TSN33_HUMAN
ID TSN33_HUMAN Reviewed; 283 AA.
AC Q86UF1;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Tetraspanin-33;
DE Short=Tspan-33;
DE AltName: Full=Penumbra;
DE Short=hPen;
DE AltName: Full=Proerythroblast new membrane;
GN Name=TSPAN33; Synonyms=PEN;
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].
RC TISSUE=Bone marrow;
RX PubMed=16213355; DOI=10.1016/j.cancergencyto.2005.03.017;
RA Chen Z., Pasquini M., Hong B., DeHart S., Heikens M., Tsai S.;
RT "The human Penumbra gene is mapped to a region on chromosome 7 frequently
RT deleted in myeloid malignancies.";
RL Cancer Genet. Cytogenet. 162:95-98(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBUNIT, AND TISSUE SPECIFICITY.
RX PubMed=17158226; DOI=10.1182/blood-2006-09-046672;
RA Heikens M.J., Cao T.M., Morita C., Dehart S.L., Tsai S.;
RT "Penumbra encodes a novel tetraspanin that is highly expressed in erythroid
RT progenitors and promotes effective erythropoiesis.";
RL Blood 109:3244-3252(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP FUNCTION, INTERACTION WITH ADAM10, AND SUBCELLULAR LOCATION.
RX PubMed=26686862; DOI=10.1007/s00018-015-2111-z;
RA Jouannet S., Saint-Pol J., Fernandez L., Nguyen V., Charrin S.,
RA Boucheix C., Brou C., Milhiet P.E., Rubinstein E.;
RT "TspanC8 tetraspanins differentially regulate the cleavage of ADAM10
RT substrates, Notch activation and ADAM10 membrane compartmentalization.";
RL Cell. Mol. Life Sci. 73:1895-1915(2016).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH ADAM10 AND PLEKHA7.
RX PubMed=30463011; DOI=10.1016/j.celrep.2018.10.088;
RA Shah J., Rouaud F., Guerrera D., Vasileva E., Popov L.M., Kelley W.L.,
RA Rubinstein E., Carette J.E., Amieva M.R., Citi S.;
RT "A Dock-and-Lock Mechanism Clusters ADAM10 at Cell-Cell Junctions to
RT Promote alpha-Toxin Cytotoxicity.";
RL Cell Rep. 25:2132-2147(2018).
CC -!- FUNCTION: Plays an important role in normal erythropoiesis (By
CC similarity). It has a role in the differentiation of erythroid
CC progenitors (By similarity). Regulates maturation and trafficking of
CC the transmembrane metalloprotease ADAM10 (PubMed:26686862,
CC PubMed:30463011). Negatively regulates ligand-induced Notch activity
CC probably by regulating ADAM10 activity (PubMed:26686862). Mediates
CC docking of ADAM10 to zonula adherens by interacting with ADAM10 and, in
CC a PDZD11-dependent manner, with the zonula adherens protein PLEKHA7
CC (PubMed:30463011). {ECO:0000250|UniProtKB:Q8R3S2,
CC ECO:0000269|PubMed:26686862, ECO:0000269|PubMed:30463011}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:17158226). Interacts (via
CC extracellular domain) with ADAM10 (via extracellular domain)
CC (PubMed:26686862, PubMed:30463011). Interacts (via cytoplasmic domain)
CC with PLEKHA7 (via WW domains); the interaction is dependent on PDZD11
CC being bound to PLEKHA7 and facilitates the docking of ADAM10 to zonula
CC adherens (PubMed:30463011). {ECO:0000269|PubMed:17158226,
CC ECO:0000269|PubMed:26686862, ECO:0000269|PubMed:30463011}.
CC -!- INTERACTION:
CC Q86UF1; O14672: ADAM10; NbExp=3; IntAct=EBI-12045841, EBI-1536151;
CC Q86UF1; Q8N5K1: CISD2; NbExp=3; IntAct=EBI-12045841, EBI-1045797;
CC Q86UF1; O95471: CLDN7; NbExp=3; IntAct=EBI-12045841, EBI-740744;
CC Q86UF1; O75208: COQ9; NbExp=3; IntAct=EBI-12045841, EBI-724524;
CC Q86UF1; Q6PI48: DARS2; NbExp=3; IntAct=EBI-12045841, EBI-3917045;
CC Q86UF1; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-12045841, EBI-781551;
CC Q86UF1; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-12045841, EBI-18304435;
CC Q86UF1; Q05329: GAD2; NbExp=3; IntAct=EBI-12045841, EBI-9304251;
CC Q86UF1; P48165: GJA8; NbExp=3; IntAct=EBI-12045841, EBI-17458373;
CC Q86UF1; Q5T7V8: GORAB; NbExp=3; IntAct=EBI-12045841, EBI-3917143;
CC Q86UF1; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-12045841, EBI-13345167;
CC Q86UF1; Q8TED1: GPX8; NbExp=3; IntAct=EBI-12045841, EBI-11721746;
CC Q86UF1; O95279: KCNK5; NbExp=3; IntAct=EBI-12045841, EBI-3934936;
CC Q86UF1; Q92876: KLK6; NbExp=3; IntAct=EBI-12045841, EBI-2432309;
CC Q86UF1; Q8TAF8: LHFPL5; NbExp=3; IntAct=EBI-12045841, EBI-2820517;
CC Q86UF1; Q9GZY8-5: MFF; NbExp=3; IntAct=EBI-12045841, EBI-11956541;
CC Q86UF1; O14880: MGST3; NbExp=3; IntAct=EBI-12045841, EBI-724754;
CC Q86UF1; Q9H2K0: MTIF3; NbExp=3; IntAct=EBI-12045841, EBI-3923617;
CC Q86UF1; O14524-2: NEMP1; NbExp=3; IntAct=EBI-12045841, EBI-10969203;
CC Q86UF1; Q53GL0: PLEKHO1; NbExp=3; IntAct=EBI-12045841, EBI-949945;
CC Q86UF1; Q8NC24: RELL2; NbExp=3; IntAct=EBI-12045841, EBI-10269209;
CC Q86UF1; Q96DD7: SHISA4; NbExp=3; IntAct=EBI-12045841, EBI-18035902;
CC Q86UF1; Q9Y3P8: SIT1; NbExp=3; IntAct=EBI-12045841, EBI-6977215;
CC Q86UF1; Q9NQQ7-3: SLC35C2; NbExp=3; IntAct=EBI-12045841, EBI-17295964;
CC Q86UF1; O43278-2: SPINT1; NbExp=3; IntAct=EBI-12045841, EBI-12078338;
CC Q86UF1; Q9BVX2: TMEM106C; NbExp=4; IntAct=EBI-12045841, EBI-2821497;
CC Q86UF1; Q96B21: TMEM45B; NbExp=3; IntAct=EBI-12045841, EBI-3923061;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26686862};
CC Multi-pass membrane protein {ECO:0000305}. Cell junction, adherens
CC junction {ECO:0000269|PubMed:30463011}. Cytoplasm
CC {ECO:0000269|PubMed:30463011}. Note=Is localized to zonula adherens by
CC PLEKHA7 by a PDZD11-dependent interaction.
CC {ECO:0000269|PubMed:30463011}.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in erythroblasts.
CC {ECO:0000269|PubMed:17158226}.
CC -!- SIMILARITY: Belongs to the tetraspanin (TM4SF) family. {ECO:0000305}.
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DR EMBL; BC044244; AAH44244.1; -; mRNA.
DR EMBL; AY236849; AAO91940.1; -; mRNA.
DR EMBL; AF276891; AAQ14314.1; -; mRNA.
DR CCDS; CCDS5810.1; -.
DR RefSeq; NP_848657.1; NM_178562.4.
DR AlphaFoldDB; Q86UF1; -.
DR SMR; Q86UF1; -.
DR BioGRID; 131040; 67.
DR IntAct; Q86UF1; 33.
DR MINT; Q86UF1; -.
DR STRING; 9606.ENSP00000483872; -.
DR TCDB; 8.A.40.1.11; the tetraspanin (tetraspanin) family.
DR GlyGen; Q86UF1; 1 site.
DR iPTMnet; Q86UF1; -.
DR PhosphoSitePlus; Q86UF1; -.
DR SwissPalm; Q86UF1; -.
DR BioMuta; TSPAN33; -.
DR DMDM; 74727485; -.
DR EPD; Q86UF1; -.
DR jPOST; Q86UF1; -.
DR MassIVE; Q86UF1; -.
DR MaxQB; Q86UF1; -.
DR PaxDb; Q86UF1; -.
DR PeptideAtlas; Q86UF1; -.
DR PRIDE; Q86UF1; -.
DR ProteomicsDB; 69814; -.
DR Antibodypedia; 17866; 210 antibodies from 26 providers.
DR DNASU; 340348; -.
DR Ensembl; ENST00000486685.3; ENSP00000483872.1; ENSG00000158457.6.
DR GeneID; 340348; -.
DR KEGG; hsa:340348; -.
DR MANE-Select; ENST00000486685.3; ENSP00000483872.1; NM_178562.5; NP_848657.1.
DR UCSC; uc033ahb.2; human.
DR CTD; 340348; -.
DR DisGeNET; 340348; -.
DR GeneCards; TSPAN33; -.
DR HGNC; HGNC:28743; TSPAN33.
DR HPA; ENSG00000158457; Tissue enhanced (kidney).
DR MIM; 610120; gene.
DR neXtProt; NX_Q86UF1; -.
DR OpenTargets; ENSG00000158457; -.
DR PharmGKB; PA142670690; -.
DR VEuPathDB; HostDB:ENSG00000158457; -.
DR eggNOG; KOG3882; Eukaryota.
DR GeneTree; ENSGT00940000159484; -.
DR HOGENOM; CLU_055524_0_3_1; -.
DR InParanoid; Q86UF1; -.
DR OMA; MHPHHFT; -.
DR OrthoDB; 1416189at2759; -.
DR PhylomeDB; Q86UF1; -.
DR TreeFam; TF313002; -.
DR PathwayCommons; Q86UF1; -.
DR Reactome; R-HSA-977225; Amyloid fiber formation.
DR SignaLink; Q86UF1; -.
DR SIGNOR; Q86UF1; -.
DR BioGRID-ORCS; 340348; 16 hits in 1065 CRISPR screens.
DR GenomeRNAi; 340348; -.
DR Pharos; Q86UF1; Tbio.
DR PRO; PR:Q86UF1; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q86UF1; protein.
DR Bgee; ENSG00000158457; Expressed in kidney epithelium and 173 other tissues.
DR Genevisible; Q86UF1; HS.
DR GO; GO:0005912; C:adherens junction; IEA:UniProtKB-SubCell.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0046930; C:pore complex; IMP:UniProtKB.
DR GO; GO:0097197; C:tetraspanin-enriched microdomain; IEA:Ensembl.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0046931; P:pore complex assembly; IMP:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; IDA:UniProtKB.
DR GO; GO:0051604; P:protein maturation; IDA:UniProtKB.
DR Gene3D; 1.10.1450.10; -; 1.
DR InterPro; IPR018499; Tetraspanin/Peripherin.
DR InterPro; IPR000301; Tetraspanin_animals.
DR InterPro; IPR008952; Tetraspanin_EC2_sf.
DR PANTHER; PTHR19282; PTHR19282; 1.
DR Pfam; PF00335; Tetraspanin; 1.
DR PIRSF; PIRSF002419; Tetraspanin; 1.
DR SUPFAM; SSF48652; SSF48652; 1.
PE 1: Evidence at protein level;
KW Cell junction; Cell membrane; Cytoplasm; Disulfide bond; Glycoprotein;
KW Membrane; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..283
FT /note="Tetraspanin-33"
FT /id="PRO_0000282922"
FT TOPO_DOM 1..24
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 25..45
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 46..64
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 65..85
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 86..96
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 97..117
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 118..235
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 236..256
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 257..283
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 172
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 283 AA; 31538 MW; A551E9F2EF04FABC CRC64;
MARRPRAPAA SGEEFSFVSP LVKYLLFFFN MLFWVISMVM VAVGVYARLM KHAEAALACL
AVDPAILLIV VGVLMFLLTF CGCIGSLREN ICLLQTFSLC LTAVFLLQLA AGILGFVFSD
KARGKVSEII NNAIVHYRDD LDLQNLIDFG QKKFSCCGGI SYKDWSQNMY FNCSEDNPSR
ERCSVPYSCC LPTPDQAVIN TMCGQGMQAF DYLEASKVIY TNGCIDKLVN WIHSNLFLLG
GVALGLAIPQ LVGILLSQIL VNQIKDQIKL QLYNQQHRAD PWY
