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Overview

Uniprot ID	O08873
Protein Name	MAP kinase-activating death domain protein
Gene Name	Madd
Organism	Rattus norvegicus

Kla Sites from experimental identification

Position	Flanking peptide
1446	INMTYCPKTKVLCLW

Function

Guanyl-nucleotide exchange factor that regulates small GTPases of the Rab family (PubMed:9020086). Converts GDP-bound inactive form of RAB27A and RAB27B to the GTP-bound active forms (By similarity). Converts GDP-bound inactive form of RAB3A, RAB3C and RAB3D to the GTP-bound active forms, GTPases involved in synaptic vesicle exocytosis and vesicle secretion (PubMed:9020086). Plays a role in synaptic vesicle formation and in vesicle trafficking at the neuromuscular junction (By similarity). Involved in up-regulating a post-docking step of synaptic exocytosis in central synapses (By similarity). Probably by binding to the motor proteins KIF1B and KIF1A, mediates motor-dependent transport of GTP-RAB3A-positive vesicles to the presynaptic nerve terminals (By similarity). Plays a role in TNFA-mediated activation of the MAPK pathway, including ERK1/2 (By similarity). May link TNFRSF1A with MAP kinase activation (By similarity). May be involved in the regulation of TNFA-induced apoptosis (By similarity)

Protein Sequence

10 MVQKKFCPRL 20 LDYLVIVGAR 30 HPSSDSVAQT 40 PELLRRYPLE 50 DHPEFPLPPD 60 VVFFCQPEGC 70 LSVRQRRMSL 80 RDDTSFVFTL 90 TDKDTGVTRY 100 GICVNFYRSF 110 QKRMPKEKAE 120 GGAGPRGKEG 130 AHAPCASEEA 140 ATESSESGST 150 LQPPSADSTP 160 DVNQSPRGKR 170 RAKAGNRSRN 180 STLTSLCVLS 190 HYPFFSTFRE 200 CLYTLKRLVD 210 CCSERLLGKK 220 PGIPRGVQRD 230 TMWRIFTGSL 240 LVEEKSSALL 250 HDLREIEAWI 260 YRLLRSPVPV 270 SGQKRVDIEV 280 LPQEVQQALT 290 FALPDPSRFT 300 LVDFPLHLPL 310 ELLGVDACLQ 320 VLTCILLEHK 330 VVLQSRDYNA 340 LSMSVMAFVA 350 MIYPLEYMFP 360 VIPLLPTCMA 370 SAEQLLLAPT 380 PYIIGVPASF 390 FLYKLDFKMP 400 DDVWLVDLDS 410 NRVIAPTNAE 420 VLPILPEPES 430 LELKKHLKQA 440 LASMSLNTQP 450 ILNLEKFHEG 460 QETPLLLGRF 470 SNDLQSTPST 480 EFNPLIYGND 490 VDSVDVATRV 500 AMVRFFNSAN 510 VLQGFQMHTR 520 TLRLFPRPVV 530 AFQAGSFLAS 540 RPRQTPFAEK 550 LARTQAVEYF 560 GEWILNPSNY 570 AFQRIHNNTF 580 DPALIGDKPK 590 WYAHQLQPIH 600 YRVYDSNSQL 610 AEALSVPPER 620 DSESDPTDDS 630 GSDSMDYDDS 640 SSSYSSLGDF 650 VSEMMKCDIN 660 GDTPNVDPLT 670 HAALGDASEV 680 EIDELQPQKE 690 GEEPGPDSEN 700 SQENLPLRSS 710 SSTTASSSPS 720 TIVHGAHSEP 730 ADSTEVGDKA 740 ATGISKPLPP 750 VPPSICKSTV 760 DRRQTETGEG 770 SVCQRTYDHP 780 YFEPQYGSPA 790 EEDDDEQGES 800 YTPRFSQHAS 810 GSRAQKLLRP 820 NSLKLASDSD 830 AESDSRASSP 840 NSTVSNNSTE 850 GFGGIMSFAS 860 SLYRNHSTSF 870 SLSNLTLPTK 880 GAREKTTPFP 890 SLKGNRRALV 900 DQKSSVIKHS 910 PTVKREPPSP 920 QGRSSNSSEN 930 QQFLKEVVHS 940 VLDGQGVGWL 950 NMKKVRRLLE 960 SEQLRVFVLS 970 KLSRAVQSED 980 DARQDVIQDV 990 EISRKVYKGM 1000 LDLLKCTVLS 1010 LEQSYAHAGL 1020 GGMASIFGLL 1030 EIAQTHYYSK 1040 EPDKRKRSPT 1050 ENVNTPVGKD 1060 PGLAGRGDPK 1070 AMAQLRVPQL 1080 GPRAPSATGR 1090 GPKELDTRSL 1100 KEENFVASVG 1110 PEVIKPVFDL 1120 GETEEKKSQI 1130 SADSGVSLAS 1140 ASQRTDQDSV 1150 IGVSPAVMIR 1160 SSSQDSEVSN 1170 SSGETLGADS 1180 DLSSNAGDGP 1190 GGEGSAHLAS 1200 SRATLSDSEI 1210 ETNSATSTIF 1220 GKAHSLKPKE 1230 KPASSPVRSS 1240 EDVSQRVYLY 1250 EGLLGRDKGS 1260 MWDQLEDAAM 1270 ETFSISKERS 1280 TLWDQMQFWE 1290 DAFLDAVMLE 1300 REGMGMDQGP 1310 QEMIDRYLSL 1320 GEHDRKRLED 1330 DEDRLLATLL 1340 HNLISYMLLM 1350 KVNKNDIRKK 1360 VRRLMGKSHV 1370 GLVYSQQINE 1380 VLDQLTNLNG 1390 RDLSIRSSGS 1400 RHMKKQTFVV 1410 HAGTDTNGDI 1420 FFMEVCDDCV 1430 VLRSNIGTVY 1440 ERWWYEKLIN 1450 MTYCPKTKVL 1460 CLWRRNGSET 1470 QLNKFYTKKC 1480 RELYYCVKDS 1490 MERAAARQQS 1500 IKPGPELGGE 1510 FPVQDMKTGE 1520 GGLLQVTLEG 1530 INLKFMHNQV 1540 FIELNHIKKC 1550 NTVRGVFVLE 1560 EFVPEIKEVV 1570 SHKYKTPMAH 1580 EICYSVLCLF 1590 SYVAAVRSSE 1600 EDLRTPPRPV SS

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:1904115	axon cytoplasm
Cellular Component	GO:0005829	cytosol
Cellular Component	GO:0016020	membrane
Cellular Component	GO:0005886	plasma membrane
Cellular Component	GO:0045202	synapse
Cellular Component	GO:0008021	synaptic vesicle
Molecular Function	GO:0005085	guanyl-nucleotide exchange factor activity
Biological Process	GO:0048490	anterograde synaptic vesicle transport
Biological Process	GO:0097194	execution phase of apoptosis
Biological Process	GO:2001234	negative regulation of apoptotic signaling pathway
Biological Process	GO:0060125	negative regulation of growth hormone secretion
Biological Process	GO:1902277	negative regulation of pancreatic amylase secretion
Biological Process	GO:0043410	positive regulation of MAPK cascade
Biological Process	GO:0042981	regulation of apoptotic process
Biological Process	GO:0051726	regulation of cell cycle
Biological Process	GO:2001236	regulation of extrinsic apoptotic signaling pathway
Biological Process	GO:1902041	regulation of extrinsic apoptotic signaling pathway via death domain receptors
Biological Process	GO:0032483	regulation of Rab protein signal transduction

Reference

[1] Chen Y, Sun W, Sun Z, Zhao H, Wu T et al.. Effect of electroacupuncture on hippocampal protein lactylation in a rat model of vascular dementia.. Front Neurol 16:1629474. 2025. PMID: 40963935.