ID RIPK4_HUMAN Reviewed; 832 AA. AC P57078; Q96KH0; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2000, sequence version 1. DT 27-MAR-2024, entry version 195. DE RecName: Full=Receptor-interacting serine/threonine-protein kinase 4; DE EC=2.7.11.1; DE AltName: Full=Ankyrin repeat domain-containing protein 3; DE AltName: Full=PKC-delta-interacting protein kinase; GN Name=RIPK4; Synonyms=ANKRD3, DIK; 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] (ISOFORM 2). RC TISSUE=Fetal kidney, and Fetal lung; RA Shimizu N., Kudoh J., Shibuya K.; RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10830953; DOI=10.1038/35012518; RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U., RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.; RT "The DNA sequence of human chromosome 21."; RL Nature 405:311-319(2000). RN [3] RP PROTEOLYTIC CLEAVAGE AT ASP-388 AND ASP-426, INTERACTION WITH TRAF1; TRAF2; RP TRAF3 AND TRAF5, AND FUNCTION. RX PubMed=12446564; DOI=10.1093/embo-reports/kvf236; RA Meylan E., Martinon F., Thome M., Gschwendt M., Tschopp J.; RT "RIP4 (DIK/PKK), a novel member of the RIP kinase family, activates NF- RT kappa B and is processed during apoptosis."; RL EMBO Rep. 3:1201-1208(2002). RN [4] RP UBIQUITINATION AT LYS-51 AND LYS-145, UBIQUITINATION BY BIRC2/C-IAP1 AND RP BIRC3/C-IAP2, AND INTERACTION WITH BIRC2/C-IAP1; BIRC3/C-IAP2 AND RP XIAP/BIRC4. RX PubMed=21931591; DOI=10.1371/journal.pone.0022356; RA Bertrand M.J., Lippens S., Staes A., Gilbert B., Roelandt R., De Medts J., RA Gevaert K., Declercq W., Vandenabeele P.; RT "cIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin RT chains to receptor interacting proteins kinases 1 to 4 (RIP1-4)."; RL PLoS ONE 6:E22356-E22356(2011). RN [5] RP FUNCTION, AND VARIANT BPS ASN-81. RX PubMed=22197488; DOI=10.1016/j.ajhg.2011.11.013; RA Mitchell K., O'Sullivan J., Missero C., Blair E., Richardson R., RA Anderson B., Antonini D., Murray J.C., Shanske A.L., Schutte B.C., RA Romano R.A., Sinha S., Bhaskar S.S., Black G.C., Dixon J., Dixon M.J.; RT "Exome sequence identifies RIPK4 as the Bartsocas-Papas syndrome locus."; RL Am. J. Hum. Genet. 90:69-75(2012). RN [6] RP VARIANTS [LARGE SCALE ANALYSIS] ASN-462; MET-463; TYR-562; HIS-669 AND RP SER-749. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). RN [7] RP VARIANTS BPS ASN-121 AND ILE-184, AND CHARACTERIZATION OF VARIANTS BPS RP ASN-121 AND ILE-184. RX PubMed=22197489; DOI=10.1016/j.ajhg.2011.11.014; RA Kalay E., Sezgin O., Chellappa V., Mutlu M., Morsy H., Kayserili H., RA Kreiger E., Cansu A., Toraman B., Abdalla E.M., Aslan Y., Pillai S., RA Akarsu N.A.; RT "Mutations in RIPK4 cause the autosomal-recessive form of popliteal RT pterygium syndrome."; RL Am. J. Hum. Genet. 90:76-85(2012). RN [8] RP INVOLVEMENT IN CHANDS, AND VARIANT CHANDS ASP-163. RX PubMed=23610050; DOI=10.1002/ajmg.a.35913; RA Gripp K.W., Ennis S., Napoli J.; RT "Exome analysis in clinical practice: expanding the phenotype of Bartsocas- RT Papas syndrome."; RL Am. J. Med. Genet. A 161A:1058-1063(2013). RN [9] RP INVOLVEMENT IN CHANDS, VARIANT CHANDS LYS-284, AND TISSUE SPECIFICITY. RX PubMed=26129644; DOI=10.1002/ajmg.a.37233; RA Gollasch B., Basmanav F.B., Nanda A., Fritz G., Mahmoudi H., Thiele H., RA Wehner M., Wolf S., Altmueller J., Nuernberg P., Frank J., Betz R.C.; RT "Identification of a novel mutation in RIPK4 in a kindred with phenotypic RT features of Bartsocas-Papas and CHAND syndromes."; RL Am. J. Med. Genet. A 167A:2555-2562(2015). RN [10] RP VARIANTS BPS LEU-189; PRO-496 AND HIS-666. RX PubMed=25691407; DOI=10.1002/ajmg.a.36896; RA Leslie E.J., O'Sullivan J., Cunningham M.L., Singh A., Goudy S.L., RA Ababneh F., Alsubaie L., Ch'ng G.S., van der Laar I.M., Hoogeboom A.J., RA Dunnwald M., Kapoor S., Jiramongkolchai P., Standley J., Manak J.R., RA Murray J.C., Dixon M.J.; RT "Expanding the genetic and phenotypic spectrum of popliteal pterygium RT disorders."; RL Am. J. Med. Genet. A 167A:545-552(2015). CC -!- FUNCTION: Involved in stratified epithelial development. It is a direct CC transcriptional target of TP63. Plays a role in NF-kappa-B activation. CC {ECO:0000269|PubMed:12446564, ECO:0000269|PubMed:22197488}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; CC EC=2.7.11.1; CC -!- SUBUNIT: Interacts with PRKCB (By similarity). Interacts with TRAF1, CC TRAF2, TRAF3 and TRAF5. Interacts with BIRC2/c-IAP1, BIRC3/c-IAP2 and CC XIAP/BIRC4. {ECO:0000250, ECO:0000269|PubMed:12446564, CC ECO:0000269|PubMed:21931591}. CC -!- INTERACTION: CC P57078; Q13490: BIRC2; NbExp=3; IntAct=EBI-4422308, EBI-514538; CC P57078; Q13489: BIRC3; NbExp=3; IntAct=EBI-4422308, EBI-517709; CC P57078; O14641: DVL2; NbExp=4; IntAct=EBI-4422308, EBI-740850; CC P57078; Q9NWT6: HIF1AN; NbExp=4; IntAct=EBI-4422308, EBI-745632; CC P57078; P98170: XIAP; NbExp=2; IntAct=EBI-4422308, EBI-517127; CC P57078-2; Q9Y4H4: GPSM3; NbExp=3; IntAct=EBI-12854608, EBI-347538; CC P57078-2; Q99932-2: SPAG8; NbExp=3; IntAct=EBI-12854608, EBI-11959123; CC P57078-2; B2RUY7: VWC2L; NbExp=3; IntAct=EBI-12854608, EBI-11747707; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Membrane {ECO:0000250}; Peripheral CC membrane protein {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P57078-1; Sequence=Displayed; CC Name=2; CC IsoId=P57078-2; Sequence=VSP_004862; CC -!- TISSUE SPECIFICITY: Expressed in hair follicles and skin. CC {ECO:0000269|PubMed:26129644}. CC -!- PTM: May be phosphorylated by MAP3K2 and MAP3K3. {ECO:0000250}. CC -!- PTM: Proteolytically cleaved by during Fas-induced apoptosis. Cleavage CC at Asp-388 and Asp-426. {ECO:0000269|PubMed:12446564}. CC -!- PTM: Polyubiquitinated with 'Lys-48' and 'Lys-63'-linked chains by CC BIRC2/c-IAP1 and BIRC3/c-IAP2, leading to activation of NF-kappa-B. CC {ECO:0000269|PubMed:21931591}. CC -!- DISEASE: Bartsocas-Papas syndrome (BPS) [MIM:263650]: An autosomal CC recessive disorder characterized by multiple popliteal pterygia leading CC to severe arthrogryposis, ankyloblepharon filiforme adnatum, filiform CC bands between the jaws, synostosis of the carpal/tarsal and phalangeal CC bones in the hands and feet, digital hypoplasia/aplasia, complete soft- CC tissue syndactyly, lack of nails, lack of scalp hair, eyebrows and CC eyelashes, blepharophimosis, cleft lip and/or palate, and hypoplastic CC external genitalia. Early lethality is common, although survival into CC childhood and beyond has been reported. {ECO:0000269|PubMed:22197488, CC ECO:0000269|PubMed:22197489, ECO:0000269|PubMed:25691407}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: CHAND syndrome (CHANDS) [MIM:214350]: An autosomal recessive CC syndrome characterized by ankyloblepharon, sparse, curly and woolly CC hair, nail dysplasia, and oral frenula. {ECO:0000269|PubMed:23610050, CC ECO:0000269|PubMed:26129644}. Note=The disease may be caused by CC variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr CC protein kinase 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; AB047783; BAB56136.1; -; mRNA. DR EMBL; AP001743; BAA95526.1; -; Genomic_DNA. DR CCDS; CCDS13675.1; -. [P57078-2] DR AlphaFoldDB; P57078; -. DR SMR; P57078; -. DR DIP; DIP-40722N; -. DR IntAct; P57078; 405. DR STRING; 9606.ENSP00000332454; -. DR BindingDB; P57078; -. DR ChEMBL; CHEMBL6083; -. DR DrugBank; DB12010; Fostamatinib. DR DrugCentral; P57078; -. DR iPTMnet; P57078; -. DR PhosphoSitePlus; P57078; -. DR BioMuta; RIPK4; -. DR DMDM; 10719883; -. DR CPTAC; CPTAC-2927; -. DR CPTAC; CPTAC-2928; -. DR EPD; P57078; -. DR jPOST; P57078; -. DR MassIVE; P57078; -. DR MaxQB; P57078; -. DR PaxDb; 9606-ENSP00000332454; -. DR PeptideAtlas; P57078; -. DR ProteomicsDB; 56989; -. [P57078-1] DR ProteomicsDB; 56990; -. [P57078-2] DR Pumba; P57078; -. DR Antibodypedia; 9243; 323 antibodies from 27 providers. DR Ensembl; ENST00000332512.8; ENSP00000332454.3; ENSG00000183421.12. [P57078-2] DR Ensembl; ENST00000352483.3; ENSP00000330161.2; ENSG00000183421.12. [P57078-1] DR MANE-Select; ENST00000332512.8; ENSP00000332454.3; NM_020639.3; NP_065690.2. [P57078-2] DR UCSC; uc002yzn.2; human. [P57078-1] DR AGR; HGNC:496; -. DR GeneCards; RIPK4; -. DR HGNC; HGNC:496; RIPK4. DR HPA; ENSG00000183421; Tissue enhanced (esophagus). DR MalaCards; RIPK4; -. DR MIM; 214350; phenotype. DR MIM; 263650; phenotype. DR MIM; 605706; gene. DR neXtProt; NX_P57078; -. DR OpenTargets; ENSG00000183421; -. DR Orphanet; 1234; Bartsocas-Papas syndrome. DR Orphanet; 1401; CHAND syndrome. DR VEuPathDB; HostDB:ENSG00000183421; -. DR eggNOG; KOG0192; Eukaryota. DR eggNOG; KOG0504; Eukaryota. DR GeneTree; ENSGT00940000159908; -. DR HOGENOM; CLU_015188_0_0_1; -. DR InParanoid; P57078; -. DR OMA; HSKENTC; -. DR PhylomeDB; P57078; -. DR TreeFam; TF106506; -. DR PathwayCommons; P57078; -. DR SignaLink; P57078; -. DR SIGNOR; P57078; -. DR ChiTaRS; RIPK4; human. DR Pharos; P57078; Tchem. DR PRO; PR:P57078; -. DR Proteomes; UP000005640; Chromosome 21. DR RNAct; P57078; Protein. DR Bgee; ENSG00000183421; Expressed in esophagus squamous epithelium and 130 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW. DR GO; GO:0002009; P:morphogenesis of an epithelium; IMP:UniProtKB. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB. DR CDD; cd14025; STKc_RIP4_like; 1. DR Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 3. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR002110; Ankyrin_rpt. DR InterPro; IPR036770; Ankyrin_rpt-contain_sf. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR PANTHER; PTHR24198; ANKYRIN REPEAT AND PROTEIN KINASE DOMAIN-CONTAINING PROTEIN; 1. DR PANTHER; PTHR24198:SF65; RECEPTOR-INTERACTING SERINE_THREONINE-PROTEIN KINASE 4; 1. DR Pfam; PF12796; Ank_2; 3. DR Pfam; PF13637; Ank_4; 2. DR Pfam; PF00069; Pkinase; 1. DR PRINTS; PR01415; ANKYRIN. DR SMART; SM00248; ANK; 10. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF48403; Ankyrin repeat; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS50297; ANK_REP_REGION; 1. DR PROSITE; PS50088; ANK_REPEAT; 9. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; P57078; HS. PE 1: Evidence at protein level; KW Alternative splicing; ANK repeat; ATP-binding; Cytoplasm; Disease variant; KW Ectodermal dysplasia; Isopeptide bond; Kinase; Membrane; KW Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; Repeat; KW Serine/threonine-protein kinase; Transferase; Ubl conjugation. FT CHAIN 1..832 FT /note="Receptor-interacting serine/threonine-protein kinase FT 4" FT /id="PRO_0000086613" FT DOMAIN 22..286 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REPEAT 485..514 FT /note="ANK 1" FT REPEAT 518..547 FT /note="ANK 2" FT REPEAT 551..580 FT /note="ANK 3" FT REPEAT 584..613 FT /note="ANK 4" FT REPEAT 617..647 FT /note="ANK 5" FT REPEAT 651..680 FT /note="ANK 6" FT REPEAT 684..713 FT /note="ANK 7" FT REPEAT 717..746 FT /note="ANK 8" FT REPEAT 750..780 FT /note="ANK 9" FT REPEAT 782..811 FT /note="ANK 10" FT REGION 325..368 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 389..424 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 330..355 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 143 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 28..36 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 51 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT SITE 388..389 FT /note="Cleavage" FT /evidence="ECO:0000269|PubMed:12446564" FT SITE 426..427 FT /note="Cleavage" FT /evidence="ECO:0000269|PubMed:12446564" FT CROSSLNK 51 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:21931591" FT CROSSLNK 145 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:21931591" FT VAR_SEQ 278..325 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.1" FT /id="VSP_004862" FT VARIANT 12 FT /note="A -> G (in dbSNP:rs6586239)" FT /id="VAR_030160" FT VARIANT 81 FT /note="I -> N (in BPS; dbSNP:rs387906922)" FT /evidence="ECO:0000269|PubMed:22197488" FT /id="VAR_067331" FT VARIANT 121 FT /note="I -> N (in BPS; loss of function; FT dbSNP:rs387906923)" FT /evidence="ECO:0000269|PubMed:22197489" FT /id="VAR_067332" FT VARIANT 163 FT /note="G -> D (in CHANDS; uncertain significance; FT dbSNP:rs764278537)" FT /evidence="ECO:0000269|PubMed:23610050" FT /id="VAR_081473" FT VARIANT 177 FT /note="S -> N (in dbSNP:rs12482626)" FT /id="VAR_030161" FT VARIANT 184 FT /note="T -> I (in BPS; loss of function)" FT /evidence="ECO:0000269|PubMed:22197489" FT /id="VAR_067333" FT VARIANT 189 FT /note="P -> L (in BPS; uncertain significance)" FT /evidence="ECO:0000269|PubMed:25691407" FT /id="VAR_085697" FT VARIANT 284 FT /note="E -> K (in CHANDS; uncertain significance)" FT /evidence="ECO:0000269|PubMed:26129644" FT /id="VAR_081474" FT VARIANT 462 FT /note="I -> N (in dbSNP:rs55809511)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041050" FT VARIANT 463 FT /note="V -> M (in dbSNP:rs55645753)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041051" FT VARIANT 496 FT /note="A -> P (in BPS; uncertain significance)" FT /evidence="ECO:0000269|PubMed:25691407" FT /id="VAR_085698" FT VARIANT 562 FT /note="N -> Y (in dbSNP:rs55829311)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041052" FT VARIANT 666 FT /note="R -> H (in BPS; uncertain significance; FT dbSNP:rs763794698)" FT /evidence="ECO:0000269|PubMed:25691407" FT /id="VAR_085699" FT VARIANT 669 FT /note="R -> H (in dbSNP:rs56056485)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041053" FT VARIANT 749 FT /note="P -> S (in dbSNP:rs35537517)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041054" FT CONFLICT 714 FT /note="M -> V (in Ref. 1; BAB56136)" FT /evidence="ECO:0000305" SQ SEQUENCE 832 AA; 91611 MW; 5D8FFFD5F04F7ECB CRC64; MEGDGGTPWA LALLRTFDAG EFTGWEKVGS GGFGQVYKVR HVHWKTWLAI KCSPSLHVDD RERMELLEEA KKMEMAKFRY ILPVYGICRE PVGLVMEYME TGSLEKLLAS EPLPWDLRFR IIHETAVGMN FLHCMAPPLL HLDLKPANIL LDAHYHVKIS DFGLAKCNGL SHSHDLSMDG LFGTIAYLPP ERIREKSRLF DTKHDVYSFA IVIWGVLTQK KPFADEKNIL HIMVKVVKGH RPELPPVCRA RPRACSHLIR LMQRCWQGDP RVRPTFQGNG LNGELIRQVL AALLPVTGRW RSPGEGFRLE SEVIIRVTCP LSSPQEITSE TEDLCEKPDD EVKETAHDLD VKSPPEPRSE VVPARLKRAS APTFDNDYSL SELLSQLDSG VSQAVEGPEE LSRSSSESKL PSSGSGKRLS GVSSVDSAFS SRGSLSLSFE REPSTSDLGT TDVQKKKLVD AIVSGDTSKL MKILQPQDVD LALDSGASLL HLAVEAGQEE CAKWLLLNNA NPNLSNRRGS TPLHMAVERR VRGVVELLLA RKISVNAKDE DQWTALHFAA QNGDESSTRL LLEKNASVNE VDFEGRTPMH VACQHGQENI VRILLRRGVD VSLQGKDAWL PLHYAAWQGH LPIVKLLAKQ PGVSVNAQTL DGRTPLHLAA QRGHYRVARI LIDLCSDVNV CSLLAQTPLH VAAETGHTST ARLLLHRGAG KEAMTSDGYT ALHLAARNGH LATVKLLVEE KADVLARGPL NQTALHLAAA HGHSEVVEEL VSADVIDLFD EQGLSALHLA AQGRHAQTVE TLLRHGAHIN LQSLKFQGGH GPAATLLRRS KT //