ID UNC5C_MOUSE Reviewed; 931 AA. AC O08747; Q8CD16; DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1997, sequence version 1. DT 12-AUG-2020, entry version 152. DE RecName: Full=Netrin receptor UNC5C; DE AltName: Full=Protein unc-5 homolog 3; DE AltName: Full=Protein unc-5 homolog C; DE AltName: Full=Rostral cerebellar malformation protein {ECO:0000303|PubMed:9126743}; DE Flags: Precursor; GN Name=Unc5c; GN Synonyms=Rcm {ECO:0000303|PubMed:11533026}, GN Unc5h3 {ECO:0000303|PubMed:12451134}; 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 [MRNA] (ISOFORM 1), FUNCTION, DISEASE, AND TISSUE RP SPECIFICITY. RC STRAIN=C57B6/SJL; RX PubMed=9126743; DOI=10.1038/386838a0; RA Ackerman S.L., Kozak L.P., Przyborski S.A., Rund L.A., Boyer B.B., RA Knowles B.B.; RT "The mouse rostral cerebellar malformation gene encodes an UNC-5-like RT protein."; RL Nature 386:838-842(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC STRAIN=C57BL/6J; TISSUE=Testis; 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 [3] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=9389662; RA Przyborski S.A., Knowles B.B., Ackerman S.L.; RT "Embryonic phenotype of Unc5h3 mutant mice suggests chemorepulsion during RT the formation of the rostral cerebellar boundary."; RL Development 125:41-50(1998). RN [4] RP FUNCTION, AND INTERACTION WITH DCC. RX PubMed=10399920; DOI=10.1016/s0092-8674(00)80804-1; RA Hong K., Hinck L., Nishiyama M., Poo M.-M., Tessier-Lavigne M., Stein E.; RT "A ligand-gated association between cytoplasmic domains of UNC5 and DCC RT family receptors converts netrin-induced growth cone attraction to RT repulsion."; RL Cell 97:927-941(1999). RN [5] RP PHOSPHORYLATION AT TYR-568, MUTAGENESIS OF TYR-568, AND INTERACTION WITH RP DCC AND PTPN11. RX PubMed=11533026; DOI=10.1074/jbc.m103872200; RA Tong J., Killeen M., Steven R., Binns K.L., Culotti J., Pawson T.; RT "Netrin stimulates tyrosine phosphorylation of the UNC-5 family of netrin RT receptors and induces Shp2 binding to the RCM cytodomain."; RL J. Biol. Chem. 276:40917-40925(2001). RN [6] RP FUNCTION. RX PubMed=12451134; DOI=10.1523/jneurosci.22-23-10346.2002; RA Finger J.H., Bronson R.T., Harris B., Johnson K., Przyborski S.A., RA Ackerman S.L.; RT "The netrin 1 receptors Unc5h3 and Dcc are necessary at multiple choice RT points for the guidance of corticospinal tract axons."; RL J. Neurosci. 22:10346-10356(2002). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-502, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain; 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 [8] RP FUNCTION, INTERACTION WITH DSCAM, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, RP DEVELOPMENTAL STAGE, AND PHOSPHORYLATION. RX PubMed=22685302; DOI=10.1074/jbc.m112.340174; RA Purohit A.A., Li W., Qu C., Dwyer T., Shao Q., Guan K.L., Liu G.; RT "Down syndrome cell adhesion molecule (DSCAM) associates with RT uncoordinated-5C (UNC5C) in netrin-1-mediated growth cone collapse."; RL J. Biol. Chem. 287:27126-27138(2012). RN [9] RP INTERACTION WITH FLRT3, AND SUBCELLULAR LOCATION. RX PubMed=22405201; DOI=10.1016/j.neuron.2012.01.018; RA O'Sullivan M.L., de Wit J., Savas J.N., Comoletti D., Otto-Hitt S., RA Yates J.R. III, Ghosh A.; RT "FLRT proteins are endogenous latrophilin ligands and regulate excitatory RT synapse development."; RL Neuron 73:903-910(2012). RN [10] RP TISSUE SPECIFICITY. RX PubMed=25419706; DOI=10.1038/nm.3736; RG Alzheimer's Disease Genetics Consortium; RA Wetzel-Smith M.K., Hunkapiller J., Bhangale T.R., Srinivasan K., RA Maloney J.A., Atwal J.K., Sa S.M., Yaylaoglu M.B., Foreman O., Ortmann W., RA Rathore N., Hansen D.V., Tessier-Lavigne M., Mayeux R., Pericak-Vance M., RA Haines J., Farrer L.A., Schellenberg G.D., Goate A., Behrens T.W., RA Cruchaga C., Watts R.J., Graham R.R.; RT "A rare mutation in UNC5C predisposes to late-onset Alzheimer's disease and RT increases neuronal cell death."; RL Nat. Med. 20:1452-1457(2014). RN [11] RP FUNCTION, INTERACTION WITH TUBB3, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, RP AND DEVELOPMENTAL STAGE. RX PubMed=28483977; DOI=10.1523/jneurosci.2617-16.2017; RA Shao Q., Yang T., Huang H., Alarmanazi F., Liu G.; RT "Uncoupling of UNC5C with Polymerized TUBB3 in Microtubules Mediates RT Netrin-1 Repulsion."; RL J. Neurosci. 37:5620-5633(2017). CC -!- FUNCTION: Receptor for netrin required for axon guidance CC (PubMed:22685302, PubMed:10399920). Mediates axon repulsion of neuronal CC growth cones in the developing nervous system upon ligand binding CC (PubMed:10399920, PubMed:22685302). NTN1/Netrin-1 binding might cause CC dissociation of UNC5C from polymerized TUBB3 in microtubules and CC thereby lead to increased microtubule dynamics and axon repulsion CC (PubMed:28483977). Axon repulsion in growth cones may also be caused by CC its association with DCC that may trigger signaling for repulsion CC (PubMed:10399920). Might also collaborate with DSCAM in NTN1-mediated CC axon repulsion independently of DCC (PubMed:22685302). Also involved in CC corticospinal tract axon guidance independently of DCC (PubMed:9126743, CC PubMed:9389662, PubMed:12451134). Involved in dorsal root ganglion axon CC projection towards the spinal cord (By similarity). It also acts as a CC dependence receptor required for apoptosis induction when not CC associated with netrin ligand (By similarity). CC {ECO:0000250|UniProtKB:O95185, ECO:0000250|UniProtKB:Q761X5, CC ECO:0000269|PubMed:10399920, ECO:0000269|PubMed:12451134, CC ECO:0000269|PubMed:22685302, ECO:0000269|PubMed:28483977, CC ECO:0000269|PubMed:9126743, ECO:0000269|PubMed:9389662}. CC -!- SUBUNIT: Interacts with DCC (via cytoplasmic domain) (PubMed:10399920, CC PubMed:11533026). Interacts (tyrosine phosphorylated form) with PTPN11 CC (PubMed:11533026). Interacts (via extracellular domain) with FLRT3 (via CC extracellular domain) (PubMed:22405201). Interacts (via Ig-like C2-type CC domain) with DSCAM (via extracellular domain) (PubMed:22685302). CC Interacts (via death domain) with DAPK1 (By similarity). Interacts (via CC cytoplasmic domain) with TUBB3; this interaction is decreased by CC NTN1/Netrin-1 (PubMed:28483977). {ECO:0000250|UniProtKB:O95185, CC ECO:0000269|PubMed:10399920, ECO:0000269|PubMed:11533026, CC ECO:0000269|PubMed:22405201, ECO:0000269|PubMed:22685302, CC ECO:0000269|PubMed:28483977}. CC -!- INTERACTION: CC O08747; Q9ERD7: Tubb3; NbExp=3; IntAct=EBI-21004500, EBI-2255594; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22405201}; CC Single-pass type I membrane protein {ECO:0000255}. Cell surface CC {ECO:0000250|UniProtKB:O95185}. Cell junction, synapse, synaptosome CC {ECO:0000250|UniProtKB:Q761X5}. Cell projection, dendrite CC {ECO:0000269|PubMed:22685302}. Cell projection, axon CC {ECO:0000269|PubMed:22685302}. Cell projection, growth cone CC {ECO:0000269|PubMed:22685302, ECO:0000269|PubMed:28483977}. Cell CC projection, lamellipodium {ECO:0000269|PubMed:28483977}. Cell CC projection, filopodium {ECO:0000269|PubMed:28483977}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O08747-1; Sequence=Displayed; CC Name=2; CC IsoId=O08747-2; Sequence=VSP_011702; CC -!- TISSUE SPECIFICITY: Expressed in cortical and cerebellar neurons, CC including cells of the external and internal granular layer and of the CC Purkinje cell layer (at protein level) (PubMed:22685302, CC PubMed:28483977). Mainly expressed in regions of differentiating CC neurons (PubMed:9126743). Highly expressed in brain and lung CC (PubMed:9126743, PubMed:9389662). Expressed in the cerebellum and the CC neurons of the hippocampus, with enrichment in neurons of the CA3 CC hippocampal pyramidal layer (PubMed:25419706). Weakly expressed in CC testis, ovary, spleen, thymus and bladder (PubMed:9126743). Expressed CC at very low level in kidney, intestine and salivary gland CC (PubMed:9126743). {ECO:0000269|PubMed:22685302, CC ECO:0000269|PubMed:25419706, ECO:0000269|PubMed:28483977, CC ECO:0000269|PubMed:9126743, ECO:0000269|PubMed:9389662}. CC -!- DEVELOPMENTAL STAGE: Detected at 15 dpc in the cortex and cerebellum CC and at postnatal day 2 and 4 in the cerebellum (at protein level). CC {ECO:0000269|PubMed:22685302, ECO:0000269|PubMed:28483977}. CC -!- PTM: Phosphorylated on different cytoplasmic tyrosine residues CC (PubMed:11533026). Phosphorylation of Tyr-568 leads to an interaction CC with PTPN11 phosphatase, suggesting that its activity is regulated by CC phosphorylation/dephosphorylation (PubMed:11533026). Tyrosine CC phosphorylation is netrin-dependent (PubMed:11533026, PubMed:22685302). CC {ECO:0000269|PubMed:11533026, ECO:0000269|PubMed:22685302}. CC -!- PTM: Proteolytically cleaved by caspases during apoptosis. The cleavage CC does not take place when the receptor is associated with netrin ligand. CC Its cleavage by caspases is required to induce apoptosis. CC {ECO:0000250|UniProtKB:Q761X5}. CC -!- DISEASE: Note=Defects in Unc5c are the cause of rostral cerebellar CC malformation (Rcm). Rcm is characterized by cerebellar and midbrain CC defects, apparently as a result of abnormal neuronal migration. CC {ECO:0000269|PubMed:9126743}. CC -!- SIMILARITY: Belongs to the unc-5 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; U72634; AAB54103.1; -; mRNA. DR EMBL; AK031655; BAC27495.1; -; mRNA. DR CCDS; CCDS17873.1; -. [O08747-1] DR CCDS; CCDS80034.1; -. [O08747-2] DR RefSeq; NP_033498.1; NM_009472.4. [O08747-1] DR SMR; O08747; -. DR BioGRID; 204445; 4. DR IntAct; O08747; 1. DR STRING; 10090.ENSMUSP00000101843; -. DR GlyGen; O08747; 2 sites. DR iPTMnet; O08747; -. DR PhosphoSitePlus; O08747; -. DR MaxQB; O08747; -. DR PaxDb; O08747; -. DR PRIDE; O08747; -. DR Antibodypedia; 2665; 262 antibodies. DR Ensembl; ENSMUST00000075282; ENSMUSP00000074758; ENSMUSG00000059921. [O08747-2] DR Ensembl; ENSMUST00000106236; ENSMUSP00000101843; ENSMUSG00000059921. [O08747-1] DR Ensembl; ENSMUST00000142762; ENSMUSP00000118212; ENSMUSG00000059921. [O08747-2] DR GeneID; 22253; -. DR KEGG; mmu:22253; -. DR UCSC; uc008roe.2; mouse. [O08747-1] DR CTD; 8633; -. DR MGI; MGI:1095412; Unc5c. DR eggNOG; KOG1480; Eukaryota. DR GeneTree; ENSGT00950000182815; -. DR HOGENOM; CLU_014383_0_0_1; -. DR InParanoid; O08747; -. DR KO; K07521; -. DR TreeFam; TF316767; -. DR BioGRID-ORCS; 22253; 0 hits in 18 CRISPR screens. DR ChiTaRS; Unc5c; mouse. DR PRO; PR:O08747; -. DR Proteomes; UP000000589; Chromosome 3. DR RNAct; O08747; protein. DR Bgee; ENSMUSG00000059921; Expressed in ureter smooth muscle and 285 other tissues. DR Genevisible; O08747; MM. DR GO; GO:0030424; C:axon; IDA:UniProtKB. DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell. DR GO; GO:0030425; C:dendrite; IDA:UniProtKB. DR GO; GO:0030175; C:filopodium; IDA:UniProtKB. DR GO; GO:0030426; C:growth cone; IDA:UniProtKB. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB. DR GO; GO:0043025; C:neuronal cell body; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:MGI. DR GO; GO:0045202; C:synapse; IEA:UniProtKB-KW. DR GO; GO:0005042; F:netrin receptor activity; IDA:MGI. DR GO; GO:0005043; F:netrin receptor activity involved in chemorepulsion; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; ISO:MGI. DR GO; GO:0015631; F:tubulin binding; IPI:UniProtKB. DR GO; GO:0033564; P:anterior/posterior axon guidance; IMP:MGI. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0007411; P:axon guidance; IDA:UniProtKB. DR GO; GO:0007420; P:brain development; IMP:MGI. DR GO; GO:0061643; P:chemorepulsion of axon; IMP:UniProtKB. DR GO; GO:1990791; P:dorsal root ganglion development; ISS:UniProtKB. DR GO; GO:0038007; P:netrin-activated signaling pathway; IGI:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:MGI. DR GO; GO:0030334; P:regulation of cell migration; IMP:MGI. DR CDD; cd08799; Death_UNC5C; 1. DR Gene3D; 2.20.100.10; -; 2. DR Gene3D; 2.60.40.10; -; 2. DR InterPro; IPR011029; DEATH-like_dom_sf. DR InterPro; IPR000488; Death_domain. DR InterPro; IPR042154; Death_UNC5C. DR InterPro; IPR007110; Ig-like_dom. DR InterPro; IPR036179; Ig-like_dom_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR013098; Ig_I-set. DR InterPro; IPR003599; Ig_sub. DR InterPro; IPR003598; Ig_sub2. DR InterPro; IPR000884; TSP1_rpt. DR InterPro; IPR036383; TSP1_rpt_sf. DR InterPro; IPR037936; UNC5. DR InterPro; IPR033772; UPA. DR InterPro; IPR000906; ZU5_dom. DR PANTHER; PTHR12582; PTHR12582; 1. DR Pfam; PF00531; Death; 1. DR Pfam; PF07679; I-set; 1. DR Pfam; PF00090; TSP_1; 1. DR Pfam; PF17217; UPA; 1. DR Pfam; PF00791; ZU5; 1. DR SMART; SM00005; DEATH; 1. DR SMART; SM00409; IG; 1. DR SMART; SM00408; IGc2; 1. DR SMART; SM00209; TSP1; 2. DR SMART; SM00218; ZU5; 1. DR SUPFAM; SSF47986; SSF47986; 1. DR SUPFAM; SSF48726; SSF48726; 2. DR SUPFAM; SSF82895; SSF82895; 2. DR PROSITE; PS50835; IG_LIKE; 1. DR PROSITE; PS50092; TSP1; 2. DR PROSITE; PS51145; ZU5; 1. PE 1: Evidence at protein level; KW Alternative splicing; Apoptosis; Cell junction; Cell membrane; KW Cell projection; Developmental protein; Disulfide bond; Glycoprotein; KW Immunoglobulin domain; Membrane; Phosphoprotein; Receptor; KW Reference proteome; Repeat; Signal; Synapse; Synaptosome; Transmembrane; KW Transmembrane helix. FT SIGNAL 1..40 FT /evidence="ECO:0000255" FT CHAIN 41..931 FT /note="Netrin receptor UNC5C" FT /id="PRO_0000036076" FT TOPO_DOM 41..380 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 381..401 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 402..931 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 62..159 FT /note="Ig-like" FT DOMAIN 161..256 FT /note="Ig-like C2-type" FT DOMAIN 260..314 FT /note="TSP type-1 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210" FT DOMAIN 316..368 FT /note="TSP type-1 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210" FT DOMAIN 530..673 FT /note="ZU5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00485" FT DOMAIN 850..929 FT /note="Death" FT REGION 402..931 FT /note="Required for netrin-mediated axon repulsion of FT neuronal growth cones" FT /evidence="ECO:0000269|PubMed:22685302" FT REGION 694..712 FT /note="Interaction with DCC" FT /evidence="ECO:0000269|PubMed:10399920" FT SITE 415..416 FT /note="Cleavage; by caspase-3" FT /evidence="ECO:0000250|UniProtKB:Q761X5" FT MOD_RES 502 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:21183079" FT MOD_RES 568 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:11533026" FT CARBOHYD 236 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 361 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 83..144 FT /evidence="ECO:0000250|UniProtKB:Q6ZN44" FT DISULFID 95..142 FT /evidence="ECO:0000250|UniProtKB:Q6ZN44" FT DISULFID 188..239 FT /evidence="ECO:0000250|UniProtKB:Q6ZN44" FT DISULFID 272..309 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210" FT DISULFID 276..313 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210" FT DISULFID 287..299 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210" FT DISULFID 328..362 FT /evidence="ECO:0000250|UniProtKB:Q6ZN44" FT DISULFID 332..367 FT /evidence="ECO:0000250|UniProtKB:Q6ZN44" FT DISULFID 340..352 FT /evidence="ECO:0000250|UniProtKB:Q6ZN44" FT VAR_SEQ 370 FT /note="A -> GFIYPISTEHRPQNEYGFSS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:16141072" FT /id="VSP_011702" FT MUTAGEN 568 FT /note="Y->F: Abolishes interaction with PTPN11, leading to FT an increased level of phosphorylation." FT /evidence="ECO:0000269|PubMed:11533026" FT CONFLICT 16 FT /note="L -> I (in Ref. 2; BAC27495)" FT /evidence="ECO:0000305" FT CONFLICT 733 FT /note="H -> R (in Ref. 2; BAC27495)" FT /evidence="ECO:0000305" FT CONFLICT 924 FT /note="S -> Y (in Ref. 2; BAC27495)" FT /evidence="ECO:0000305" SQ SEQUENCE 931 AA; 103063 MW; 8A5D951A4EECA179 CRC64; MRKGLRATAA RCGLGLGYLL QMLVLPALAL LSASGTGSAA QDDEFFHELP ETFPSDPPEP LPHFLIEPEE AYIVKNKPVN LYCKASPATQ IYFKCNSEWV HQKDHVVDER VDETSGLIVR EVSIEISRQQ VEELFGPEDY WCQCVAWSSA GTTKSRKAYV RIAYLRKTFE QEPLGKEVSL EQEVLLQCRP PEGIPVAEVE WLKNEDIIDP AEDRNFYITI DHNLIIKQAR LSDTANYTCV AKNIVAKRKS TTATVIVYVN GGWSTWTEWS VCNSRCGRGY QKRTRTCTNP APLNGGAFCE GQSVQKIACT TLCPVDGRWT SWSKWSTCGT ECTHWRRREC TAPAPKNGGK DCDGLVLQSK NCTDGLCMQA APDSDDVALY VGIVIAVTVC LAITVVVALF VYRKNHRDFE SDIIDSSALN GGFQPVNIKA ARQDLLAVPP DLTSAAAMYR GPVYALHDVS DKIPMTNSPI LDPLPNLKIK VYNSSGAVTP QDDLAEFSSK LSPQMTQSLL ENEALNLKNQ SLARQTDPSC TAFGTFNSLG GHLIIPNSGV SLLIPAGAIP QGRVYEMYVT VHRKENMRPP MEDSQTLLTP VVSCGPPGAL LTRPVILTLH HCADPSTEDW KIQLKNQAVQ GQWEDVVVVG EENFTTPCYI QLDAEACHIL TENLSTYALV GQSTTKAAAK RLKLAIFGPL CCSSLEYSIR VYCLDDTQDA LKEVLQLERQ MGGQLLEEPK ALHFKGSIHN LRLSIHDIAH SLWKSKLLAK YQEIPFYHIW SGSQRNLHCT FTLERLSLNT VELVCKLCVR QVEGEGQIFQ LNCTVSEEPT GIDLPLLDPA STITTVTGPS AFSIPLPIRQ KLCSSLDAPQ TRGHDWRMLA HKLNLDRYLN YFATKSSPTG VILDLWEAQN FPDGNLSMLA AVLEEMGRHE TVVSLAAEGQ Y //