MELT_HUMAN
ID MELT_HUMAN Reviewed; 833 AA.
AC Q14D04; D3DNL0; F5GZ91; Q2TAA9; Q3MIX2; Q6PEL3; Q86TL5; Q8TCR3; Q96SP7;
AC Q9C0H1; Q9H9Q7;
DT 21-AUG-2007, integrated into UniProtKB/Swiss-Prot.
DT 22-AUG-2006, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Ventricular zone-expressed PH domain-containing protein homolog 1;
DE AltName: Full=Protein melted;
GN Name=VEPH1; Synonyms=KIAA1692, VEPH;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=11214970; DOI=10.1093/dnares/7.6.347;
RA Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:347-355(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLY-263.
RC TISSUE=Brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [5]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP PRO-522.
RC TISSUE=Brain, Kidney, and Skin;
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 [7]
RP IDENTIFICATION.
RX PubMed=15388229; DOI=10.1016/j.biochi.2004.07.010;
RA Muto E., Tabata Y., Taneda T., Aoki Y., Muto A., Arai K., Watanabe S.;
RT "Identification and characterization of Veph, a novel gene encoding a PH
RT domain-containing protein expressed in the developing central nervous
RT system of vertebrates.";
RL Biochimie 86:523-531(2004).
RN [8]
RP IDENTIFICATION.
RX PubMed=16054033; DOI=10.1016/j.devcel.2005.07.004;
RA Teleman A.A., Chen Y.-W., Cohen S.M.;
RT "Drosophila Melted modulates FOXO and TOR activity.";
RL Dev. Cell 9:271-281(2005).
RN [9]
RP FUNCTION, INTERACTION WITH TGFBR1, AND SUBCELLULAR LOCATION.
RX PubMed=26039994; DOI=10.1073/pnas.1504671112;
RA Shathasivam P., Kollara A., Ringuette M.J., Virtanen C., Wrana J.L.,
RA Brown T.J.;
RT "Human ortholog of Drosophila Melted impedes SMAD2 release from TGF-beta
RT receptor I to inhibit TGF-beta signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:E3000-E3009(2015).
CC -!- FUNCTION: Interacts with TGF-beta receptor type-1 (TGFBR1) and inhibits
CC dissociation of activated SMAD2 from TGFBR1, impeding its nuclear
CC accumulation and resulting in impaired TGF-beta signaling. May also
CC affect FOXO, Hippo and Wnt signaling. {ECO:0000269|PubMed:26039994}.
CC -!- SUBUNIT: Interacts with TGFBR1. {ECO:0000269|PubMed:26039994}.
CC -!- INTERACTION:
CC Q14D04; Q14160: SCRIB; NbExp=2; IntAct=EBI-1043669, EBI-357345;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26039994};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:Q9VS24}; Cytoplasmic
CC side {ECO:0000250|UniProtKB:Q9VS24}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q14D04-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14D04-2; Sequence=VSP_027433;
CC Name=3;
CC IsoId=Q14D04-3; Sequence=VSP_027431, VSP_027432;
CC Name=4;
CC IsoId=Q14D04-4; Sequence=VSP_047655, VSP_047656;
CC -!- DOMAIN: The PH domain is required for membrane targeting.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the MELT/VEPH family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB14165.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAB21783.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB051479; BAB21783.1; ALT_INIT; mRNA.
DR EMBL; AK022666; BAB14165.1; ALT_INIT; mRNA.
DR EMBL; AK027625; BAB55243.1; -; mRNA.
DR EMBL; AL713656; CAD28465.2; -; mRNA.
DR EMBL; AC020630; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC092944; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471052; EAW78705.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78706.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78707.1; -; Genomic_DNA.
DR EMBL; BC042159; AAH42159.1; -; mRNA.
DR EMBL; BC057999; AAH57999.1; -; mRNA.
DR EMBL; BC101660; AAI01661.1; -; mRNA.
DR EMBL; BC111017; AAI11018.1; -; mRNA.
DR EMBL; BC113555; AAI13556.1; -; mRNA.
DR CCDS; CCDS3179.1; -. [Q14D04-1]
DR CCDS; CCDS54661.1; -. [Q14D04-3]
DR CCDS; CCDS54662.1; -. [Q14D04-2]
DR CCDS; CCDS54663.1; -. [Q14D04-4]
DR RefSeq; NP_001161383.1; NM_001167911.1. [Q14D04-2]
DR RefSeq; NP_001161384.1; NM_001167912.1. [Q14D04-1]
DR RefSeq; NP_001161387.1; NM_001167915.1. [Q14D04-3]
DR RefSeq; NP_001161388.1; NM_001167916.1. [Q14D04-3]
DR RefSeq; NP_001161389.1; NM_001167917.1. [Q14D04-4]
DR RefSeq; NP_078897.2; NM_024621.2. [Q14D04-1]
DR AlphaFoldDB; Q14D04; -.
DR BioGRID; 122799; 6.
DR IntAct; Q14D04; 4.
DR STRING; 9606.ENSP00000354919; -.
DR GlyGen; Q14D04; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q14D04; -.
DR PhosphoSitePlus; Q14D04; -.
DR BioMuta; VEPH1; -.
DR DMDM; 121946695; -.
DR jPOST; Q14D04; -.
DR MassIVE; Q14D04; -.
DR MaxQB; Q14D04; -.
DR PaxDb; Q14D04; -.
DR PeptideAtlas; Q14D04; -.
DR PRIDE; Q14D04; -.
DR ProteomicsDB; 24965; -.
DR ProteomicsDB; 60341; -. [Q14D04-1]
DR ProteomicsDB; 60342; -. [Q14D04-2]
DR ProteomicsDB; 60343; -. [Q14D04-3]
DR TopDownProteomics; Q14D04-2; -. [Q14D04-2]
DR Antibodypedia; 18417; 46 antibodies from 16 providers.
DR DNASU; 79674; -.
DR Ensembl; ENST00000362010.7; ENSP00000354919.2; ENSG00000197415.12. [Q14D04-1]
DR Ensembl; ENST00000392832.6; ENSP00000376577.2; ENSG00000197415.12. [Q14D04-1]
DR Ensembl; ENST00000392833.6; ENSP00000376578.2; ENSG00000197415.12. [Q14D04-2]
DR Ensembl; ENST00000468233.5; ENSP00000417268.1; ENSG00000197415.12. [Q14D04-3]
DR Ensembl; ENST00000494677.5; ENSP00000419193.1; ENSG00000197415.12. [Q14D04-3]
DR Ensembl; ENST00000537559.5; ENSP00000443868.1; ENSG00000197415.12. [Q14D04-4]
DR GeneID; 79674; -.
DR KEGG; hsa:79674; -.
DR MANE-Select; ENST00000362010.7; ENSP00000354919.2; NM_001167912.2; NP_001161384.1.
DR UCSC; uc003fbj.3; human. [Q14D04-1]
DR CTD; 79674; -.
DR DisGeNET; 79674; -.
DR GeneCards; VEPH1; -.
DR HGNC; HGNC:25735; VEPH1.
DR HPA; ENSG00000197415; Tissue enhanced (adrenal gland, kidney, lung).
DR MIM; 609594; gene.
DR neXtProt; NX_Q14D04; -.
DR OpenTargets; ENSG00000197415; -.
DR PharmGKB; PA134952229; -.
DR VEuPathDB; HostDB:ENSG00000197415; -.
DR eggNOG; KOG3723; Eukaryota.
DR GeneTree; ENSGT00390000018660; -.
DR HOGENOM; CLU_010394_0_0_1; -.
DR InParanoid; Q14D04; -.
DR OMA; VYPKQPD; -.
DR OrthoDB; 139521at2759; -.
DR PhylomeDB; Q14D04; -.
DR TreeFam; TF314736; -.
DR PathwayCommons; Q14D04; -.
DR SignaLink; Q14D04; -.
DR SIGNOR; Q14D04; -.
DR BioGRID-ORCS; 79674; 11 hits in 1072 CRISPR screens.
DR ChiTaRS; VEPH1; human.
DR GenomeRNAi; 79674; -.
DR Pharos; Q14D04; Tbio.
DR PRO; PR:Q14D04; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q14D04; protein.
DR Bgee; ENSG00000197415; Expressed in pigmented layer of retina and 123 other tissues.
DR ExpressionAtlas; Q14D04; baseline and differential.
DR Genevisible; Q14D04; HS.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0010314; F:phosphatidylinositol-5-phosphate binding; IBA:GO_Central.
DR GO; GO:0060392; P:negative regulation of SMAD protein signal transduction; IDA:UniProtKB.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0009966; P:regulation of signal transduction; IBA:GO_Central.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR039888; Melted-like.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR PANTHER; PTHR21630; PTHR21630; 1.
DR Pfam; PF00169; PH; 1.
DR SMART; SM00233; PH; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Membrane; Reference proteome.
FT CHAIN 1..833
FT /note="Ventricular zone-expressed PH domain-containing
FT protein homolog 1"
FT /id="PRO_0000297955"
FT DOMAIN 716..819
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 201..319
FT /note="Interaction with TGFBR1"
FT /evidence="ECO:0000269|PubMed:26039994"
FT REGION 458..505
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 663..833
FT /note="Interaction with TGFBR1"
FT /evidence="ECO:0000269|PubMed:26039994"
FT VAR_SEQ 177
FT /note="G -> V (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_047655"
FT VAR_SEQ 178..833
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_047656"
FT VAR_SEQ 178..213
FT /note="NTMLLRVLPAVYEKQPQPINRHLTELLALMSQLEQP -> MVRKLSLGTCFG
FT RYLKVFSSSIYGLWEARPRVLEAN (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_027431"
FT VAR_SEQ 214..833
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_027432"
FT VAR_SEQ 626..670
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_027433"
FT VARIANT 208
FT /note="S -> C (in dbSNP:rs34559487)"
FT /id="VAR_034692"
FT VARIANT 263
FT /note="V -> G (in dbSNP:rs1378796)"
FT /evidence="ECO:0000269|PubMed:17974005"
FT /id="VAR_034693"
FT VARIANT 271
FT /note="S -> C (in dbSNP:rs1378795)"
FT /id="VAR_034694"
FT VARIANT 319
FT /note="M -> V (in dbSNP:rs11923380)"
FT /id="VAR_034695"
FT VARIANT 329
FT /note="L -> V (in dbSNP:rs34823544)"
FT /id="VAR_034696"
FT VARIANT 365
FT /note="R -> Q (in dbSNP:rs16827563)"
FT /id="VAR_034697"
FT VARIANT 501
FT /note="S -> L (in dbSNP:rs59504298)"
FT /id="VAR_061683"
FT VARIANT 522
FT /note="S -> P (in dbSNP:rs11918974)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_034698"
FT CONFLICT 259
FT /note="I -> M (in Ref. 2; BAB55243)"
FT /evidence="ECO:0000305"
FT CONFLICT 808
FT /note="E -> A (in Ref. 2; BAB55243)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 833 AA; 94745 MW; 34995B4AB43474A4 CRC64;
MHQLFRLVLG QKDLSRAGDL FSLDDSEIED SLTEALEQIK IISSSSDYQT NNNDQAVVEI
CITRITTAIR ETESIEKHAK ALVGLWDSCL EHNLRPFGKD EDTPHAKIAS DIMSCILQNY
NRPPVMALAI PIAVKFLHRG NKELCRNMSN YLSLAAITKA DLLADHTEVI VKSILQGNTM
LLRVLPAVYE KQPQPINRHL TELLALMSQL EQPEQYHLLR LLHVAAKKKQ LEVVQKCIPF
LIGHLKDSTH NDIILNILIE IAVYEPVALN SFLPMLKEIG ERFPYLTGQM ARIYGAVGHV
DEERARSCLT YLVSQLANME HSFHHILLLE IKSITDTFSS ILGPQSRDIF RMSNSFTAIA
KLLTRQLENT KAGSGRRKIS TEIEFPEKLE ETKLIVTENE DHEKLQVKIQ AFEDKINAGS
NTPGSIRRYS LGQVSKEERK NIRFNRSKSL AFHTMLTKGV GSDDGEDENR GDIPASISLS
EIDPLGQGND KLPFKTDTER SQLGESSVSY PNIIHIDSEN LSETVKENSQ EETPETTASP
IEYQDKLYLH LKKNLSKVKA YAMEIGKKIP VPDQCTIEDT VRSCVAKLFF TCSLKGHYCL
YSKSSFILIS QEPQPWIQIM FLFQQSLFPE PLSIQSHSVQ FLRALWEKTQ AGGAHSFETA
MMESTFPQQK DLDQVQLHLE EVRFFDVFGF SETAGAWQCF MCNNPEKATV VNQDGQPLIE
GKLKEKQVRW KFIKRWKTRY FTLAGNQLLF QKGKSKDDPD DCPIELSKVQ SVKAVAKKRR
DRSLPRAFEI FTDNKTYVFK AKDEKNAEEW LQCINVAVAQ AKERESREVT TYL
