NCKPL_MOUSE
ID NCKPL_MOUSE Reviewed; 1134 AA.
AC Q8K1X4;
DT 15-MAR-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Nck-associated protein 1-like {ECO:0000305};
DE AltName: Full=Hematopoietic protein 1 {ECO:0000303|PubMed:19015308};
GN Name=Nckap1l {ECO:0000312|MGI:MGI:1926063};
GN Synonyms=Hem1 {ECO:0000312|MGI:MGI:1926063};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., 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., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N;
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, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=19015308; DOI=10.1084/jem.20080340;
RA Park H., Staehling-Hampton K., Appleby M.W., Brunkow M.E., Habib T.,
RA Zhang Y., Ramsdell F., Liggitt H.D., Freie B., Tsang M., Carlson G.,
RA Friend S., Frevert C., Iritani B.M.;
RT "A point mutation in the murine Hem1 gene reveals an essential role for
RT Hematopoietic protein 1 in lymphopoiesis and innate immunity.";
RL J. Exp. Med. 205:2899-2913(2008).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Liver, Lung, and Spleen;
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 expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23424621; DOI=10.1371/journal.pone.0054902;
RA Chan M.M., Wooden J.M., Tsang M., Gilligan D.M., Hirenallur-S D.K.,
RA Finney G.L., Rynes E., Maccoss M., Ramirez J.A., Park H., Iritani B.M.;
RT "Hematopoietic protein-1 regulates the actin membrane skeleton and membrane
RT stability in murine erythrocytes.";
RL PLoS ONE 8:E54902-E54902(2013).
CC -!- FUNCTION: Essential hematopoietic-specific regulator of the actin
CC cytoskeleton. Controls lymphocyte development, activation,
CC proliferation and homeostasis, erythrocyte membrane stability, as well
CC as phagocytosis and migration by neutrophils and macrophages
CC (PubMed:19015308, PubMed:23424621). Component of the WAVE2 complex
CC which signals downstream of RAC to stimulate F-actin polymerization
CC (PubMed:23424621). Required for stabilization and/or translation of the
CC WAVE2 complex proteins in hematopoietic cells (PubMed:19015308). Within
CC the WAVE2 complex, enables the cortical actin network to restrain
CC excessive degranulation and granule release by T-cells. Required for
CC efficient T-lymphocyte and neutrophil migration (By similarity).
CC Exhibits complex cycles of activation and inhibition to generate waves
CC of propagating the assembly with actin. Also involved in mechanisms
CC WAVE independent to regulate myosin and actin polymerization during
CC neutrophil chemotaxis (By similarity). In T-cells, required for proper
CC mechanistic target of rapamycin complex 2 (mTORC2)-dependent AKT
CC phosphorylation, cell proliferation and cytokine secretion, including
CC that of IL2 and TNF (By similarity). {ECO:0000250|UniProtKB:P55160,
CC ECO:0000269|PubMed:19015308, ECO:0000269|PubMed:23424621}.
CC -!- SUBUNIT: In hematopoietic cells, component of the WAVE2 complex
CC composed of ABI1, CYFIP1/SRA1, NCKAP1L/HEM1 and WASF2/WAVE2. Interacts
CC with ARHGAP4, PIK3C3/VPS34 and PPP1R12A/MYPT1. Interacts with mammalian
CC target of rapamycin complex 2 (mTORC2) components, including MTOR and
CC RICTOR. {ECO:0000250|UniProtKB:P55160}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:P55160}; Single-
CC pass membrane protein {ECO:0000255}. Cytoplasm
CC {ECO:0000250|UniProtKB:P55160}. Note=Localizes to the leading edge of
CC polarized neutrophils. {ECO:0000250|UniProtKB:P55160}.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in developing and mature
CC hematopoietic cells. Also detected in urogenital tissues, including
CC testis. {ECO:0000269|PubMed:19015308}.
CC -!- DISRUPTION PHENOTYPE: Mutants exhibit lymphopenia, neutrophilia and
CC anemia. T cell development is disrupted at the CD4(-)CD8(-) to
CC CD4(+)CD8(+) cell stages and T cell activation and adhesion are
CC impaired. Neutrophils fail to migrate in response to chemotactic agents
CC and are deficient in their ability to phagocytose bacteria. They show
CC enhanced Th17 cells production (PubMed:19015308). The anemia is
CC microcytic, hypochromic and characterized by abnormally shaped
CC erythrocytes with aberrant F-actin foci and decreased lifespan
CC (PubMed:23424621). {ECO:0000269|PubMed:19015308,
CC ECO:0000269|PubMed:23424621}.
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DR EMBL; AK083390; BAC38898.1; -; mRNA.
DR EMBL; AC131721; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC037096; AAH37096.1; -; mRNA.
DR CCDS; CCDS37236.1; -.
DR RefSeq; NP_705725.1; NM_153505.4.
DR RefSeq; XP_006520318.2; XM_006520255.3.
DR AlphaFoldDB; Q8K1X4; -.
DR SMR; Q8K1X4; -.
DR IntAct; Q8K1X4; 1.
DR MINT; Q8K1X4; -.
DR STRING; 10090.ENSMUSP00000035400; -.
DR iPTMnet; Q8K1X4; -.
DR PhosphoSitePlus; Q8K1X4; -.
DR EPD; Q8K1X4; -.
DR MaxQB; Q8K1X4; -.
DR PaxDb; Q8K1X4; -.
DR PeptideAtlas; Q8K1X4; -.
DR PRIDE; Q8K1X4; -.
DR ProteomicsDB; 252925; -.
DR Antibodypedia; 27500; 166 antibodies from 25 providers.
DR DNASU; 105855; -.
DR Ensembl; ENSMUST00000047405; ENSMUSP00000035400; ENSMUSG00000022488.
DR GeneID; 105855; -.
DR KEGG; mmu:105855; -.
DR UCSC; uc007xyf.1; mouse.
DR CTD; 3071; -.
DR MGI; MGI:1926063; Nckap1l.
DR VEuPathDB; HostDB:ENSMUSG00000022488; -.
DR eggNOG; KOG1917; Eukaryota.
DR GeneTree; ENSGT00390000016619; -.
DR HOGENOM; CLU_004450_0_0_1; -.
DR InParanoid; Q8K1X4; -.
DR OMA; VYNCAHE; -.
DR OrthoDB; 138196at2759; -.
DR PhylomeDB; Q8K1X4; -.
DR TreeFam; TF313683; -.
DR Reactome; R-MMU-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-MMU-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-MMU-5663213; RHO GTPases Activate WASPs and WAVEs.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR Reactome; R-MMU-9013404; RAC2 GTPase cycle.
DR Reactome; R-MMU-9013423; RAC3 GTPase cycle.
DR BioGRID-ORCS; 105855; 5 hits in 72 CRISPR screens.
DR PRO; PR:Q8K1X4; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q8K1X4; protein.
DR Bgee; ENSMUSG00000022488; Expressed in granulocyte and 142 other tissues.
DR ExpressionAtlas; Q8K1X4; baseline and differential.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031209; C:SCAR complex; IMP:UniProtKB.
DR GO; GO:0005096; F:GTPase activator activity; ISS:UniProtKB.
DR GO; GO:0030295; F:protein kinase activator activity; ISS:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; ISS:UniProtKB.
DR GO; GO:1904841; F:TORC2 complex binding; ISS:UniProtKB.
DR GO; GO:0070358; P:actin polymerization-dependent cell motility; ISS:UniProtKB.
DR GO; GO:0001782; P:B cell homeostasis; IMP:UniProtKB.
DR GO; GO:0050853; P:B cell receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0000902; P:cell morphogenesis; IBA:GO_Central.
DR GO; GO:0030031; P:cell projection assembly; IBA:GO_Central.
DR GO; GO:0006935; P:chemotaxis; ISS:UniProtKB.
DR GO; GO:0030866; P:cortical actin cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:0048821; P:erythrocyte development; IEA:Ensembl.
DR GO; GO:0034101; P:erythrocyte homeostasis; IMP:UniProtKB.
DR GO; GO:0030011; P:maintenance of cell polarity; ISS:UniProtKB.
DR GO; GO:0002262; P:myeloid cell homeostasis; IMP:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0043318; P:negative regulation of cytotoxic T cell degranulation; ISS:UniProtKB.
DR GO; GO:0032700; P:negative regulation of interleukin-17 production; IMP:UniProtKB.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IMP:UniProtKB.
DR GO; GO:0035509; P:negative regulation of myosin-light-chain-phosphatase activity; ISS:UniProtKB.
DR GO; GO:0048812; P:neuron projection morphogenesis; IBA:GO_Central.
DR GO; GO:0030593; P:neutrophil chemotaxis; ISS:UniProtKB.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IMP:UniProtKB.
DR GO; GO:0045579; P:positive regulation of B cell differentiation; IMP:UniProtKB.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; ISS:UniProtKB.
DR GO; GO:0043372; P:positive regulation of CD4-positive, alpha-beta T cell differentiation; IMP:UniProtKB.
DR GO; GO:0043378; P:positive regulation of CD8-positive, alpha-beta T cell differentiation; IMP:UniProtKB.
DR GO; GO:0033630; P:positive regulation of cell adhesion mediated by integrin; IMP:UniProtKB.
DR GO; GO:0045648; P:positive regulation of erythrocyte differentiation; IMP:UniProtKB.
DR GO; GO:0045588; P:positive regulation of gamma-delta T cell differentiation; IMP:UniProtKB.
DR GO; GO:0002687; P:positive regulation of leukocyte migration; ISS:UniProtKB.
DR GO; GO:0045621; P:positive regulation of lymphocyte differentiation; IMP:UniProtKB.
DR GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; IMP:UniProtKB.
DR GO; GO:1902624; P:positive regulation of neutrophil migration; ISS:UniProtKB.
DR GO; GO:0060100; P:positive regulation of phagocytosis, engulfment; IMP:UniProtKB.
DR GO; GO:0042327; P:positive regulation of phosphorylation; ISS:UniProtKB.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; IMP:UniProtKB.
DR GO; GO:1904515; P:positive regulation of TORC2 signaling; ISS:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; IMP:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISS:UniProtKB.
DR GO; GO:0043029; P:T cell homeostasis; IMP:UniProtKB.
DR InterPro; IPR019137; Nck-associated_protein-1.
DR PANTHER; PTHR12093; PTHR12093; 1.
DR Pfam; PF09735; Nckap1; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..1134
FT /note="Nck-associated protein 1-like"
FT /id="PRO_0000439210"
FT TRANSMEM 999..1019
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 638..671
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 648..671
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 1134 AA; 128905 MW; 5780D0AF3B00E767 CRC64;
MSLTSAYQLK LAEKLTILND RGQGVLIRMY NIKKTCSDSK SKPPFLLEKS MESCLKYINK
KFPNIDVRNS TQHLGPVHRE KAEIIRFLTN YYQSFVDVME FRDHVYELLN TIDACQCHFD
INLNFDFTRS YLDLIVTYTS VILLLSRIED RRILIGMYNC AHEMLHGHSD PSFARLGQMV
LEYDHPLKKL TEEFGPHTKA VSGALLSLHF LFVRRNQGAE QWRSAQLLSL ISSPPAMINP
ANSDTMACEY LSVEVMERWI IIGFLLCHGC LNSNSQCQKL WKLCLEGSLY ITLIREDVLQ
VHKVTEDLFS SLKGYSKRVA DIKESKEHAI TNSGQFHCQR RQFLRTAVKE LETVLNDEPG
LLGPKALFAF MALSFIRDEV TWLVRHTENV TKTKTPEDYA DSSIAELLFL LEEIRALVRR
HIKVIQQYHL QYLARFDVLV LSDIIQNLSV CPEEESVIMS SFVSILSSLN LKQVDNEEKF
DFSGLRLDWF RLQAYTSVSK APLHLHENPD LAKVMNLIIF HSQMLDSVEK MLVETSDLST
FCFHLRTFEK MFATTLEEPT MLRYTIAFPL ICAHFVHCVH EMCPEEYPHL KNHGLHHCNS
FLEDLAKQTS NCVLEICAEQ RNLNEQLLPK HCATTISKAK NKKSMKQRQA PRKGEPERDK
PGAESHRKNR SLVTNMDKLH LNLTELALAM NHVHSFSVFE HTIFPSEYLS SHLEARLNRA
IVTLAGYNAT TQEILRPSEL LAGVKAYISF IQSLAQFLGA DASRIVRNAL LQQTQPLDSS
GEQTVTTLYT NWYLESLLRQ ASSGAIVLSP AMQAFISLPR DGEQNFSAEE FSDISEMRAL
AEILGPYGMK FLSENLMWHV TSQIVELKKL VVENMDILVQ IRSNFSKPEL MASLLPQLTG
AENVLKRMTI IGVILSFRAM AQEGLQEVFS AHCPFLMGPI ECLKEFVTPD TDIKVTLSVF
ELACAAGVSC DIDPALVAAI ANLKADNSSP EEEYKVACLL LIFLAVSLPL LATDPSSFFS
IEKDGYNNNI HCLTKAIIQV SAALFTLYNK NIETHLKEFL VVASVSLLQL GQETDKLKTR
NRESISLLMR LVVEESPFLT LDMLESCFPY VLLRNAYREV SRAFYLNRLP ASSH
