ID TSN4_HUMAN Reviewed; 238 AA.
AC O14817; Q6IAP6;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 24-JAN-2024, entry version 171.
DE RecName: Full=Tetraspanin-4;
DE Short=Tspan-4;
DE AltName: Full=Novel antigen 2;
DE Short=NAG-2;
DE AltName: Full=Transmembrane 4 superfamily member 7;
GN Name=TSPAN4; Synonyms=NAG2, TM4SF7;
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].
RX PubMed=9360996; DOI=10.1074/jbc.272.46.29181;
RA Tachibana I., Bodorova J., Berditchevski F., Zutter M.M., Hemler M.E.;
RT "NAG-2, a novel transmembrane-4 superfamily (TM4SF) protein that complexes
RT with integrins and other TM4SF proteins.";
RL J. Biol. Chem. 272:29181-29189(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9714763; DOI=10.1016/s0167-4781(98)00087-6;
RA Todd S.C., Doctor V.S., Levy S.;
RT "Sequences and expression of six new members of the tetraspanin/TM4SF
RT family.";
RL Biochim. Biophys. Acta 1399:101-104(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Teratocarcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [8]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-161.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [9]
RP VARIANT [LARGE SCALE ANALYSIS] MET-67.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- SUBUNIT: Forms a complex with integrins.
CC -!- INTERACTION:
CC O14817; Q8NEC5: CATSPER1; NbExp=3; IntAct=EBI-8652667, EBI-744545;
CC O14817; Q9H2X0: CHRD; NbExp=3; IntAct=EBI-8652667, EBI-947551;
CC O14817; Q9UHP7-3: CLEC2D; NbExp=3; IntAct=EBI-8652667, EBI-11749983;
CC O14817; Q02930-3: CREB5; NbExp=3; IntAct=EBI-8652667, EBI-10192698;
CC O14817; A8MQ03: CYSRT1; NbExp=6; IntAct=EBI-8652667, EBI-3867333;
CC O14817; Q9H8M9: EVA1A; NbExp=3; IntAct=EBI-8652667, EBI-715362;
CC O14817; A0A0C3SFZ9: FCHO1; NbExp=3; IntAct=EBI-8652667, EBI-11977403;
CC O14817; O43559: FRS3; NbExp=3; IntAct=EBI-8652667, EBI-725515;
CC O14817; Q9Y223-2: GNE; NbExp=3; IntAct=EBI-8652667, EBI-11975289;
CC O14817; P28799: GRN; NbExp=3; IntAct=EBI-8652667, EBI-747754;
CC O14817; Q96NT3-2: GUCD1; NbExp=3; IntAct=EBI-8652667, EBI-11978177;
CC O14817; P49639: HOXA1; NbExp=3; IntAct=EBI-8652667, EBI-740785;
CC O14817; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-8652667, EBI-10171774;
CC O14817; Q9BYQ6: KRTAP4-11; NbExp=3; IntAct=EBI-8652667, EBI-10302392;
CC O14817; Q9BYR2: KRTAP4-5; NbExp=3; IntAct=EBI-8652667, EBI-11993254;
CC O14817; Q3LI66: KRTAP6-2; NbExp=3; IntAct=EBI-8652667, EBI-11962084;
CC O14817; Q9BYQ4: KRTAP9-2; NbExp=3; IntAct=EBI-8652667, EBI-1044640;
CC O14817; Q9BYQ3: KRTAP9-3; NbExp=3; IntAct=EBI-8652667, EBI-1043191;
CC O14817; Q5T7P2: LCE1A; NbExp=3; IntAct=EBI-8652667, EBI-11962058;
CC O14817; O14633: LCE2B; NbExp=3; IntAct=EBI-8652667, EBI-11478468;
CC O14817; Q5TA82: LCE2D; NbExp=3; IntAct=EBI-8652667, EBI-10246750;
CC O14817; Q5TA76: LCE3A; NbExp=3; IntAct=EBI-8652667, EBI-9394625;
CC O14817; Q5T5A8: LCE3C; NbExp=3; IntAct=EBI-8652667, EBI-10245291;
CC O14817; Q9BYE3: LCE3D; NbExp=3; IntAct=EBI-8652667, EBI-6658837;
CC O14817; Q5TA78: LCE4A; NbExp=3; IntAct=EBI-8652667, EBI-10246358;
CC O14817; Q8N386: LRRC25; NbExp=3; IntAct=EBI-8652667, EBI-11304917;
CC O14817; Q99750: MDFI; NbExp=3; IntAct=EBI-8652667, EBI-724076;
CC O14817; Q13064: MKRN3; NbExp=3; IntAct=EBI-8652667, EBI-2340269;
CC O14817; Q7Z3S9: NOTCH2NLA; NbExp=4; IntAct=EBI-8652667, EBI-945833;
CC O14817; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-8652667, EBI-22310682;
CC O14817; Q92570: NR4A3; NbExp=3; IntAct=EBI-8652667, EBI-13644623;
CC O14817; P32242: OTX1; NbExp=3; IntAct=EBI-8652667, EBI-740446;
CC O14817; A2BDE7: PHLDA1; NbExp=3; IntAct=EBI-8652667, EBI-14084211;
CC O14817; Q9NRQ2: PLSCR4; NbExp=3; IntAct=EBI-8652667, EBI-769257;
CC O14817; O95470: SGPL1; NbExp=3; IntAct=EBI-8652667, EBI-1046170;
CC O14817; Q8WW24: TEKT4; NbExp=3; IntAct=EBI-8652667, EBI-750487;
CC O14817; Q96A25: TMEM106A; NbExp=3; IntAct=EBI-8652667, EBI-3915978;
CC O14817; A8MV65-2: VGLL3; NbExp=3; IntAct=EBI-8652667, EBI-11957216;
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed in multiple tissues but is absent in
CC brain, lymphoid cells, and platelets.
CC -!- SIMILARITY: Belongs to the tetraspanin (TM4SF) family. {ECO:0000305}.
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DR EMBL; AF022813; AAC51864.1; -; mRNA.
DR EMBL; AF054841; AAC69717.1; -; mRNA.
DR EMBL; AK291089; BAF83778.1; -; mRNA.
DR EMBL; BT006776; AAP35422.1; -; mRNA.
DR EMBL; CR457108; CAG33389.1; -; mRNA.
DR EMBL; CH471158; EAX02409.1; -; Genomic_DNA.
DR EMBL; BC000389; AAH00389.1; -; mRNA.
DR EMBL; BC019314; AAH19314.1; -; mRNA.
DR EMBL; BC093031; AAH93031.1; -; mRNA.
DR CCDS; CCDS7721.1; -.
DR PIR; A59265; A59265.
DR RefSeq; NP_001020405.1; NM_001025234.1.
DR RefSeq; NP_001020406.1; NM_001025235.1.
DR RefSeq; NP_001020407.1; NM_001025236.1.
DR RefSeq; NP_001020408.1; NM_001025237.1.
DR RefSeq; NP_001020409.1; NM_001025238.1.
DR RefSeq; NP_001020410.1; NM_001025239.1.
DR RefSeq; NP_003262.1; NM_003271.4.
DR RefSeq; XP_005253159.1; XM_005253102.1.
DR AlphaFoldDB; O14817; -.
DR SMR; O14817; -.
DR BioGRID; 112961; 51.
DR IntAct; O14817; 40.
DR MINT; O14817; -.
DR STRING; 9606.ENSP00000380553; -.
DR GlyCosmos; O14817; 2 sites, No reported glycans.
DR GlyGen; O14817; 2 sites.
DR iPTMnet; O14817; -.
DR PhosphoSitePlus; O14817; -.
DR SwissPalm; O14817; -.
DR BioMuta; TSPAN4; -.
DR EPD; O14817; -.
DR jPOST; O14817; -.
DR MassIVE; O14817; -.
DR MaxQB; O14817; -.
DR PaxDb; 9606-ENSP00000380553; -.
DR PeptideAtlas; O14817; -.
DR ProteomicsDB; 48255; -.
DR Pumba; O14817; -.
DR Antibodypedia; 10103; 95 antibodies from 19 providers.
DR DNASU; 7106; -.
DR Ensembl; ENST00000397397.7; ENSP00000380552.2; ENSG00000214063.12.
DR Ensembl; ENST00000397404.5; ENSP00000380553.1; ENSG00000214063.12.
DR Ensembl; ENST00000397406.5; ENSP00000380554.1; ENSG00000214063.12.
DR Ensembl; ENST00000397408.5; ENSP00000380555.1; ENSG00000214063.12.
DR Ensembl; ENST00000397411.6; ENSP00000380558.2; ENSG00000214063.12.
DR Ensembl; ENST00000409543.6; ENSP00000386513.2; ENSG00000214063.12.
DR GeneID; 7106; -.
DR KEGG; hsa:7106; -.
DR MANE-Select; ENST00000397397.7; ENSP00000380552.2; NM_003271.5; NP_003262.1.
DR UCSC; uc001lsd.2; human.
DR AGR; HGNC:11859; -.
DR CTD; 7106; -.
DR DisGeNET; 7106; -.
DR GeneCards; TSPAN4; -.
DR HGNC; HGNC:11859; TSPAN4.
DR HPA; ENSG00000214063; Low tissue specificity.
DR MIM; 602644; gene.
DR neXtProt; NX_O14817; -.
DR OpenTargets; ENSG00000214063; -.
DR PharmGKB; PA36560; -.
DR VEuPathDB; HostDB:ENSG00000214063; -.
DR eggNOG; KOG3882; Eukaryota.
DR GeneTree; ENSGT00940000160434; -.
DR InParanoid; O14817; -.
DR OMA; KADTYCT; -.
DR OrthoDB; 3234802at2759; -.
DR PhylomeDB; O14817; -.
DR TreeFam; TF352892; -.
DR PathwayCommons; O14817; -.
DR SignaLink; O14817; -.
DR BioGRID-ORCS; 7106; 18 hits in 1152 CRISPR screens.
DR ChiTaRS; TSPAN4; human.
DR GeneWiki; TSPAN4; -.
DR GenomeRNAi; 7106; -.
DR Pharos; O14817; Tbio.
DR PRO; PR:O14817; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O14817; Protein.
DR Bgee; ENSG00000214063; Expressed in stromal cell of endometrium and 199 other cell types or tissues.
DR ExpressionAtlas; O14817; baseline and differential.
DR Genevisible; O14817; HS.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0031982; C:vesicle; IDA:UniProtKB.
DR GO; GO:0003823; F:antigen binding; IDA:UniProtKB.
DR GO; GO:0005178; F:integrin binding; IPI:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; IDA:UniProtKB.
DR CDD; cd03165; NET-5_like_LEL; 1.
DR Gene3D; 1.10.1450.10; Tetraspanin; 1.
DR InterPro; IPR018499; Tetraspanin/Peripherin.
DR InterPro; IPR000301; Tetraspanin_animals.
DR InterPro; IPR018503; Tetraspanin_CS.
DR InterPro; IPR008952; Tetraspanin_EC2_sf.
DR PANTHER; PTHR19282; TETRASPANIN; 1.
DR PANTHER; PTHR19282:SF40; TETRASPANIN-4; 1.
DR Pfam; PF00335; Tetraspanin; 1.
DR PIRSF; PIRSF002419; Tetraspanin; 1.
DR PRINTS; PR00259; TMFOUR.
DR SUPFAM; SSF48652; Tetraspanin; 1.
DR PROSITE; PS00421; TM4_1; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..238
FT /note="Tetraspanin-4"
FT /id="PRO_0000219241"
FT TOPO_DOM 1..13
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 14..34
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 35..55
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 56..76
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 77..85
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 86..106
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 107..201
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 202..222
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 223..238
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 152
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 161
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT VARIANT 67
FT /note="I -> M (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036616"
SQ SEQUENCE 238 AA; 26118 MW; A6B9A5633065A492 CRC64;
MARACLQAVK YLMFAFNLLF WLGGCGVLGV GIWLAATQGS FATLSSSFPS LSAANLLIIT
GAFVMAIGFV GCLGAIKENK CLLLTFFLLL LLVFLLEATI AILFFAYTDK IDRYAQQDLK
KGLHLYGTQG NVGLTNAWSI IQTDFRCCGV SNYTDWFEVY NATRVPDSCC LEFSESCGLH
APGTWWKAPC YETVKVWLQE NLLAVGIFGL CTALVQILGL TFAMTMYCQV VKADTYCA
//
