ID NECP1_MOUSE Reviewed; 275 AA. AC Q9CR95; Q3TH13; Q78JW3; Q8C4P1; DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 2. DT 14-OCT-2015, entry version 102. DE RecName: Full=Adaptin ear-binding coat-associated protein 1; DE AltName: Full=NECAP endocytosis-associated protein 1; DE Short=NECAP-1; GN Name=Necap1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; RC TISSUE=Cerebellum, Embryonic head, Embryonic heart, and Lung; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., RA Davis M.J., Wilming L.G., Aidinis V., Allen J.E., RA Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., RA Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., RA Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., RA Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., RA di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., RA Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., RA Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., RA Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., RA Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., RA Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., RA Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., RA Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., RA Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., RA Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., RA Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., RA Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., RA Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., RA Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., RA Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., RA Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., RA Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., RA Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., RA Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., RA Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., RA Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., RA Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., RA Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., RA Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., RA Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., RA Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Czech II; TISSUE=Mammary gland; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP IDENTIFICATION, INTERACTION WITH AP1G1 AND AP2A1, TISSUE SPECIFICITY, RP SUBCELLULAR LOCATION, AND FUNCTION. RX PubMed=14555962; DOI=10.1038/sj.embor.7400004; RA Ritter B., Philie J., Girard M., Tung E.C., Blondeau F., RA McPherson P.S.; RT "Identification of a family of endocytic proteins that define a new RT alpha-adaptin ear-binding motif."; RL EMBO Rep. 4:1089-1095(2003). RN [4] RP MUTAGENESIS OF TRP-272; VAL-273; GLN-274 AND PHE-275, AND INTERACTION RP WITH AP2A1; AP2A2 AND AP1G1. RX PubMed=15359277; DOI=10.1038/sj.emboj.7600378; RA Ritter B., Denisov A.Y., Philie J., Deprez C., Tung E.C., Gehring K., RA McPherson P.S.; RT "Two WXXF-based motifs in NECAPs define the specificity of accessory RT protein binding to AP-1 and AP-2."; RL EMBO J. 23:3701-3710(2004). RN [5] RP INTERACTION WITH GGA1; GGA2; GGA3 AND AP1G1. RX PubMed=14665628; DOI=10.1074/jbc.M311873200; RA Mattera R., Ritter B., Sidhu S.S., McPherson P.S., Bonifacino J.S.; RT "Definition of the consensus motif recognized by gamma-adaptin ear RT domains."; RL J. Biol. Chem. 279:8018-8028(2004). RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Heart, Kidney, Liver, Lung, Pancreas, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and RT expression."; RL Cell 143:1174-1189(2010). RN [7] RP DEVELOPMENTAL STAGE. RX PubMed=24399846; DOI=10.1136/jmedgenet-2013-102030; RA Alazami A.M., Hijazi H., Kentab A.Y., Alkuraya F.S.; RT "NECAP1 loss of function leads to a severe infantile epileptic RT encephalopathy."; RL J. Med. Genet. 51:224-228(2014). RN [8] RP STRUCTURE BY NMR OF 1-133. RA Denisov A.Y., Ritter B., McPherson P.S., Gehring K.; RT "Solution structure of NECAP1 protein."; RL Submitted (JUL-2005) to the PDB data bank. CC -!- FUNCTION: Involved in endocytosis. {ECO:0000250}. CC -!- SUBUNIT: Interacts with AP1G1 and AP2A1 components of the adapter CC protein complexes AP-1 and AP-2. Interacts with the GAE domain CC proteins GGA1, GGA2 and GGA3. {ECO:0000269|PubMed:14555962, CC ECO:0000269|PubMed:14665628, ECO:0000269|PubMed:15359277}. CC -!- INTERACTION: CC P49418:AMPH (xeno); NbExp=6; IntAct=EBI-7592476, EBI-7121510; CC O08838:Amph (xeno); NbExp=7; IntAct=EBI-7592476, EBI-80080; CC O08839:Bin1 (xeno); NbExp=8; IntAct=EBI-7592476, EBI-80095; CC P98078:Dab2; NbExp=2; IntAct=EBI-7592476, EBI-1391846; CC O00291:HIP1 (xeno); NbExp=3; IntAct=EBI-7592476, EBI-473886; CC O60641:SNAP91 (xeno); NbExp=2; IntAct=EBI-7592476, EBI-1105187; CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, clathrin-coated vesicle CC membrane {ECO:0000269|PubMed:14555962}. Cell membrane CC {ECO:0000269|PubMed:14555962}. Note=Colocalizes with AP-2 at the CC plasma membrane. CC -!- TISSUE SPECIFICITY: Expressed primarily in brain (at protein CC level). {ECO:0000269|PubMed:14555962}. CC -!- DEVELOPMENTAL STAGE: Expressed in the brain and spinal cord at CC 14.5 dpc (at protein level). {ECO:0000269|PubMed:24399846}. CC -!- DOMAIN: The WXXF motifs mediate binding of accessory proteins to CC the ear-domain of AP-1, GGAs and AP-2 through hydrophobic CC interactions. Selective binding to the GAE domains of AP-1 or to CC the alpha-ear domain of AP-2 is tuned by the acidic context CC surrounding the motif and the properties of the second residue of CC the motif itself. The WXXF motif 1, which is preceded by an acidic CC residue and has a glycine in second position mediates specific CC interaction with AP-1. The WXXF motif 2, which is followed by the CC C-terminal carboxyl group negative charge, allows specific CC interaction with AP-2. CC -!- SIMILARITY: Belongs to the NECAP family. {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; AK004805; BAB23577.2; -; mRNA. DR EMBL; AK005263; BAB23915.2; -; mRNA. DR EMBL; AK081598; BAC38266.1; -; mRNA. DR EMBL; AK168500; BAE40385.1; -; mRNA. DR EMBL; BC011466; AAH11466.2; -; mRNA. DR EMBL; BK000656; DAA01433.1; -; mRNA. DR CCDS; CCDS20505.1; -. DR RefSeq; NP_080543.2; NM_026267.2. DR UniGene; Mm.288114; -. DR PDB; 1TQZ; NMR; -; A=1-133. DR PDBsum; 1TQZ; -. DR ProteinModelPortal; Q9CR95; -. DR SMR; Q9CR95; 1-133. DR DIP; DIP-44062N; -. DR IntAct; Q9CR95; 12. DR MINT; MINT-4125077; -. DR STRING; 10090.ENSMUSP00000032477; -. DR PhosphoSite; Q9CR95; -. DR MaxQB; Q9CR95; -. DR PaxDb; Q9CR95; -. DR PRIDE; Q9CR95; -. DR GeneID; 67602; -. DR KEGG; mmu:67602; -. DR UCSC; uc009dpt.1; mouse. DR CTD; 25977; -. DR MGI; MGI:1914852; Necap1. DR eggNOG; NOG329551; -. DR HOVERGEN; HBG060621; -. DR InParanoid; Q9CR95; -. DR OMA; ESQEMDN; -. DR OrthoDB; EOG76X61J; -. DR PhylomeDB; Q9CR95; -. DR TreeFam; TF314482; -. DR Reactome; R-MMU-432722; Golgi Associated Vesicle Biogenesis. DR ChiTaRS; Necap1; mouse. DR EvolutionaryTrace; Q9CR95; -. DR NextBio; 325013; -. DR PRO; PR:Q9CR95; -. DR Proteomes; UP000000589; Unplaced. DR Bgee; Q9CR95; -. DR CleanEx; MM_NECAP1; -. DR ExpressionAtlas; Q9CR95; baseline and differential. DR Genevisible; Q9CR95; MM. DR GO; GO:0030125; C:clathrin vesicle coat; IDA:UniProtKB. DR GO; GO:0005905; C:coated pit; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0006897; P:endocytosis; IMP:UniProtKB. DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW. DR Gene3D; 2.30.29.30; -; 1. DR InterPro; IPR012466; NECAP-1. DR InterPro; IPR011993; PH/PTB_dom. DR Pfam; PF07933; DUF1681; 1. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Complete proteome; Cytoplasmic vesicle; KW Endocytosis; Membrane; Protein transport; Reference proteome; Repeat; KW Transport. FT CHAIN 1 275 Adaptin ear-binding coat-associated FT protein 1. FT /FTId=PRO_0000213068. FT MOTIF 252 255 WXXF motif 1. FT MOTIF 272 275 WXXF motif 2. FT MUTAGEN 270 270 S->D: Loss of binding to AP-2 and can FT bind to AP-1; when associated with G-273. FT MUTAGEN 272 272 W->A,F,Y: Loss of binding to AP-2. FT {ECO:0000269|PubMed:15359277}. FT MUTAGEN 273 273 V->A,D,E,I: No effect on binding to AP-2. FT {ECO:0000269|PubMed:15359277}. FT MUTAGEN 273 273 V->G: Loss of binding to AP-2 and can FT bind to AP-1; when associated with D-270. FT {ECO:0000269|PubMed:15359277}. FT MUTAGEN 273 273 V->L,N,P,S: Loss of binding to AP-2. FT {ECO:0000269|PubMed:15359277}. FT MUTAGEN 274 274 Q->A,M,N,S,T: No effect on binding to AP- FT 2. {ECO:0000269|PubMed:15359277}. FT MUTAGEN 275 275 F->A,F,Y: Loss of binding to AP-2. FT {ECO:0000269|PubMed:15359277}. FT MUTAGEN 275 275 F->W: No effect on binding to AP-2. FT {ECO:0000269|PubMed:15359277}. FT STRAND 15 21 {ECO:0000244|PDB:1TQZ}. FT STRAND 27 30 {ECO:0000244|PDB:1TQZ}. FT HELIX 33 36 {ECO:0000244|PDB:1TQZ}. FT STRAND 39 41 {ECO:0000244|PDB:1TQZ}. FT STRAND 43 50 {ECO:0000244|PDB:1TQZ}. FT STRAND 53 61 {ECO:0000244|PDB:1TQZ}. FT STRAND 70 74 {ECO:0000244|PDB:1TQZ}. FT STRAND 82 84 {ECO:0000244|PDB:1TQZ}. FT STRAND 92 98 {ECO:0000244|PDB:1TQZ}. FT TURN 99 101 {ECO:0000244|PDB:1TQZ}. FT STRAND 102 109 {ECO:0000244|PDB:1TQZ}. FT HELIX 113 127 {ECO:0000244|PDB:1TQZ}. SQ SEQUENCE 275 AA; 29639 MW; B238B083746FF915 CRC64; MAAELEYESV LCVKPDVSVY RIPPRASNRG YRASDWKLDQ PDWTGRLRIT SKGKIAYIKL EDKVSGELFA QAPVEQYPGI AVETVTDSSR YFVIRIQDGT GRSAFIGIGF TDRGDAFDFN VSLQDHFKWV KQETEISKES QEMDNRPKLD LGFKEGQTIK LSIGNITAKK GGASKPRASG TGGLSLLPPP PGGKVTIPPP SSSVAISNHV TPPPIPKSNH GGNDSDILLD LDSPAPVSTS APAPVSTSND LWGDFSTASS SVPNQAPQPS NWVQF //