Pro-neuregulin-1, membrane-bound isoform

UniProt data

UniProt name: NRG1_HUMAN (Q02297)

Gene name: NRG1; Synonyms=GGF, HGL, HRGA, NDF, SMDF

Organism: Homo sapiens (Human).

Function: Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. The multiple isoforms perform diverse functions such as inducing growth and differentiation of epithelial, glial, neuronal, and skeletal muscle cells; inducing expression of acetylcholine receptor in synaptic vesicles during the formation of the neuromuscular junction; stimulating lobuloalveolar budding and milk production in the mammary gland and inducing differentiation of mammary tumor cells; stimulating Schwann cell proliferation; implication in the development of the myocardium such as trabeculation of the developing heart. Isoform 10 may play a role in motor and sensory neuron development. Binds to ERBB4 (PubMed:10867024, PubMed:7902537). Binds to ERBB3 (PubMed:20682778). Acts as a ligand for integrins and binds (via EGF domain) to integrins ITGAV:ITGB3 or ITGA6:ITGB4. Its binding to integrins and subsequent ternary complex formation with integrins and ERRB3 are essential for NRG1-ERBB signaling. Induces the phosphorylation and activation of MAPK3/ERK1, MAPK1/ERK2 and AKT1 (PubMed:20682778). Ligand-dependent ERBB4 endocytosis is essential for the NRG1-mediated activation of these kinases in neurons (By similarity). {ECO:0000250|UniProtKB:P43322, ECO:0000269|PubMed:10867024, ECO:0000269|PubMed:1348215, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:7902537}.

Subcellular location: Isoform 10: Membrane; Single-pass type I membrane protein. Note=May possess an internal uncleaved signal sequence.

Transmembrane domains:

  1. 243-265, 23 AA, Helical; Note=Internal signal sequence. {ECO:0000255}.

Sequence: 640 AA

10 20 30 40 50 60 MSERKEGRGK GKGKKKERGS GKKPESAAGS QSPALPPRLK EMKSQESAAG SKLVLRCETS 70 80 90 100 110 120 SEYSSLRFKW FKNGNELNRK NKPQNIKIQK KPGKSELRIN KASLADSGEY MCKVISKLGN 130 140 150 160 170 180 DSASANITIV ESNEIITGMP ASTEGAYVSS ESPIRISVST EGANTSSSTS TSTTGTSHLV 190 200 210 220 230 240 KCAEKEKTFC VNGGECFMVK DLSNPSRYLC KCQPGFTGAR CTENVPMKVQ NQEKAEELYQ 250 260 270 280 290 300 KRVLTITGIC IALLVVGIMC VVAYCKTKKQ RKKLHDRLRQ SLRSERNNMM NIANGPHHPN 310 320 330 340 350 360 PPPENVQLVN QYVSKNVISS EHIVEREAET SFSTSHYTST AHHSTTVTQT PSHSWSNGHT 370 380 390 400 410 420 ESILSESHSV IVMSSVENSR HSSPTGGPRG RLNGTGGPRE CNSFLRHARE TPDSYRDSPH 430 440 450 460 470 480 SERYVSAMTT PARMSPVDFH TPSSPKSPPS EMSPPVSSMT VSMPSMAVSP FMEEERPLLL 490 500 510 520 530 540 VTPPRLREKK FDHHPQQFSS FHHNPAHDSN SLPASPLRIV EDEEYETTQE YEPAQEPVKK 550 560 570 580 590 600 LANSRRAKRT KPNGHIANRL EVDSNTSSQS SNSESETEDE RVGEDTPFLG IQNPLAASLE 610 620 630 ATPAFRLADS RTNPAGRFST QEEIQARLSS VIANQDPIAV

CATM prediction

The sequence of NRG1_HUMAN returned 1 potential models

The positions at the dimer's interface are highlighted in yellow. The position at the crossing point is highlighted in orange.

# Sequence and interface d θ Z' ω' Score
  240       250       260      
|    +    |    +    |    +   		 (Å) (°) (Å) (°)  
Model 1 QKRVLTITGICIALLVVGIMCVVAYCKTK 7.3 -47.1° 1.3 45.0 -15.6

Click on the model number to visualize its details below.

MODEL 1 DETAILS

Precited structure:


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Download model 1 structure: PDB, PyMOL session

List of hydrogen bonds:

Donor Acceptor Distance
B, 245, THR, HA A, 244, LEU, O 3.48Å
B, 248, GLY, HA1 A, 245, THR, O 3.09Å
B, 249, ILE, HA A, 248, GLY, O 3.26Å
A, 245, THR, HA B, 244, LEU, O 3.48Å
A, 248, GLY, HA1 B, 245, THR, O 3.09Å
A, 249, ILE, HA B, 248, GLY, O 3.26Å