hemisphere of cerebellum and 128 other tissues.
DR ExpressionAtlas; Q13367; baseline and differential.
DR Genevisible; Q13367; HS.
DR GO; GO:0030123; C:AP-3 adaptor complex; IC:ComplexPortal.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0030665; C:clathrin-coated vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005769; C:early endosome; IC:ComplexPortal.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0097708; C:intracellular vesicle; TAS:GO_Central.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0008089; P:anterograde axonal transport; ISS:UniProtKB.
DR GO; GO:0048490; P:anterograde synaptic vesicle transport; ISS:UniProtKB.
DR GO; GO:0035654; P:clathrin-coated vesicle cargo loading, AP-3-mediated; IC:ComplexPortal.
DR GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR GO; GO:0046907; P:intracellular transport; IC:ComplexPortal.
DR GO; GO:0016183; P:synaptic vesicle coating; IC:ComplexPortal.
DR GO; GO:0036465; P:synaptic vesicle recycling; IC:ComplexPortal.
DR GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR026740; AP3_beta.
DR InterPro; IPR029390; AP3B_C.
DR InterPro; IPR026739; AP_beta.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR002553; Clathrin/coatomer_adapt-like_N.
DR InterPro; IPR013041; Clathrin_app_Ig-like_sf.
DR PANTHER; PTHR11134; PTHR11134; 1.
DR Pfam; PF01602; Adaptin_N; 1.
DR Pfam; PF14796; AP3B1_C; 1.
DR PIRSF; PIRSF037096; AP3_complex_beta; 1.
DR SMART; SM01355; AP3B1_C; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF49348; SSF49348; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasmic vesicle; Epilepsy; Golgi apparatus;
KW Membrane; Phosphoprotein; Protein transport; Reference proteome; Transport.
FT CHAIN 1..1082
FT /note="AP-3 complex subunit beta-2"
FT /id="PRO_0000193748"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 272..295
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 666..802
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 666..680
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 715..729
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 730..760
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 272
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 282
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JME5"
FT VAR_SEQ 1..937
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17453999"
FT /id="VSP_043905"
FT VAR_SEQ 89..120
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054918"
FT VAR_SEQ 656
FT /note="V -> VEEEDLSLIETHVGLLGEYT (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_054919"
FT CONFLICT 332..346
FT /note="APKAEVGVIAKALVR -> GPRRKWRHRQGAGA (in Ref. 1;
FT AAC50219)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1082 AA; 119059 MW; EE2AC45263F4552E CRC64;
MSAAPAYSED KGGSAGPGEP EYGHDPASGG IFSSDYKRHD DLKEMLDTNK DSLKLEAMKR
IVAMIARGKN ASDLFPAVVK NVACKNIEVK KLVYVYLVRY AEEQQDLALL SISTFQRGLK
DPNQLIRASA LRVLSSIRVP IIVPIMMLAI KEAASDMSPY VRKTAAHAIP KLYSLDSDQK
DQLIEVIEKL LADKTTLVAG SVVMAFEEVC PERIDLIHKN YRKLCNLLID VEEWGQVVII
SMLTRYARTQ FLSPTQNESL LEENAEKAFY GSEEDEAKGA GSEETAAAAA PSRKPYVMDP
DHRLLLRNTK PLLQSRSAAV VMAVAQLYFH LAPKAEVGVI AKALVRLLRS HSEVQYVVLQ
NVATMSIKRR GMFEPYLKSF YIRSTDPTQI KILKLEVLTN LANETNIPTV LREFQTYIRS
MDKDFVAATI QAIGRCATNI GRVRDTCLNG LVQLLSNRDE LVVAESVVVI KKLLQMQPAQ
HGEIIKHLAK LTDNIQVPMA RASILWLIGE YCEHVPRIAP DVLRKMAKSF TAEEDIVKLQ
VINLAAKLYL TNSKQTKLLT QYVLSLAKYD QNYDIRDRAR FTRQLIVPSE QGGALSRHAK
KLFLAPKPAP VLESSFKDRD HFQLGSLSHL LNAKATGYQE LPDWPEEAPD PSVRNVEVPE
WTKCSNREKR KEKEKPFYSD SEGESGPTES ADSDPESESE SDSKSSSESG SGESSSESDN
EDQDEDEEKG RGSESEQSEE DGKRKTKKKV PERKGEASSS DEGSDSSSSS SESEMTSESE
EEQLEPASWS RKTPPSSKSA PATKEISLLD LEDFTPPSVQ PVSPPAIVST SLAADLEGLT
LTDSTLVPSL LSPVSGVGRQ ELLHRVAGEG LAVDYTFSRQ PFSGDPHMVS VHIHFSNSSD
TPIKGLHVGT PKLPAGISIQ EFPEIESLAP GESATAVMGI NFCDSTQAAN FQLCTQTRQF
YVSIQPPVGE LMAPVFMSEN EFKKEQGKLM GMNEITEKLM LPDTCRSDHI VVQKVTATAN
LGRVPCGTSD EYRFAGRTLT GGSLVLLTLD ARPAGAAQLT VNSEKMVIGT MLVKDVIQAL
TQ
