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   27-MAR-2024, entry version 181.
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; 30.
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; 9606-ENSP00000440984; -.
DR   PeptideAtlas; Q13367; -.
DR   ProteomicsDB; 59351; -. [Q13367-1]
DR   ProteomicsDB; 59352; -. [Q13367-2]
DR   ProteomicsDB; 7189; -.
DR   ProteomicsDB; 7190; -.
DR   Pumba; Q13367; -.
DR   Antibodypedia; 28110; 152 antibodies from 28 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   AGR; HGNC:567; -.
DR   DisGeNET; 8120; -.
DR   GeneCards; AP3B2; -.
DR   HGNC; HGNC:567; AP3B2.
DR   HPA; ENSG00000103723; Group enriched (brain, parathyroid gland, 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; 7857at2759; -.
DR   PhylomeDB; Q13367; -.
DR   TreeFam; TF314605; -.
DR   PathwayCommons; Q13367; -.
DR   SignaLink; Q13367; -.
DR   SIGNOR; Q13367; -.
DR   BioGRID-ORCS; 8120; 12 hits in 1149 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 130 other cell types or tissues.
DR   ExpressionAtlas; Q13367; baseline and differential.
DR   GO; GO:0030123; C:AP-3 adaptor complex; NAS: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; NAS: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; NAS:ComplexPortal.
DR   GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR   GO; GO:0046907; P:intracellular transport; NAS:ComplexPortal.
DR   GO; GO:0016183; P:synaptic vesicle coating; NAS:ComplexPortal.
DR   GO; GO:0036465; P:synaptic vesicle recycling; NAS:ComplexPortal.
DR   GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
DR   Gene3D; 1.25.10.10; Leucine-rich Repeat Variant; 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; ADAPTOR COMPLEX SUBUNIT BETA FAMILY MEMBER; 1.
DR   PANTHER; PTHR11134:SF11; AP-3 COMPLEX SUBUNIT BETA-2; 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; ARM repeat; 1.
DR   SUPFAM; SSF49348; Clathrin adaptor appendage domain; 1.
DR   Genevisible; Q13367; HS.
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
//